Pregnancy-related vital registration is important to inform policy to reduce maternal, fetal and newborn mortality, yet few systems for capturing accurate data are available in low-middle income countries where the majority of the mortality occurs. Furthermore, methods to effectively implement high-quality registration systems have not been described. The goal of creating the registry described in this paper was to inform public health policy makers about pregnancy outcomes in our district so that appropriate interventions to improve these outcomes could be undertaken and to position the district to be a leader in pregnancy-related public health research.We created a prospective maternal and newborn health registry in Belgaum, Karnataka State, India. To initiate this registry, we worked with the Ministry of Health to first establish estimated birth rates and define the catchment areas of the clusters, working within the existing health system and primary health centers. We also undertook household surveys to identify women likely to become pregnant. We then implemented monitoring measures to ensure high quality and completeness of the maternal newborn health registry. All pregnant women in the catchment area were identified, consented and enrolled during pregnancy, with follow-up visits to ascertain pregnancy outcomes and mother/infant status at 42-days postpartum.From 2008 through 2014, we demonstrated continued improvements in both the coverage for enrollment and accuracy of reporting pregnancy outcomes within the defined catchment area in Belgaum, India. Nearly 100% of women enrolled had follow-up at birth and 99% had 42-day follow-up. Furthermore, we facilitated earlier enrollment of women during pregnancy while achieving more timely follow-up and decreased time of reporting from the date of the pregnancy event.We created a pregnancy-related registry which includes demographic data, risk factors, and outcomes allowing for high rates of ascertainment and follow-up while working within the existing health system. Understanding the elements of the system used to create the registry is important to improve the quality of the results. Tracking of pregnancies and their outcomes is an important step toward reducing maternal and perinatal mortality. Globally, it is estimated that about 289,000 maternal deaths, 2.6 million stillbirths, and 2.9 million neonatal deaths currently take place each year -3. The mVital registration, with a long and rich history in the United States and Western Europe, has been critical to the documentation of incidence and causes of maternal, fetal and neonatal death in these regions. Additionally, vital registration systems have proven value in the identification of factors to which temporal changes in pregnancy-related deaths may be associated . Such reWhere functional vital statistics registries do not exist, countries may estimate births and deaths through suboptimal mechanisms such as surveys. These surveys are done on a periodical basis and thus make tracking of trends difficult. Furthermore, they are often comprised of small numbers and thus have estimates of uncertainty with wide confidence intervals, particularly for maternal, fetal and neonatal mortality . If nearIn India, vital statistics data are available from four major sources: (1) Indirect Estimates from the Decennial Census first initiated in 1881 (2) The Civil Registration System (CRS) which was initiated in 1958; (3) The Sample Registration System (SRS) which began in 1970 and, finally, (4) The National Family Health Survey (NFHS) which was initiated in 1992 -14. The In 1951, India added family planning into its national health care policy to address individual needs and also to contain its population growth. Consequently, the primary health center (PHC) was established as the service nodal point for identifying couples that required birth control services and was incorporated into the “Eligible Couple Survey Register” (ECSR). These registers are still maintained at the PHCs and sub-centers.In Karnataka, India, the registration of births and deaths became operational throughout the state beginning in 2000. Healthcare providers serving the district health system and other officials at the village and sub-district levels collect vital events information. While, the accuracy and completeness of these government statistics are perceived to be relatively good, they are not as complete as many formal functioning pregnancy and vital statistics registries in more developed countries. Of note, abortions and stillbirths, especially, are likely to be under-reported and/or misclassified.Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD) funded the Global Network for Women’s and Children’s Health Research, incorporating a site based in Belgaum in Karnataka State, India. Among the research initiatives funded was the First Breath trial which was implemented in Belgaum in collaboration with the District Health System [In 2000, the U.S. h System . For theThe Maternal Newborn Health Registry (MNHR) is a prospective, population-based observational study that was initiated to better understand and quantify trends in outcomes of pregnancy and childbirth in rural PHCs clusters so as to provide data on abortions, stillbirths, newborn and maternal mortality ,18. ThisThe MNHR receives inputs from the register of Married Women of Reproductive Age  at the PHCs and sub-centers. The MWRA register contains information regarding couples eligible to receive contraception services, those who are infertile and those yet to reach menopause. It also identifies those couples wishing to, and who are likely to conceive, within the following year. The MWRA is updated every year by a house-to-house survey (occurring over a 3-months period) conducted by auxiliary nurse midwives (ANMs), Anganwadi workers (AWWs) and accredited social health activists (ASHAs). In addition to informing public health needs, the MWRA provides early identification for pregnancies and informs enrollment in the MNHR. Building on the MWRA, the data collection for the MNHR began in May 2008 in 20 geographic areas, each incorporating a PHC with ≥300 annual deliveries and covering a total population of about 660,000, which is also encompassed in the MWRA catchment area. Although one of the primary sources used to identify pregnant women is the MWRA, registry staff and other health workers attempt to identify all pregnant women, married or not, in the catchment area and these women are included in the registry.In central and southern India, where Karnataka is located, it is common, particularly among nulliparous women, to stay with relatives and deliver where those relatives reside. Similarly, pregnant women may enter the catchment area to deliver at the home of relatives. Recording movement of pregnant women for delivery was one of the major problems we had to overcome to approach 100% ascertainment. Thus, pregnant women were eligible for inclusion in the MNHR if they were residents of the study clusters during pregnancy, regardless of delivery location. Women were also eligible if they lived outside the geographic area but delivered within the MNHR catchment area. All identified women who met criteria were included in the registry after they had provided written informed consent.All women identified as likely to conceive were followed up by monthly visits through the MWRA. After a missed menstrual period and a pregnancy confirmed by a pregnancy test, an eligible woman is then invited to be enrolled in the MNHR by ASHA workers. Once the woman has been enrolled, the MNHR registry administrators (RAs), who are medical officers of the PHCs, obtain consent and complete data entry forms for the MNHR. This methodology of screening for pregnancy has also enabled us to document spontaneous abortions and medical terminations of pregnancy (MTPs) at the community level. These data had not been previously collected.Three forms are used to collect study data, are available elsewhere . 1) The The1.After the forms obtained at the three specific times discussed above are compiled by the RA, the completed forms are then verified and collected by the data entry operators on fixed days of the week. Data are entered into an electronic database at regional data centers located at the sub-district level and transmitted to a central data management center. The quality of data received is regularly monitored by a research coordinator, who oversees the study, and field research officers, who are generally medical officers with oversight of field activities, together with RAs and data entry operators at the regional data centers. Cleaning and editing data and transmission to the Global Network Data Coordinating Center (DCC), located at a central location in the U.S. are ongoing activities. Combined data are processed and analyzed at the DCC for data consistencies and completeness. The DCC sends monthly monitoring reports which are discussed by the study team  and serve as process and outcome indicators. Inconsistencies and unexpected findings or trends, when they occur, are verified and corrective steps initiated during monthly meetings conducted at the study site headquarters in Belgaum.Data quality was monitored in a number of ways. The monitoring metrics included: 1) the number of days taken to complete the forms and record of all relevant events, 2) the proportion of women consented for inclusion in the study from the total of pregnancy women screened who were eligible, 3) the rates of MTP, miscarriages, stillbirths and live births, as well as 4) the proportion of follow-up through 42 days postpartum. The monthly monitoring reports contain these elements which allow the team to further check and validate the results.An important feature of the quality measurement is having an estimate of the number of births that should occur in each cluster. We use an estimate of the crude birth rate (CBR) within the study clusters as an indicator of completeness of registration of pregnancy outcomes and as a check to ensure complete capture of all births. The CBR was computed from the live births and the estimated population of the cluster. Significant differences of the number of births registered from those expected are investigated.The time taken in completion after the event of interest and its entry into the data management system has also been considered as a quality indicator, along with documentation of the extent of birth weights recorded and the presence of a healthcare provider at the time of delivery.Between 2008 and 2014, the MNHR catchment area comprised a total population of approximately 660,000 (Table Early registration of pregnancy (less than 12 weeks gestation) among all those enrolled in the MNHR increased from 5.9% in 2008-09 to 34.0% in 2013-14  cluster-wide consistency checks; (2) monitoring time lag in completing the data collection from occurrence of the event to its subsequent electronic data