Fine needle aspiration biopsy (FNAB) is an accurate test commonly used to determine whether thyroid nodules are malignant in adults. However, less is known about its diagnostic accuracy for this purpose in children, where conduct of FNAB is less frequent, more technically challenging, and pre-test probabilities of malignancy are often higher. The purpose of this systematic review is to evaluate the diagnostic accuracy of FNAB for the detection of malignancy in pediatric thyroid nodules.We will search electronic bibliographic databases  from their date of inception, reference lists of included articles, proceedings from relevant conferences, and the table of contents of the Journal of Pediatric Surgery (January 2007–present). Two reviewers will independently screen titles and abstracts and identify diagnostic accuracy studies involving FNAB of the thyroid in children. We will include studies comparing FNAB to a reference standard of surgical histopathology or clinical follow-up for detection of malignancy in pediatric thyroid nodules. Two investigators will independently extract data and assess risk of bias using the Quality of Diagnostic Accuracy Studies-II tool. Pooled estimates of sensitivity, specificity, and positive and negative likelihood ratios will be calculated using bivariate random-effects and hierarchical summary receiver operating characteristic models. In the presence of between-study heterogeneity, we will conduct stratified meta-analyses and meta-regression to determine whether diagnostic accuracy estimates vary by country of origin, use of ultrasound guidance during FNAB, qualifications of the individuals performing/interpreting FNAB, adherence to the Bethesda criteria for cytology classification, length of clinical follow-up, timing of data collection, patient selection methods, and presence of verification bias.This meta-analysis will determine the diagnostic accuracy of FNAB for detection of malignancy in pediatric thyroid nodules and explore whether heterogeneity observed across studies may be explained by variations in patient population, FNAB technique or interpretation, and/or study-level risks of bias. This will be the first study to determine the accuracy of Bethesda cytological classification levels of FNAB . We expect that our results will help in guiding clinical decision-making in children with thyroid nodules.CRD42014007140PROSPERO No.  Thyroid nodules are uncommon in children, with a prevalence ranging from 0.05 to 2% –6. NodulSome authors have advocated that the increased malignant potential of thyroid nodules in children justifies the liberal use of surgical exploration in several pediatric populations . HoweverFine needle aspiration biopsy (FNAB), also known as fine needle aspiration cytology, has been used since the early 1980s to classify the cytology of (and thereby diagnose) suspicious superficial soft tissue lesions. Improvements in ultrasound (US) technology have led to increased detection of incidental thyroid nodules and, consequently, more frequent use of FNAB . A generIn 2007, the Thyroid FNAB State of the Science Conference addressed the varying terminology in FNAB reporting, concluding that inconsistencies prevented comparisons of diagnoses across different sites. Prior to the conference, most pathologists classified FNAB cytology as inadequate, benign, malignant, or indeterminate using variable definitions. Discussions at this conference resulted in the publication of the Bethesda System for Reporting Thyroid Cytopathology  in 2009. The Bethesda criteria classify FNAB samples as non-diagnostic, benign, atypia/follicular lesion of undetermined significance, follicular neoplasm or suspicious for follicular neoplasm, suspicious for malignancy, or malignant . The lar. [Although a meta-analysis was published in 2009 evaluating the accuracy of FNAB for detection of malignancy in pediatric thyroid nodules, another systematic review is urgently required for several reasons . First, . , potenti.  did not . –26. In pThis study adopts recommendations on the conduct and reporting of systematic reviews and meta-analyses outlined by the Preferred Reporting Items in Systematic Reviews and Meta-Analyses statement, the Meta-Analysis of Observational Studies in Epidemiology proposal, and the Cochrane Diagnostic Test Accuracy Working Group –30. The In pediatric patients with a thyroid nodule, is FNAB as accurate as surgical histopathology or clinical follow-up for the detection of thyroid malignancy?Patients ≤18 years of age, or those defined as exclusively pediatric patients by the authors, with a thyroid nodule that is palpable or seen on diagnostic imagingPopulationFNAB of the thyroid nodule, with or without US guidanceInterventionSurgical histopathology or clinical follow-upComparisonTest accuracy for detection of thyroid malignancy as defined by the authors, including true and false positives and negatives, sensitivity and specificity, and positive and negative likelihood ratiosOutcomeDiagnostic accuracy studies DesignPICOD componentsTest accuracy of FNAB for as defined by the authorsPrimary outcomeTest accuracy of FNAB for classification of lesions according to the Bethesda criteria . This outcome was chosen as secondary instead of primary to allow for a comprehensive evaluation of the accuracy of FNAB for classifying thyroid nodules in children (according to both Bethesda and non-Bethesda criteria)Test accuracy of FNAB with or without US guidance for detection of thyroid malignancySecondary outcomesJournal of Pediatric Surgery from January 2007 onward. To identify unpublished and/or ongoing studies, we will contact experts in the field and search clinical trials registries , reference lists of included articles, and conference proceedings of major pediatric surgery  and pediatric endocrinology (European Society for Pediatric Endocrinology and Pediatric Endocrine Society/Lawson Wilkins Pediatric Endocrine Society) meetings from 2007 to 2015.We will search Ovid MEDLINE and EMBASE, the Cochrane Database of Systematic Reviews, and Evidence-Based Medicine from their date of first inception, without language, publication date, or other restrictions. PubMed will also be searched to capture articles not yet indexed in MEDLINE. We will also use the PubMed “related articles” feature for articles included in the systematic review and manually search the table of contents for the With the assistance of an information scientist/medical librarian, we developed search filters encompassing the themes thyroid, biopsy, and pediatrics, using a combination of keywords and Medical Subject Heading (MeSH)/Emtree terms Table . These tPatients ≤18 years of age or described to be pediatric by the author(s)FNAB performed on the thyroidAfter removing duplicate citations, two investigators  will independently screen all remaining titles and abstracts in duplicate. This initial screen will be broad intentionally to avoid missing potentially relevant citations. We will subsequently review the full text of any citations that appear to satisfy the following criteria:Those articles identified for full text review will subsequently be read independently in full by the same two investigators  to determine their eligibility for inclusion in the systematic review. We will use the following inclusion/exclusion criteria based on PICOD:The study population consisted of patients ≤18 years of age , with a thyroid nodule that is palpable or seen on diagnostic imagingData for at least ten pediatric patients were reported PopulationThe index test was FNAB of a thyroid nodule, with or without US guidanceInterventionThe reference standard was surgical histopathology or clinical follow-upComparisonThe studies examined test accuracy for detection of thyroid malignancy as defined by the authors, including true and false positives and negatives, sensitivity and specificity, and positive and negative likelihood ratiosSufficient data were presented to tabulate the results comparing FNAB to surgical pathology or clinical follow-up into two-by-two contingency tables Fig. Fig. 1TwoOutcomeDiagnostic accuracy studies (single gated) that compare the results of an index test to the results of a reference standard on the same subjects –35DesignInclusion criteriaDuplicate data setsArticles with smaller cohorts will be excludedAuthors will be contacted to clarify their patient population if the degree of overlap is unclearOverlapping data setsNon-human studiesStudies involving patients with exclusively malignant or benign thyroid surgical histopathologyNon original dataExclusion criteriaTwo investigators  will pilot test inclusion and exclusion criteria using 20 randomly selected articles to ensure complete investigator agreement of the criteria. Agreement regarding inclusion and exclusion of full-text articles between the two investigators  will be quantified using the kappa statistic. A kappa statistic greater than 0.6 will be considered moderate agreement . DisagreFirst authorTitleYear of publicationStudy informationRetrospective, prospectiveDirectionality of data collectionConsecutive, randomParticipant selection methodIncluding whether thyroid surgery was listed as a prerequisite for enrolmentInclusion and exclusion criteriaCountry of origin, single versus multi-siteStudy settingStudy design and methodologySample sizeAge, genderParticipant characteristicsPatient sample informationNumber of biopsies, complications, use of US guidance, qualifications of the individual performing FNAB FNAB descriptionAdherence to Bethesda or other criteria, qualifications of pathologist reporting results FNAB reportingExperimental (index) test (FNAB)Type of surgery performed Length of time between FNAB and surgeryResults of surgical histopathology Qualifications of pathologist reporting results Number of patients who did not proceed from FNAB to surgeryLength and type of follow-up Number of patients lost to follow-upReference standard testBlinding of the pathologists to the results of FNAB and surgical histopathologyFigure This table will be used to generate pooled estimates of diagnostic accuracy  as our primary outcomeData to populate a two-by-two table Fig.  to assesTo evaluate the test accuracy of each FNAB diagnostic category to predict malignancy, the six-by-six data will be condensed into multiple two-by-two contingency tables by altering the threshold of interpretation of FNAB results as test negative or positive. Figure Figure These tables will be used to generate multiple pooled estimates of diagnostic accuracy  for each comparisonFor our secondary outcome analysis, where possible, we will extract data to populate six-by-six tables Fig.  to assesStudy results and analysisTwo investigators  will extract data from all eligible diagnostic studies independently and in duplicate using a predesigned Microsoft Access 2010  database form. This database form will be pilot tested on a random sample of five included studies until reliable data extraction is confirmed (kappa statistic > 0.6) . We willNon-English language literature will be translated by interpreters. Agreement between the two investigators  will be ensured by consensus or arbitration by a third party (DJR or DMR) as needed.The risk of bias of each article will be evaluated independently by two investigators  and reported according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool . The preSpectrum bias occurs when study participants do not represent the population of interest due to inappropriate patient selection. This is an anticipated source of bias in articles where thyroid surgery forms part of the inclusion criteria. These exclusively surgical cohorts likely represent a distinct subset of the population with more worrisome findings and a higher pre-test probability for malignancy, leading to potential differences in diagnostic accuracy results. Another example of spectrum bias includes studies targeting hypothyroid or hyperthyroid patients specifically, where extrapolation to the general pediatric population with thyroid nodules may be inappropriate.Threshold bias develops when pathologists use varying definitions to report FNAB results. This leads to a greater likelihood to diagnose benign or malignant disease based on an individual pathologist’s threshold of concern. The Bethesda criteria were introduced to standardize FNAB classification and minimize threshold bias. Studies reporting results by Bethesda versus other criteria will be compared to evaluate the potential contribution of threshold bias to diagnostic accuracy.Disease progression bias is a concern when the interval between the index test and reference standard is long enough to potentially allow progression of disease from benign to malignant or from one type of malignant disease to another. An index test may be negative and