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Objectives: Microsatellite instability-high (MSI-H) and deficient DNA mismatch repair (dMMR) status have emerged as actionable biomarkers for advanced endometrial cancer (aEC). The objective of this study was to assess clinical outcomes and treatment patterns among MSI-H/dMMR aEC patients who had disease progression following prior systemic therapy (FPST) in the US., Methods: Endometrial Cancer Health Outcomes (ECHO) was a retrospective, medical chart review study of patients with MSI-H/dMMR aEC who had disease progression between 07/01/2016 and 12/31/2018 FPST and were not candidates for curative surgery. Data on patient demographics, clinical and treatment characteristics, and clinical outcomes were collected. Kaplan-Meier analyses were performed to estimate real-world progression-free survival (rwPFS) and overall survival (OS), stratified by drug class., Results: A total of 124 eligible patients who initiated second-line chemotherapy ± bevacizumab or immunotherapy were included. Mean age was 61.4 years at aEC diagnosis and 86.3% of patients were stage IIIB-IV. Median rwPFS and OS were 4.0 months (95% CI: 2.0-9.0) and 7.0 months (95% CI: 5.0-18.0), respectively, among 21 patients who received chemotherapy ± bevacizumab, and 29.0 months (95% CI: 18.0-NE) and not reached (95% CI: 30.0-NA), respectively, among 103 patients who received immunotherapy. Most patients (n = 92) received pembrolizumab; among these patients, rwPFS and OS were 29.0 months (95% CI: 18.0-NE) and 30 months (95% CI: 30.0-NA), respectively., Conclusions: Real-world evidence suggests that pembrolizumab monotherapy provides considerable clinical benefits and has become the standard of care for MSI-H/dMMR aEC patients FPST who are not candidates for curative surgery in real-world settings., Competing Interests: Declaration of Competing Interest Sneha Kelkar, Shelby Corman & Nifasha Rusibamayila report support from Merck & Co., Inc. during the conduct of the study; and consulting fees from Merck & Co., Inc. Vimalanand Prabhu and Robert Orlowski are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc., Rahway, NJ, USA. Vimalanand Prabhu reports stock from Merck & Co., Inc., Rahway, NJ, USA; and other financial interests from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.. Cynthia Macahilig & Shardul Odak report support from RTI-Health Solutions during the conduct of the study. Robert Orlowski reports support from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA during the conduct of the study; patents with Merck & Co., Inc., Rahway, NJ, USA; and stock from Merck & Co., Inc., Rahway, NJ, USA. Linda Duska reports support from Merck & Co., Inc. during the conduct of the study; grants/contracts from Genentech/Roche, Cerulean/NextGen/(GOG 3008), AbbVie/(GOG 3005), Tesaro, Pfizer, GlaxoSmithKlein/Novartis, Morab, MorphoTek, Merck & Co., Inc., Aduro BioTech, Syndax, Ludwig, LEAP Therapeutics, Eisai, Lycera, Inovio, Advaxis, Mersana, Verastem, Ellipses, Corcept, Plexxicon, Constellation, Arch, Mirasol, and Quest Pharmtech; royalties from Elsevier and JB Learning; consulting fees from MorphoTek, Merck & Co., Inc., Genentech/Roche, Advance Medical, UpToDate, Parexel, State of California and ClearView Health Care; personal fees from expert review; and leadership/board roles in ASCO, National Cancer Institute and British Journal of OB/GYN., (Copyright © 2022 Merck Sharp & Dohme LLC., a subsidiary Merck & Co., Inc., Rahway, NJ, USA, The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Microsatellite instability (MSI) due to defective DNA mismatch repair has emerged as an actionable biomarker in advanced endometrial cancer (aEC). Currently, there are no treatment patterns and outcomes data in non-MSI-high (non-MSI-H) or mismatch repair proficient (pMMR) aEC patients following prior systemic therapy (FPST). Our goal was to describe real-world data in this population in the US in 2019 and prior years., Methods: Endometrial Cancer Health Outcomes (ECHO) is a retrospective patient chart review study conducted in the US. Patients with non-MSI-H/pMMR aEC and progression between 06/01/2016-06/30/2019 FPST were eligible. Data collected included patient demographics, clinical and treatment characteristics, and clinical outcomes. Kaplan-Meier analyses were performed to estimate time to treatment discontinuation, real-world progression-free survival (rwPFS), and overall survival (OS), separately by treatment