Lack of respectful maternity care (RMC) is increasingly recognized as a human rights issue and a key deterrent to women seeking facility-based deliveries. Ensuring facility-based RMC is essential for improving maternal and neonatal health, especially in sub-Saharan African countries where mortality and non-skilled delivery care remain high.Few studies have attempted to quantitatively identify patient and delivery factors associated with RMC, and none has modeled the influence of provider characteristics on RMC. This study aims to help fill these gaps through collection and analysis of interviews linked between clients and providers, allowing for description of both patient and provider characteristics and their association with receipt of RMC.Friendliness/Comfort/Attention; Information/Consent; and Non-abuse/Kindness—developed from the first three components of PCA. Significance level was set at p < 0.05.We conducted cross-sectional surveys across 61 facilities in Kigoma Region, Tanzania, from April to July 2016. Measures of RMC were developed using 21-items in a Principal Components Analysis (PCA). We conducted multilevel, mixed effects generalized linear regression analyses on matched data from 249 providers and 935 post-delivery clients. The outcomes of interest included three dimensions of RMC—Friendliness/Comfort/Attention RMC included age  and self-reported complications (reported complications versus did not: Coef − 0.41). Significant provider-level determinants included perception of fair pay (Perceives fair pay versus unfair pay: Coef 0.46), cadre (Nurses/midwives versus Clinicians: Coef − 0.46), and number of deliveries in the last month (11–20 versus < 11 deliveries: Coef − 0.35).Significant client-level determinants for perceived Information/Consent RMC included labor companionship (Companion versus none: Coef 0.37) and religiosity (Attends services at least weekly versus less often: Coef − 0.31). Significant provider-level determinants included perception of fair pay (Perceives fair pay versus unfair: Coef 0.37), weekly work hours (Coef 0.01), and age .Significant client-level determinants for Non-abuse/Kindness RMC included the predictors of age (age 50+ versus 20–29 years: Coef 0.34) and access to electronic mentoring (Access to two mentoring types versus none: Coef 0.37).Significant provider-level determinants for These findings illustrate the value of including both client and provider information in the analysis of RMC. Strategies that address provider-level determinants of RMC  may improve RMC and subsequently address uptake of facility delivery. Friendliness, Comfort, and Attention, 2) Information and Consent, and 3) Non-abuse and Kindness. Client age, self-reported delivery complications, provider perception of fair pay, cadre, and number of deliveries attended were important factors for receipt of RMC related to Friendliness, Comfort, and Attention. Having a birth companion, client religiosity, provider perception of fair pay, and provider age were important factors for receipt of RMC related to Information/Consent. Provider age and access to electronic mentoring were important factors for receipt of RMC related to Non-abusive/Kindness. Strategies that promote equitable pay, give providers short-term respite away from maternity care, and increase access to mentoring opportunities may improve RMC and uptake of facility delivery.Lack of respectful maternity care (RMC) discourages women from seeking facility-based deliveries. RMC is essential for improving maternal and newborn health in sub-Saharan African countries where rates of maternal deaths and non-skilled delivery care are high. We conducted surveys in 61 facilities in Kigoma Region, Tanzania from April to July 2016. Principal components analysis was used to identify three dimensions of RMC. Multilevel regression analyses were conducted on matched data from 249 providers and 935 post-delivery clients. Our outcomes of interest included three dimensions of RMC: 1) Worldwide maternal deaths remain common, with approximately 830 women dying each day from known and largely preventable causes . Access Lack of respectful maternity care (RMC), which includes disrespect and abuse (D&A), has been increasingly recognized –14 and dThe presence of provider-client interpersonal barriers is increasingly suspected to interfere with attempts to increase skilled birth attendance. Bowser and Hill’s review describes seven manifestations of D&A which constitute the current typology in the D&A literature: physical abuse, non-consented care, non-dignified care , discrimination, abandonment, and detainment in facilities . Such beWorldwide, an alarmingly high prevalence of women have reported mistreatment according to these typologies of D&A, with reports ranging from 20 to 78% , 31, 33.Qualitative studies have identified several potential patient factors associated with lack of RMC. These include the following: race/ethnicity and religion, depending upon context –37; age,While qualitative studies have identified factors associated with RMC, few studies have quantitatively examined the associations between individual patient characteristics and report of D&A. In Tanzania, women who had attended secondary education or greater, primiparous women, those with experience of low mood in the past year, and those with a personal history of physical abuse or rape were more likely to report experiences of D&A during their delivery; married women were less likely to report D&A . In a foTo our knowledge, published research to date has not modeled relationships between health care provider demographic or practice characteristics and provision of RMC. Qualitative studies, however, including in-depth interviews with providers of maternity care, have generated several hypotheses. Provider training itself is thought to create “distancing” and separation between providers and patients, potentially generating insensitivity toward women in childbirth , 48 throTo date, there is no standardized or widely agreed upon way to define or measure either RMC or D&A. Scales for measurement of RMC have recently been proposed in Ethiopia  and in tThis novel study utilizes interviews linked between clients and providers from hospitals, health centers, and dispensaries to describe receipt and delivery of RMC, allowing for description of both patient and provider characteristics and their association with receipt of RMC. This study also contributes to the science around RMC by constructing measures of RMC based on domains from the WRA RMC Charter.We conducted cross-sectional surveys consisting of facility-based client exit interviews and provider interviews across 61 facilities  in Kigoma Region, Tanzania from April 30 to July 1, 2016.2 and is located in the northwest corner of Tanzania, bordering Lake Tanganyika, the Democratic Republic of Congo, and Burundi. Kigoma Region’s population in 2012 was 2,127,930 with an annual growth rate of 2.4% and 370,374 households , nurses/midwives [Nurse Officers/Assistant Nurse Officers/Registered Nurses/Midwives/Enrolled Nurses], other staff [Medical Attendants/Maternal and Child Health Aides]). Medical Doctors and specialists were excluded from participation due to the small number in the region. A sample of 189 provider interviews was needed to detect a 5% relative mean change in key variables of interest with 90% power and an alpha of 0.05 (assuming a 50% reference proportion).Convenience sampling was used to enroll women as they exited delivery care services. Clients were eligible if they were 15 to 49 years of age and received delivery care services at the facility. Due to the focus of the project on routine labor and delivery care, clients were excluded if they delivered at home or on the way to the facility, had a cesarean section delivery, or experienced a stillbirth or neonatal death. A sample of 908 client interviews was needed to detect a 15% absolute difference in the variables of interest 90% power and an Client Post-Delivery Exit Interview Questionnaire captured sociodemographic characteristics, perceptions of and satisfaction with services, and pregnancy history and intention. The Provider Interview Questionnaire and Self-administered Knowledge Test were designed to capture information about provider demographic characteristics, education and training, supervision and mentorship, clinical knowledge, perceptions of the work environment, and current labor and delivery practices.Interview guides were developed in English and translated into Swahili. Questionnaires were pre-tested in January 2016. Final questionnaires were translated from English to Swahili and back-translated to English. Informed consent was obtained from each respondent and confirmed with the respondent’s thumbprint. All client and provider interviews were administered face-to-face by an interviewer in Swahili. Interviews were conducted at the facility on the day of discharge, most commonly on the same day of delivery or the following day. The Discharge time, Facility supplies, Facility cleanliness, and Wait time). The remaining 25-item measure displayed strong internal consistency with Cronbach’s alpha of 0.83 and an inter-item correlation of 0.17. In support of criterion validity, Spearman testing found that the RMC measure was positively associated with the variable Client satisfaction with care .An initial 29 items were taken from the survey data to develop the RMC measure; these items were chosen based on domains from the WRA Respectful Maternity Care Charter and previously published research on RMC , 33, 40.The 25 items were then entered into a Principal Components Analysis (PCA) to establish dimensionality of the scale with the aim of retaining the maximum amount of variance possible. The mean Kaiser-Meyer-Olkin measure of sampling adequacy was 0.81 and all individual item measures were greater than 0.68, indicating strong relationships among scale items . VisualiAdvise on comfort measures, Friendliness, Visit regularly, and Pay close attention. This first component was therefore termed the RMC Dimension 1 (RMC-D1), defined by the domains of Friendliness, Comfort, and Attention. Items that loaded highest on the second principal component included Consent before procedures/exams, Explain what will happen, Explain procedures/exams beforehand, and Post-delivery counseling index. This second component was therefore termed RMC Dimension 2 (RMC-D2), defined by the domains of Information and Consent. Items that loaded highest on the third principal component included Absence of physical abuse, Absence of emotional abuse, Encouragement, and Kindness. This component was therefore termed RMC Dimension 3 (RMC-D3), defined by Non-abuse and Kindness.Items that loaded highest on the first principal component included RMC-D1 score, RMC-D2 score, and RMC-D3 score to represent receipt of three dimensions of RMC.The outcome variables of interest included the continuous variables Client age: 15 to 19, 20 to 29, 30 to 39, 40 to 49 years of age, age unknown by client;Literacy: Able to read and write, Unable to both read and write;Highest education attended: No education, primary, secondary, college or university;Total live births: Two or fewer, three or more;Marital