the reference test positive due to rapid development of malignancy, rather than signify an inaccurate index test. To assess the risk of disease progression bias, an appropriate time frame between FNAB and surgery and length of clinical follow-up would need to be defined. However, this interval is not well described in the literature as the latency period for development of thyroid malignancy after discovery of a nodule may extend for years, despite exposure to known risk factors , 40. As Partial verification bias occurs when results of the index test influence whether or not the patient receives the reference standard. There is significant potential for this type of bias among the studies that will be included in this systematic review as benign cytology may decrease the likelihood of any type of follow-up, whether surgical or clinical, unless there are other significant risk factors for malignancy. Partial verification bias frequently leads to inflated diagnostic accuracy as benign FNAB results may be assumed inappropriately to represent true negative disease . DiffereAs a supplement to the QUADAS-2 tool, we will also examine the timing of data collection , the qualifications of the individual performing the FNAB  or the interpreting pathologist , and adherence of cytology reporting to the Bethesda versus other criteria.Disagreements between the two investigators  will be resolved by consensus or arbitration by a third party (DJR or DMR).True and false positives and negatives will be defined by two-by-two contingency tables Fig.  for the I2- and Q-statistics [Bivariate random-effects models will be used to derive pooled estimates of sensitivity, specificity, and positive and negative likelihood ratios for detection of malignancy with FNAB , 45, 46.atistics .In the presence of inter-study heterogeneity, we will use the bivariate model to conduct subgroup analyses and meta-regression to determine whether a number of pre-defined covariates may explain variation in reported diagnostic performance results across studies , 48–50. All statistical analyses will be performed using Stata version 13.1 , including the “midas” and “metandi” command packages , 43, 55.Thyroid nodules can provoke anxiety in children, families, and physicians alike due to diagnostic uncertainty in the setting of greater potential for malignancy. The ability of a diagnostic test to distinguish malignant from benign disease is paramount for clinicians to provide appropriate counselling regarding treatment and prognostication. In addition to providing a systematic review and meta-analysis of the diagnostic accuracy of FNAB in pediatric thyroid nodules for the detection of malignancy, this will be the first study to determine the accuracy of FNAB according to the Bethesda criteria. In doing this, our results may serve as a better guide for clinical decision-making in children with thyroid nodules.Although the American Thyroid Association endorses FNAB as the standard of care in North America for the evaluation of thyroid nodules in adults and children, the evidence supporting this recommendation is likely based on the results of studies conducted among adults. Pediatric studies may be limited by several study-level biases. Thus, this systematic review and meta-analysis will rigorously examine the potential magnitude of influence that individual study-level biases may have on the diagnostic accuracy of FNAB. Other specific aims to be addressed by this study include determining the value of adherence to the Bethesda criteria, US guidance, and the qualifications of the individual performing and interpreting the FNAB on the diagnostic accuracy of FNAB. If these factors are found to enhance diagnostic accuracy, this may support the need for routine referral of children with thyroid nodules to specialty centres where US and FNAB-trained personnel are available to improve patient care and outcomes.


Antioxidant defence system, a highly conserved biochemical mechanism, protects organisms from harmful effects of reactive oxygen species (ROS), a by-product of metabolism. Both invertebrates and vertebrates are unable to modify environmental physical factors such as photoperiod, temperature, salinity, humidity, oxygen content, and food availability as per their requirement. Therefore, they have evolved mechanisms to modulate their metabolic pathways to cope their physiology with changing environmental challenges for survival. Antioxidant defences are one of such biochemical mechanisms. At low concentration, ROS regulates several physiological processes, whereas at higher concentration they are toxic to organisms because they impair cellular functions by oxidizing biomolecules. Seasonal changes in antioxidant defences make species able to maintain their correct ROS titre to take various physiological functions such as hibernation, aestivation, migration, and reproduction against changing environmental physical parameters. In this paper, we have compiled information available in the literature on seasonal variation in antioxidant defence system in various species of invertebrates and vertebrates. The primary objective was to understand the relationship between varied biological phenomena seen in different animal species and conserved antioxidant defence system with respect to seasons. Types of seasons and their duration may vary from one ecological region to another and influence the physiology of the inhabiting flora and fauna . VariatiMetabolism is a direct reflection of cellular respiration where molecular oxygen is tetraelectronically reduced to water in electron transport chain of mitochondria to generate ATP to meet their energy requirement . NeverthThere are several reports in literature which have clearly demonstrated alterations in concentrations of various pollutants in air and water with respect to seasons , 15. GenBeing highly reactive and nonspecific in nature, ROS usually oxidize biomolecules such as lipids, carbohydrates, proteins, and DNA and, thereby, impair normal cellular functions. A shift in balance between oxidants to antioxidants in favour of oxidants is termed as “oxidative stress.” Oxidative stress is considered as cause or effects of several pathophysiological conditions, diseases, and aging processes .2•− to H2O2. Hydrogen peroxide is neutralized by two enzymes. One of them is catalase (CAT) and the other one is glutathione peroxidase (GPx) [2O2 to oxygen and water, whereas GPx reduces H2O2 and organic hydroperoxides by coupling them with oxidation of reduced glutathione (GSH). Glutathione reductase (GR) plays a major role in generating reduced glutathione from oxidized glutathione by oxidizing NADPH. Subsequently, NADPH is generated from NADP by the enzyme glucose-6-phosphate dehydrogenase (G6PDH) . Antioxidant enzymes are ubiquitous and highly conserved in their catalytic nature. Some of them are present in multiple forms. The first member of this cascade is superoxide dismutase (SOD) which dismutates Ose (GPx) . Catalas (G6PDH) . SOD is t stress . Nonenzyt stress .Animals have developed various physiological strategies such as hibernation, aestivation, and migration because they do not have control over the physical components of the environment such as food availability, temperature, and day length . Since aThe central focus of this mini review is to compile pieces of information available in literature on various parameters related to ROS and antioxidant defences in some vertebrates and invertebrates of different phyla with respect to seasons under one platform. Since components of antioxidant defence system are highly conservative, it will be interesting to find out how different species manipulate their antioxidant defences to adjust themselves to seasons.Metabolic activities and mitochondrial functions of invertebrates are regulated by several components of seasons such as photoperiod, temperature, humidity, and food availability –22. SincHowever, the major limitation in the use of antioxidant molecules or OS parameters as biomarkers to monitor environmental pollution is the lack of basic information on their seasonal variation. It is essential to ascertain the normal seasonal changes in antioxidant defence parameters before using them to monitor environment contamination. The lack of systematic information on the responses of antioxidant defences and OS markers of species to pollutants makes it difficult to use them as biomarkers to assess pollution. Laeonereis acuta, a polychaete, is commonly found in estuaries. The species is also used as biomarkers for pollution studies. Antioxidant enzymes such as SOD and CAT and OS parameter such as lipid peroxidation were investigated in the species with respect to seasons [Annelids (phylum Annelida) include ringworms, earthworms, and leeches. Annelids have adapted to various ecological zones which span aquatic (both marine and freshwater environments) to terrestrial environment. Seasonal variation of antioxidant defence system in species of this phylum is scanty. seasons . A highe seasons . It indi Mytilus edulis inhabiting same intertidal zone of France in two consecutive autumns were reported [ Mytilus to air was more (6 h/12 h) at high shore than that at low shore (2 h/12 h). The authors cautioned that for ecotoxicological studies due importance must be given on sampling sites [Molluscs (phylum Mollusca) encompass a large number of species that spread from aquatic to terrestrial ecosystem. Impacts of tidal heights on activities of antioxidant enzymes in gills and digestive glands ofreported . Resultsng sites . Mytilus galloprovincialis collected from an unpolluted site in Adriatic Sea of the species in October which was accompanied with an increase in CAT activity and LPx level [ Mytilus galloprovincialis were measured to monitor heavy metal pollution of the water of the Saronikos Gulf of Greece [It was reported that DNA strand fragmentation was elevated in tissues ofPx level . The autPx level . Activitf Greece . The autf Greece . A carefCrassostrea rhizophorae) also exhibits seasonal variation. Total oxygen radical scavenging capacity, level of LPx, and activity of GST in gills of immature adult mangrove oysters collected from polluted and nonpolluted sites of Brazilian coast were investigated in detail by Zanette et al. [Antioxidant defence system in oyster , small antioxidants (ascorbic acid and GSH), and OS markers (LPx and H2O2) were carried out in gills and digestive glands of natural population of green lipped mussel (Perna viridis) in Bambolim beach area of Goa, India [ P. viridis exhibited seasonal variation and, secondly, components of antioxidant capacity of tissues with respect to seasons varied from each other. Considering antioxidant defence parameters, both enzymatic and nonenzymatic components, the authors were of the opinion that changing environmental factors during seasons have crucial impact on regulating antioxidant defence mechanism in this species.Due to the sedentary nature, sessile-filter feeding, wide geographical distribution, and abundant availability,a, India . The autBalanus balanoides). They are dominant species in rocky shores. The authors noticed high levels of antioxidant enzymes and GST in digestive gland of the species in premonsoon period or summer followed by gradual decrease in their activities in monsoon with minimum levels in winter. Microsomal LPx exhibited a reverse trend of seasonal variation to that of antioxidant enzymes. Also the authors noticed a positive correlation between PAH and levels of antioxidant enzymes in the tissue.Most arthropod species are land dwellers and few are aquatic in nature. Niyogi et al.  studied Apis mellifera) revealed that levels of antioxidant enzymes and peroxides were higher in active season (August-September) in comparison to the other months [Scylla serrata) exhibited seasonal changes that are tissue as well as gender specific [A study on different antioxidant enzymes in honey bee  collected from creosote inlet of Elizabeth River were noticed from early to late summer [ Anguilla anguilla (European eel) and Mugil cephalus (stripped mullet), in Mediterranean lagoons in different seasons. Although responses of antioxidant defence parameters of fishes were influenced by temperature and reproductive cycle, the pattern of responses was species specific. Unlike striped mullet, antioxidant defence parameters of eels were independent of sexual maturation but were markedly influenced by high temperature of summer.Literature reveals that most of the studies related to seasonal variation of antioxidant defences in fish are investigated with respect to pollutants present in water. A decrease in GSH content and an increase in GR activity in hepatopancreas of kill fish population  from Southern Brazil suggested that changes in