entry, as well as; (3) identifying missing birth weights, reflected in accurate recording of birth weight in more than 94% of all births and more than 99% of neonatal deaths. To assure the completeness of the data, a comparison of expected number of pregnancies with actual number of pregnancies was monitored.A question that might arise in the reader’s mind is whether a system such as that described in this paper is replicable in the rest of India. In India, the types of government workers mobilized for registry data collection in Belgaum are also available in each district throughout the country. Similarly, the systems upon which the MNHR was built are generally present. Therefore, we believe that if there is political will to carefully collect quality data, and a motivating entity such as the university staff and the MOH personnel in the Belgaum area, a similar registry could be created elsewhere. As a start, the MOH has implemented an electronic Mother Child Tracking System, modelled on the MNHR, nationally to monitor the outcomes of pregnancies.There are a number of lessons learned from the creation of the MNHR in this area of India. Most important, is that from the beginning, this registry was a joint effort by the research group at the university hospital and the public health infrastructure of the MOH. Research-quality data was perceived as crucially important to both groups. Second, because both groups wanted information on both the births in the resident population as well as the births occurring in the geographic area regardless of residency of the mother, strong efforts were made to capture both types of births. This information is especially useful to health planners and providers in and out of the study area. Third, it became obvious that triangulating outcomes in the various ongoing government registries as a check on data in the MNHR was crucial in getting as close to complete registration as possible. Fourth, the use of the CBR as a way to estimate the expected number of births in each cluster was a very useful check to help insure completeness of registration. Fifth, the use of the existing MWRA registry is an important feature of the system. By knowing who is likely to conceive in the near future combined with frequent surveillance, the MNHR administrators can determine pregnancy outcomes, including miscarriages and MTPs, which historically have been poorly collected in many geographic areas.There have been difficulties in managing the MNHR as well. Finding and retaining trained staff at every level and sustaining their motivation year after year has been a continuing challenge. Shortages of physicians and other trained personnel has been a problem. In part because of an increased burden posed on them by a multitude of national programs, the PHC staff have had less time to perform their registry duties and thus over the years, independent staff have been increasingly recruited to function as RAs. With staff turnover, training and retraining of staff has been an important feature of the MNHR and has helped to ensure data quality and timeliness. Most important in the creation and maintenance of the MNHR was the practice of holding frequent meetings with stake-holders including the rural community, the district health officials and the MOH of Karnataka State to address concerns as they arose.Use of the MWRA registry also is a crucial tool for identifying women for enrollment into pre-pregnancy studies as well as studies requiring first trimester enrollment. Since the norm in many low resource settings is for women to enroll in prenatal care at 20 weeks or later, use of the MWRA registry enables studies to be undertaken that otherwise would be difficult or impossible in these settings. Finally, this paper describes some of the measures used to monitor the quality of the data collected over the time the MNHR has been in existence. These include measures such as the percent of pregnancies registered in the first trimester, the timeliness of reporting within specified limits, and the amount of missing data such as measured birth weights for live births and stillbirths. Improvement in many of these metrics was documented. The ongoing comprehensive monitoring of a number of quality metrics allows the NMHR administrators to have good faith that the data received from this site is of exceptional quality.In summary, this report details many of the steps that need to be taken in any low-resource area without a good vital statistics system to establish a credible pregnancy outcome registry. We believe these steps are applicable anywhere there is a desire to really understand which residents in a geographic area are getting pregnant as well as who is delivering in the area, and the outcome of their pregnancies. An ongoing monitoring system better allows the registry administrators and interested reviewers to understand the quality of the data. Knowledge regarding the reproductive health status in the registry should identify key areas for implementation of evidence-based interventions that will assist in meeting India’s Newborn Action Plan and help achieve single digit neonatal mortality and stillbirth rates by 2030 . While cThe authors declare that they have no conflict of interest.BSK conceived the paper and wrote the first draft; EMM, RLG, RJD and SSG participated in writing and RLG, SSG, EMM and NLS edited the draft. NVH, NKT, SSG, and SCM monitor study data collection and analyses. JLM conducted study analyses with EMM. All authors reviewed and approved the final manuscript.Reviewer reports for this article can be found in Additional file Click here for file


RNs and studentsdaily registered patients, took history (at admission), performed physicalassessments, and established nursing diagnoses, nursing plans/prescriptions, andassessed care delivered to 17 patients using software. Indicators concerning theincidence and prevalence of nursing diagnoses, rate of effectiveness, riskdiagnoses, and rate of effective prevention of complications were computed.  the Risk for imbalanced body temperature was the most frequent diagnosis(23.53%), while the least frequent was Risk for constipation (0%). The Risk forImpaired skin integrity was prevalent in 100% of the patients, while Risk foracute confusion was the least prevalent (11.76%). Risk for constipation and Riskfor impaired skin integrity obtained a rate of risk diagnostic effectiveness of100%. The rate of effective prevention of acute confusion and falls was 100%.  the efficacy of the Nursing Process using indicators was analyzed because theseindicators reveal how nurses have identified patients' risks and conditions, andplanned care in a systematized manner. One of the tools that should be used in the implementation of SNC is theNursing Process (NP), a scientific method nurses can use to apply technical-scientificand practical knowledge into clinical practice. Its effective application leads to improved healthcare quality, encouragesthe construction of evidence-based theoretical and scientific knowledge, helps in thedevelopment of protocols, grounds teaching and clinical rationales, and the managementof costs and planning of resource allocation to quality nursing services(-).The Systematization of Nursing Care (SNC) is indicated as a method capable of improvingthe quality of nursing care because it provides scientific support, security anddirection to the performance of the nursing staff's activities-3. Onpractice. Its efservices-6..The increased volume of data accruing from recording NP stages favors the developmentand broader use of computer systems, which enables the pursuit of actions to be directedbased on organized data that becomes available to professionals through nursinginformation systems.The computerized system with Nursing Process in Intensive Therapy (SIPETi) consists ofsoftware based on the Theory of Basic Human Needs, especially designed by Wanda deAguiar Horta for adult Intensive Care Units (ICUs). It contains essential data for therecording of investigations, diagnoses, planning, implementation and assessment of thedelivery of nursing care, in addition to the results and indicators of such care. SIPETiwas experimentally applied in an ICU to establish its applicability. Data, however, werenot sufficient to generate all indicators concerning nursing care delivery proposed inthe system's assessment module.Given the need to provide tools to nurses seeking quality in their nursing care by usingindicators that address the NP, it is necessary for nurses to have the standardized andcomputerized nursing data that are essential to assessing the effectiveness of care andverification of contributions to outcomes achieved by patients. .Additionally, it is also necessary that studies address the relationship among NursingDiagnoses (NDx), interventions, and outcomes, showing the contributions made by NP andits importance to the quality of systematizing care.Since SIPETi was developed to generate indicators capable of establishing thisrelationship, the system's assessment module, from which data can be retrieved, needs tobe validated for the system to be used with this purpose. This study's general objective was to analyze NP efficacy using indicators generated bysoftware in an adult ICU located in Belo Horizonte, MG, Brazil. The specific objectivesincluded identifying the incidence and prevalence of nursing diagnoses in a group ofinpatients in an ICU in Belo Horizonte and identify the rate of risk diagnosticeffectiveness and effectiveness rate in the prevention of complications among inpatientsincluded in the study.This cross-sectional study was conducted in an adult ICU in Belo Horizonte, MG, Brazil,with patients hospitalized in the first two beds of the ICU during four months of 2013. This ICU was chosen because its nursing carewas already systematized through the NP since 2008. The NP steps are performed dailywith all the ICU inpatients. For that, nurses use worksheets they create themselves in acomputerized system. The use of software with daily input was initiated for some of thepatients during its implementation, as a test. These two beds were chosen because theyare separated from the remaining beds within the ICU's physical structure and also dueto the need to establish a number of patients that would enable data collection to beperformed by the professionals who volunteered for the task together with theresearchers, all specifically trained to collect data using the computerized system. In the event a patient included in the study was transferred to a bed not selected forthis study, his/her monitoring within the ICU would be performed up to discharge,removal to another unit, or death. Patients were excluded if admitted to one of theselected beds but discharged, transferred to another unit, or if they died before thefirst data collection using the software..Individual and collective training was implemented to qualify the RNs and nursingstudents who would feed the SIPETi. Theoretical-practical content was addressed by oneof the researchers. Agreement regarding implementation of the NP stages and itsdocumentation in the computerized system was established among the RNs and studentsthrough Batista's concordance test. Three RNs and three students were considered able toperform data collection, as they obtained a level of agreement greater than80%.The RNs and students properly trained took turns daily to register patients andhistory-taking (at admission), physical assessment, establishment of Nursing Diagnoses(NDx), nursing planning/prescription, and assessment of care provided to the patientsadmitted to the first two beds in the ICU up to discharge, transfer, or death. Afterinformation was included in SIPETi, data necessary for the computation of nursingindicators were retrieved.