status: Not in union, in union;Frequency of attendance at religious services: Less than once a week, once a week or more often;Companion in labor: No, yes;Companion at time of delivery: No, yes;Self-reported delivery complicationsSESThe client-level variables of interest included:Provider age: 20 to 29, 30 to 39, 40 to 49, 50 years or older;Sex: Male, female;Highest education completed: Primary, secondary, college or university;Cadre: Clinicians, nurses/midwives, other staff;Years in cadre: Continuous;Years at the facility: Continuous;Work hours per week: Continuous;Number of deliveries attended in last month: One to 10, 11 to 20, 21 to 30, 31 or more, Don’t know;Has on-site supervisor: No, yes;Job satisfaction: Very satisfied, a little satisfied, neither satisfied nor dissatisfied, a little dissatisfied, very dissatisfied;Perception paid fairly for job duties: No, yes;Perception of adequacy of training for job duties: No, yes;Perception in-service training has helped job performance: No, yes;Access to Electronic mentoring opportunities: Access to zero, one, two, or three opportunities related to e-learning, emergency call system, and teleconference;Recent complications summative index: Has dealt with zero, one, two, three, or four types of complications in the last month related to hemorrhage, eclampsia, obstructed labor, and puerperal sepsis;Delivery ever-training summative index3: Pre- or in-service delivery training in 25 items, continuous;Delivery pre-service summative index3: Pre-service delivery training in 25 items, continuous;Delivery in-service summative index3: In-service delivery training in 25 items, continuous;Recent delivery practice summative index3: Provision of delivery services in 25 items in the last 3 months, continuous; andClinical knowledge test score: Percent correct on 64 knowledge questions on the topics of antenatal care, routine delivery, newborn, complications, partograph, and postpartum.The provider-level variables of interest included:p < 0.10) with the dependent variables were included in multivariate modeling. Multilevel, mixed-effects generalized linear models were fitted for the first three RMC PCA scores  to identify variables with a significant adjusted relationship (p < 0.05). Clustering of data by facility was further accounted for through inclusion of a facility identification cluster variable.Client and provider data were matched by asking providers on duty at the time of the delivery and by asking clients which provider most commonly provided their care; only matched client and provider interviews were included in the analysis. Data analyses were conducted using Stata 14.1. Bivariate analyses were conducted to identify client and provider variables associated with the outcome variables of interest; variables with a significant unadjusted relationship  were interviewed. Following exclusion of data from non-matched clients and providers, data from 935 delivery clients and 249 providers  were used in the analysis.From April 30–July 1, 2016, a total of 960 delivery clients and 361 providers  and received care at a health center (50.6%). The majority of clients included in the study were married (91.0%), attended at least weekly religious services (86.4%), and have attended primary school education (67.3%). Nearly 45% of clients reported having a birth companion with them during labor (44.7%), while only 12% reported having a birth companion with them at the time of delivery. About 13% of clients reported that they experienced delivery complications (12.9%). , while less than half reported that the provider introduced themselves (45.6%). Two-thirds of clients reported the provider explained what to expect in labor (63.0%). Regarding procedures and exams, most clients reported that the provider asked for consent (80.4%), explained the procedures and exams ahead of time (70.7%), and gave them the results (87.5%). One-third of clients reported the provider encouraged them to have a companion (32.7%). About three-quarters of clients reported feeling comfortable asking the provider questions (75.4%) and reported believing the information they gave to the provider would remain confidential (77.2%). Nearly all clients reported receiving privacy during exams and counseling (94.2%), although a few reported that other clients could overhear their conversations with the provider (7.9%). On average, clients received 6.7 out of 12 post-delivery counseling elements , and about three-quarters of clients reported the provider was very kind (76.0%) and very encouraging (79.4%). Nearly nine of 10 clients reported the provider advised them about comfort measures (88.7%); however, receipt of comfort measures from the provider was low at an average of less than two out of six comfort measures (1.3). Clients overwhelmingly reported the provider paid close attention to them during labor (93.5%) and came when they called for them (97.7%). Physical and emotional abuse was reported infrequently by clients at 1.3% and 2.7%, respectively. , while one-fifth of providers were 50 years or older (21.7%). The majority of providers included in the study were female (64.7%), college/university educated (66.7%), and in the nurse/midwife cadre (61.0%). On average, providers reported working about 10.3 years in their cadre and 7.5 years at their facility, and reported working an average of 54.8 work hours per week. Two-thirds of providers (63.9%) reported conducting from one to 10 deliveries in the last month. Providers reported receiving in-service training on an average of 8 training elements; almost 9 of 10 providers reported in-service training has helped their job performance. Nearly half of providers reported not having access to electronic mentoring opportunities (48.2%). Less than half of providers stated they were satisfied with their job (44.6%), and less than one-fifth of providers feel they are paid fairly for their job duties (18.5%). On average, providers correctly answered 55.1% of the clinical knowledge questions. . Clients who reported that they experienced delivery complications had significantly lower RMC-D1 scores compared to clients who did not report complications . The client variable of RMC-D1 score included the following: Delivery ever-training summative index, Delivery pre-service summative index, Recent delivery practice summative index, Recent complications summative index, Access to electronic mentoring opportunities, and Perception in-service training has helped job performance. . Clients of Nurses/midwives had significantly lower RMC-D1 scores compared to clients of clinicians . Clients of providers who reported attending 11 to 20 deliveries in the last month had significantly lower RMC-D1 scores compared to clients of providers who attended 1 to 10 deliveries . Provider variables not found to have a significant adjusted association with The intraclass correlation (ICC) defines the proportion of the total variance that can be attributed to the hierarchal grouping by the provider variable. Net of all independent variables included in the final RMC-D1 model, 18% of the total variance (ICC = 0.18) is explained by the provider level.Information and Consent, are displayed in Client age, Highest education attended, Total live births, SES, Frequency of attendance at religious services, Companion in labor, Companion at time of delivery; Provider age, Number of deliveries attended in last month, Access to electronic mentoring opportunities, Perception paid fairly for job duties, and Work hours per week.Results of bivariate analyses for RMC-D2 – RMC-D2 score included Age, Highest education attended, Wealth quintile, Total live births, and Companion at time of delivery. . Clients who reported attending religious services at least weekly had significantly lower RMC-D2 scores compared to clients who reported less than weekly attendance . Client-level variables found not to have a significant adjusted relationship with RMC-D2 score included Number of deliveries attended in last month and Access to electronic mentoring opportunities. Net of all independent variables included in the final RMC-D2 model, nearly one-quarter of the total variance (ICC = 0.24) is explained by the provider level. . Clients of providers who reported working more hours per week had significantly higher RMC-D2 scores compared to clients of providers who work fewer hours . Clients of providers aged 30 to 39 and 40 to 49 years had significantly lower RMC-D2 scores compared to clients of providers aged 20 to 29 years . Provider variables not found to have a significant adjusted association with Non-abuse and Kindness, are displayed in Client age, Marital status, Companion in labor, Self-reported delivery complications; Provider age, Cadre, Delivery ever-training summative index score, Delivery in-service summative index score, Number of deliveries attended in the last month, and Access to electronic mentoring opportunities.Results of bivariate analyses for RMC-D3 – RMC-D3 score. Clients of providers who were aged 50 years or more had significantly higher RMC-D3 scores compared to clients of providers in the 20 to 29 year age group . Clients of providers who reported access to two types of electronic mentoring had significantly higher RMC-D3 scores compared to clients of providers with no access to electronic mentoring opportunities . The provider variables of Age, Cadre, Delivery ever-training summative index score, Delivery in-service summative index score, and Number of deliveries attended in the last month were not found to have a significant adjusted association with RMC-D3 score. Net of all independent variables included in the final RMC-D3 model, only 3% of the total variance (ICC = 0.03) is explained by the provider level. , information and consent (RMC-D2), and non-abuse and kindness (RMC-D3) during labor and delivery are differentially influenced by characteristics of clients and their providers.too young to become a mother. Multiple qualitative studies and reviews thereof have pointed to younger women, particularly adolescents, as potential targets of discrimination and potential recipients of less respectful care [Client factors were significantly associated with the first two dimensions of RMC relating to friendliness, comfort, and attention (RMC-D1), and information and consent (RMC-D2). In our analyses, client age mattered; clients in their 30’s and 40’s perceived receiving significantly higher levels of RMC related to friendliness, comfort, and attention compared to clients in their teens. It is possible that health care providers interact and treat teens differently simply because they are younger than the providers are themselves, or it is possible that the providers perceive teens as ful care , 11, 14.ful care . Our finful care .Whether or not the client reported to have had delivery complications also influenced the first dimension of RCM; clients who reported delivery complications had a lower RMC score related to friendliness, comfort, and attention compared to those without perceived complications. There are two potential explanations for this finding: 1) the stress that providers experience during complications and emergencies may make them more likely to exhibit disrespectful