antioxidant enzymes with relation to season were not only species specific but also tissue specific [Barbus barbus) in spring than in summer but CAT activity was found to be in reverse order. It was reported that levels of CAT and GR enzymes in liver of Senegalese sole  exhibited seasonal variation [A comparative study on seasonal variation in antioxidant defence parameters and OS indices in tissues of four species of fish , a seasonal variation in OS in terms of generation of ROS was attributed to low availability of food [Hirundo rustica) by Raja-aho et al. [Birds are homeotherms. Some reports indicate occurrence of seasonal variation in their antioxidant defence system and OS status. Habitat and photoperiodism may be responsible for the observed seasonal variation of OS metabolism in their tissues. Poor habitat due to unavailability of food may induce intensive foraging activity which may increase generation of ROS in birds. In case of Seychelles warblers ( of food . A detaio et al. . It was o et al. .Mammals inhabiting temperate zone usually exhibit seasonal changes in their morphology, behavior, and physiology in order to cope with changing environment. Therefore, they can exhibit seasonal variation in their antioxidant defence system and OS status. Photoperiod has been shown to affect lipid droplets and LPx in bank vole . SeveralIn the present review an attempt is made to summarize information available in the literature on seasonal changes in antioxidant defence system and OS markers in invertebrates as well as in vertebrates. It is inferred that seasonal variation in antioxidant defence system may be an evolutionary strategy by animals for different adaptations against various physical aspects of environment. Also a far-fetched implication of changes in seasonal factors on global food chain cannot be denied as larval or embryonic forms of invertebrates constitute first line of primary productivity. It is apparent that various cues of seasons may regulate metabolic functions in tissues through appropriate receptors which in turn decide ROS and antioxidant defences in tissues and, thereby, govern various physiological activities in the animals .


Integration of HIV into child survival platforms is an evolving territory with multiple connotations. Most literature on integration of HIV into other health services focuses on adults; however promising practices for children are emerging. These include the Double Dividend (DD) framework, a new programming approach with dual goal of improving paediatric HIV care and child survival. In this commentary, the authors discuss why integrating HIV testing, treatment and care into child survival platforms is important, as well as its potential to advance progress towards global targets that call for, by 2020, 90% of children living with HIV to know their status, 90% of those diagnosed to be on treatment and 90% of those on treatment to be virally suppressed (90–90–90).Integration is critical in improving health outcomes and efficiency gains. In children, integration of HIV in programmes such as immunization and nutrition has been associated with an increased uptake of HIV infant testing. Integration is increasingly recognized as a case-finding strategy for children missed from prevention of mother-to-child transmission programmes and as a platform for diffusing emerging technologies such as point-of-care diagnostics. These support progress towards the 90–90–90 targets by providing a pathway for early identification of HIV-infected children with co-morbidities, prompt initiation of treatment and improved survival. There are various promising practices that have demonstrated HIV outcomes; however, few have documented the benefits of integration on child survival interventions. The DD framework is well positioned to address the bidirectional impacts for both programmes.Integration provides an important programmatic pathway for accelerated progress towards the 90–90–90 targets. Despite this encouraging information, there are still challenges to be addressed in order to maximize the benefits of integration. Yet defining and measuring integration remains elusive. In the health sector, integration of services in primary health care (PHC) can be traced back to the Alma Ata declaration adopted in 1978, which recognized the importance of primary health care as key to achieving the goal of “Health For All” . For decevidence .integration as the management and delivery of health services, where clients receive a continuum of preventive and curative services according to their needs over time and across different levels of the health system [The World Health Organization defines h system . In prach system . There ih system –8; howevThis paper examines why integrating HIV services into child survival platforms is important and discusses promising strategies, opportunities and challenges of integrating HIV services into selected child survival programmes to improve both HIV and child survival outcomes. This includes the Double Dividend (DD) framework, a new programming approach that describes the bidirectional benefits of integrating HIV services with child survival platforms . The artThe rationale for integration dwells on its potential to improve service delivery, health outcomes and efficiencies . For exaIntegration of HIV testing in child survival programmes is increasingly recognized as a case-finding strategy for children who were missed in prevention of mother-to-child transmission of HIV (PMTCT) programmes or who were infected late during the breastfeeding period. This issue is crucial, as global coverage of early infant diagnosis remains low at 39% among the 22 priority countries that contribute to over 90% of new paediatric HIV infections globally . In spitRecent successes of the PMTCT programmes in reducing HIV transmission in the prenatal and postnatal periods provide another reason for integration of services for children. There are fewer HIV-infected children being born and identified through successful PMTCT programmes . TherefoThere are two approaches for integrating HIV testing into child survival platforms that can be considered: general integrated platforms, such as in immunization sites, where integration would enable universal HIV testing or screening of all children, versus targeted integration, where the focus for testing would be on a subset of high risk children . The choice of these approaches is likely determined by each country's HIV epidemic context and health system characteristics. For instance, integration of HIV testing into routine immunization sessions may be ideal in high HIV prevalence countries , whereasBeyond integration of HIV testing, there is a need to establish feasible approaches to improving retention of HIV-exposed infants and HIV-infected infants and children in HIV care and treatment services within maternal and child health (MCH) settings. What is seen in the literature is that most of the focus of integration is on HIV testing and it does not examine delivery of paediatric HIV treatment through MCH service delivery points. In Mozambique, care of HIV-exposed and -infected children is being delivered together with care for other at-risk children through “Child at Risk” clinics providing an integrated model of service delivery for all paediatric health issues.Many countries have integrated HIV testing into one or more child survival platforms; however few have documented the specific outcomes due to lack of robust evaluation designs. There are a few instances, such as integration of HIV testing in immunization and nutrition programmes, paediatric inpatient units and community or home-based programmes –36, thatHIV and immunization integrationIncreased uptake of HIV testing through immunization services has been well described . In someHIV and nutrition integrationMalnourished children infected with HIV have an increased risk of mortality . RoutineHIV testing in children’s clinics and wardsThere is mounting experience in providing HIV testing to hospitalized or out-patient paediatric populations in high HIV prevalence settings. In Zambia over 87% of paediatric patients admitted to one hospital received HIV testing . Of thosHIV integration in community-based programmesFor decades, a community component of paediatric HIV response has been overlooked. Promising community-based paediatric HIV practices are now evident. The “Tingathe” community project in Malawi successfully used community health workers, with increased uptake of maternal and infant HIV testing . Home-baThe DD is a framework intended to catalyze actions toward the dual goals of accelerating paediatric HIV prevention, care and treatment, while contributing to improvements in child survival . It callThrough preliminary analysis undertaken during a think tank exercise in Harare, the architects of DD identified five key areas where integration of HIV and child survival platforms can be mutually beneficial and therefore improve child outcomes – in postnatal care settings, immunization clinics, nutrition points, IMCI and integrated community case management for pneumonia, diarrhoea and malaria. The DD framework proposes four operational steps that will enable countries to 1) identify major causes of U5MR, paediatric HIV infections and the unmet care needs in these areas; 2) design integrated approaches for programming in child survival and paediatric HIV based on the needs assessment; 3) deliver and monitor the package of integrated services developed; and 4) work to ensure sustainability.There are several novel dimensions to the framework: an expanded definition of the paediatric HIV-affected population to include HIV-exposed uninfected children; targeted integration of paediatric HIV in broader maternal, newborn and child health (MNCH) platforms; and greater understanding of the role that paediatric HIV infection plays in relation to common childhood diseases such as pneumonia, malaria and diarrhoea. The DD calls for a major shift in paediatric HIV programming, away from its current vertical delivery model, with the overall aim of identifying areas where investments of effort and resources will maximize prevention, care and treatment outcomes while contributing to strengthened child survival platforms.The DD comes during dialogues of post-millennium development goals and new calls to action for child and newborn health, with new targets and timelines for achieving goals . New gloAs the world moves towards sustainable development goals, we have an unprecedented opportunity to reduce the silos existing in the implementation of paediatric HIV programmes. In 2011, in the United Nations General Assembly High Level Meeting on HIV, heads of state committed to eliminating parallel systems and integrating HIV services into health and broader development programming. Efforts are needed to ensure HIV-infected children are included in the Universal Health Coverage Initiative , health The majority of critical gaps that hamper HIV service delivery also threaten basic health services. In many countries, MNCH, particularly post-natal platforms, is underdeveloped, under-utilized and in most cases under-funded. The extent and monitoring of outcomes following integration remains a challenge. For instance, most literature has focused on integration of HIV and child survival platforms at the service delivery level , with liAddressing persistent gaps in the provision of paediatric HIV services and ultimately the global targets of 90–90–90 by 2020 requires innovative approaches. Integration, as one of the programmatic innovations, has the potential to accelerate this goal through intensified case finding in child survival platforms, timely treatment initiation, improved retention and ultimately long-term survival of children exposed to or infected with HIV. Implementing the approaches that integrate HIV testing into child survival platforms (as presented in The field of integration of HIV into child survival platforms is evolving with remarkable prospects. Its potential role in case identification, treatment initiation and dissemination of new technologies should form a critical part of strategies towards the achievement of the 90–90–90 goals. The potential for the field of integration could be additionally enhanced by combining with emerging technological advances such as PoC diagnostics and optimized paediatric antiretroviral drug formulations. Defining the bidirectional dividends, including the burden of HIV in other major child health diseases, will enhance optimal care and joint investments. Adequate investments and implementation research are needed to ensure that optimal integrated models are identified and scaled up, both to achieve the goals of 90–90–90 in paediatric HIV and to improve child survival outcomes.