(-). Additionally, falls and pressure ulcers have been mentioned as the mainevents to be prevented for the safety of patients used to compose the SIPETi database, as well as to be used as indicators ofthe quality of nursing care,.NDx concerning Risk for constipation, Risk for acute confusion, Risk for imbalance inbody temperature, Risk for impaired skin integrity, and Risk for falls and therespective actions prescribed during the entire hospitalization, within the studiedperiod, were selected for the calculation of indicators. These NDx were chosen becausestudies show these are among the most frequent NDx presented by critical patientsadmitted in ICUs-11. Apatients used to, which belong to the set of essential nursing data, were selected:The following indicators, proposed by the Order of Nurses of Portugal, which Incidence:A case concerning a given diagnosis was considered to be new when identified after thepatient's first assessment, that is, after admission. Note that a diagnosis under whicha patient is admitted is not considered to be a new case, even if the diagnosis isresolved and identified again afterwards. Prevalence:In this study, a case of a given diagnosis was considered when it was identified at somepoint during the patient's hospitalization.Rate of risk diagnosis effectiveness:The number of cases of patients who developed a real condition was identified based onreal nursing diagnoses or adverse events, as described in Rate of effective prevention of complications:In SIPETi, nursing actions are prescribed for a certain diagnosis, enabling thecomputation of the rate of effectiveness in the prevention of complications.Data concerning the calculation of indicators were generated by SIPETi. Percentages wereestablished and the results of these computations are presented in tables. A total of 142 patients were admitted to the ICU during data collection. Seventeen (12%)patients occupied the beds selected for this study and all these composed the study'ssample. Ten of these patients were male and represented 59% of the total. Age rangedfrom 26 to 91 years old, with an average age of 68 years old and a median of 76 yearsold. All the patients were hospitalized using health insurance plans. Duration ofhospitalization ranged from three to 42 days, with 13 days on average and a median ofnine days.The NDx Risk for imbalanced body temperature and Risk for impaired skin integrity werethe most incident: 23.53% and 11.76%, respectively. The NDx Risk for acute confusion andRisk for falls had an incidence of 5.88%, while Risk for constipation had an incidenceof 0%.In regard to prevalence, Risk for impaired skin integrity was prevalent in 17 (100%)patients, followed by Risk for imbalanced body temperature and Risk for falls, bothprevalent in 15 (88.23%) patients. Risk for constipation was prevalent in 13 (76.47%)patients, while the least prevalent was Risk for acute confusion; only two (11.76%)patients were affected by it.We verified that Risk for constipation and Risk for impaired skin integrity obtained thehighest rate of diagnostic accuracy, that is, all the patients who developedconstipation or skin lesions, were previously diagnosed with Risk for constipation andRisk for impaired skin integrity, respectively. The rate of diagnostic effectiveness for Risk for imbalanced body temperature was 85.7%and 0% for Risk for acute confusion. The rate of diagnostic effectiveness was notestablished for Risk for falls because the event did not occur. Data concerning the calculation of the rates of risk diagnostic effectiveness arepresented in The rate of effectiveness in the prevention of complications such as acute confusion andfalls was 100%. The same indicator was observed for the NDx Risk for constipation, Riskfor imbalanced body temperature, and Risk for impaired skin integrity: 76.9%, 73.4% and70.6%, respectively. Data used for calculating rate of effectiveness in the preventionof complications for the diagnoses selected for this study are presented in . Another study also identified this NDx in most patients hospitalized in anadult ICU.The NDx Risk for constipation was not identified during the stay of any of the patients,though it obtained high prevalence. This shows that all the patients had the Risk forconstipation identified at the time of admission. This finding is due to the fact thatNDx have risk factors commonly found in patients admitted to ICUs, such as insufficientphysical activity, the use of sedatives and opioids, and vasopressor drugs, amongothers. Anothedult ICU.The NDx Risk for falls had low incidence because it was identified in only one patientduring hospitalization. Its prevalence, however, was high. This means that Risk forfalls was identified in most patients at the time of admission. This finding is due tothe fact that the risk factors of this specific ND are common among patients admitted inthe studied ICU, such as being older than 65 years old, acute disease, and impairedphysical mobility.The NDx Risk for acute confusion had low incidence and prevalence. These indexes can beassociated with the fact that some of the factors related to acute confusion includebeing older than 60 years old and having dementia, while the latter is often confoundedwith acute confusion itself, leading to errors of omitting the NDx. Since the diagnosticpossibilities presented by SIPETi result from mapping evidence included in the physicalassessment module, neither advanced age nor dementia are mapped in the NDx modulebecause they are documented in the registration and history-taking modules. The factthat SIPETi still does not allow adding a nursing diagnosis that is not mapped toconstant changes found in physical assessments may explain the low incidence andprevalence of this ND.. One study shows that risk factors such as immobility and mechanicalfactors are among the risks most frequently found concerning Risk for impaired skinintegrity among patients hospitalized in ICUs. The high prevalence of the NDx Risk for impaired skin integritycorroborates data found in another study, which also predicted this ND for 100% of thewomen hospitalized in an ICU.The NDx Risk for imbalanced body temperature and Risk for impaired skin integrity wereidentified in four patients after admission, constituting an incidence of 23.53%. Bothpresented high prevalence because they were predicted for 15 (88.23%) and 17 (100%)patients, respectively. This contrast between low incidence and high prevalence for bothNDs may be explained by the fact that patients admitted to an ICU usually present riskfactors for these NDx. Risk for imbalanced body temperature presents risk factors suchas extreme age, inactivity, sedation, changed metabolic rate, medications that causevasoconstriction and vasodilatation, among others, which are common in severely illpatients. One st in ICUs. The hiThree patients were identified with the ND Acute confusion, though none of thempresented the Risk documented on the previous day, explaining a rate of diagnosticaccuracy of 0%. This finding may also be explained by the same reason that was apossible explanation of the low incidence and prevalence of this ND; that is, theomission of an ND due to a failure in the process of investigation and diagnosis and/orthe fact that this ND does not appear to be a diagnostic possibility because some of itsrisk factors are included in the registration and history-taking modules, neither ofwhich are included in the NDx module.Three patients were diagnosed with Intestinal constipation (none with perceivedconstipation), but all had the ND Risk for constipation identified on the day before theidentification of the condition, translating into a rate of diagnostic accuracy of 100%.This finding, allied with the high prevalence of this ND in the study, reflects theattention nurses have paid to constipation. The occurrence of many risk factors for thisdiagnosis such as those of a pharmacological, functional, physiological, mechanical, andpsychological nature, allied with a characteristic that is common among patients inICUs, being bedridden and a consequent reduction in physical activity, may explain whynurses easily identify patients at risk. Another piece of information that contributesto this assertion is the fact that this ND presented an incidence of 0%; that is, it wasnot identified during the hospitalization but at the time most of the patients wereadmitted.Six patients were identified with Hypothermia or Hyperthermia, while one presented bothduring hospitalization; that is, there were seven cases and none of them was identifiedwith Inefficient thermoregulation. Because only in one case did the patient diagnosedwith hyperthermia not present documented Risk for imbalanced body temperature, the rateof diagnostic effectiveness was 85.7%.Five patients were identified with the ND Impaired skin integrity during hospitalizationand none of the patients presented Impaired tissue integrity. Among these, 17 patientsdeveloped lesions during hospitalization in the ICU. It was established, for the study'spurpose, that the number of lesions developed in the ICU associated with ND Risk forImpaired skin integrity or Impaired tissue integrity would be considered the number ofcases that developed a given real condition (skin lesion). This is the case because apatient is identified with both ND Impaired skin (or tissue) integrity and Risk forimpaired skin integrity. Hence, if a real condition develops, that is, a skin lesion, itmay not be identified by identifying the diagnostic title only. Therefore, there isimportance in describing in the physical assessment when a skin lesion develops in theICU so that it is characterized as an adverse event, that is, a real condition.Additionally, because more than one lesion was identified per patient in just a few daysand the indicator of rate of risk diagnosis effectiveness is intended to verify theeffectiveness of diagnosing the risk before the condition develops, when a patient wasreported as having more than one lesion developing on the same day was considered asingle case. Hence, the number of cases considered for the denominator of