behavior; or 2) the experience of complications lowers the client’s overall perception of the delivery experience.Companionship in labor was found to be a positive factor for receipt of RMC related to information and consent; clients with a companion in labor received a higher level of RMC-D2. This finding is not surprising as providers may feel more accountable for providing better information and counseling when someone in addition to the client is present; a companion may also help increase the client’s understanding of information. Interestingly, more frequent attendance at religious services was a significant determinant of receipt of a lower level of RMC related to information and consent. It is possible that more religious women may interpret or receive these components differently than their less religious counterparts; alternatively, providers may display a particular bias against giving information to these women. Collectively, these findings provide a better understanding of how client characteristics—or provider perceptions and biases related to those characteristics—may influence provision of respectful care.Provider factors were also significantly associated with the first two dimensions of RMC, and were the only factors of significance for the third non-abuse and kindness dimension of RMC. Nurses/midwives as compared to clinicians, and providers who attended 11 to 20 deliveries in the last month as compared to providers who attended fewer deliveries, were found to provide lower levels of RMC related to friendliness, comfort, and attention. These findings suggest that the high workload of labor and delivery care—commonly found among nurses/midwives—may lead to less positive interpersonal interactions with clients. Nurse/midwifes may experience prolonged contact with labor and delivery clients, as opposed to the often intermittent contact that clinicians experience, which may reduce a provider’s ability to give friendly, comforting, and attentive care day after day. Evidence bolstering this hypothesis comes from psychology research on the depleting effect of decision fatigue on subsequent self-control and active initiative : provideinequity) positively influences interpersonal interactions and care provision, and likely reflects an underlying attitude that providers feel appreciated and motivated to do their work. Numerous qualitative studies and reviews thereof have highlighted health worker descriptions of low salaries as a particular stressful aspect of negative work environments resulting in unprofessional behavior [While job satisfaction was not found to be correlated with RMC, providers who perceived they were paid fairly for their work duties as compared to those who did not feel this way provided significantly better RMC related to friendliness, comfort, and attention, and RMC related to information and consent. These findings suggest that the perception of pay equity  or perceptions  that would not be known otherwise. Another strength of this work is that we operationalized select independent variables in new ways. For example, provider-level meaningful change in receipt of RMC. Additionally, PCA rarely matches conceptual frameworks perfectly, especially for complex constructs such as RMC. Though strong patterns emerged in our PCA, not every item clustered with the most logical component .It is critical to understand the limitations of our work. First, the study was cross-sectional with non-random sampling, eliminating our ability to make causal inferences and generalize findings. Previously collected household-level Reproductive Health Survey (RHS) data in Kigoma from 2016 and a planned 2018 RHS in Kigoma provides a timely opportunity to analyze representative RMC data. Second, our questionnaire did not have items that fit into Article V and Article VII of the WRA RMC Charter, limiting our ability to account for certain known risk factors for receipt of non-respectful care. History of self-reported depression and history of past abuse or rape have both been associated with higher rates of abuse in health care settings in both high-resource , 60 and The site of client interviews at facilities poses an additional important limitation, likely generating an underestimation of true prevalence of D&A and an overestimation of receipt of RMC. Two independent studies of D&A treatment during facility delivery in Tanzania have demonstrated markedly lower reports of D&A from interviewed clients when interviewed at the site of the facility, with significant increases in reporting upon follow up in the community , 33. AnoThese findings highlight potential areas of focus for programmatic and policy work, as well as future directions to move the RMC research agenda forward. Given our results that Nurses/midwives and providers who conduct a higher number of deliveries provide lower levels of RMC, improving the work environment for labor and delivery providers may improve delivery care. Strategies that aim to reduce workplace stress—including reduction of moral distress and decision fatigue—and improve providers’ perceptions of workplace support, self-efficacy in providing quality care, and underlying attitude toward work, may contribute to improved interpersonal interactions between clients and providers. Such approaches might include offering high frequency rotational schedules to give labor and delivery providers short-term respite away from providing maternity care. Strategies that increase access to mentoring and peer-to-peer learning opportunities (with fair access across cadres) may improve workplace support, self-efficacy, and enhance feelings of being a respected and valued member of the team. Pre-service and in-service training on RMC, as well as close mentorship following training, is essential to determine the influence of training on knowledge transfer and behavior change. Additionally, ensuring providers receive equitable pay, on-time, every time may increase provider’s sense of worth and underlying attitude towards work.To move the RMC scientific agenda forward, additional research using matched patient and provider data may improve understanding of the relative importance of patient and provider determinants of RMC. In addition, studies embedded in conceptual models of RMC are needed that aim to standardize and validate measures of RMC. Measures that can be validated across cultural and geographic settings would be particularly valuable so that RMC data can be compared and synthesized across studies. Future analyses would be strengthened through the addition of interaction terms to illuminate the complexities of patient and provider relationships and how these influence respectful care. Given our hypothesis that moral distress and decision fatigue contribute to lack of RMC, future analyses would greatly benefit from inclusion of measures for these constructs. Furthermore, future research may benefit from over-sampling of clinician providers in order to increase the power to detect differences between clinicians and other cadres, and potential differences by gender that were not detected here. Finally, women in low-resource settings may have relatively low expectations of maternity care compared to women in middle- or high-resource settings. Measuring expectations of care and the influence of cultural and gender norms in future research would help advance our understanding of women’s experience of RMC and how expectations and context influence measurement and comparison of RMC across settings.Despite disrespectful maternity care being increasingly recognized as a key deterrent to women seeking facility-based deliveries, there is less consensus about the comparative importance of patient and provider determinants for RMC. Our findings demonstrate that patient and provider factors differentially influence three dimensions of RMC. Future research is needed that aims to standardize RMC measurement through the lens of a conceptual model of RMC and rooted in a human rights perspective. Strategies that promote more equitable pay, offer rotational schedules with short-term respite away from providing maternity care, and increased access to mentoring and peer-to-peer learning platforms may improve RMC and uptake of facility delivery in low-resource settings. An enhanced understanding of the relationships between patient and provider characteristics may improve the provision of quality labor and delivery services and should be considered in the design of maternity care programs, policies, and future research.


To assess the progress in scaling up ART provision among HIV-positive TB patients in 19 countries in sub-Saharan Africa with high TB and HIV burdens, TB and HIV data collected by the World Health Organization (WHO) were reviewed. The results found that the percentage of HIV-positive TB patients receiving ART increased from 37% in 2010 to 69% in 2013. However, many TB cases among persons who are HIV-positive go unreported  for persons with human immunodeficiency virus (HIV) infection worldwide, resulting in an overall decrease in HIV incidence and acquired immunodeficiency syndrome (AIDS)–related mortality . In the μL) should initiate ART within 2 weeks of starting TB treatment  at a minimum, plus TB contact history for children . Access μL to achieve the mortality reduction benefits of ART. Although studies have shown an increased risk for TB immune reconstitution inflammatory syndrome with earlier initiation of ART among such cases, the risk for mortality from this syndrome has been found to be negligible  are vulnerable to tuberculosis (TB), which is the leading cause of mortality among persons living with HIV worldwide. Antiretroviral therapy (ART) reduces the incidence of HIV-associated TB, reduces mortality among HIV-positive TB patients, and is recommended for all HIV-positive TB patients, regardless of CD4 count.What is added by this report?In 19 countries in sub-Saharan Africa with high numbers of TB patients with HIV, provision of ART for reported HIV-positive TB patients increased from 37% in 2009 to 69% in 2013. However, many TB cases among persons who are HIV-positive go unreported, and only 38% of the estimated number of HIV-positive new TB patients received ART in 2013.What are the implications for public health practice?The ART coverage gap of 62% of HIV-positive TB patients represents the proportion of persons with TB disease and HIV infection who should be on life-saving ART but are not yet receiving treatment. Continued scale-up of ART provision for HIV-positive TB patients is needed to reduce the morbidity and mortality of HIV-associated TB and decrease the global burden of TB and HIV.TB and HIV data frequently come from separate TB and HIV reporting and recording systems, which are not harmonized in many settings. Improving TB and HIV monitoring and evaluation, with better integration and interoperability of TB and HIV data systems, would enhance data exchange and also improve the quality of ART coverage data for TB patients. This would facilitate early detection of treatment gaps and challenges, improve routine monitoring, inform quality improvement efforts, and help guide resource allocation to improve ART provision for HIV-positive TB patients.