Childbirth and the postnatal period, spanning from right after birth to the following several weeks, presents a time in which the number of deaths reported still remain alarmingly high. Worldwide, about 800 women die from pregnancy- or childbirth-related complications daily while almost 75% of neonatal deaths occur within the first seven days of delivery and a vast majority of these occur in the first 24 hours. Unfortunately, this alarming trend of mortality persists, as287,000 women lost their lives to pregnancy and childbirth related causes in 2010. Almost all of these deaths were preventable and occurred in low-resource settings, pointing towards dearth of adequate facilities in these parts of the world. The main objective of this paper is to review the evidence based childbirth and post natal interventions which have a beneficial impact on maternal and newborn outcomes. It is a compilation of existing, new and updated interventions designed to help physicians and policy makers and enable them to reduce the burden of maternal and neonatal morbidities and mortalities. Interventions during the post natal period that were found to be associated with a decrease in maternal and neonatal morbidity and mortality included: advice and support of family planning, support and promotion of early initiation and continued breastfeeding; thermal care or kangaroo mother care for preterm and/or low birth weight babies; hygienic care of umbilical cord and skin following delivery, training health personnel in basic neonatal resuscitation; and postnatal visits. Adequate delivery of these interventions is likely to bring an unprecedented decrease in the number of deaths reported during childbirth. The number of deaths reported during childbirth and postnatal period still remain alarmingly high. Worldwide, about 800 women die from pregnancy- or childbirth-related complications daily and approximately 287,000 women lost their lives to pregnancy and childbirth related causes in 2010 . Almost th MDG focuses on reducing child mortality and is closely associated with maternal health MDG. In developing countries alone, if mothers start practicing early initiation of breastfeeding, it is estimated that it can save as many as 1.45 million lives annually by reducing deaths mainly due to lower respiratory tract infections and diarrhoeal diseases [Since the postnatal period is a critical time to deliver interventions, failure to do so leads to detrimental effects on the survival and future health of both mother and neonate. Many women die as a result of complications during and following childbirth. The major complications that account for 80% of all maternal deaths are severe bleeding (mostly bleeding after childbirth), infections , high blood pressure during pregnancy (pre-eclampsia and eclampsia), and unsafe abortion. The remainder are caused by or associated with infectious diseases during pregnancy such as malaria and AIDS. A practical and viable strategy for reducing maternal and neonatal morbidity and mortality rates from preventable causes and meeting maternal health related Millennium Development Goal (MDG) targets, is by integrating improved childbirth facilities and postnatal care for newborns and mothers . The 4thdiseases . To reduThis paper reviews and highlights the effectiveness of essential childbirth and immediate postnatal interventions for mothers and newborns during the parturition and postnatal period. This paper will help decision makers to deploy necessary interventions for improved maternal and newborn outcomes.The methodology has been described in detail elsewhere . In shorHistorically and cross-culturally, women have been attended and supported by other women during childbirth. However, since the middle of the 20th century, in many countries as the majority of women gave birth in hospital rather than at home, continuous support during labour has become an exception rather than the routine. Concerns about dehumanization of women’s birth experiences  have led to calls for a return to continuous, one-to-one support by women for women during labour . Common A systematic review by Hodnett et al. reported that women allocated to continuous support were more likely to have a spontaneous vaginal birth (risk ratio (RR) 1.08, 95% confidence interval (CI) 1.04, 1.12) and less likely to have intrapartum analgesia  or report dissatisfaction . In addition their labour were shorter (mean difference (MD) -0.58 hours, 95% CI -0.86, -0.30), they were less likely to have a caesarean  or instrumental vaginal birth , regional analgesia , or a baby with a low 5-minute Apgar score  . ContinuThe single most important risk factor for post-partum maternal infection is caesarean delivery . Women uProphylactic antibiotics in women undergoing caesarean section substantially reduce the incidence of febrile morbidity , wound infection , endometritis  and serious maternal infectious complications  . Based oExcessive bleeding or postpartum haemorrhage (PPH) during or after childbirth is a life-threatening complication and a major contributor to maternal mortality worldwide . Primaryi) Oxytocin for PPHProphylactic oxytocin showed benefits in reducing blood loss >500ml  and need for therapeutic oxytocics  compared to no uterotonic . While ai) Active management of third stage of labourIn this section we included reviews that compared AMTSL with expectant management . According to the latest guideline of WHO, AMTSL as a prophylactic intervention is composed of three steps: 1) administration of a uterotonic, preferably oxytocin, immediately after birth of the baby; 2) controlled cord traction (CCT) to deliver the placenta; and 3) massage of the uterine fundus after the placenta is delivered. In 2012, the results of a large WHO-directed, multi-centre clinical trial .Active management of third stage of labor showed reduction in the risk of haemorrhage at time of birth (>1000ml)  and of maternal haemoglobin (Hb) <9g/dL following birth  . CompareFive to ten percent of pregnancies continue beyond 294 days (42 completed weeks) and are described as being ‘post-term’ or ‘postdate’ . Both thCompared with a policy of expectant management, a policy of labour induction was associated with fewer  perinatal deaths . The number needed to treat to benefit (NNTB) with induction of labour in order to prevent one perinatal death was 410 95% CI 322, 1492) . Another2, 1492 .Primary PPH requires a multidisciplinary approach. First line treatment is with uterotonic  accompanied with bimanual compression of the uterus. The second line therapy is surgical, usually hysterectomy to prevent death from uterine haemorrhage.i) Uterine massageThe review by Hofmeyr et al. included two randomised controlled trials . The firii) Use of uterotonicOral or sublingual misoprostol when compared with placebo was found to be effective in reducing severe PPH  and blood transfusion . Compared with conventional injectable uterotonic, oral misoprostol was associated with higher risk of severe PPH  and use of additional uterotonic, but with a trend towards fewer blood transfusions  . The comThe provision of contraceptive education is now considered a standard component of postpartum care. Family planning advice and education about contraception are commonly provided to women who have just given birth and is frequently provided as part of discharge planning . DecisioOral contraceptive education program (one time) versus routine counselling led to a decrease in the incidence of known pregnancy by one year (odds ratio (OR) 0.81; 95%CI: 0.11, 6.04), increase in the rate of continuation of oral contraceptives at one year  and a greater chance of switched contraceptives by one year . ContracAnaemia after the birth of a baby (postpartum anaemia) is a common problem throughout the world and for most women is self-limiting, resolving within a week . For somWhen compared with iron therapy only, erythropoietin increases the likelihood of lactation at discharge  and decrease the need for blood transfusion  .However,Inflammation of the lining of the womb (postpartum endometritis), also known as puerperal fever, is caused by infection entering the womb (uterus) during childbirth. It occurs in about 1 to 3% of births, and is up to ten times more common after caesarean section. Prolonged rupture of membranes and multiple vaginal examinations also increase the risk. Endometritis causes fever, uterine tenderness and unpleasant-smelling lochia, and it can have serious complications such as abscess formation, sepsis and blood clots. It is also an important cause of maternal mortality worldwide, although this is very rare in HICs with the use of antibiotics.Fifteen studies comparing clindamycin and aminoglycoside with another regimen found more treatment failures with the other regimen . Failures of those regimens with poor activity against penicillin resistant anaerobic bacteria were more likely  . The comAntiretroviral (ARV) drugs reduce viral replication and can reduce mother-to-child transmission of HIV either by lowering plasma viral load in pregnant women or through post-exposure prophylaxis in their newborns. In HICs, highly active antiretroviral therapy (HAART) which usually comprises three drugs has reduced the mother-to-child transmission rates to around 1-2%. Recent evidence published in Lancet Infectious Diseases based on the Kesho Bora Studies shows that giving a combination of three ARV drugs to pregnant mothers with HIV infection from the last trimester, through delivery and six months of breastfeeding reduces the risk of transmitting HIV to the baby and improves survival. Infants of mothers whose virus is fully suppressed (undetectable) by triple-ARVs at the time of delivery have a very low risk of HIV infection (only 2.7% by the age of one year).It is therefore important to start ARVs early in pregnancy, ideally before pregnancy, for all women who require ART (CD4 count at or below 350 cells/mm3).The Kesho Bora study shows that a significant reduction in infant infection can be achieved when pregnant women with a CD4 immune cell count of 200-500 cells/ mm3 are given a combination of three ARVs to prevent transmission. This treatment should start in their last trimester of pregnancy, continuing through birth and six months of breastfeeding. This was shown to reduce the risk of transmitting HIV to the baby and improved survival compared with babies of mothers with HIV who are given the current WHO-recommended short-course ARV regimen in late pregnancy and around the time of delivery . These fAn optimal thermal environment is desirable for preterm infants. When an infant is challenged by cold, the baby attempts to conserve body heat by vasoconstriction and to maintain body temperature via thermogenesis by the metabolism of brown adipose tissue and an increase in oxygen consumption. The increase in energy expenditure may reduce weight gain . A numbeThe intervention includes (1) barriers to heat loss applied to any part of the body of the preterm and/or low birth weight (LBW) infant within 10 minutes after birth in the delivery suite. These would consist of coverings such as transparent plastic wraps and bags made of low-density polyethylene (LDPE) or semi-permeable membranes such as opsite or Tegaderm and other additional swaddling materials or wraps (excluding delivery room blankets) such as the ’silver swaddler’; 2) External heat sources (non-routine) initiated within 10 minutes after birth in the delivery suite such as skin-to-skin care and heated/gel/chemical mattresses. Plastic wraps or bags were found to be effective in reducing heat losses in infants <28 weeks' gestation (Weighted Mean Difference (WMD) 0.68°C; 95% CI 0.45, 0.91), but not in infants between 28 to 31 week's gestation. Plastic caps were effective in reducing heat losses in infants <29 weeks' gestation . There was insufficient evidence to suggest that either plastic wraps or plastic caps reduce the risk of death within hospital stay. On the other