this indicatorwas ten. For all these cases, the ND Risk for impaired skin integrity was identified onthe day before the lesion developed, reflecting a rate of diagnostic effectiveness of100%. It is worth noting that the ND Impaired skin integrity was identified for thepatients with skin lesions without considering the rupture of skin secondary to theintroduction of invasive devices like venous access for instance.. In addition to a concern regarding the complications this adverse eventmay cause, falls are less common in ICUs because patients are usually bedridden due tothe need for continuous monitoring and are not always in a condition where walking ortransferring themselves to an armchair during any given time is possible. Anotherpotential explanation for a lack of falls is due to the fact that nursing actions "tomaintain high bed rails" and "to identify the patient's cognitive or physical deficits that can increase the risk of falls" areamong the most prevalent in this study.The rate of diagnostic accuracy regarding Risk for falls could not be established sincethere was no occurrences of falls among the study's patients. It is worth noting,however, that this ND was one of the most prevalent, with 88.23%. One study also showedlow occurrence of falls in the ICU, corresponding to 0.05%. In add.The highest rate of prevention of complications observed was related to Risk for Acuteconfusion and Risk for falls: all the patients diagnosed with these risks received adocumented action and did not develop the real condition, in this case, acute confusionor a fall. This finding confirms one of the advantages of using software in theprescription of specific actions for each nursing diagnosis. When nursing diagnoses andinterventions are interconnected, they facilitate individualized nursingcare.The rate of effectiveness in the prevention of complications for Risk for constipationwas 76.9%. Three of the 13 patients identified with this ND developed constipation andten did not. Even though all had documented actions to avoid constipation, it is knownthat constipation has various related risk factors that hinder direct nursing care, suchas advanced age, restricted manipulation secondary to hemodynamic instability, suspendeddiet, and history of chronic constipation, among other factors.The ND Risk for imbalanced body temperature was predicted for 15 patients but 11 did notdevelop hyperthermia, hypothermia or inefficient thermoregulation, culminating in a rateof effective prevention of complications of 73.4%. A documented action was prescribed toall of the patients to prevent complications, including the monitoring of bodytemperature every two hours, which was prescribed to all the study's patients. The rate of effective prevention of complications was 70.6% for Risk for Impaired skinintegrity. Of the 17 patients (100%) identified with this risk, 12 did not developImpaired skin integrity or Impaired tissue integrity during hospitalization. A total of17 skin lesions developed among five patients. Of these, 13 were pressure ulcers, whilenine developed in a single patient, whose risk to develop pressure ulcers, according toBraden scale, was moderate on the day in which three ulcers were verified and high onthe remaining days. Data collected in this study enabled analyzing indicators generated by software in anICU because the indicators reveal how nurses have identified patients' risks andconditions and planned care in a systematized manner. Note that the indicator of rate of risk diagnoses accuracy enabled detecting howefficiently the risk of patients to develop a given condition was evaluated. Thisindicator reinforces the importance of a holistic nursing approach to patients,especially history-taking and physical assessment, given the identification of patients'risk factors, and consequently, the establishment of preventive actions.Through the indicator of rate of effective prevention of complications it was possibleto identify the effectiveness of preventive actions prescribed to the patients. It isworth noting that the actions must be based on evidence, with strong recommendationsfrom the literature, strengthening nursing care with a scientific basis. It is, however, necessary that further studies addressing larger samples and other NDxbe conducted in order to enable a more comprehensive assessment of NP efficacy. Given the undeniable need to provide tools to nurses and establish strategies to measureand improve the quality of nursing care, it is important that essential data concerningnursing be standardized and computerized to assess the effectiveness of care and hownursing care contributed to the outcomes achieved by the patients. In this sense, it isessential to establish indicators that address NP.It is not possible to infer which given nursing intervention was decisive in keeping acondition from developing, though they certainly contributed. Further research focusingon the efficacy of actions is needed to prevent the occurrence of complications amongpatients hospitalized in ICUs and, for that, it is necessary that nurses establishnursing prescriptions for each diagnosis identified among the patients under theircare.


Certain dipteran flies larvae causing invasion of the tissues and organs of the humans or other vertebrates are called as myiasis, which feed on hosts dead or living tissues. It is well documented in the skin and hot climate regions; underdeveloped countries are affected more commonly. Oral cavity is affected rarely and it can be secondary to serious medical conditions. Poor oral hygiene, alcoholism, senility, or suppurating lesions can be associated with the oral myiasis. Inflammatory and allergic reactions are the commonest clinical manifestations of the disease. In the present case, gingiva of maxillary anterior region was affected by larval infection in a 13-year-old mentally retarded patient.  F. W. Hope. Zumpt defined myiasis as the dipterous larva invading the human or other vertebrate animals and feeding on host's dead or living tissue, liquid body substances, and ingested food for certain period of time [The term myiasis is derived from the Greek word “myia,” which is used for fly and it means invasion of organs or tissues of vertebrate animals or humans by dipteral larvae. The term myiasis was coined in 1940 by of time .It is restricted to summer months in temperate zones and all year round in the tropics, as the flies which are responsible for myiasis prefer a warm and humid environment. Myiasis is less common in humans than in the vertebrate animals .The ear, nose, eyes, lungs, skin, anus, and vagina are the most common sites affected in myiasis , 5. The The present paper describes a rare case of gingival myiasis in a 13-year-old mentally retarded patient.A 13-year-old male patient presented to the hospital with a complaint of swelling and discomfort in maxillary anterior region since 10–12 days. On medical examination, the patient was found to be mentally retarded. The patient was from low socioeconomic background and residing in a rural area. On extra oral examination, the upper lip was swollen causing slight protrusion on the left side . SystemiThe most common protocol followed for the myiasis was given for this patient. It consists of flushing affected area with turpentine oil, followed by administration of local anesthesia and removal of maggots by simple tweezers. Around 11–13 maggots were removed from the affected site . Ivermec Musca domestica (common housefly). The larvae of the housefly were of cylindrical shape but tapering towards the head, were typical creamy white in color, and had 13 segments, of which 12 were apparent, as the first 2 were partly fused. The head was containing one pair of dark hooks.The maggots were preserved in 10% formalin and sent to a parasitology department of medical college for identification, where they were identified as larvae ofAfter 1 month, the lesional site was found to be healed properly. On the follow-up of the patient, after 6 months, he was absolutely alright and no parasitic infestation was found in oral cavity.The oral myiasis, parasitic infestation of the human, is a rare condition, which mainly occurs in the rural areas. The flies of the order Diptera (maggots) are the main parasites affecting humans , 6. The In the present case, the causative agent was identified to be of common housefly. Similar type of case reports of common housefly affecting maxillary anterior region intraorally was also reported by Bhagawati et al.  and PereThe life cycle of a fly consists of 4 stages: egg stage, larval stage, the pupa, and finally the adult fly. Direct inoculation into wounds and ingestion of infected materials like meat are the two ways causing infestation of the maggots in the humans. For the larval development of these flies, the intermediate host is required and the flies can lay more than 500 eggs at a time directly over the diseased tissue , 6, 12. The action of proteolytic enzymes released by the surrounding bacteria causes decomposition of the tissue and helps in the feeding of the maggots , 14. LarLarvae position themselves with their heads down to expose their posterior spiracles to the air, which makes their respiration possible. Approximately 8–10 days are required for the larvae to develop into prepupal stage after their penetration into the tissues and then they leave the host. The backward segmental hooks are useful for the anchoring of the larvae to the surrounding tissue. The larvae are photophobic; hence, they tend to hide deep into the tissues for a suitable niche to develop into pupa .Oral myiasis usually has male predilection because of outdoor activities and habit of neglecting oral hygiene. It is commonly seen in adults, but cases in children have also been reported. In case of oral myiasis, the most common site involved is the anterior segments of the maxillary and mandibular jaws and the palate , 6.In the present case, gingiva of the maxillary anterior site was affected. Reddy et al. , BhagawaClinical picture of the pulsating larvae is sufficient for the diagnosis of the oral myiasis and for the species identification it should be sent to the specialized laboratories. Mechanical removal of larvae is the most commonly used treatment , 6. LocaIn our case, turpentine oil was applied followed by local anaesthesia and removal of the maggots by tweezer followed by antibiotic course of ivermectin, which was similar to the treatment suggested by Reddy et al. , SankariOral myiasis is an uncommon condition. Parasitic infestations can be reduced by raising the quality of life and improving the personal hygiene measurements. Mental and physically disabled patients need special care to maintain oral hygiene. As dentists, it is our duty to raise awareness that a special needs patient should be exposed to proper dental intervention on regular basis as early as possible to promote cooperation and to prevent the occurrence of the disease.