Can a model incorporating patient-specific (comorbidities and age) and acute myeloid leukemia (AML)-specific features  predict mortality after AML treatment?In a multicenter cohort study of 1100 patients, we demonstrated that (1) comorbidities had a significant impact on 1-year mortality after initial therapy for AML, (2) an augmented hematopoietic cell transplant–comorbidity index (HCT-CI) was the best suited index for comorbidity evaluation in AML, and (3) an AML composite model of augmented HCT-CI, age, and cytogenetic/molecular risks has a strong AUC of 0.76 for 1-year mortality.An AML composite model can guide decision-making about treatment of AML. To our knowledge, this multicenter analysis is the first to test and validate (1) the prognostic impact of comorbidities on 1-year mortality after initial therapy of acute myeloid leukemia (AML) and (2) a novel, risk-stratifying composite model incorporating comorbidities, age, and cytogenetic and molecular risks.To accurately estimate risks of mortality by developing and validating a composite model that combines the most significant patient-specific and AML-specific features.P < .10 constructed a multivariate Cox proportional hazards model in which the impact of each covariate was adjusted for that of all others. Then, the adjusted hazard ratios were used as weights. Performances of models were compared using C statistics for continuous outcomes and area under the curve (AUC) for binary outcomes.This is a retrospective cohort study. A series of comorbidities, including those already incorporated into the hematopoietic cell transplantation–comorbidity index (HCT-CI), were evaluated. Patients were randomly divided into a training set (n = 733) and a validation set (n = 367). In the training set, covariates associated with 1-year overall mortality at a significance level of Initial therapy for AML.Death within 1 year after initial therapy for AML.A total of 1100 patients, ages 20 to 89 years, were treated for AML between January 1, 2008, and December 31, 2012, at 5 academic institutions specialized in treating AML; 605 (55%) were male, and 495 (45%) were female. In the validation set, the original HCT-CI had better C statistic and AUC estimates compared with the AML comorbidity index for prediction of 1-year mortality. Augmenting the original HCT-CI with 3 independently significant comorbidities, hypoalbuminemia, thrombocytopenia, and high lactate dehydrogenase level, yielded a better C statistic of 0.66 and AUC of 0.69 for 1-year mortality. A composite model comprising augmented HCT-CI, age, and cytogenetic/molecular risks had even better predictive estimates of 0.72 and 0.76, respectively.In this cohort study, comorbidities influenced 1-year survival of patients with AML, and comorbidities are best captured by an augmented HCT-CI. The augmented HCT-CI, age, and cytogenetic/molecular risks could be combined into an AML composite model that could guide treatment decision-making and trial design in AML. Studying physical, cognitive, and social health might further clarify the prognostic role of aging. Targeting comorbidities with interventions alongside specific AML therapy might improve survival. This cohort study examines the prognostic association of comorbidities on 1-year mortality after initial therapy of acute myeloid leukemia and a risk-stratifying composite model that incorporates comorbidities, age, and cytogenetic/molecular risks. Acute myeloid leukemia (AML) is the most common form of acute leukemia,Mortality in AML, in part, reflects its inherent resistance to therapy and, in part, the deleterious, and at times, lethal effects of treatment. Quantifying both of these risks is critical to the fundamental decision of whether patients should receive any specific therapy and, if so, whether it should be less or more “intense.” Therapy guidelines, such as those of the National Comprehensive Cancer Network (NCCN), have tended to focus largely on an arbitrary age cutoff of 60 or 65 years as the arbiter of the appropriateness of therapeutic intensity.We have shown that accounting for comorbidities can provide valuable information on the risks associated with allogeneic hematopoietic cell transplantation (HCT).We followed the Enhancing the QUAlity and Transparency of Health Research (EQUATOR) reporting guidelines using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis Or Diagnosis (TRIPOD) criteria.This is a retrospective hospital-based cohort study of data collected by review of electronic medical records and computer databases for 1100 patients. All patients were consecutively and concurrently treated at each of the AML specialty centers between January 1, 2008, and December 31, 2012. Data were randomly divided into a training set (n = 733) and a validation set (n = 367) for development and validation of the model, respectively. This protocol was approved by the institutional review boards of the Fred Hutchinson Cancer Research Center (FHCRC) and the collaborating sites. All data regarding treatment and demographic information were utilized according to the Declaration of Helsinki. Information was originally recorded and collected for medical purposes; therefore, consent was waived by the institutional review boards of the collaborating institutions.Five academic sites with designated inpatient and outpatient facilities for treatment of AML contributed to this study under the coordination of the FHCRC. The other 4 collaborating sites were Cleveland Clinic, Cleveland, Ohio; Massachusetts General Hospital, Boston; Stanford University, Stanford, California; and the University of Utah, Salt Lake City. Inclusion criteria were (1) age 20 years or older, (2) newly diagnosed non-M3 AML, and (3) initial treatment given during the study period defined herein. Patients receiving palliative care only were excluded from the data set. The different regimens used to treat these patients were classified as low, intermediate, or high intensity as indicated in eTable 1 in the Death within 1 year from initial therapy was the outcome of interest because it includes both early deaths due to regimen-related toxic effects or to lack of response and/or relapse of AML,P < .10 were used to construct a multivariate Cox proportional hazards model in which the impact of each comorbidity or covariate was adjusted for that of all others. To develop both a new AML-specific comorbidity index and a composite multirisk factor model, we used adjusted hazard ratio (HR) estimates for 1-year mortality from the multivariate model. The adjusted HRs were converted into integer weights according to our previously established criteriaThe distribution of death according to time is described in eTable 2 of the t test from the 50 bootstrap samples. Kaplan-Meier curves for survival were computed for risk groups defined by the different indices.Each risk model was validated in an independent set of 367 patients . Overall, 605 patients (55%) were male, and 495 (45%) were female. eTable 4 in the 3 cells/μL), and high LDH level (>200 U/L) values met the predetermined significance level (P < .10) in univariate analyses to be considered in multivariate models. In the multivariate analysis, 9 comorbidities met the predetermined cutoffs (HR >1.2) for adjusted HRs to be assigned a score for the AML-CI , while an LDH value greater than 1000 U/L was assigned a score of 2.0 . Those 9 comorbidities constituted the new AML-CI.eTable 2 in the e AML-CI .  cytogenetic/molecular risk groups,P = .004) and AUC (P = .01)  . Age andP = .01) ; when boP < .001) and AUC of 0.76 (0.03) (P < .001) of the AML-CM were statistically significantly higher compared with those  of the augmented HCT-CI. The AML-CM also outperformed the Karnofsky performance status (KPS) . Visual representations of the higher C statistic and AUC values and hence better discriminative ability afforded by the AML-CM compared with age, KPS, ELN cytogenetic/molecular risk, the HCT-CI, the AML-CI, and the augmented HCT-CI can be found in the When age and cytogenetic/molecular risk groups were added to the augmented HCT-CI to form the AML-CM, this new composite model had a C statistic of 0.72 and AUC of 0.76 for 1-year mortality, and an AUC of 0.78 for 8-week mortality; all exceeded those of individual risk factors or models including performance status . For 1-yThe higher performance of the AML-CM persisted in comparison with KPS. The AML-CM provided better discrimination of mortality rates compared with all other risk factors, as illustrated in the Patients with AML have a relatively high early mortality rate of 37.5% at 8 weeksIn the current study, we have shown and validated that comorbidities have a significant impact on early and 1-year mortality among patients newly diagnosed with AML undergoing upfront therapies. In addition, we have demonstrated that an augmented HCT-CI performs better than either an AML-CI or the original HCT-CI in predicting early and late mortality. The HCT-CI has been in practice since 2005, making it quite familiar to and easily applicable by physicians. Most notably, when we incorporated comorbidities together with age and cytogenetic/molecular risks per the ELN classification into a composite model (AML-CM), this risk model performed better than each of the risk components alone . Just asNCT01929408). Finally, we did not incorporate regimen intensity, albeit predictive of mortality, in our model since this is the decision that we plan to improve based on the AML-CM scores.On the one hand, the inability to develop a comorbidity index specific to AML that outperforms the original HCT-CI matches our experience in another setting, the prediction of graft-vs-host disease after allogeneic HCT.NCT01929408) seeks to prospectively validate the AML-CM in patients with newly diagnosed AML. The AML-CM was designed to primarily predict survival at 1 year. The 1-year end point is intuitively appealing, and incorporates both treatment-related mortality and inherent resistance to antileukemic therapy. In contrast, an earlier end point may have lent undue significance to the former and a significantly later end point undue significance to the latter consideration. Nevertheless, the AML-CM strongly predicted earlier mortality at 8 weeks after initial therapy. Finally, although many patients receiving therapies of differing intensities were included, the intensity of therapy was not randomly assigned. We arbitrarily categorized those regimens based on feedback from all study collaborators into 3 levels of intensity. However, we did not incorporate regimen intensity, albeit predictive of mortality, in our model since what constitutes high-, intermediate-, and low-intensity therapy is arguable, and we are in the process of developing objective means to assess regimen intensity and to formally assess the benefits of regimens, thus defined, according to AML-CM scores.Limitations of the current study include the retrospective nature of data collection, potentially leading to failure to capture important data that might not have been recorded. However, the frequent use of laboratory data, most of which are consistently available in databases, to define comorbidities likely reduced the possibility of missing comorbidities. Most notably, the collected data for components of the HCT-CI were almost complete. Moreover, missing data on a few other comorbidities or covariates did not exceed 10%, and we have no reason to believe that missing data from retrospective medical record review were systematically related to outcome or other predictive factors. We confirmed that missing vs nonmissing data were not associated with outcome in this study. Regarding reproducibility of comorbidity assessments, while we did not perform analyses on interrater (IRR) and test-retest reliabilities for the augmented HCT-CI, we used recently described methods for comorbidity evaluation that indicated an IRR greater than 0.90 by weighted κ statistics.subjective assessment of a patient’s fitness. The use of the AML-CM by community internists will allow objective identification of those older patients with AML, who have traditionally been offered palliative care but who might be better served by referral to receive either conventional or investigational AML therapy. Consequently, some patients with AML who currently may not be referred for specific treatment will be referred in the future, leading to improved survival of patients nationwide. Conversely, the AML-CM could identify patients so unlikely to benefit from AML therapy that they could be spared the various risks and toxic effects of such therapies. In the future, the AML-CM might also be used to identify which patients would benefit more from intensive chemotherapy and which will be better served by targeted, less-intensive therapies, and we are organizing a national effort to examine this question. Whether the AML-CM calculated at diagnosis of AML can be later used to decide on allogeneic HCT vs non-HCT therapies is currently being studied in an ongoing observational study (NCT01929408). The AML-CM may also allow for more objective comparisons of outcomes with different therapies or with the same treatment at different centers. Finally, the identification of patients with high comorbidity burden at diagnosis will provide impetus for interventions to reduce the effects of these comorbidities before or simultaneously with the administration of initial AML therapy.The previous limitations notwithstanding, our results have significant clinical and scientific applications. Currently, decisions about initial therapy for newly diagnosed AML are based largely on age and an often http://www.AMLCompositeModel.org).We have developed a novel AML composite model that allows us to balance the effect of age with the effects of the patients’ overall health, as assessed by comorbidities, and the aggressiveness of their AML, as assessed by cytogenetic/molecular features. The AML-CM outperforms age and KPS in predicting early and late mortality and hence could replace these conventional covariates when making treatment decisions or comparing trial results. This model could prove useful to the US Food and Drug Administration when monitoring clinical trials to ensure adequate representation of high-risk patients in these trials and, hence, generalizability of trial results to the whole AML population. To facilitate the future use of this model, we are constructing a web-based calculator (