hand, skin-to-skin care was shown to be effective in reducing the risk of hypothermia when compared to conventional incubator care for infants . The transwarmer mattress reduced the incidence of hypothermia on admission to NICU in very LBW infants  . These fThe benefits of breastfeeding on mother and newborn have been well documented, and the WHO recommends that all mothers initiate breastfeeding within the first hour after giving birth ,51. TimiA review of interventions to promote breastfeeding showed increased rates of initiation of breastfeeding  ; anotherAn umbilical cord infection may be clinically obvious while sometime tracking of bacteria along the umbilical vessels might not be apparent but can lead to septicemia, or other focal infections such as septic arthritis as a result of blood-borne spread ,59. In sAntiseptic versus dry cord care/placebo decreased cord infection rates ; alcohol showed lower cord infection rates as well . Antiseptics that were aqueous based and alcohol based were effective for cord separation:  and  respectively, when compared with powder based antiseptics . A singlAt birth, the lungs of newborn babies are filled with fluid. This fluid must be cleared and replaced with air after birth. While most babies manage by themselves, one in every 20 to 30 newborns receives resuscitation at birth, mostly for absent or ineffective breathing. Effective ventilation is the key to successful neonatal resuscitation. Positive pressure ventilation is initiated with manual ventilation devices which may or not deliver positive end-expiratory pressure (PEEP).A review by OO'Donnell et al. found insufficient evidence to determine the efficacy and safety of PEEP during positive pressure ventilation at neonatal resuscitation . VentilaEarly onset of bacterial infection is an important cause of morbidity and mortality in newborn infants. Various factors that increase the risk of neonatal infection have been identified. It is unclear whether asymptomatic newborn infants born to mothers with one or more of these risk factors should receive antibiotics prophylactically rather than selectively if only clinical or microbiological evidence of sepsis emerges.A review  identifiNeonatal sepsis is defined as a clinical syndrome of bacteremia with systemic signs and symptoms of infection in the first 4 weeks of life. Infection remains a major cause of illness and death in the neonatal period ,71. TreaFor early onset neonatal sepsis (<48 hours), monotherapy versus combination therapy showed a decrease in mmortality in the first 28 days of life  . For latPreterm birth (before 37 completed weeks of gestation) is the most important direct cause of neonatal mortality and it accounts for an estimated 27% of the four million neonatal deaths every year ,77. In tKMC led to a decrease in neonatal mortality   , necrotizing enterocolitis , and death  . LBW babPulmonary surfactant is a substance produced by the lung alveoli and prevents the lungs from collapsing during expiration by decreasing surface tension. It is noted that babies who are born before 30 weeks, approximately 60% of them will develop respiratory distress syndrome (RDS) because lung maturity is directly proportional to the level of surfactant that is present in the newborn .A review evaluated outcomes in infants given synthetic surfactant (pre-ventilatory or post-ventilatory) compared with control treatment which consisted of intratracheal administration of normal saline or air placebo. The different types of synthetic surfactant used in these trials were DPPC plus high density lipoprotein, powdered DPPC and phosphatidylglycerol and DPPC plus phosphatidylglycerol in saline. Studies also compared surfactant  given asEven though surfactant therapy has shown to improve outcomes for premature infants with RDS it is important to note that this therapy should not be used as an alternative to prolonging premature deliveries in order to increase lung maturity, or giving mothers antenatal corticosteroids with the aim to prevent RDS from developing -91.A meta-analysis supports decrease in the risk of pneumothorax , pulmonary interstitial emphysema , patent ductus arteriosus , intraventricular haemorrhage , broncho-pulmonary dysplasia , neonatal mortality , broncho-pulmonary dysplasia or death at 28 days , mortality prior to hospital discharge  and mortality during the first year of life . Treatment with synthetic surfactant increases the risk of apnea of prematurity  . ExistinApnea of prematurity, which is commonly seen in infants who are born before 34 weeks of gestation, is defined as a pause in breathing for greater than twenty seconds or an apneic event that is less than twenty seconds but is associated with bradycardia and/or cyanosis ,95. ContA meta-analysis demonstrates that high frequency positive pressure ventilation (HFPPV) compared to conventional ventilation (CMV) was associated with a reduction in the risk of air leak . Assist control ventilation (ACV) or synchronized intermittent mandatory ventilation (SIMV) compared to CMV was associated with a shorter duration of ventilation . ACV compared to SIMV was associated with a trend to a shorter duration of weaning . Neither HFPPV nor triggered ventilation was associated with a significant reduction in the incidence of BPD . NIPPV vExtremely high levels of bilirubin (severe jaundice) can lead to brain damage. Severe jaundice in newborns can occur as a result of a variety of causes including rhesus hemolytic disease, ABO incompatibility, atypical antibodies etc. Removal of blood from the affected infant and replacing with fresh blood from the blood bank (exchange transfusion) is used as a treatment for severe jaundice in newborn infants.Phototherapy is used to treat newborn infants with hyperbilirubinaemia. Fibreoptic phototherapy is a new mode of phototherapy which is reported to lower serum bilirubin (SBR) while minimizing disruption of normal infant care. Fibreoptic phototherapy was found to be more effective at lowering SBR (serum bilirubin) than no treatment but less effective than conventional phototherapy. Fibreoptic phototherapy was equally as effective as conventional phototherapy in preterm infants and when two fibreoptic devices were used simultaneously  and change in SBR per day over whole treatment period: . A combination of fibreoptic and conventional phototherapy was more effective than conventional phototherapy alone (duration of phototherapy):  .Fibreoptic phototherapy has a place in the management of neonatal hyperbilirubinaemia. It is probably a safe alternative to conventional phototherapy in term infants with physiological jaundice.Double volume exchange transfusion is commonly used in newborns with severe jaundice in order to prevent kernicterus and other toxicity related to hyperbilirubinemia. A single trial fulfilling the criteria for inclusion identified 20 full term babies requiring exchange transfusion for hemolytic jaundice due to ABO incompatibility. These infants were randomly allocated to receive single or double volume exchange transfusion. Total bilirubin levels immediately after exchange transfusion were not significantly different in either group. There was insufficient evidence to support or refute the use of single volume exchange transfusion as opposed to double volume exchange transfusion in jaundiced newborns .This paper summarized all the essential childbirth and postnatal interventions for improved maternal and newborn health. The interventions were preventive and therapeutic aimed at preventing illnesses and improve survival of mothers and babies. The importance of these interventions has been addressed in previous publications -106. HowAmong the childbirth interventions, the review highlighted the role of injecting oxytocin immediately after childbirth for the prevention and management of postpartum hemorrhage, which is lethal and is responsible for large number of maternal deaths if unattended. Similarly, practicing good hygiene and recognition of early signs of infection after childbirth can be instrumental in saving lives. Detection and management of pre-eclampsia and use of magnesium sulphate can lower a woman’s risk of developing eclampsia and other life-threatening complications. For postnatal interventions, care of the neonate and mother in the hours following the delivery is vital and must be adequate to prevent the high risk of mortality and morbidity associated with it. The benefits of breastfeeding have been well documented; however the timing of start of breastfeeding is very important, with studies suggesting much greater benefits of early vs. late feeding . HygieniChildbirth and postnatal care faces many challenges in LMICs whereby establishing contact between the pregnant mother, postpartum mother, or neonate is difficult since home births and seclusion may be a community practice or tradition. However, the importance of community based delivery strategies to increase access to needed care is paramount to bringing about a positive change in the developing countries. Although not all the interventions discussed in this paper can be delivered in community, training community midwives and detailing proper linkages with local health facilities is very vital. Referrals from community to health facilities for interventions such as, management of postpartum hemorrhage and cesarean sections is very critical. Therefore, training midwives and follow-ups through home visits may assist in increasing the coverage and improving the quality of home-based postnatal care services for mothers and newborns. This goal can be achieved through increased utilization of basic postnatal services by mothers and newborns, increased identification and referral of post-partum women and newborns with health problems to health care facilities, and provision of quality home based postnatal care for mothers and newborns .This paper is a comprehensive and through summary of essential childbirth and postnatal interventions for health care practitioners and decision makers who can integrate these interventions into health system for improved maternal and child health. If implemented properly to target a wider audience, keeping in mind the barriers to implementation, then major progress may be made in meeting the MDG’s and higher maternal and neonatal maternal mortality would be ceased. The strength of this paper is that it included and summarized evidence from all the recent Cochrane and non-Cochrane reviews on childbirth and postnatal interventions for mothers and newborns. However, at times the quality of all included studies within the review could not be ensured which limited the quality of the data obtained.Maternal and newborn health exists in a synergistic relation. Most maternal deaths are avoidable provided timely and adequate delivery of health-care solutions to prevent or manage complications. An access to antenatal care in pregnancy, skilled care during childbirth, and care and support in the weeks after childbirth should be provided to all women. The review discussed all childbirth and postnatal interventions which have an impact on reducing maternal, neonatal mortality and which are suitable for delivery in LMICs. The implementations of discussed interventions promise a much needed improvement is maternal and neonatal outcomes around the world. However, some of these interventions must be prioritized over others depending on the clinical indications and keeping in view the limited resources in developing countries. Timely provision of these interventions holds unparalleled significance, particularly those that are delivered during and immediately after childbirth, in places where majority of the births occur, at home.We do not have any financial or non-financial competing interests for this review.The reviewer reports for this article can be found in Additional File Peer review reports.Click here for file