The incidence of hip fractures in older adults in India is likely to increase dramatically in the coming decades as a result of an aging population and increasing life expectancy. Currently, more than 600,000 adults over 60 years of age suffer a hip fracture annually in India. This paper outlines a protocol for a qualitative study investigating the care seeking behavior of older adults with hip fractures: to determine the processes in decision making, identify causes for delay in obtaining care, and identify potential barriers and facilitators to seeking appropriate care in time.The planned study will consider Odisha, an eastern state in India with limited health care facility, as a suitable case study. It is proposed to conduct 30 in-depth interviews in two administrative districts of Odisha. The participants will be patient and their carers in seven health facilities- four public hospitals, two private hospitals and one traditional bone-setting facility. The study relies on a purposive sampling strategy. Ethics permission will be sought from each participating institution and participants. The participants will be adults aged 50 years or older of both sexes arriving at the recruiting centers with a history of fall or injury, pain in the hip region and inability to walk and X-ray confirmed diagnosis of proximal femoral fracture and their primary carer. Trained qualitative research team will conduct these interviews. A thematic framework approach will be used to analyze the data using NVivo 9 software.The data collected from the interviews will be analysed to explore the cause of the hip fracture, events following the injury, the experiences of patients from the time of sustaining the injury, pain relief measures, decision to seek care, understanding of the urgency for treatment, causes for delay in receiving treatment, funding sources, cost liabilities for the family, financing mechanisms for out of pocket expenditure and the burden for caring.The findings of this study will provide an increased understanding of the care seeking behaviors of older adults with hip fracture, and inform contextually appropriate changes in healthcare program and policy aimed at improving health outcomes. The incidence of hip fractures in older adults in India is likely to increase dramatically in the coming decades as a result of an aging population and increasing life expectancy. By 2020, it is estimated that India will have a population of 1305 million of which 82.2 million 6.3 %) will be over 65 years  and the .3 % willAs time to surgery from a hip fracture is key to improving outcomes, the speed of arrival at the surgical centre following the fracture is crucial. Various factors contribute to delays in reaching treatment centres and receiving appropriate care. The framework of the three-delay model, developed for analysing barriers to emergency caesarean section, identified decision making to seek care as the first cause for delay, transportation as the second cause for delay and the third delay is in receiving care within the hospital . This moThe decision-making processes to seek care are influenced by a multitude of factors. Cultural and religious beliefs, faith, limited societal knowledge, inequities of age and gender, poor access to health facilities and financial barriers drives care-seeking behavior . Faith iFamily members with financial and caring responsibilities often take the major role in deciding treatment options and may cause age and gender inequities .The supply side of care, cost and ease of access significantly influence care-seeking behavior. Surgical facilities for fracture treatment in India are mostly limited to tertiary care hospitals in urban areas and at great distances. In Kerala, the state with the best healthcare standards in India, elderly adults mostly seek private care  whereas Understanding the decision-making processes to seek care, which contributes to the first delay, will identify processes and attitudes that are barriers to implementation of best practices in the management of hip fractures in India. The proposed study will be conducted in Odisha, an eastern state in India with a population of 43 million and more than 9 % over 60 years of age. The Public Health System in Orissa comprises various levels of facilities in each of the 30 adminstartive district, and tertiary care facilities for referral .Each district hospital (DH) serves a population of approximately 1.3–2 million population. Few of these DH are equipped for orthopaedic surgery and majority of patients seek care in private hospitals, mostly in urban areas. The poor can afford care only at public tertiary care facilities, which are overcrowded and at a great distance from their homes. There are no data from Odisha or India on the care-seeking pattern of older adults, as to when, why and how they choose a treatment facility. Our proposed study aims to document the present care seeking pathways for older adults with hip fractures in Odisha.The aim of the study is to provide evidence to strengthen the health systems for the delivery of evidence based care for older adults with hip fractures in Odisha. The specific objectives of the study are to explore the care seeking behavior of older adults with hip fractures: to determine the processes in decision making, identify causes for delay in obtaining care, and identify potential barriers and facilitators to seeking appropriate care in time.This is an exploratory study using qualitative methods. Qualitative research takes a detailed approach to the phenomena under the study in order to understand it more thoroughly. Therefore, in-depth interviews are a suitable method for this approach because of their emphasis on people’s lived experience. They are considered to be well suited for locating the meanings that people place on the events, processes, and structures of their lives and their perceptions, presuppositions and assumptions . MoreoveThe study relies on a purposive sampling strategy. The study will be carried out in Khordha and Cuttack administrative districts of Odisha. Hip fractures arriving at Khorda District Head quarter Hospital (DHH) are often referred to the nearest non-teaching tertiary care facility at Capital Hospital (CH) in Bhubaneswar or the government SCB Medical College Hospital (SCBMCH), Cuttack. Three public hospitals  and two private hospital in a geographical area, Kalinga Institute of medical sciences (KIMS), Bhubaneswar, Ashwini Hospital & Trauma Centre, Cuttack have been identified as participating sites for the study. To identify factors influencing decisions to seek treatment with traditional osteopaths, hip fracture patients seeking care with the regional osteopath at Kalupada will also be included in the study.It is proposed to conduct 30 in-depth interviews with patients and carers in different healthcare facilities. Purposively,seven institutions;four public hospitals and two private hospitals and one traditional bone-setting center have been identified as sites for the study. Ethics permission will be sought from each participating hospital. The patients will be recruited purposively after they are admitted to the care facilities. The clinicians will identify patients as per the inclusion criteria of the study, introduce researcher to the patient and facilitate consent procedure.The inclusion criteria for the study are adults aged 50 years or older of both sexes arriving at the recruiting centers with a history of fall or injury, pain in the hip region and inability to walk and, X-ray confirmed diagnosis of proximal femoral fracture, also known as a hip fracture. Patients with pathological fractures and terminal malignancies will be excluded. The person with the hip fracture will be the informant for the study and the primary carer will be requested for additional information. Participants will be provided with verbal and written information in local language on the aims and methods of the study and consent will be obtained from the participants prior to the interview. They will also be informed that all data collected will be stored safely and only used by researchers, maintaining confidentiality.In-depth, qualitative interviews will be carried out by the research team with the assistance of an interview guide . LiteratThe interview will explore the experiences of patients from the time of sustaining the injury, exploring the cause of the hip fracture, events following the injury, the experience of patients from the time of sustaining the injury, pain relief measures, decision to seek care, understanding of the urgency for treatment, causes for delay in receiving treatment, funding sources, cost liabilities for the family, financing mechanism for out of pocket expenditure and the burden for caring. A questionnaire will be developed using categories identified from the data collected from the interviews.Thirty patients with hip fracture will be interviewed within the care setting as per convenience of the participants. Trained qualitative research team members will conduct these interviews and each team will comprise of a moderator and note-taker. Field notes will be taken by the note-taker at all occasions. Odia transcriptions of all interviews and then translate to English. All the interviews will be audio-recorded (with participants’ consent) and will be transcribed verbatim and then translated to English. Data will be analysed using conventional qualitative methods that seek to identify themes which are relevant both across and in cases . All traPatient’s experience following hip fracture and awareness of the consequences of the injuryFactors influencing delay in treatment: carer involvement in decision making, household finance in care seeking decisions, availability and access to treatment, transport, and availability of surgical care in local hospitalSocio-cultural factors: Belief in a particular discipline of treatment, preference for the treatment and patient satisfactionThe data collected from the interviews will be analyzed to identify factors influencing decision making in the family to seek care for older adults with hip fracture, the choice of care facility, influence of equity and gender in receiving appropriate care in time. The study will inform on the following:This exploratory study will provide an in-depth understanding of the processes involved in seeking care for older adults with hip fracture in the recruitment area. Qualitative research generally takes more time to collect the data when compared to quantitative research. In addition, information collected through qualitative methods is contextual and may not be generalizable in other settings. Therefore, in order to maximize the benefits of interview, data quantification is necessary. A structured questionnaire will be developed using categories identified from the data collected through in-depth interviews . The queThe proposed study conducted in two purposively selected district portrayed the situation for hip fracture care in Odisha state. As socio economic condition and health care delivery system are not uniform throughout the country, the result cannot be generalized. Such studies are therefore needed in different parts of India and other developing countries.The study has been evaluated and approved by the ethics committee of the Center for Disease Control  (IEC/04/2014 dated 1.10.2014) and Government of Odisha (224/SHRMU dated 31.07.2014). The findings from this study will be disseminated through peer-reviewed publications and national & international conferences. Articles will also be submitted to other types of media to increase the awareness on the issue.