category., Results: A total of 165 eligible patients initiated second-line therapy with chemotherapy ± bevacizumab (n = 140) or hormonal therapy (n = 25). Median age was 66.0 years at aEC diagnosis, 70.2% were Stage IIIB-IV, 40.0% had ECOG ≥ 2 at second-line therapy initiation. Median rwPFS was 5.0 months (95% CI: 4.0-6.0) for patients receiving chemotherapy ± bevacizumab and 5.5 months (95% CI: 3.0-29.0) for those receiving hormonal therapy. Median OS was 10.0 months (95% CI: 8.0-13.0) and 9.0 months (95% CI: 6.0-NA) in these groups, respectively., Conclusions: Non-MSI-H/pMMR patients who initiated second-line therapy with chemotherapy ± bevacizumab or hormonal therapy had poor clinical outcomes with a median survival less than 1 year and rwPFS less than 6 months. This was the first study to define the clinical unmet need in patients with non-MSI-H/pMMR aEC with conventional therapy., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Sneha Kelkar, Shelby Corman & Nifasha Rusibamayila are employees of Open Health and report that Open Health received consulting fees/funding support from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA during the conduct of the study; Vimalanand Prabhu is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and reports stock from Merck & Co., Inc.; Jingchuan Zhang reports support from Eisai Inc. during the conduct of the study; meeting/travel support from Eisai Inc.; and other financial interests from Eisai Inc. Cynthia Macahilig & Shardul Odak report support from RTI-Health Solutions during the conduct of the study. Linda Duska reports that University of Virginia School of Medicine, Charlottesville, VA received grants/contracts to support clinical research trials from Genentech/Roche, Cerulean/NextGen/(GOG 3008), AbbVie/(GOG 3005), Tesaro, Pfizer, GlaxoSmithKlein/Novartis, Morab, MorphoTek, Merck & Co., Inc., Aduro BioTech, Syndax, Ludwig, LEAP Therapeutics, Eisai, Lycera, Inovio, Advaxis, Mersana, Verastem, Ellipses, Corcept, Plexxicon, Constellation, Arch, Mirasol, and Quest Pharmtech Dr. Duska has received royalties from Elsevier and JB Learning; consulting fees from MorphoTek, Genentech/Roche, Advance Medical, UpToDate, Parexel, State of California and ClearView Health Care; personal fees from legal expert review; and payment for leadership/board roles in ASCO, National Cancer Institute and British Journal of OB/GYN.]., (© 2022 Merck Sharp & Dohme LLC., a subsidiary Merck & Co., Inc.,, The Author(s).)

The Program to Reduce Maternal Deaths in Tanzania was a 13-year (2006-2019) effort in the Kigoma region that evolved over 3 phases to improve and sustain the availability of, access to, and demand for high-quality maternal and reproductive health care services. The Program intended to bring high-quality care closer to more communities. Cutting across the Program was the routine collection of monitoring and evaluation data. The Program achieved significant reductions in maternal and perinatal mortality, a significant increase in the modern contraceptive prevalence rate, and a significant decline in the unmet need for contraception. By 2017, it was apparent that the Program was on track to meet or surpass many of the targets established by the Government of Tanzania. Over the following 2-plus years, efforts to sustain Program interventions intensified. In April 2019, the Program fully transitioned to Government of Tanzania oversight. Four key lessons were learned during implementation that are relevant to governments, donors, and implementing organizations working to reduce maternal mortality: (1) multistakeholder partnerships are critical; (2) demand creation for services, while critical, must rest on a foundation of well-functioning and high-quality clinical services; (3) it is imperative to not only collect robust monitoring and evaluation data, but to be responsive in real time to what the data reveal; and, (4) it is necessary to develop a deliberate sustainability strategy from the start. The Program in Kigoma demonstrates that decentralizing high-quality maternal and reproductive health services in remote, low-resource settings is both feasible and effective and should be considered in places with similar contexts. By embedding the Program in the existing health system, and through efforts to build local capacity, the improvements seen in Kigoma are likely to be sustained. Follow-up evaluations are planned, providing an opportunity to more directly assess sustainability., (© Prasad et al.)