To estimate rates of community-level influenza-like-illness (ILI) and influenza-associated ILI in rural north India.During 2011, we conducted household-based healthcare utilization surveys (HUS) for any acute medical illness (AMI) in preceding 14days among residents of 28villages of Ballabgarh, in north India. Concurrently, we conducted clinic-based surveillance (CBS) in the area for AMI episodes with illness onset ≤3days and collected nasal and throat swabs for influenza virus testing using real-time polymerase chain reaction. Retrospectively, we applied ILI case definition (measured/reported fever and cough) to HUS and CBS data. We attributed 14days of risk-time per person surveyed in HUS and estimated community ILI rate by dividing the number of ILI cases in HUS by total risk-time. We used CBS data on influenza positivity and applied it to HUS-based community ILI rates by age, month, and clinic type, to estimate the community influenza-associated ILI rates.The HUS of 69,369 residents during the year generated risk-time of 3945 person-years (p-y) and identified 150  ILI episodes . Among 1,372 ILI cases enrolled from clinics, 126  had laboratory-confirmed influenza (A (H3N2) = 72; B = 54). After adjusting for age, month, and clinic type, overall influenza-associated ILI rate was 4.8/1,000 p-y; rates were highest among children <5 years  and persons≥60 years .We present a novel way to use HUS and CBS data to generate estimates of community burden of influenza. Although the confidence intervals overlapped considerably, higher point estimates for burden among young children and older adults shows the utility for exploring the value of influenza vaccination among target groups. Influenza is recognized to be an important cause of morbidity and mortality worldwide including low- and middle-income countries (LMICs) in tropical regions but data on influenza disease burden in most of these countries remain sparse . In addiOne reason for the lack of data on outpatient and non-medically attended illness is that community-based burden studies with laboratory confirmation of influenza virus infection are resource-intensive and challenging to conduct. In some high-income countries where the catchment populations that attend health facilities are known, the incidence of outpatient influenza-like illness (ILI) and influenza-associated ILI , 6 have Ballabgarh is a block of Faridabad district in the state of Haryana which is located approximately 40 km south of New Delhi, India. The HDSS site at Ballabgarh has been previously described . BrieflyFrom July 2010 to January 2012, community-based cross-sectional healthcare utilization surveys (HUS) were conducted across the study villages. Trained field investigators visited an average of 365 households per week and interviewed at least one adult respondent in each visited household. All household members registered with the HDSS system were eligible for inclusion. Information on whether residents in the household had experienced any acute medical illness (AMI) during the preceding 14 days was collected We defined AMI as any illness irrespective of symptoms excluding injury and those related to obstetric or surgical problems with onset in the past 14 days among any member of the household. We collected detailed symptom data for each AMI episode using a structured interview . We alsoDuring December 2010 to January 2012, systematic surveillance was conducted in the outpatient clinics of PHCs and outreach clinics at sub-centers to enroll AMI patients defined similarly to that used for the HUS but with illness onset within the preceding three days; AMI cases with onset more than 3 days were excluded to increase the probability of virus detection. We also identified key private practitioners in the study villages who were identified on the HUS as frequently used for medical care by community members and systematically enrolled patients with AMI from these private clinics. The study staff systematically visited two to three outpatient clinics and enrolled the first five eligible cases per clinic with an average of 10–12 AMI cases per day, collecting data from each case on clinical symptoms and signs using structured interviews and a brief clinical exam.Nasal and throat swabs were collected only from AMI patients enrolled at clinics, placed together in viral transport media, immediately stored in cold boxes or refrigerated, and transported to the laboratory within 48 hours of collection for further processing of samples. All specimens were tested at the All India Institute of Medical Sciences  using real-time reverse transcription polymerase chain reaction (rRT-PCR) for influenza A (A(H1N1), A(H1N1pdm09), and A(H3N2) and B viruses using CDC protocols . SamplesFor the current study, we used concurrently collected data from the HUS and CBS from January to December 2011 Figs . We thenAssuming similar prevalence of influenza virus infection among ILI cases in both clinics and households, we estimated the influenza-associated ILI cases in the community by multiplying the proportion of ILI cases positive for influenza in the clinics by ILI cases in the community identified on the HUS; we performed these calculations by month, age group and type of health facility . We then estimated age-stratified and total incidence of influenza-associated ILI in the community by dividing the estimated number of influenza-associated ILI cases in the community by person-year of risk time. We used chi-square to test for statistical significance between the proportions. We calculated 95% confidence intervals (95% CI) for the rates assuming a Poisson distribution. We used Stata/SE 14.1 (StataCorp LP) and MS Excel 2013 for data analysis.The study protocol was approved by the institutional ethics committees of the All India Institute of Medical Sciences, New Delhi; National Institute of Virology, Pune in India, and U.S. Centers for Disease Control and Prevention, USA. We requested written informed consent from all patients enrolled in outpatient clinics and heads of households included in the HUS.During the study period, 69,369 individuals in 11,816 households were reached at least once with a total of 103,872 contacts  during the study period. Assuming 14 days of risk-time for each contact, the total cumulative risk-time for all age groups was 3945 person-years (p-y) . From thDuring the same period, 2,431 AMI  cases were screened and 1,372 ILI cases  were detected in the CBS . The majOf the ILI cases identified through clinic surveillance, 126  tested positive for influenza viruses, of which 72 (57%) were positive for influenza A(H3N2) and 54 (43%) for influenza B virus. The prevalence of laboratory-confirmed influenza virus among ILI patients attending clinics was significantly different (p = 0.01) between age groups with highest prevalence among the 5–14 year olds . We also tested non-ILI AMI cases enrolled in the clinics, and found influenza positivity among non-ILI clinic attendees  was lower than the ILI cases. The monthly prevalence of laboratory-confirmed influenza infection among all ILI cases ranged from 0–25% with the highest prevalence occurring during July through September.Overall, the estimated influenza-associated ILI rate during 2011 was 4.8 (95% CI: 2.9–7.5) per 1000 p-y . InfluenUsing a novel method using existing HUS, clinic, and virological data, we demonstrate that young children and older adults experienced the highest rates of both community ILI and influenza-associated ILI during 2011 in our study population in a rural northern Indian village. This is consistent with age trends in other LMICs with similar data, including Bangladesh, Brazil, and China , 8, 13, Our estimates of 4.8 2.9–7.5) per 1000 p-y of influenza-associated ILI were lower than estimates of influenza-associated outpatient visits reported from neighboring countries of Bangladesh (66–170 per 1000 p-y) and Thailand (14.2/1000 p-y) . However–7.5 per Our study also documented that 99% of community residents with ILI sought some form of healthcare for their illness and thus likely incurred some expense associated with their illness. In addition, a large proportion of persons with ILI sought care from providers in the private sector and from local unqualified practitioners, which is common practice in India  and has Our study has several limitations. First, our approach of relying on a single household adult respondent to provide data for all household members might have led to underreporting of ILI cases, especially those with mild symptoms, leading to an underestimation of ILI and influenza-associated ILI rates in the community. However, we believe that keeping the recall period to the last 14 days likely helped minimize recall issues. Further, given the observation that the majority of community ILI cases had sought clinic-based care, under-estimation due to recall bias is likely to be minimal. Second, although influenza tends to be more severe often requiring medical care, however, we assumed the prevalence of influenza virus infection among the clinic attendees was similar to that in the community, which is difficult to confirm in the absence of laboratory-confirmation among ILI cases in the community. However, similarities in the age and seasonal distribution of ILI cases identified by the HUS and through CBS as well as frequent clinic-based treatment seeking for ILI observed in the HUS support this assumption. Third, we only collected data for a single year although rates of ILI are known to vary substantially across years depending upon circulating influenza virus strains. Further, the confidence interval calculated assuming Poisson distribution around the incidence estimates may not have adequately captured the uncertainties with the sampling system used. Despite these limitations, we demonstrate the use of a community-based estimation approach in a low-income setting to estimate rates of ILI and influenza-associated ILI including both medically-attended and non-medically attended illness. Our study is unique in that it includes both non-medically attended illnesses and illnesses for which care was sought from unqualified providers or the private sector, both of which are often missed in studies of influenza disease burden. Our approach also demonstrates the feasibility of utilizing HDSS platforms for conducting community-based disease burden estimations through a combination of outpatient surveillance and HUS in developing countries where the health facilities frequently lack a defined catchment population.We demonstrate the use of an approach similar to the WHO recommended approach for influenza disease burden estimation in a low resource setting. Our study documents that point estimates of rates of ILI and influenza-associated ILI were highest among young children and the older adults in this rural community in northern India in 2011. These findings suggest further studies exploring utility for the development of influenza vaccination strategies for target age groups especially in low and middle income countries.S1 File(PDF)Click here for additional data file.S2 File(CSV)Click here for additional data file.S3 File(CSV)Click here for additional data file.S4 File(CSV)Click here for additional data file.S5 File(XLSX)Click here for additional data file.