Road traffic crashes have been an increasing threat to the wellbeing of road users worldwide; an unacceptably high number of people die or become disabled from them. While high-income countries have successfully implemented effective interventions to help reduce the burden of road traffic injuries (RTIs) in their countries, low- and middle-income countries (LMICs) have not yet achieved similar results. Both scientific research and capacity development have proven to be useful for preventing RTIs in high-income countries. In 1999, a group of leading researchers from different countries decided to join efforts to help promote research on RTIs and develop the capacity of professionals from LMICs. This translated into the creation of the Road Traffic Injuries Research Network (RTIRN) – a partnership of over 1,100 road safety professionals from 114 countries collaborating to facilitate reductions in the burden of RTIs in LMICs by identifying and promoting effective, evidenced-based interventions and supporting research capacity building in road safety research in LMICs. This article presents the work that RTIRN has done over more than a decade, including production of a dozen scientific papers, support of nearly 100 researchers, training of nearly 1,000 people and 35 scholarships granted to researchers from LMICs to attend world conferences, as well as lessons learnt and future challenges to maximize its work. Road traffic injuries (RTIs) were the eighth leading cause of death in the world in 2010, whereas in 1990 they occupied the tenth position; this represents an increase of 46% in the total number of deaths due to RTIs during this period . LMICs aThe Global Forum for Health Research made evident that, of the billions of US dollars spent on health research annually, less than 10% was spent on addressing the health problems relevant to 90% of the world’s population (including RTIs) – the ‘10/90 gap’ . In 2004Scientific research has proven to be useful for preventing RTIs in high-income countries. While there is still a continuing need for research in high-income countries that might also be useful for LMICs, it is important to note that few resources have been allocated for RTI research in many LMICs , 7. As sThis paper discusses a global response to these types of challenges by the Road Traffic Injuries Research Network (RTIRN), describing its contribution in developing research capacity and building networking mechanisms for professionals in LMICs. The paper covers the history and founding principles of RTIRN, as well as activities that the network is carrying out with measurable outputs after more than a decade of intensive and international collaborative efforts. The paper concludes with lessons learnt during this time and identifies future challenges in order to maximize the impact of RTIRN.RTIRN is an independent partnership of individuals and institutions from around the world that collaborate to advance research on the impact and causes of RTIs in LMICs and to identify appropriate interventions to the problem. The partnership evolved from a June 1999 meeting at the Global Forum for Health Research in Geneva, Switzerland, during which a session on Road Traffic Injuries in Developing Countries stirred significant interest among participants. In April 2000, the first meeting of interested partners was held in Kampala, Uganda, and in 2002 the Network was officially formed. The Global Forum for Health Research was essential in keeping the partners together and provided opportunities to present and discuss their research findings during annual meetings. With the recognition that neglecting RTI research in LMICs significantly contributes to the ‘10/90 gap’ in health research, RTIRN emerged as a distinct effort to address this disequilibrium.The vision of RTIRN is to reduce the burden of RTIs, particularly in LMICs, through conducting, promoting and utilizing research. Its goal is to establish networking mechanisms and assist in the creation of partnerships between RTI researchers and institutions globally to support research and research capacity in LMICs. In order to achieve this, RTIRN has set a series of specific objectives and basic principles of operation Table . The objRTIRN is comprised of 1) the Board; (2) the Secretariat; and (3) RTIRN partners, which together make up its constituent bodies  have worked for the Network, contributing to achieving its mission and objectives.Finally, the RTIRN partnership is a collection of individuals collaborating on RTI research in LMICs. Partners represent independent academics, individual researchers, research institutions, students, users of research, and both public and private agencies. Partners play an important role in providing broad direction to RTIRN. They contribute in various ways such as sharing information and opportunities with the RTIRN community and engaging in different projects and activities of the Network. As of March 5, 2015, there were 1,122 RTIRN partners, representing 114 countries Fig. . Of noteOne of the key activities of the Network has been to support professionals and researchers in LMICs generate evidence and help build national capacity. RTIRN has supported two rounds of a small grants program, several research projects and a multi-country initiative Table .RTIRN has been able to support two rounds of a small grants program, which was an open call for researchers in LMICs to apply for any road safety-related topic and secure a peer-reviewed award. RTIRN awarded 13 grants, which allowed 56 professionals to conduct research on priority topics such as road design, alcohol use, inappropriate speed and vulnerable road users, e.g. pedestrians and motorcyclists Table . The demA strategy used by RTIRN to support research capacity development in LMICs has been to support career development of professionals in road safety. RTIRN awarded 1-year grants to early career (junior) researchers and postgraduate students from LMICs working in the field of injury prevention and road safety in their country of origin Table . These jRTIRN also offered grants to senior researchers from LMICs to support a sabbatical to provide secure time to write papers and proposals, or visit and develop collaborations with other international colleagues . The proThe use of non-standard motorcycle helmets has the potential to undermine multinational efforts aimed at reducing the burden of RTIs associated with motorcycle crashes. However, little was known about the prevalence or factors associated with their use; therefore, RTIRN launched a multi-country study in collaboration with nine institutions in LMICs from five different WHO regions. The study conducted cross-sectional surveys, market surveys, and reviewed legislation and enforcement practices around non-standard helmets, generating evidence to inform key stakeholders on this important issue. The implementation model for this study allowed local researchers and practitioners to gain experience in RTI research together with international experts. This model allowed for optimal learning for researchers through inbuilt mentoring and led to a final publication in the scientific literature .RTIRN organizes regional workshops designed to train local and national participants from different backgrounds working on road safety, including those from government, NGOs, and academia. Led by a team of international road safety experts with broad experience in road safety research and training, these workshops were organized to cover several components of road safety (risk factors to enforcement) to ensure that targeted regions will benefit from the latest information . ParticiThe Network also encouraged networking by providing scholarships to attend the World Conferences on Injury Prevention and Safety Promotion. This included 13 young professionals from LMICs supported to the seventh world conference in Vienna in 2004 and 22 to the tenth conference in London. In fact, for 2010, this represented 30% of all scholarships provided during the world conference. These 35 scholarships represented an average investment of only US$ 1,850 per person.In 2010, RTIRN began a webinar series that brings state-of-the-art lectures and speakers to LMIC researchers at a very low cost , Vietnamese, Chinese, and Portuguese. All the newsletters are available on the RTIRN webpage, as well as through listserv distribution. Since April 2011 (when monitoring of downloads began), of the 59 different versions of the newsletter, a total of 1,867 have been downloaded. In 2011, RTIRN also started an annual Best Contribution Award to stimulate partners to keep sharing their work with the Network; this award has been won by two individuals.www.rtirn.net) to introduce the Network to a wider community and promote accountability to partners and funders by displaying activities being carried out. The site serves as an information centre for those interested in road safety, including upcoming events and publications produced by the Network and its partners. The website also showcases plans and actions in favour of the UN Decade of Action for Road Safety 2011–2020. The Online Forums on the website allows partners to discuss and comment on topics of common interest.RTIRN developed a website (www.facebook.com/RTIRN) and Twitter (@RTIRN) accounts. All of these provide a venue for the exchange of ideas and information, and disseminate products and results of activities. The Network’s Facebook page has nearly 422 fans, receives an average of 435 visits per year and there are around three new posts/shares per week; while the RTIRN Twitter account has more than 381 followers and we follow 151 partners.In March 2011, RTIRN also launched Facebook (The RTIRN listserv is used to share different opportunities from grant applications, conferences and webinars to job announcements; over time, many partners have indicated that the listserv is key to helping them expand their reach to other researchers and road safety professionals. This allows RTIRN to facilitate networking and interaction amongst partners with different expertise from different contexts.The work carried out by RTIRN has not gone unnoticed at a global level. In 2004, WHO acknowledged the important work of RTIRN in capacity building ; RTIRN wRTIRN has continued to grow steadily and more partners have joined each year – an indication that partners both believe in the work carried out by RTIRN but also recognize that there are benefits in being part of the network. As mentioned above, at least 12 scientific papers have been published , 23–25 dRTIRN appears to be the only academic- or research-oriented, free, global network for those working on road safety, and thus it has closed an important gap, especially for LMICs. The Network is comprised of a large group of committed road safety professionals who have been able to support this international effort for more than a decade. Since its inception, RTIRN has promoted the conduct and implementation of research for reducing the impact of RTIs in LMICs. RTIRN recognizes that one