Background: Our objective was to characterize the incidence, risk factors and clinical features of acute kidney injury (AKI) in patients receiving dabrafenib and trametinib., Methods: We performed a retrospective cohort study examining the kidney outcomes of patients in a large healthcare system who received dabrafenib/trametinib between 2010 and 2019. The primary outcome was AKI, defined as a 1.5-fold increase in serum creatinine from baseline within a 12-month study period. AKI severity and etiology was determined for each case by chart review. Logistic regression was used to evaluate baseline predictors of AKI., Results: A total of 199 patients who received dabrafenib in our healthcare system from 2010 to 2019 were included in the analysis. Forty-two patients (21%) experienced AKI within 12 months; 10 patients (5% of the total cohort, 24% of AKI patients) experienced AKI occurring during a dabrafenib/trametinib-induced febrile syndrome characterized by fever, chills, gastrointestinal symptoms and elevated liver enzymes. Preexisting liver disease was the only significant predictor of AKI in the cohort. One patient had biopsy-proven granulomatous acute interstitial nephritis that resolved with corticosteroids., Conclusions: Oncologists and nephrologists should be aware that AKI is common after dabrafenib/trametinib and a substantial number of cases occur in the setting of treatment-induced pyrexia., (© The Author(s) 2020. Published by Oxford University Press on behalf of the ERA.)

Background: Hyponatremia due to endocrinopathies such as adrenal insufficiency and hypothyroidism has been reported in patients receiving immune checkpoint inhibitors (ICIs). We determined the risk and predictors of hyponatremia and other electrolyte abnormalities in a 'real-world' sample of patients receiving ICIs to treat advanced malignancies., Methods: This was a retrospective observational study of all patients who received ICIs from a single cancer center between 2011 and 2018. Patients were followed for 12 months after initiation of ICIs or until death. Common Terminology for Cancer Adverse Events version 5.0 criteria were used to grade the severity of hyponatremia and other electrolyte abnormalities. The predictors of severe (Grade 3 or 4) hyponatremia were determined using a multivariable logistic regression model. The etiology of Grade 3 or 4 hyponatremia was determined by chart review., Results: A total of 2458 patients were included. Their average age was 64 years [standard deviation (SD) 13], 58% were male and 90% were white. In the first year after starting ICIs, 62% experienced hyponatremia (sodium <134 mEq/L) and 136 (6%) experienced severe hyponatremia (<124 mEq/L). Severe hyponatremia occurred on average 164 days (SD 100) after drug initiation. Only nine cases of severe hyponatremia were due to endocrinopathies (0.3% overall incidence). Risk factors for severe hyponatremia included ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor) use, diuretic use and non-White race. Other severe electrolyte abnormalities were also commonly observed: severe hypokalemia (potassium <3.0 mEq/L) occurred in 6%, severe hyperkalemia (potassium ≥6.1 mEq/L) occurred in 0.6%, severe hypophosphatemia (phosphorus <2 mg/dL) occurred in 17% and severe hypocalcemia (corrected calcium <7.0 mg/dL) occurred in 0.2%., Conclusions: Hyponatremia is common in cancer patients receiving ICIs. However, endocrinopathies are an uncommon cause of severe hyponatremia., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Pivotal trials in inflammatory bowel disease (IBD) demonstrate that earlier use of biologics is associated with greater likelihood of response/remission, but multiple studies have identified that in the real world, biologic treatment is often delayed, thereby limiting optimal effectiveness and increasing likelihood of adverse outcomes. Further assessment of patient, provider, and payor factors that contribute to therapy choice is needed. We assessed utilization of vedolizumab (VDZ) and performed a real-world assessment using administrative datasets. Here, we describe the different treatment patterns and demographics of patients who received VDZ., Methods: We identified VDZ-treated patients (aged ≥18 years) with Crohn's disease (CD) or ulcerative colitis (UC) in the MarketScan commercial and Medicare claims databases from 2017 to 2019 and included those who had continuous enrollment in the same health plan for ≥12 months prior to their initial IBD diagnostic claim, ≥1 VDZ claim after the initial IBD diagnosis, and continuous