Hyponatremia is the most common electrolyte disorder and also a predictor of mild cognition impairment. However, the association between hyponatremia and dementia in long follow up periods is rarely investigated. A retrospective cohort study was performed using the claims data of all insured residents who were covered by Taiwan’s universal health insurance from 2000 to 2011. A total of 4900 hyponatremia patients and 19545 matched comparisons were recruited for the analysis. The incidences of hyponatremia and dementia were diagnosed with clinical protocol and defined using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). Cox proportional hazard regression and Kaplan–Meier curves were used for the analyses. Independent of adjusting factors, hyponatremia patients had 2.36-fold higher chances of suffering dementia, including Alzheimer’s disease (AD) and non-AD dementia, than the comparisons. Severe hyponatremia patients had higher risks of suffering dementia than the non-severe hyponatremia patients (adjusted hazard ratio: 4.29 (95% CI: 3.47–5.31) versus 2.08 (95% CI: 1.83–2.37)). A dose response relationship was observed between hyponatremia and dementia. Those hyponatremia patients with baseline or incident stroke had significantly higher chances of suffering dementia compared with those patients without hyponatremia and stroke. Stroke is a significant modifier of the relationship between hyponatremia and dementia. Cerebrovascular disease after incident hyponatremia must be prevented to reduce the incidence of dementia. Hyponatremia is not only the most common electrolyte disorder but is also associated with higher infection rate , cardiovDementia is a progressive, incurable disease that greatly influences the quality of life of the affected patients. About 35.6 million individuals worldwide are suffering from this disease, and this number is expected to triple in value by 2050. DementiThis study is the first to explore such association based on a retrospective cohort study from a nationwide database. This study attempts to determine the following: (1) the association between hyponatremia and dementia, including Alzheimer’s disease (AD) and non-AD dementia; (2) the relationship among hyponatremia, stroke, and dementia; and (3) the dose response relationship between hyponatremia severity and dementia.The Taiwan Department of Health consolidated 13 insurance programs to establish the Taiwan National Health Insurance program (NHI program) in March 1995. Over 99% of Taiwanese residents are covered by this program. The National Health Insurance Research Database (NHIRD) comprises NHI program registration files and original claims data for reimbursement. This database was established by the National Health Research Institute, which was authorized to manage insurance data. As a sub-dataset of NHIRD, the Longitudinal Health Insurance Database (LHID 2000) includes claims data for one million people who have been randomly selected from the total insured population between 1996 and 2011. We selected our sample from LHID 2000 to investigate the association between hyponatremia and dementia. This database also contained information on the demographic status of the insured individuals and the claims data for inpatient and outpatient care. The personal information of the participants was concealed to protect their privacy. We ensured that all data were de-identified and analyzed anonymously. This study was also exempted from full ethical review by the institutional review board of China Medical University (CMUH104-REC2-115). The diagnosis of each patient was identified using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM).Using the retrospective population-based cohort design, we identified 4900 new hyponatremia (ICD-9-CM code 276.1) patients, whose first-time hyponatremia diagnoses were used as index year (2000 to 2009). Given that severe symptomatic hyponatremia patients could be treated with hypertonic saline  in clinical settings, we defined the severe hyponatremia group as those hyponatremia patients who required 3% sodium chloride treatment. By contrast, the non-severe hyponatremia group included hyponatremia patients that did not require 3% sodium chloride treatment. For comparison cohort (non-hyponatremia cohort), we randomly selected 19545 subjects without hypernatremia (ICD-9-CM: 276.0) and hyponatremia diagnosis at a 1:4 ratio. These cohorts were frequency-matched by age (per five years), gender, and index year.The follow-up person–years at the end of 2011 were calculated for each subject until the diagnosis of dementia  or withdrawal from the insurance system. We categorized dementia into AD (ICD-9-CM: 331.0) and non-AD (ICD-9-CM: 290 and 294.1). Those subjects with a history of dementia at the baseline were excluded from the study. All dementia-related comorbidities, including diabetes (ICD-9-CM: 250), hypertension (ICD-9-CM: 401 to 405), hyperlipidemia (ICD-9-CM: 272), ischemic heart disease (ICD-9-CM: 410 to 414), heart failure (ICD-9-CM: 428), mental illness (ICD-9-CM: 290 to 319), stroke (ICD-9-CM: 430 to 438), liver cirrhosis , atrial fibrillation (ICD-9-CM: 427.31), chronic renal disease (ICD-9-CM: 585), parkinsonism (ICD-9-CM: 332), and cancer (ICD-9-CM: 140 to 208), were identified before the index date. Diuretics use was evaluated before the index date and was then divided into furosemide, thiazide, and other diuretics. In addition, we defined the visiting numbers as sum of both outpatient and inpatient visit for hyponatremia per year to be representative of severity of hyponatremia. To explore the interaction effect between hyponatremia and stroke on dementia risk, we defined baseline stroke as the occurrence of stroke event before the index date of hyponatremia and defined incident stroke as the occurrence of stroke event after the index date of hyponatremia.P <0.05 in the two-tailed tests.We performed chi-square and student's t tests to examine the differences among the categorical and continuous variables, respectively. We employed analysis of variance to analyze the differences in the mean age and follow-up years of patients in the severe hyponatremia group, patients in the non-severe hyponatremia group, and comparison cohorts. The incidence rate ratio of dementia was measured via Poisson regression analysis. The multivariable Cox proportional hazards model was used to adjust dementia-related comorbidities and to estimate the risk of dementia, which was represented by adjusted hazard ratio (aHR) and 95% confidence interval (95% CI). Kaplan–Meier analysis was performed to measure the cumulative dementia incidence for the three study groups, and the log-rank test was performed to assess the differences of cumulative incidence among these groups. All statistical analyses were performed using the SAS 9.4 statistical package , with a significance level of After considering about the same conditions of dementia-related comorbidities, To the best of our knowledge, this study is the first nationwide database study to reveal the significant influence of hyponatremia on the occurrence of dementia. Hyponatremia patients had 2.36-fold higher chances of suffering dementia after adjusting other confounding factors. Our findings were consolidated by the effects of the significant dose response relationship between severe and non-severe hyponatremia on dementia occurrence.Dementia can be divided into different subtypes according to their cause . As the Although we lacked data on the level of serum sodium, we partially compensated for this limitation by investigating the dose response relationship between severe and non-severe hyponatremia. The severity of hyponatremia was measured based on symptoms instead of serum sodium level. All patients with severe symptomatic hyponatremia also received 3% saline in practice. Therefohypoxia is a major factor in hyponatremia that contributes to brain damage. This condition is usually observed among patients that face hyponatremia encephalopathy through two mechanisms, namely, neurogenic pulmonary edema and hypercapnia respiratory failure.[The association between hyponatremia and dementia could be explained in several ways. Hyponatremia could lead to brain damage through multiple mechanisms, predisposing to dementia. Hyponatremia leads to cerebral edema in the acute phase. Cerebral edema was closely linked to neuronal death by the Na/K ATPase dysfunction and the formation of reactive oxygen species. Moreove failure. Hypoxia  failure. but also failure.; in addi failure..In chronic hyponatremia, hyponatremia is associated with dementia through multiple mechanisms. First, renin–angiotensin–system (RAS) activation may have a role in the formation of dementia. Hyponatremia serves not only as a marker but also as a contributory factor to RAS activation. Such acStroke is notorious for doubling the risk of suffering dementia (post-stroke dementia), including both AD and non-AD dementia. RecurreHyponatremia has a mutual interaction with stroke. Hyponatremia was associated with increased incidence of cerebrovascular diseases , 3 and aThis study has several limitations. First, we had no detailed information about the level of serum sodium, but tried to compensate for this limitation by dividing the sample into severe and non-severe hyponatremia patients. Second, we could not consider all possible confounders of dementia, such as smoking habits, alcohol use, other prescription drugs, vitamin deficiency, education, physical activity, and genetic factors. Third, we could not differentiate the severity and location of stroke, which could also influence the occurrence of dementia.In sum, hyponatremia increases the risk of dementia, including both AD and non-AD dementia. Severe hyponatremia carries a much higher risk of dementia. Baseline or incident stroke can modify the relationship between hyponatremia and dementia. To prevent the occurrence of dementia after hyponatremia, clinical physicians must prevent secondary insults, such as cerebrovascular diseases.