of the main concerns in road safety research is the lack of support for research and has devoted itself to securing funds to support researchers and their institutions. This work depends on the voluntary time and commitment of Board members, Secretariat staff, and partners. Thus, it is important that the work of RTIRN be widely disseminated so that funding agencies, donors and philanthropic institutions will invest their resources with the Network, which will help ensure continued success in the future.RTIRN has faced several challenges, and continues to do so, with creativity. First, the core team is voluntary and the commitment of board members can be potentially limited by other competing responsibilities. However, the limitation of board terms, commitment of individuals and strong interest by senior professionals has been sustained over 12 years. Second, it is important to mentor the next generation of board members and one approach being explored is the integration of young professionals into the Board. This would create incentives for young professionals to work hard and learn from others in the field, thus helping build the capacity. Third, like other networks, RTIRN needs to keep partners interested and engaged in activities. A recent innovation has been the move from online web-based forums to enhanced presence on social media such as Facebook and Twitter. Finally, encouraging speakers to share their experience through webinars has proved challenging at times – many senior professionals do not feel comfortable working with this type of technology, which does not allow for direct interaction with the audience. However, recruitment of experienced professionals used to online teaching has helped launch several webinars.In order to achieve the UN Decade of Action for Road Safety 2011–2020 objectives, more efforts should be made in terms of capacity building and allocating resources for RTI research in many LMICs. Both scientific research and capacity development have proven to be useful for preventing RTIs in high-income countries and, of course, research continues to play an important role in those regions. RTIRN, as the only academic- or research-oriented, free, global network for those working on road safety, filled the gap by creating a dedicated group for road safety researchers, and has motivated funding agencies to invest key resources in support of road safety professionals from LMICs . As sugg


This review identifies the current challenges in the investigation of VOCs as potential cancer biomarkers, by the critical evaluation of available matrices for the in vivo and in vitro approaches in this field and by comparison of the main extraction and detection techniques that have been applied to date in this area of study. It also summarises complementary in vivo, ex vivo, and in vitro studies conducted to date in order to try to identify volatile biomarkers of cancer.An early diagnosis and appropriate treatment are crucial in reducing mortality among people suffering from cancer. There is a lack of characteristic early clinical symptoms in most forms of cancer, which highlights the importance of investigating new methods for its early detection. One of the most promising methods is the analysis of volatile organic compounds (VOCs). VOCs are a diverse group of carbon-based chemicals that are present in exhaled breath and biofluids and may be collected from the headspace of these matrices. Different patterns of VOCs have been correlated with various diseases, cancer among them. Studies have also shown that cancer cells  Cancer is the second leading cause of death in the world. It has been estimated that there were 7.6 million fatal cases of cancer  and around 12.4 million new cancer cases in the year 2008 worldwide. Deaths from cancer are forecasted to continue to grow to over 13.1 million in 2030 . In addi in vitro [VOCs are a diverse group of carbon-based chemicals that are classified on the basis of their retention time and boiling point (ranging from 50°C to 260°C) . VOCs arin vitro . Differein vitro , asthma in vitro , cystic in vitro , diabetein vitro , tubercuin vitro , chronicin vitro , heart ain vitro , and irrin vitro . These c in vitro and in vivo approaches applied in this field. The investigation of targeted VOCs only  as candidate cancer biomarkers is also discussed. Next this paper reviews complementary in vivo, ex vivo, and in vitro studies conducted to date in order to find volatile biomarkers of cancer. Finally, the main extraction techniques and analytical techniques that have been applied to date in the area of the studies of potential volatile biomarkers of cancer are compared.This review firstly discusses sample matrices that were used in the studies of potential VOC biomarkers of cancer and critically evaluatesIn order to investigate VOCs as cancer biomarkers, analysis of the exhaled breath of patients with different types of cancer has become very popular in recent years , 24. AltStudies have shown that chemical changes in blood due to the presence of cancer are echoed in an alteration of the composition of VOCs in the breath of patients , 26. TheBreath analysis, compared to blood and urine tests, is noninvasive and a sample may be easily collected at any point and in varying quantities, which makes it easy to repeat . FurtherThere are different opinions about how detailed knowledge is required for a successful breath diagnostic test. Some argue that there is no need to know the origin of a volatile compound biomarker, as long as it can be used to distinguish disease from a healthy state , 34. OthMoreover, since the beginning of breath analysis in the 1970s  standardAlthough VOCs detected in blood and urine are “in the body” analytes, it still does not mean they are of endogenous origin. Some inhaled VOCs may bind to or dissolve in blood  and be sBlood was used as a matrix for VOC collection in a number of studies of lung cancer , 59, chiMany studies have also investigated volatile biomarkers in urine samples of patients with various cancers such as breast , gastroe in vitro studies over other matrices include easier control of experimental variables and more easily interpreted results, due to the absence of factors such as gender, age, and interindividual variation (with the exception of primary cell cultures) [The investigation of VOCs produced by cancerous cells in the microenvironment as the source of biomarkers should hypothetically help with the dilemma of their origin, as advantages ofultures) . They alultures) , 70. In vitro studies aiming to find potential volatile markers of cancer essentially apply the extracellular metabolite investigative approach. Endometabolomic studies require cell disruption, and then concentration of the extracted compounds (mainly with the use of evaporation). VOCs could be easily lost during these steps [The cell metabolome is comprised of the endometabolome, which is represented by all metabolites inside the cell, and the exometabolome, which is made up of all metabolites present in the extracellular cell culture medium. The profile of these metabolites in the surrounding medium depends on the uptake and extraction of the compounds by the cells and reflects their metabolic activity via their response to experimental variables.se steps . in vitro in different types of cancer and using different techniques, and in all of them there were differences observed in the composition of volatile metabolites produced by cancer and normal cells [A number of studies have been performed to investigate potential VOC cancer biomarkersal cells –81.However, some studies found differences in VOC levels, or VOCs produced, between not only different cell lines of the same cancer (showing that their metabolic pathways are different) but also the same cell line , 79–82.  in vitro studies of VOCs include the analysis of different matrices, the use of different cell culture media, the period of cell cultivation, the different cell density, the different cell controls used, the different statistical methods used, and finally the differing methodology.In the cell/tissue HS analysis of VOCs there are also differences in the techniques used, and a lack of standardisation and normalisation of the data, even when the same technique is used, which may influence variations in VOC patterns between different studies. The aspects to be considered (apart from the technique used)  in terms in vitro, highlighting the possibility of finding biomarkers of apoptosis and necrosis induced by drugs [Length of incubation periods and differing types of culture  as well as supplementation of cell culture medium have been shown to have an influence on the composition of the VOCs in the samples , 84–86. by drugs .The main matrices analysed to study VOCs generated by cells are (i) HS of the cell-free culture medium of a target cell and (ii) HS of the medium still containing the cells. The HS of cell lysate (preconcentrated supernatant of the lysed cells) is another matrix employed, but has only been used in a few studies, solely for the determination of targeted VOCs produced by cancer cells treated with drugs .There are some substantial differences in terms of the extraction procedure details for the main two matrices. For example, analysis of culture media with cells usually takes place at 37°C , while analysis of media only may employ a higher temperature. Also, the efficiency of analysis of media only samples can be improved by the addition of salts or by a change of pH, while such changes are not possible when cells are present. On the other hand, the analysis of media with cells ensures that no VOCs are lost during storage. Finally, the vessel used for cell culture is of great importance. Some researchers use glass vials as they have very limited release of volatile chemicals  , 88. in vivo and in vitro, investigating VOCs as potential biomarkers of cancer, have poor correlations . They postulate that the overlap between VOCs found in the exhaled breath of lung cancer patients and compounds produced by lung cancer cells in vitro (approximately one-quarter being common to both matrices) is not sufficient at the moment for in vitro culture to be a good model for the VOCs present in exhaled breath. The authors propose that it could be due to cell cultivation in hyperoxic conditions (atmospheric oxygen concentration) emphasising it as a potential limitation of the in vitro studies performed to date. Tumours have been shown to grow in hypoxic (oxygen depleted) or anoxic (oxygen absent) conditions as opposed to normal tissues [ in vitro approach.A recent review by Kalluri et al.  makes a  tissues . CellulaHowever, another issue related to cell culture conditions could also result in the different VOCs present in the HS of cell culture and samples taken from the patient. Standard 2D cell culture conditions may have a great impact on the cell metabolic behaviour, thereby losing accuracy when looking for biomarkers when compared to 3D culture that better mimics the growth of the tumour . in vivo