enrollment for ≥12 months prior to and after their initial UC or CD diagnosis. Patients exposed to VDZ, anti-TNF, or other biologic therapy in the 12-month pre-index period were excluded. We pre-defined 5 treatment pathways: (1) EARLY VDZ - VDZ within 30 days of first IBD diagnostic claim; (2) DELAYED VDZ 1 - immunomodulators and then switch to VDZ; (3) DELAYED VDZ 2 - corticosteroids with immunomodulators prior to VDZ; (4) DELAYED VDZ 3 - 5-ASA with corticosteroids prior to VDZ; or (5) DELAYED VDZ 4 - 5-ASA with corticosteroids and immunomodulators prior to VDZ. Differences in patient baseline characteristics among these treatment pathways were analyzed descriptively., Results: We identified 136,315 patients with UC and 103,591 with CD, from which 1,342 patients with UC (median age 43 years; 51.0% male; 96.4% commercially insured; 86.4% diagnosed in 2017) and 964 with CD (median age 45 years; 43.6% male; 94.6% commercially insured; 88.6% diagnosed in 2017) received VDZ and met criteria. The proportions of patients by treatment pathway were (UC|CD): EARLY VDZ (6.6%|9.6%); DELAYED VDZ 1 (7.5%|19.0%); DELAYED VDZ 2 (14.8%|36.8%); DELAYED VDZ 3 (37.6%|19.0%); DELAYED VDZ 4 (33.4%|15.6%). Among patients with UC, EARLY VDZ vs DELAYED VDZ cohorts had median age of 40 vs 44 years and proportion of men of 46.1% vs 51.4%. Among patients with CD, EARLY VDZ vs DELAYED VDZ had median age of 43 vs 45 years and proportion of men of 39.8%% vs 43.9%. For both indications, no meaningful differences among treatment groups by geographic region, payor type (i.e., commercial vs Medicare), and year of diagnosis were observed., Conclusion: In this administrative real-world dataset, fewer than 10% of patients with IBD were treated with VDZ within 30 days of diagnosis, and these patients were more likely to be younger and women. These findings are distinct from guidelines suggesting VDZ may be used earlier, or due to its safety profile, preferentially in older patients at higher risk for infection. Further analyses of safety and effectiveness outcomes are underway., (Copyright © 2021 by The American College of Gastroenterology.)

Background: In patients with genitourinary cancers, the effect of immune checkpoint inhibitors (ICIs) on kidney function is unknown., Patients and Methods: This is a retrospective cohort study of patients with renal cell carcinoma (RCC) and urothelial carcinoma who received ICIs at two major cancer centers between 2012 and 2018. Cumulative incidence and Fine and Gray subdistribution hazard models were performed to determine predictors of the co-primary outcomes, (1) acute kidney injury (AKI) and (2) sustained estimated glomerular filtration rate (eGFR) loss, defined as a >20% decline in eGFR sustained ≥90 days. We also determined the association between immune-related adverse events (irAE) and adverse kidney outcomes among patients surviving ≥1 year., Results: 637 patients were included; 320 (50%) patients had RCC and 317 (50%) patients had urothelial carcinoma. Half of the cohort had eGFR<60 mL/min/1.73 m 2  at baseline. irAEs, AKI, and sustained eGFR loss were common, occurring in 33%, 25% and 16%, respectively. Compared to patients with urothelial carcinoma, patients with RCC were more likely to develop irAEs (aHR 1.61, 95% CI 1.20-2.18) and sustained eGFR loss (aHR 1.97, 95% CI 1.24-3.12), but not AKI (aHR 1.53, 95% CI 0.97-2.41). Among patients surviving ≥1 years, experiencing a non-renal irAE was associated with a significantly higher risk of sustained eGFR loss (aHR 1.71, 95% CI 1.14-2.57)., Conclusion: AKI and sustained eGFR loss are common in patients with genitourinary cancers receiving ICIs. irAEs may be a novel risk factor for kidney function decline among patients receiving ICIs., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HS, SS, IA, ML, SZ, NR, DC, DEL, KR, CS, MDK, MES have nothing to declare. OR: Research support from Merck. Speaker for activities supported by educational grants from BMS and Merck. Consultant for Merck, Celgene, Five Prime, GSK, Bayer, Roche/Genentech, Puretech, Imvax, Sobi. In addition, Dr. Rahma has a patent “Methods of using pembrolizumab and trebananib” pending. BM: discloses payment for consulting with Bayer, Astellas, Astra Zeneca, Seattle Genetics, Exelixis, Nektar, Pfizer, Janssen, Genentech, Eisai, BMS, Calithera, Dendreon and EMD Serono. He received research support to Dana Farber Cancer Institute (DFCI) from Bristol Myers Squibb, Calithera, Exelixis, Seattle Genetics. GS: Advisory Board: BMS, Genentech, EMD Serono, Merck, Sanofi, Seattle