Transcranial direct current stimulation (tDCS) has been proposed as a technique for brain activity modulation. In this technique, a weak current  is delivered to scalp through two sponge electrodes. There are two types of tDCS stimulation: cathodal and anodal, which inhibit and facilitate neuronal activity, respectively Hansen, .tDCS has been shown to be effective in Alzheimer's disease (AD). Several studies have revealed that tDCS application can improve memory performance in Alzheimer's patients (APs) (Ferrucci et al., Current pathway through brain plays a key role in the observed effects. Currently, modeling studies provide the only way for determining the pattern of current flow during tDCS. In recent years, finite element modeling has been suggested as a reliable and helpful tool in clinical therapeutic applications (Bikson et al., A critical issue which is required to be considered in modeling studies is the inter-individual anatomical variations. A modeling study has shown the profound role of individual cortical morphology in determination of current flow distribution for healthy people (Datta et al., We hypothesize that change in cortical thickness due to brain atrophy has significant effects on current flow pattern. These anatomical alterations may shift the stimulated areas and peak current density location in head. They may even alter the expected results from tDCS application.We suggest that cortical thickness is required to be considered in modeling studies to obtain more precise pattern of current flow in head and the stimulated brain regions. Specifically, AD affects differently on each patient's brain structure. We suggest developing individualized models based on each patient's MRI data. These models can be used by clinicians to find the optimal electrode montage and current amplitude for each patient.Using Individual-based models for designing clinical protocols could provide us with better interpretation of the results.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Oxidative stress has been implicated as both a physiological cost of reproduction and a driving force on an animal's lifespan. Since increased reproductive effort is generally linked with a reduction in survival, it has been proposed that oxidative stress may influence this relationship. Support for this hypothesis is inconsistent, but this may, in part, be due to the type of tissues that have been analyzed. In Damaraland mole-rats the sole reproducing female in the colony is also the longest lived. Therefore, if oxidative stress does impact the trade-off between reproduction and survival in general, this species may possess some form of enhanced defense. We assessed this relationship by comparing markers of oxidative damage  and antioxidants  in various tissues including plasma, erythrocytes, heart, liver, kidney and skeletal muscle between wild-caught reproductive and non-reproductive female Damaraland mole-rats. Reproductive females exhibited significantly lower levels of PC across all tissues, and lower levels of MDA in heart, kidney and liver relative to non-reproductive females. Levels of TAC and SOD did not differ significantly according to reproductive state. The reduction in oxidative damage in breeding females may be attributable to the unusual social structure of this species, as similar relationships have been observed between reproductive and non-reproductive eusocial insects. Investment in the production of offspring is customarily linked to compromised survival, as prolific reproduction tends to be coupled with a relatively shorter life span Tamias striatus) Oxidative stress arises when the production of reactive oxygen species (ROS), which damage proteins, lipids and DNA, exceeds the capacity of antioxidants and repair mechanisms to prevent or mitigate ROS damage Oxidative stress is also associated with numerous pathologies see , and theMyodes gareolus) lipid oxidation was lower in skeletal muscle and kidney and protein oxidation tended to be lower in the heart of reproductive females relative to non-reproductive females, whereas there was no difference in levels of oxidative damage in the liver between reproductive and non-reproductive females It is important to note that many investigations into the relationship between reproduction and oxidative stress have measured biomarkers of oxidative stress only in serum or plasma samples see . While tFukomys damarensis), which, along with naked mole-rats , are argued to be the only truly eusocial mammalsUpon investigating oxidative stress in various tissues, the aforementioned studies also reveal that in some species reproducing females are experiencing less oxidative damage than those that do not reproduce. This relationship has been observed in social insect species see  and, intIf reproductive mole-rats experience less oxidative stress than their non-reproductive cohorts, this may serve as a mechanism that underlies their extended lifespan. To determine this, we measured oxidative stress in several different tissues of reproductive and non-reproductive female Damaraland mole-rats, predicting that reproductive females have less oxidative damage and better antioxidant defense relative to their non-reproductive cohorts, and that there will be variation between tissue types as to how this difference in relation to reproduction is manifested. Although it has been suggested that a comparison between reproductive and non-reproductive females can be confounded by a female's ability to adjust reproductive investment Research protocols were approved by the animal ethics committee at the University of Pretoria and complied with their guidelines for animal research (protocol number EC008-12).ad libitum access to a combination of sweet potatoes, carrots, apples and gemsbok squash.We selected 9 reproductive and 14 non-reproductive females from colonies at the University of Pretoria that had been recently collected  immediately following decapitation and snap froze them in liquid nitrogen. We homogenized liver, heart, skeletal muscle and kidney on ice in 10% weight per volume 100 mM HEPES (N-2 hydroxyethylpiperazine-N′-2-ethanesulfonic acid) buffer solution for 1 (liver and kidney) or 2  minutes on an Ultra Turrax T18 Basic Homogenizer , and stored all homogenates in a -80 freezer until time of analysis.Oxidative stress represents an imbalance between ROS production, resulting in oxidative damage, and antioxidant defenses or repair mechanisms, and is thus more accurately characterized by including a range of assays of these damage and protection mechanisms −1. We collected data using a fluorescence detector  set at 515 nm (excitation) and 553 nm (emission). For calibration, we prepared a standard curve using a TEP stock solution (5 µM in 40% ethanol) serially diluted using 40% ethanol. Results are expressed as nmol MDA per g tissue or ml plasma.We measured concentrations of MDA in all tissue homogenates  and in plasma using high performance liquid chromatography (HPLC) as described by Nussey et al. We measured concentrations of PC in all tissue homogenates  and in plasma. Oxidation or oxidative cleavage of proteins results in the production of carbonyl groups We measured SOD activity in all tissue homogenates  and in erythrocytes. SOD is an enzymatic antioxidant that catalyses the dismutation of superoxide anions to oxygen and hydrogen peroxide We measured TAC in homogenates of liver, kidney and heart, and in plasma. We did not measure TAC in skeletal muscle because intracellular antioxidant defenses (e.g. SOD) are likely to be more important in this tissue type. TAC was quantified using a commercially available kit  which measures the oxidation of ABTS  by metmyoglobin, which is inhibited by non-enzymatic antioxidants contained in the sample. Oxidized ABTS can then be detected via spectrophotometry at a wavelength of 740 nm. The capacity of antioxidants in the sample to inhibit oxidation of ABTS is compared with the capacity of known concentrations of Trolox, and results are expressed as nmol of Trolox equivalents per g tissue or ml plasma.10-transformed to improve the approximation of normality. Individual markers of oxidative damage and antioxidant defense may vary in their association with reproductive state, and such relationships are likely to differ amongst tissues P>0.05) starting with the reproductive state x tissue interaction term. Significant reproductive state x tissue interactions were followed by post-hoc GLMMs for each tissue in turn, including reproductive state as a fixed factor and colony membership as a random factor. In the absence of any association with reproductive state, we were not interested in differences in oxidative damage or antioxidant defenses amongst tissues per se. Such differences are inevitable given the wide variety of tissues included in this study. Therefore, any significant main effect of tissue was not followed by post-hoc tests. Not all tissue samples were available for each individual and each assay, resulting in a variation in sample size between tissue types (th edition) . Results are reported as means ± s.e.Data were examined for normality, homoscedasticity, and outliers. For MDA and SOD, data were logue types . All anaLevels of MDA were significantly decreased in reproductive compared to non-reproductive females, although this differed amongst tissue types. Post-hoc analyses revealed that MDA was significantly lower in the heart, kidney and liver in reproductive compared to non-reproductive females, but did not differ significantly according to reproductive state in skeletal muscle or plasma . Levels Crassostrea gigas) and painted dragon lizards (Ctenophorus pictus), all exhibited increased expression of antioxidants during reproduction Lower concentrations of both markers of oxidative damage observed in reproductive females suggest that either these females produced less ROS than non-reproductive females, or that antioxidant defenses were more active in reproductive females. Mitochondrial uncoupling can result in reduced ROS production, although studies of mice have indicated that expression of the genes that code for uncoupling proteins is reduced or unchanged in breeders compared with non-breeders Apis mellifera), in which reproduction is associated with an increased production of the protein vitellogenin, which defends against oxidative stress Several physiological adjustments accompany a non-reproductive Damaraland mole-rat's transition to reproductive status, including increased body length, brain volume, reproductive hormone concentrations and pituitary sensitivity Cryptomys hottentotus)),spend much more time sleeping than the reproductive female Additionally, the reduction of oxidative stress found in reproductive Damaraland mole-rats and other species may be indicative of hormetic response, in which exposure to ROS associated with reproduction or becoming reproductive primes the female's system to defend against long-term oxidative challenges Levels of PC were reduced in all tissues of reproductive females, however, levels of MDA showed different patterns amongst tissues in relation to reproduction; MDA was reduced in heart, kidney and liver, but did not differ in skeletal muscle or plasma. This observation underscores the importance of assessing oxidative stress in more than one tissue in order to obtain a more thorough depiction of oxidative stress dynamics within an animal While several exceptions to the oxidative stress theory of aging have emerged see , our resThere is evidence that lifespan is not traded off against reproduction in some social insect species Thus, in this and other eusocial species, oxidative stress may serve as a potential link between reproduction and lifespan which could function as a basis for prospective avenues for investigating the evolution of sociality as well as life-history traits and reproductive strategies.Table S1Data used for the analyses of markers of oxidative damage and antioxidant defence in various tissues in relation to reproductive state.(DOCX)Click here for additional data file.