A maternal group B streptococcal (GBS) vaccine could prevent neonatal sepsis and meningitis. Its cost-effectiveness in low-income sub-Saharan Africa, a high burden region, is unknown.We used a decision tree model, with Markov nodes to project infants’ lifetimes, to compare maternal immunization delivered through routine antenatal care with no immunization. 37 countries were clustered on the basis of economic and health resources and past public health performance. Vaccine efficacy for covered serotypes was ranged from 50% to 90%. The model projected EOGBS (early-onset) and LOGBS (late-onset) cases and deaths, disability-adjusted life years (DALYs), healthcare costs (2014 US$), and cost-effectiveness for a representative country in each of the four clusters: Guinea-Bissau, Uganda, Nigeria, and Ghana. Maximum vaccination costs/dose were estimated to meet two cost-effectiveness benchmarks, 0.5 GDP and GDP per capita/DALY, for ranges of disease incidence (reported and adjusted for under-reporting) and vaccine efficacy.At coverage equal to the proportion of pregnant women with ≥ 4 antenatal visits (ANC4) and serotype-specific vaccine efficacy of 70%, maternal GBS immunization would prevent one-third of GBS cases and deaths in Uganda and Nigeria, where ANC4 is 50%, 42–43% in Guinea-Bissau (ANC4 = 65%), and 55–57% in Ghana (ANC4 = 87%). At a vaccination cost of $7/dose, maternal immunization would cost $320-$350/DALY averted in Guinea-Bissau, Nigeria, and Ghana, less than half these countries’ GDP per capita. In Uganda, which has the lowest case fatality ratios, the cost would be $573/DALY. If the vaccine prevents a small proportion of stillbirths, it would be even more cost-effective. Vaccination cost/dose, disease incidence, and case fatality were key drivers of cost/DALY in sensitivity analyses.Maternal GBS immunization could be a cost-effective intervention in low-income sub-Saharan Africa, with cost-effectiveness ratios similar to other recently introduced vaccines. The vaccination cost at which introduction is cost-effective depends on disease incidence and vaccine efficacy.Clinical Trial registry name and registration number: Not applicable. We focused on a central policy question – affordable vaccination cost (price plus delivery cost) per dose – and present the highest per-dose costs that would meet two possible cost-effectiveness benchmarks, 0.5 GDP per capita and GDP per capita per DALY averted. In addition, we compare cost-effectiveness ratios to those of other recently introduced new vaccines 22.1The model is structured as a decision tree that describes the two strategies offered to pregnant women, GBS vaccine or no vaccine, with embedded Markov nodes to model the lifetime consequences for their babies, using TreeAge Pro 2016 ; EOGBS and LOGBS disease incidence; and the proportion of GBS disease-causing isolates that would be covered by a pentavalent vaccine (vaccine serotype coverage) in sub-Saharan Africa; we pooled the individual study estimates in a random effects meta-analysis using Open meta-Analyst [Reported disease incidence reflects blood culturing practice and its sensitivity as a diagnostic test. We adjusted the estimates of EOGBS and LOGBS disease incidence from the meta-analysis for the proportion of neonates with clinical sepsis undergoing blood culture (90%) and for culture sensitivity (47%) 2.3The only published data on case fatality ratios in sub-Saharan Africa come from a study conducted in Malawi. Case fatality ratios (CFRs) for sepsis and meningitis, by EOGBS and LOGBS, were estimated from that study and adjusted for early versus late onset disease, as well as the underlying risk of neonatal mortality in a country, using methods described in Death rates and life expectancies are the 2014 values for the example country from the United Nations’ Population Division 2.4We assumed that GBS vaccine would be delivered to pregnant women in the third trimester and that a single dose would be given for each pregnancy during routine antenatal care. Given the need to administer the vaccine between 27 and 34 weeks of gestation to achieve peak titers in the newborn, the percentage of pregnant women with at least four antenatal visits (ANC4) was used as a proxy for vaccine coverage since women with four visits are likely to attend during the third trimester 2.5There is no information on the potential efficacy of a pentavalent GBS vaccine. Our expert panel recommended using a range of 50–90%, rather than a single estimate, for serotype-specific vaccine efficacy against EOGBS and LOGBS. Serotype coverage was assumed to be 97.4% for EOGBS and 97.7% for LOGBS, based on the meta-analysis described above 2.6Costs were adjusted to 2014 U.S. dollars using the World Bank’s annual GDP deflator series Vaccine price and delivery cost. In the model we combined price and delivery cost and evaluated vaccination cost per dose for the one dose series. In the base-case cost-effectiveness analysis, presented to establish context for the analysis of affordable vaccine costs/dose described below, we used a cost of $7/dose and a range of $2-$10, based on per-dose childhood delivery costs in LMICs Treatment costs. To develop treatment costs we surveyed sub-Saharan experts in GBS disease management to get estimates of the percentages of infants with meningitis and sepsis treated in various settings and the healthcare resources used in those settings. Thirteen of 30 experts responded to the survey. Since their responses were anonymous, we cannot differentiate resource use by cluster. To derive total costs the resource-use estimates were multiplied by WHO-CHOICE unit costs for, as appropriate, an outpatient visit, a bed-day in a paediatric ward, and a bed-day in an intensive care unit, all in secondary-level hospitals 2.7Model outputs for maternal GBS immunization and no immunization include EOGBS and LOGBS cases, EOGBS and LOGBS deaths, DALYs, and medical costs. A cost-effectiveness ratio compares two strategies and expresses the comparison as the additional cost of one strategy compared with the other for each additional DALY averted. In this study the cost-effectiveness ratios show the additional cost of maternal GBS immunization, compared with no immunization, for each DALY averted. No age weighting was used in calculating DALYs. One-way sensitivity analysis, in which one model parameter is varied, while holding all other parameters at their base-case values, was conducted to show how the cost-effectiveness of maternal GBS immunization changes as each parameter changes. Results for the most influential parameters were summarized in Tornado diagrams.Stillbirths account for 2–4% of all births in low-income sub-Saharan countries . Prelimi2.8To estimate the maximum (threshold) affordable vaccination cost/dose in each representative country, we considered two possible cost-effectiveness benchmarks, 0.5 GDP per capita (GDPpc) and GDPpc per DALY averted. Maximum vaccination cost/dose for each representative country was estimated by running a 1-way sensitivity analysis to identify the vaccination cost/dose that produced that benchmark in that country. The sensitivity analysis was repeated for each of three levels of vaccine efficacy and for adjusted and unadjusted disease incidence.To estimate an uncertainty interval for each threshold vaccination cost/dose we ran a probabilistic sensitivity analysis, holding vaccine efficacy and disease incidence at the levels used to derive the threshold cost/dose, but letting other parameters vary according to the distributions in 33.1For each representative country ANC4 varies considerably across the example countries, from 47.6% in Uganda to 87.3% in Ghana . In UganIf the coverage of maternal GBS immunization were ANC1 instead of ANC4, many more cases of disease and death would be prevented – about 60% in Guinea-Bissau, Uganda, and Ghana, all of which have ANC1 rates above 90%. In Nigeria, with ANC1 60.6%, about 40% of cases and deaths would be prevented. Because the percentage of women vaccinated affects vaccination costs, disease treatment costs and cases of disease averted by the same proportion, the cost-effectiveness ratios remain the same whether coverage is equivalent to ANC1 or ANC4, although public health impact increases as more women receive the vaccine.3.2In one-way sensitivity analysis, the same 15 parameters were consistently the most influential in all four countries, so 3.3Uganda’s maximum vaccination costs/dose are lower than those of Guinea-Bissau because Uganda has a low neonatal mortality rate, which gives it low GBS CFRs  Under these assumptions, cost/DALY was $430 in Guinea-Bissau; $454 in Uganda; $432 in Nigeria; and $382 in Ghana. Uganda’s cost/DALY went down because the assumed case fatality ratios used were so much higher than those observed in Uganda.4Efficient and affordable interventions are needed to reduce neonatal mortality, especially in parts of the world where it remains high, such as sub-Saharan Africa. Based on a decision analytic model, our analyses suggest that maternal GBS immunization with a pentavalent vaccine that covers most disease-causing GBS serotypes could be cost-effective in low-income sub-Saharan countries. Although the ability to reach large numbers of pregnant women may be constrained by the availability of antenatal care in these countries, substantial numbers of GBS cases and deaths could be prevented because disease burden is high. For example, in Nigeria, 11,000 cases and 4000 deaths (EOGBS and LOGBS) could be averted at a cost of $339 per DALY averted (2014 US$), even if only half of women receive the vaccine . Guinea In threshold analysis, we focused on the range of vaccination costs/dose that would make maternal immunization good value in these countries. Although this study may be most useful for global funders, decision makers, and researchers, recent guidance has emphasized the need for country-driven value criteria One-way sensitivity analysis showed vaccination cost (vaccine price plus delivery cost) and vaccine efficacy, both as yet unknown, to be important determinants of cost-effectiveness. EOGBS and LOGBS disease incidence and case fatality ratios, also important, will lead to variations in the cost-effectiveness of maternal GBS immunization across countries for the same vaccine price and efficacy. Other uncertain factors that were not included in the base case may also be influential. In the base case, for example, we considered only GBS sepsis and meningitis as avertable causes of newborn death and morbidity. GBS may also, however, cause some stillbirths. If these stillbirths were prevented by the vaccine, the DALYs averted would increase substantially, at no extra cost since the women would already have been vaccinated. If as many as 5% of stillbirths are associated with GBS, our analysis shows that the cost/DALY of maternal immunization could drop below $200/DALY.Our analysis, which considers only immunization costs that vary with the number of women vaccinated, suggests that coverage makes little difference to the cost per DALY averted of maternal GBS immunization. However, coverage is an important determinant of the potential public health impact of the vaccine, its ability to prevent disease and death, as shown by the differences across countries in the percentage of disease averted . We usedOur analysis contributes to understanding where future research is most needed. EOGBS and LOGBS incidence and mortality, which are poorly documented in West and Central Africa The study has several limitations. Firstly, only the variable costs of vaccination were considered. In real-world programs, there may be costs that do not vary with the number of women vaccinated, particularly when a new vaccine is first introduced (e.g. cold chain expansion). In that case cost/DALY would decline as coverage increased and the fixed overhead costs were spread over more women. Secondly, the evidence did not allow us to differentiate disease incidence, a key driver of cost-effectiveness, among countries. We differentiated case fatality ratios by linking them to neonatal mortality, but this approximation may not accurately reflect GBS case fatality. Finally, we assumed that vaccination would not result in herd protection or serotype replacement, because it would not affect gut colonization with GBS, only invasive disease. Other conjugate vaccines, such as pneumococcal vaccines, have led to decreased colonization and hence herd protection, greatly reducing their cost/DALY 5Maternal GBS immunization delivered during antenatal care visits could be a cost-effective public health intervention in low-income sub-Saharan Africa at vaccination costs/dose ranging from $2-$4 to more than $20, depending on disease incidence and vaccine efficacy. The vaccine would be most cost-effective in countries like Nigeria, Guinea Bissau, and Ghana, where the case fatality ratio is high, and less cost-effective in countries like Uganda, where it is relatively low, but its cost/DALY is within the range for newer vaccines already included in the routine childhood vaccination schedules of all these, and other, low-income countries.