Genetics/Astellas, Astrazeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Immunomedics; Research Support to Institution: Sanofi, Astrazeneca, Immunomedics; Travel costs: BMS, Astrazeneca; Speaking fees: Physicians Education Resource (PER), Onclive, Research to Practice, Medscape; Writing fees: Uptodate, Editor of Elsevier Practice Update Bladder Cancer Center of Excellence; Steering committee of trials/studies: BMS, Bavarian Nordic, Seattle Genetics, QED (all unpaid), and Astrazeneca, EMD Serono, Debiopharm (paid). SM: Salaried position as a Deputy Editor at UpToDate (Wolters Kluwer). SG: scientific coordinator for the ASCEND trial. XG: Honorarium from Exelixis. XW: Research support to Institution: BMS. MDM - MD Advisory Board for Pfizer, Exelixis, Eisai and Merck. TKC - AstraZeneca, Aveo, Bayer, Bristol Myers-Squibb, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi/Aventis, Takeda (institutional and personal) related to research, consultancy and advisory boards. TKC is supported in part by the Dana Farber/Harvard Cancer Center Kidney SPORE Program, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at DFCI., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Acute kidney injury (AKI) is a common complication in patients with severe COVID-19. We sought to compare the AKI incidence and outcomes among patients hospitalized with COVID-19 and with influenza., Methods: This was a retrospective cohort study of patients with COVID-19 hospitalized between March and May 2020 and historical controls hospitalized with influenza A or B between January 2017 and December 2019 within a large health care system. Cox proportional hazards models were used to compare the risk of AKI during hospitalization. Secondary outcomes included AKI recovery, mortality, new-onset chronic kidney disease (CKD), and ≥25% estimated glomerular filtration rate (eGFR) decline., Results: A total of 2425 patients were included; 1091 (45%) had COVID-19, and 1334 (55%) had influenza. The overall AKI rate was 23% and 13% in patients with COVID-19 and influenza, respectively. Compared with influenza, hospitalized patients with COVID-19 had an increased risk of developing AKI (adjusted hazard ratio [aHR] = 1.58; 95% confidence interval [CI], 1.29-1.94). Patients with AKI were more likely to die in the hospital when infected with COVID-19 versus influenza (aHR = 3.55; 95% CI, 2.11-5.97). Among patients surviving to hospital discharge, the rate of AKI recovery was lower in patients with COVID-19 (aHR = 0.47; 95% CI, 0.36-0.62); however, among patients followed for ≥90 days, new-onset CKD (aHR = 1.24; 95% CI, 0.86-1.78) and ≥25% eGFR decline at the last follow-up (aHR = 1.36, 95% CI, 0.97-1.90) were not significantly different between the cohorts., Conclusion: AKI and mortality rates are significantly higher in patients with COVID-19 than influenza; however, kidney recovery among long-term survivors appears to be similar., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Hepatitis C virus (HCV) infection is common and can accelerate chronic kidney disease (CKD) progression. Direct-acting antiviral (DAA) therapies against hepatitis C have consistently shown rates of sustained viral remission. However, the effect on kidney function is unknown. In a retrospective observational cohort study of HCV-infected patients receiving DAA therapies from 2013 to 2017, the slopes of estimated glomerular filtration rate (eGFR) decline were compared in the three years before DAA therapy to the slope after therapy. Pre- and post-treatment albuminuria values were also compared. In all, 1,178 patients were included; mean age of 56, 64% male, 71% white, 21% were diabetic, and 42% with cirrhosis. In patients with eGFR less than 60ml/min per 1.73m 2 , the annual decline in eGFR in the three years prior to treatment was -5.98 ml/min per year (95% confidence interval -7.30 to -4.67) and improved to -1.32 ml/min per year (95% confidence interval -4.50 to 1.88) after DAA therapy. In patients with eGFR greater than 60ml/min per 1.73m 2 the annual decline in eGFR in the three years prior to treatment was -1.43 ml/min per year (95% confidence interval -1.78 to -1.08) and after DAA therapy was -2.32 ml/min per year (95% confidence interval -3.36 to -1.03). Albuminuria improved significantly in patients without diabetes, but not in those with diabetes. Predictors of eGFR improvement included having CKD at baseline and being non-diabetic. Events of acute kidney injury were rare, occurring in 29 patients, and unrelated to antiviral therapy in 76% of cases. Thus, DAA therapy