Differences in both Sudden Infant Death Syndrome (SIDS) rates and infant care practices between white British and South Asians in UK are well known, but research has not yet examined how these two groups understand and implement SIDS-reduction guidance. This study aimed to discover how white British and Pakistani mothers in Bradford recall, understand and interpret SIDS-reduction guidance, and to explore whether and how they implement this guidance in caring for their infants.In-depth narrative interviews with 46 mothers (25 white British origin and 21 Pakistani origin) of 8–12 week old infants recruited from the pool of participants enrolled in the ‘Born in Bradford’ (BiB) cohort study.All mothers were aware of UK SIDS-reduction guidance from leaflets presented to them during antenatal or postnatal interactions with health care providers. Pakistani mothers tended to dismiss the guidance in toto as being irrelevant to their cultural practices; white British mothers dismissed, adapted and adopted aspects of the guidance to suit their preferred parenting decisions and personal circumstances. Many mothers misunderstood or misinterpreted the guidance given and explained their infant care behaviour according to their social and cultural circumstances.Current SIDS reduction information in the UK does not meet the needs of immigrant families, and is easily misinterpreted or misunderstood by mothers from all sections of the community. Tailored information acknowledging cultural differences in infant care practices is vital, as is greater discussion with all mothers about the reasons for SIDS reduction guidance.The online version of this article (doi:10.1186/s12887-016-0560-7) contains supplementary material, which is available to authorized users. Unexplained sleep-related infant mortality (Sudden Infant Death Syndrome) is closely related to infant care practices and can vary substantially between immigrant and host populations –6. DiffeThe present study aimed to elicit detailed qualitative explanations for inter-cultural differences in infant care in the bi-cultural community of Bradford and explore the cultural context in which infant care is performed in order to inform future public health interventions in this and similar ethnically diverse populations.The consolidated criteria for reporting qualitative research (COREQ) are used to describe the study methods. COREQ provides a 32-item checklist for explicit and comprehensive reporting of qualitative studies (in-depth interviews and focus groups) .n = 46) were interviewed. Of the 21 Pakistani mothers that were interviewed 5 were first generation (born in Pakistan) and sixteen were second generation (born in the UK).We aimed to conduct 50 in-depth narrative interviews to obtain qualitative data from mothers of 8–12 week old infants (this age group is the peak age-range for SIDS in the UK). Recruitment was conducted at Bradford Royal Infirmary Maternity Unit when the mothers-to-be were 28 weeks pregnant and being recruited into the ‘Born in Bradford’ (BiB) cohort study. A purposive sample of 137 BiB participants were approached and asked if they would agree to be interviewed when their infants were 8–12 weeks old; although 69 agreed to be contacted 23 were lost from the sample due to changes in contact details or relocation outside of the Bradford area--therefore 25 white British and 21 Pakistani mothers ; as much of the guidance was irrelevant to Pakistani mothers they felt that Safe Sleep guidance was not directed to them. Consequently, where the guidance conflicted with traditional Pakistani beliefs about infant sleep  mothers prioritised their traditional practices and dismissed the official guidance. White British mothers consciously adapted or dismissed several aspects of the guidance  that they felt to be not applicable or unnecessary, while questioning others . Their responses also suggested that the implementation of some SIDS-reduction practices compensated for the lack of others, highlighting parental perceptions that risk-reduction strategies can be traded against each other.Growing evidence indicates that SIDS is less prevalent among infants who sleep near their parents –13. HoweIn previous research we found that Pakistani infants were significantly less likely than white British infants to sofa-share , 8. In tAll white British mothers were aware of dangers in their baby’s sleeping environment; the majority did not use pillows or blankets preferring baby sleeping bags for night-time sleep. Pakistani mothers preferred sheets and blankets and infant ‘pillows’ (head positioners) even though they were aware of disapproval from health professionals regarding the latter. White British mothers were sceptical of the advice to avoid the side sleep position for infants, however, studies from England and New Zealand have shown that this position is unstable and infants risk rolling into the prone position –19. PartMultiple studies have confirmed an association between maternal smoking, alcohol consumption and SIDS –23. WhitPakistani mothers repeatedly asserted that UK SIDS-reduction guidelines were not applicable to them noting that pictures and diagrams within the literature did not depict their own social and cultural environments, and the messages did not acknowledge or reflect their cultural beliefs and practices; this supports the view that SIDS-reduction messaging should acknowledge the culturally valued parenting behaviours and beliefs of the target communities in order to make messages more effective –26.In summary, this study found that UK SIDS intervention strategies were limited in their effect on both Pakistani and white British families in Bradford as mothers were aware of, but did not implement, the risk-reduction guidance offered. Similar ineffectiveness has recently been reported in SIDS-reduction campaigns in north-west England  and AustAdditionally, we suggest that SIDS advice, literature and leaflets should depict the multi-cultural social and ecological contexts in which infant care is performed. Mothers may consider SIDS advice more readily if they see that the guidance acknowledges their cultural preferences. Health professionals could be trained to be more aware and understanding of how infant care decisions are mediated and performed amid differing social and cultural environments, and to provide tailored information to allow parents to work within their personal constraints to make informed choices regarding SIDS-risk reduction.UK SIDS rates have plateaued, and current public health interventions are not reducing them further. As both white British and UK Pakistani mothers resist adopting certain SIDS guidance according to their personal, social and cultural environments this suggests individually tailored approaches to SIDS-reduction would be more effective than the ‘single simple message’ approach.One of the key findings in this study was that mothers felt they could ‘trade-off’ which components of SIDS guidance to implement, and that adhering to some of the recommendations (e.g. supine sleep) counteracted lack of adherence to others (e.g. smoking); the provision of evidence to counter this perception might help increase adherence to the most efficacious interventions. Therefore, it is suggested that more emphasis is placed on those recommendations that are associated with the greatest risk reduction in order to achieve the greatest benefit; this may require specific quantitative modelling for specific populations or communities.The findings of this study suggest guidance and literature should be culturally tailored with acknowledgement, understanding and appreciation of variations in infant caregiving and discussion of the barriers to implementation encountered in different settings. Infant health messages could work with parents’ cultural values and beliefs more effectively to identify ways to promote infant health and safety for specific social and cultural environments.


Modern health services now strive for individualized treatment. This approach has been enabled by the increase in knowledge derived from neuroscience and genomics. Substance use disorders are no exception to individualized treatment even though there are no gene-specific medications yet available. What is available is the ability to quickly and precisely assess and monitor biopsychosocial variables known to vary during addiction recovery and which place addicts at increased risk of relapse. Monitoring a broad spectrum of biopsychosocial health enables providers to address diverse genome-specific changes that might trigger withdrawal from treatment or recovery relapse in time to prevent that from occurring. This paper describes modern measurement tools contained in the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) and the NIH Toolbox and suggests how they might be applied to support recovery from alcohol and other substance use disorders in both pharmacological and abstinence-oriented modalities of care. For almost two decades, leaders in the substance use disorder (SUD) field have called for a shift from an acute care model of addiction treatment to a chronic care model in which recovery—not abstinence alone—is the goal ,2. AlthoMany experts have called for routine monitoring as key to detecting symptoms early enough to re-intervene before a lapse into use or relapse into addiction occurs ,5,6,7,8.This paper describes an approach to comprehensive recovery monitoring that serves modern goals of precision medicine and individualized care. We describe barriers to comprehensive monitoring and weaknesses in commonly used measures, and we explain how modern measurement techniques can overcome those problems. We describe the development of two modern measurement systems for monitoring general medical recovery developed by the National Institutes of Health; The Patient-Reported Outcomes Measurement Information System (PROMIS) and the NIH Toolbox. Finally, we explain how those measurement systems can be applied economically and effectively to enhancing SUD recovery success.The NIH Human Genome project has created a paradigm shift among healthcare professionals eager to exploit a model of individualized care—precision medicine—which enables individualized treatments tailored to the specific genetic make-up of each patient . In the Together with the renaissance in genetics has been progress in neuroscience enabled by linking modern brain imaging techniques with genetics . Models One of the most challenging aspects of all chronic diseases is that even when treated, recovery can take a long time and require systems of care to sustain long-term health and avoid relapse . This isThis paper describes recent progress in the creation of monitoring tools that align with the goals of individualized medicine. These new tools place a small burden on both clients and providers, which permits routine monitoring on a far broader range of symptoms than current tools allow. Since they are computerized, these modern measures expand options for administration, enabling completion via personal computers, tablet PCs, and smart phones.Nobody has been more vocal about the need for recovery monitoring than A. Thomas McLellan ,23. AlonUntil the turn of the 21st century, addiction treatment and recovery has been guided by various models ranging from criminality, moral weakness, social maladaptation, and mental illness. By the mid 1980s a psychosocial model dominated the addiction field. It assumed that recovery was enabled by addressing addict mental health, and helping those in recovery to learn new behaviors that would (a) avoid social and environmental contexts associated with their life while addicted, and (b) develop appropriate social role engagement, e.g., ,31,32,33As early as 1977, George Engel  urged psi.e., the process of re-achieving self-regulating homeostatic stability of bodily functions through durable physiological and behavioral change.The role played by biology in addiction and recovery began to expand when George Koob and Michele Le Moal  introducThere are basically two models of recovery. Abstinence-oriented recovery (AOR) is the most common type of recovery. AOR involves complete abstinence from addictive substances. Thus, patients will experience a range of symptoms beginning with withdrawal as allostasis progresses over the period of five years or so that self-sustainable abstinence can take to achieve. A second model of recovery is medically-maintained recovery (MMR), which relies upon medication, such as opiate replacement therapy (ORT)  that enaRegardless of recovery model, addiction recovery spans the period of abstinence allostasis needed to restore homeostasis under AOR or the period under MMR that avoids allostasis through medication—possibly for the remainder of one’s life. In both cases, regular monitoring of diverse symptoms offers a way to detect and intervene when relapse risk has increased.Diverse symptom measurement is important because the complexity of an addict’s brain and genome ensures that addiction and recovery will always be idiosyncratic ,18; see The proverbial 900-pound gorilla that impedes frequent recovery monitoring is the measurement burden for both providers and patients ,32. MoniWhile staff burden often creates barriers to recovery monitoring, the most frequently discussed burden is the one monitoring places on patients . Even brFrequent, periodic, comprehensive monitoring is not a national norm ,41. EvenThe time-consuming length of most recovery monitoring measures is a legacy of the acute-care model of treatment that dominated the field for many decades. Measures for monitoring SUD recovery have been for the most part based on abbreviations of lengthy diagnostic assessments administered during treatment intake. Thus, even if a chronic-care model has been adopted, the measures used to implement it likely are derivations from older, acute-care legacy measures in wide use for diagnosis and treatment planning.