and in vitro studies may also arise from exogenous VOCs being included in the predictive models of cancer [ in vitro studies performed to date, in comparison to the VOC studies of breath samples and biofluids. In addition, studies which show that the VOC patterns do not change after tumour removal imply that some VOCs may be biomarkers of the risk of cancer developing, rather than being indicative of the presence of a tumour . This approach eliminates analytical technique and, in the case of the samples coming from the same patient, factors such as gender, age, and interindividual variation as the sources of possible differences in VOC patterns between in vivo, in vitro, and ex vivo samples.Without doubt, there is a need for a simultaneous investigation of the correlation of the VOC pattern in exhaled breath (and other sample types) collected from a patient and an in vitro and ex vivo to the ones found in breath from the patient.Some studies already have been conducted specifically in order to simultaneously compare VOCs produced by cancer cellsThe study of Chen et al.  aimed toAnother study compared volatile metabolites determined in a culture medium of lung cancer cell line A549 to the VOC composition in the HS of urine of mice implanted with these cells. There were seven VOCs found at significantly higher levels in both sample types when compared to normal cancer cell lines  .The study performed by Buszewski et al.  involved in vitro in different studies  such as 2-methyl-1-pentene, 4-methyloctane, 2,4-dimethylheptane, hexane, and acetic acid were also previously detected in the HS of different cancer cell lines , again in the recent study by Filipiak et al. . They de studies . Althougll lines .Poli et al. , 93 in t in vitro, in addition to the fact that the levels of some compounds changed after a longer period following an operation to remove a tumour, implies that at least some of the VOCs are produced by the tumour per se and may not be attributable to genetic predispositions. Further studies are required to confirm any of these hypotheses.The findings of both Poli et al.'s and Phillips et al.'s studies imply that changes in the VOC patterns are not biomarkers of lung cancer presence but rather are epiphenomenon of the disease development. In fact Phillips et al. , 95 propA different approach to the issue of the possible exogenous origin of proposed VOC biomarkers focuses on the detection of aldehydes , 65, 96  in vitro and exhaled breath of lung cancer patients [Higher concentrations of straight C3–C9 aldehydes , 108, aspatients .−1–pmol−1 (ppb–ppt) range in exhaled human breath and in the μmol−1–nmol−1 (ppm–ppb) range in blood and urine [Concentrations of most of the VOCs present in biological matrices are low: in the nmolnd urine , 37, 60.nd urine . Increasnd urine , 111. Mind urine . in vivo and in vitro studies of potential cancer biomarkers. In PT  the gas sample is purged through the sorbent trap by an inert gas and the VOCs are retained on the surface of the trap (Purge and trap (PT) and solid phase microextraction (SPME) are the two main extraction techniques used to date for the collection of VOCs in boththe trap . Next thSPME is an extraction technique where an extraction phase is dispersed on a fine rod made of fused silica, Stableflex, or metal alloy. The SPME device consists of two parts: the holder and, contained in it, the fiber assembly. There are two versions of the SPME holder: one for manual use and one for use with autosamplers or with a high performance liquid chromatography-SPME (HPLC-SPME) interface. The fiber unit consists of a fiber core attached via a hub to a stainless steel guiding rod, which is contained in a hollowed needle that pierces a septum. The fiber is withdrawn from this needle when sampling and the needle is removed when not in use . The fibμm CAR/PDMS coating regardless of the type of matrix tested. Its use is justified, as the fiber was initially developed for the extraction of volatile and small compounds [There are several commercially available SPME fibers for sampling a wide range of compounds that employ four polymers as stationary phases: divinylbenzene (DVB), polydimethylsiloxane (PDMS), polyacrylate (PA), and polyethyleneglycol (PEG). They are used on their own as a coat (available in different thicknesses) or in combination blended with carboxen (CAR). The coatings differ by polarity  and extraction mechanism (absorbent or adsorbent). The choice of fiber coating depends on the polarity of analytes and their molecular weight. Previous analyses of VOCs as biomarkers of cancer has been performed in most cases with the use of a 75 ompounds .−1 in full scan mode) than SPME (μgl−1 in full scan mode) [In comparison, a sorbent trap is an exhaustive extraction technique, due to chemical reactions between the stationary phase and the analytes, whereas SPME is a nonexhaustive (passive) equilibrium technique where the amounts of VOCs extracted are controlled by the series of distribution constants between the gaseous, liquid, and coating phases. Sorbent trapping is based on an adsorption process. SPME, depending on the fiber used, is an absorption technique or utilizes absorption and adsorption properties simultaneously. Sorbent trapping is a three-step process , whereas SPME is more simple in use  . The siman mode) , 119.As selection of the appropriate fiber coating for analytes is a critical stage in the SPME methodology development, there are new fiber coatings under development with higher capacity and selectivity, which would enhance sensitivity such as molecularly imprinted polymers, multiwall carbon nanotubes, sol-gel technology, and polymeric ionic liquids .μL), and is less costly than SPME [Other variations of SPME techniques such as stir bar sorptive extraction (SBSE), solid phase microextraction membrane, (or thin-film microextraction), and needle trap device have been successfully used for the collection of VOCs and so may be used in cancer studies in the future . Nhan SPME . Barash han SPME , 123 usehan SPME . Offlinehan SPME . Finallyhan SPME .The main detection techniques that have been employed in VOC cancer biomarker studies are GC-MS, proton transfer reaction-mass spectrometry (PTR-MS), selected ion flow tube-mass spectrometry (SIFT-MS), and gas sensors (electronic noses) . SamplinGC-MS is the most commonly used analytical technique for the investigation of potential VOC cancer biomarkers, due to its sensitivity and reliability in analyte identification. It gives the most detailed analytical information and identifies analytes with the most certainty, when compared to PTR-MS. The identification of VOCs with the use of PTR-MS can be tentative only as it is not possible to discriminate between compounds with the same molecular weight , 88, 133Another detection technique, ion mobility spectrometry (IMS), is not very common yet in the studies of VOCs as potential cancer biomarkers, but already has shown promising results. The first study which applied IMS for the analysis of VOCs in the exhaled breath of lung cancer patients and healthy subjects was performed by Westhoff et al. . DiscrimCompared to mass spectrometric methods, the use of electronic noses does not require skilled personnel and is less time consuming . These fIn terms of breath testing, such sensor systems could be cheap, rapid, and simple to use when they have been tailored for a specific use . However in vivo or in vitro system for study. Obviously the aim is to apply differential VOCs of cancer to a device that will enable the detection of cancer in the patient with 100% certainty, ideally noninvasively, as the less invasive a procedure is, the cheaper and more simple it will be to conduct. Whether it is going to be breath, blood, urine, or any other sample coming from the patient, at this stage, none of these matrices is ideal for looking for potential volatile biomarkers. The main reason is the uncertain origin of the detected VOCs, as their patterns may depend not only on the presence of the disease, but also on the long list of other variables such as genetic and environmental factors, age, gender, and so forth.Researchers take different approaches when looking for the potential biomarkers of cancer. The discussion starts with the issue of whether to choose an in vitro approach, there are also some uncertainties arising. The main one is that there is little known about the complexity of VOCs metabolic pathways, between the VOC being produced by the tumour cells and its presence (or absence) in the sample from the patient. Nevertheless, in vitro studies are valuable tools in advancing the aim of cancer diagnosis.Therefore, it seems obvious to complement these studies with an investigation of the VOC profiles produced by tumours at the microcellular level, where an explanation of the presence of a compound in the chromatogram is more straightforward. The studies on cells are of great informative value about the biochemistry of tumours. However, with theIdeally, research should be directed to comparing VOC patterns in the HS of cancer cells or tissues of one particular patient with the compounds detected in breath, urine, and/or blood of the same patient. Also the selection of controls is crucial, in order to eliminate as many variables as possible. Without doubt, more studies are needed for the comparison of VOCs produced by tumour cells to the ones found in breath or biofluids, as well as for comparison of VOC patterns generated by many cell lines and primary tumour samples in order to profile as many cells as possible, so that an attempt can be made to find the common VOCs for particular types of cancer.Each of the five types of analytical techniques that found application in the studies of VOCs has its advantages and disadvantages. Although it is more likely that a future tool to be used in the clinic will be an electronic sensor device, due to its cheaper cost, however, gas sensors still have poor sensitivities. Therefore other analytical techniques may be researched further. Consequently, for research purposes, it seems to be ideal to use the methods in complement.Studies of the “scent of cancer” are really elegant in the simplicity of the idea; however there are still limitations of applying this idea clinically regardless of the technique used. At the moment certainty that any VOC is a biomarker of cancer is far from straightforward. Analysis of breath and other matrices investigating potential biomarkers of cancer is still in its infancy. Evidently large-scale screening studies are first required in order to describe normal profiles of VOCs in all matrices being studied. Knowledge about VOC concentration ranges for a normal, nondiseased state and validation studies using larger populations in relation to all forms of cancer will further evaluate the promising results of the existing studies of these diseases. And here surely the path to the use of VOCs as “smellprints” of cancer in the clinic lies in using information gleaned from a variety of different approaches in complement.