The optimal revascularization technique in patients with left main coronary artery disease (CAD) remains controversial. We aimed to compare the long-term performance of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery in treatment of left main CAD.PubMed, EMBASE, and the Cochrane Library were searched until November 16, 2016.Six randomized controlled trials and 22 matched observational studies including 22,487 patients and 90,167 patient-years of follow-up were included. PCI was associated with an overall higher risk for the major adverse cardiac and cerebrovascular events (hazard ratio (HR), 1.42; 95% confidence interval (CI), 1.14–1.77), mainly driven by higher rates of myocardial infarction  and revascularization . The overall risks for all-cause death , cardiac death , stroke , and the composite safety endpoint of death, myocardial infarction, or stroke  were similar between PCI and CABG. Stratified analysis based on stent types showed that the increased risk for myocardial infarction associated with PCI was only evident in patients with bare-metal stents or early-generation drug-eluting stents (DES), but not newer-generation DES. Stratified analyses based on study designs showed largely similar findings with the overall analyses, except for a significantly higher incidence of myocardial infarction in adjusted studies  but a trend toward higher incidence in randomized trials  associated with PCI.Compared with CABG, PCI with newer-generation DES might be a safe alternative revascularization strategy for treatment of left main CAD, but is associated with more repeat revascularization.The online version of this article (doi:10.1186/s12916-017-0853-1) contains supplementary material, which is available to authorized users. Left main coronary artery disease (CAD) is associated with poor clinical outcomes; without revascularization, the 3-year mortality reaches 50% . CoronarHowever, these guidelines were mainly based on midterm findings of the SYNTAX trial , the PREThis meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline  independently screened the titles and abstracts for eligibility, and retrieved the full-text of citations with potential relevance. Any discrepancies were resolved by a third investigator (YC). All studies included in the meta-analysis had to be RCTs or matched observational studies making direct comparisons of PCI with CABG in patients with left main coronary artery stenosis. Additionally, studies had to contain at least 100 patients and report outcomes of interest with an at least 12 months’ follow-up to minimize the small study effects, due to the rarity of cardiovascular events. Observational studies had to provide adjusted estimates by either propensity matching or propensity score adjustment or multivariate adjustment to minimize the bias from baseline confounding factors. We excluded duplicated publications, animal studies, review articles, studies not comparing PCI with CABG, studies conducted in mixed population in which data for left main CAD could not be abstracted, studies with small sample size and short follow-up duration, and studies reporting unadjusted results.Primary clinical endpoints were all-cause mortality and cardiovascular mortality; secondary end points were myocardial infarction, stroke, repeat revascularization, a composite of major adverse cardiac and cerebrovascular events , and a composite safety endpoint of all-cause death, myocardial infarction, or stroke. Definitions of outcomes from each randomized trial were provided  from each study, which included the study author, publication date, number of patients, duration of study follow-up, study enrolling period, adjustment method, patient age and sex, baseline EUROSCORE and SYNTAX score, baseline ejection fraction, the percentage of patients with multi-vessel disease, diabetes, hypertension, and the risk for each study outcome, etc. Three reviewers  independently evaluated the potential risk of bias of randomized trials by applying the Cochrane Collaboration’s tool  and the I2 statistic, with I2 values of 25%, 50%, and 75% indicating low, moderate, and high heterogeneity, respectively [P < 0.10 or I2 > 50%), we calculated pooled risks by using a random-effects model and the DerSimonian–Laird method [Hazard ratios (HR) and their corresponding 95% confidence intervals (CIs) were directly retrieved from each trial and matched study. We used HR as the statistic estimate because it correctly reflects the nature of the data and accounts for censoring. The extent of heterogeneity was assessed with the Cochran Q test and the ectively . If signd method ; otherwid method . StratifAdditional file A total of 22,487 patients  receiving PCI  or CABG  were included in the analysis. Patients enrolled were mainly men (77.2%), with a median age of 65.3 years . Overall, roughly one third of patients presented with diabetes, half had hyperlipidemia, two thirds had hypertension, and one third were active smokers. When reported, the mean value of left ventricular ejection fraction ranged from 40% to 65%. The median EUROSCORE was 4.3  for PCI group and 5.0  for the CABG group. Detailed baseline characteristics of each study were presented in Table There was no significant difference in all-cause mortality between PCI and CABG   Fig. . ConsistOverall, there was a statistically significant increased risk of myocardial infarction in patients receiving PCI compared with CABG    and in patients receiving BMS or early-generation DES, this benefit was significant       Table . SubgrouOn the basis of pooled data from 28 studies that included nearly 22,500 patients  with left main CAD receiving PCI or CABG treatment, we found that PCI was associated with a higher risk for MACCE, which was evident both in studies with newer-generation DES and those with BMS or early-generation DES, mainly driven by higher rates of myocardial infarction and revascularization associated with PCI. The overall risks for all-cause death, cardiac death, stroke, and the composite safety endpoint of death, myocardial infarction, or stroke were similar between PCI and CABG. Stratified analysis showed that the increased risk for myocardial infarction associated with PCI was only evident in patients with BMS or early-generation DES but not newer-generation DES.Our study has several strengths compared with other reviews –44. FirsOur analysis and other reviews –45 showeP = 0.02). Therefore, the broad safety of PCI with newer-generation DES versus CABG still needs to be confirmed from longer-term follow-up data.Concerning the broader safety of PCI versus CABG in treating left main CAD, our and a few other meta-analyses  evaluateOur overall analysis demonstrated a statically significant difference in rate of myocardial infarction in favor of CABG in long-term follow-up. A similar finding was also observed in the large NOBLE trial , which, A number of meta-analysis showed an overall decreased stroke risk in the PCI arm compared with CABG in patients with left main CAD –45. HoweOur analysis showed a consistent finding with other reviews and randomized trials , 13 or rOur study demonstrated a remarkable benefit in favor of CABG with respect to MACCE risk in treating left main CAD. This finding is consistent in subgroups with the BMS or early-generation DES and newer-generation DES, and supported by the NOBLE trial  and a paWe acknowledge several limitations. First, the results were analyzed on trial level data but not on patient level data. Second, definitions of clinical outcomes other than mortality were based on the definitions in the original studies and thus were not completely uniform across these studies. Third, the reporting of EUROSCORE and SYNTAX score were absent in a large portion of studies, making meta-regression analyses of the effects of these variables on clinical outcomes inaccurate and was therefore not performed. Fourth, selective outcome reporting was observed in a number of observational studies, and publication bias was observed in several outcome analyses. Fifth, heterogeneity is evident in the analyses of certain outcomes. We made several subgroup and meta-regression analyses to explore the heterogeneity, and used random-effects models to incorporate heterogeneity among studies.Pooled data from nearly 22,500 patients  with left main CAD receiving revascularization treatment suggest that PCI is associated with a higher risk for MACCE in long-term follow-up, mainly driven by higher rates of myocardial infarction and revascularization. The increased risk for myocardial infarction associated with PCI was only evident in patients receiving BMS or early-generation DES but not those receiving newer-generation DES. Therefore, compared with CABG, PCI with newer-generation DES might be a safe alternative revascularization strategy for treatment of left main CAD, but is associated with more repeat revascularization.Additional file 1:PRISMA checklist. (DOCX 29 kb)Additional file 2:Supplemental information. (DOCX 1488 kb)