(1)The goal of diagnosis for treatment is not necessarily the goal of recovery monitoring. As such, most measures are skewed toward high severity of symptoms. This characteristic makes them less sensitive for detecting levels of wellness.(2)Shorter forms reduce measurement sensitivity and precision, in part because of the reduced range of symptoms addressed. To broaden the scope of measurement, it is necessary to employ additional short forms, which will increase patient burden and provider costs.(3)The validity of short form measures is dependent on a response to every item. It is not possible to skip seemingly irrelevant or tedious items. This might affect the face validity needed to sustain patient engagement over many years.(4)Scoring and interpretation of abbreviated diagnostic measures still requires some degree of formal training, and will also consume staff time to score and interpret.(5)Administration costs can reduce the frequency of monitoring.(6)Patient burden is increased by use of paper-and-pencil measures or questionnaire-guided interviews because they normally must be completed at a location and time that can interfere with patient role responsibilities such as training or work. That burden risks skipped sessions and incomplete trend data, undermining the point of monitoring to detect lapse situations.(7)Most paper-and-pencil monitoring measures require the creation of trend graphs by hand if any are to be used. This additional burden may hamper the use of trend information.(8)Most recovery monitoring measures do not adequately address biological symptoms likely to appear during allostasis.Here is a summary of the problems associated with the short-form recovery monitoring measurement approach:In 2003, the National Institutes of Health, in consultation with health outcomes experts, initiated a national program of research to address the shortcomings of recovery monitoring measures in general healthcare. That system became the basis for development of modern measures that became the NIH Patient-Reported Outcomes Management Information System (PROMIS). PROMIS was intended to take advantage of modern measurement theories and ready access to computer tools to develop a comprehensive battery of recovery monitoring measures that could overcome the shortcomings listed above. Below is a list of recovery monitoring characteristics researchers believed would overcome the many shortcomings of existing measures ,50,51,52(1)Measures should be obtainable at regular intervals to establish baseline status and enable meaningful indicators of change.(2)Measures should be brief enough to not be viewed as burdensome to the patient, address a broad enough spectrum of symptoms to seem relevant to the patient’s experience with recovery, and therefore sustain engagement over the many years of recovery.(3)Precision and sensitivity should not be sacrificed for the sake of brevity.(4)Ideally, measures should enable patients in recovery to complete them on their own, at a place and time of their convenience without the need for administration by a trained service provider.(5)Measures should not require a significant training burden to recovery support staff to administer and interpret results, as training costs can exclude staff not yet trained, and weaken outreach and support decisions when intervention is indicted by scores.(6)Measures should be self-scoring in the sense that results would be instantly recorded and converted to easily-understood trend results for each variable monitored.(7)Measures should be broad enough to be sensitive to changes in general physical and mental health as well as social functioning.(8)Measures should be modifiable or expandable without a significant increase in burden to address the individualized needs of patients in recovery such as addressing exacerbating conditions like physical health or disability, significant chronic psychiatric conditions, or housing needs.(9)Measures should be valid for all patients regardless of race, gender, age, or disease.(10)The cost of monitoring should be limited to initial integration with existing record systems, and staff time to examine and interpret trends for sustained improvement or lapse.An overarching goal for PROMIS was to develop patient-reported outcome (PRO) measures that would be valid regardless of patient characteristics such as age, sex, education, or ethnicity, as well as disease or disorder. For example, pain, fatigue, and social role disruption are common to most diseases and disorders. Validating items relevant to a broad spectrum of chronic illness enables PROMIS to achieve several important research and clinical goals. PROMIS can help to reduce measurement error in comparative research that examines symptoms such as pain which is present across a variety of conditions . PROMIS By 2010, NIH PROMIS had delivered on its promise to the field of healthcare by delivering a set of computerized patient-reported outcome (PRO) general health measures based on modern measurement theory (MMT) to monitor changes in biological, psychological, and social health status quickly and precisely. The original domain framework, presented in NIH PROMIS offers recovery-monitoring measures that meet the individualization needs of modern precision medicine models. They are brief (often two minutes or less per domain/topic), available royalty-free, measure the same domains/topics that lengthy intake assessment interviews and questionnaires target, and they exhibit validities equal to or better than older legacy measures. Moreover, they are available in a variety of languages for patients not fluent in English.The primary burden on addiction health service providers to incorporate PROMIS measures is to take the time to register and establish an account at the PROMIS Assessment Center at Northwestern University . Once reNIH Reform Act. Toolbox measures are also accessible through the PROMIS Assessment Center and NIH Toolbox [For most needs in addiction health services, PROMIS offers a sufficient variety of measures to enable an individualized-medicine approach to both treatment and recovery support of most diseases. When necessary, PROMIS measures can be augmented by banks from the NIH Toolbox to address cognitive and emotional conditions. NIH Toolbox measures were developed in response to the 2006  Toolbox . Table 2Most measures requiring paper-and-pencil forms or questionnaire-guided interviews were developed using Classical Test Theory (CTT) . These mModern psychometric methods following MMT rely on item-level validation using Item Response Theory (IRT). IRT was first introduced in the 1950s by Frederick Lord  and Warri.e., less symptomatic) and proceeds in the opposite direction. In cases where responses are ambiguous, additional items of similar difficulty are presented in order to achieve precision. Most PROMIS banks require 4–6 items and take under two minutes to obtain a precise score using CAT.CAT reduces the number of items presented without sacrificing validity and precision. Respondents are presented independently-validated items from a pool of possible items (item banks) based on previous question responses. Each item in the pool is calibrated on severity level, from highly symptomatic to a high level of well-being. Similar to a hearing test, the computer first presents an item of average endorsement difficulty, such as “I drank too much” . If the response is “Often,” the algorithm selects an item of greater difficulty such as “It was difficult for me to stop drinking after one or two drinks.” Once a high-severity item can no longer be endorsed, the program moves to the next domain/topic similar to a hearing test moving to the next frequency. Conversely, if the first response cannot be endorsed, the computer chooses an item easier to endorse   to detecHowever, EMA has recently come under criticism as too narrowly focused and sometimes overly burdensome to patients, see . In addiIt remains easier to complete computerized questions on an appliance with good screen readability such as a desktop or tablet PC. Clearly, integration of PROMIS with other smartphone applications such as EMA/EMI should be examined with care so as not to undermine measurement validity. The PROMIS Assessment Center is releasing an application for iPhones through iTunes in 2015 . HopefulNow that PROMIS general health measures can be augmented with SUD-specific domain banks, the system offers the ideal recovery monitoring tool. Relatively-speaking, PROMIS will normally be faster, better, and cheaper to use than widely-used paper-and-pencil or questionnaire-guided interviews currently in use. It represents the state-of-the-art in terms of speed, precision, and sensitivity with no demonstrated loss in validity compares to short forms and their longer legacy measures used in assessment for diagnostic and treatment planning purposes.Our goal has been to inform readers about precise, low-burden measures for assessing and monitoring recovery from alcoholism and other SUD that are royalty-free. These new measures can be found in the NIH PROMIS and NIH Toolbox systems maintained at the Assessment Center at Northwestern University. A unifying rationale is that application of individualized medicine models, even without gene-based interventions, is possible with these measures. Frequent progress monitoring using measures broad enough in scope to capture signals of relapse creates opportunities to re-intervene. Use of these tools in support of individualized medicine meets the monitoring goals that have long been called for in the literature but that have not been widely implemented due to cost and other considerations.Some researchers and healthcare providers may have delayed implementing PROMIS because they were unaware that CAT PRO measures addressing symptoms of alcohol and SUD abuse are available. In fact, the SUD banks are just now coming on line. For patients with multiple morbidities, NIH Toolbox offers complementary CAT item banks that address a variety of cognitive and emotional domains/topics.Integrating CAT measures into existing assessment systems makes sense because they are scored automatically and require no formal training to administer. Even though interpretation of assessments will still require trained professionals, the time devoted to information collection can be substantially reduced using CAT measures. Given the reduced patient burden of CAT measures coupled with expanded scope, PROMIS and Toolbox offer ample reasons to initiate frequent recovery monitoring to enable individualized medicine services now. Continued use of paper-and-pencil measures offers comparatively less precision to detect relapse while potentially disengaging patients from aftercare participation. In summary, there is adequate justification to adopt or switch to NIH CAT measures to support SUD recovery.