for HCVs infection may slow CKD progression., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Tanzania has a maternal mortality ratio of 556 per 100,000 live births, representing 21% of all deaths of women of reproductive age. Hemorrhage, mostly postpartum hemorrhage (PPH), is estimated to cause at least 25% of maternal deaths in Tanzania. In 2008, the Ministry of Health, Community Development, Gender, Elderly and Children launched interventions to improve efforts to prevent PPH. Competency-based training for skilled birth attendants and ongoing quality improvement prioritized the practice of active management of the third stage of labor (AMTSL)., Methods: A cross-sectional study was conducted in 52 health facilities in Tanzania utilizing direct observations of women during labor and delivery. Observations were conducted in 2010 and, after competency-based training and quality improvement interventions in the facilities, in 2012. A total of 489 deliveries were observed in 2010 and 558 in 2012. Steps for AMTSL were assessed using a standardized structured observation checklist that was based on World Health Organization guidelines., Results: The proportion of deliveries receiving all three AMTSL steps improved significantly by 19 percentage points (p < 0.001) following the intervention, with the most dramatic increase occurring in health centers and dispensaries (47.2 percentage point change) compared to hospitals (5.2 percentage point change). Use of oxytocin for PPH prevention rose by 37.1 percentage points in health centers and dispensaries but remained largely the same in hospitals, where the baseline was higher. There was substantial improvement in the timely provision of uterotonics (within 3 min of birth) across all facilities (p = 0.003). Availability of oxytocin, which was lower in health centers and dispensaries than hospitals at baseline, rose from 73 to 94% of all facilities., Conclusion: The quality of PPH prevention increased substantially in facilities that implemented competency-based training and quality improvement interventions, with the most dramatic improvement seen at lower-level facilities. As Tanzania continues with efforts to increase facility births, it is imperative that the quality of care also be improved by promoting use of up-to-date guidelines and ensuring regular training and mentoring for health care providers so that they adhere to the guidelines for care of women during labor. These measures can reduce maternal and newborn mortality.

The Ebola outbreak in West Africa precipitated a renewed momentum to ensure global health security through the expedited and full implementation of the International Health Regulations (IHR) (2005) in all WHO member states. The updated IHR (2005) Monitoring and Evaluation Framework was shared with Member States in 2015 with one mandatory component, that is, States Parties annual reporting to the World Health Assembly (WHA) on compliance and three voluntary components: Joint External Evaluation (JEE), After Action Reviews and Simulation Exercises. In February 2016, Tanzania, was the first country globally to volunteer to do a JEE and the first to use the recommendations for priority actions from the JEE to develop a National Action Plan for Health Security (NAPHS) by February 2017. The JEE demonstrated that within the majority of the 47 indicators within the 19 technical areas, Tanzania had either 'limited capacity' or 'developed capacity'. None had 'sustainable capacity'. With JEE recommendations for priority actions, recommendations from other relevant assessments and complementary objectives, Tanzania developed the NAPHS through a nationwide consultative and participatory process. The 5-year cost estimate came out to approximately US$86.6 million (22 million for prevent, 50 million for detect, 4.8 million for respond and 9.2 million for other IHR hazards and points of entry). However, with the inclusion of vaccines for zoonotic diseases in animals increases the cost sevenfold. The importance of strong country ownership and committed leadership were identified as instrumental for the development of operationally focused NAPHS that are aligned with broader national plans across multiple sectors. Key lessons learnt by Tanzania can help guide and encourage other countries to translate their JEE priority actions into a realistic costed NAPHS for funding and implementation for IHR (2005)., Competing Interests: Competing interests: None declared.

The 'continuum of care' is proposed as a key framework for the delivery of maternal, neonatal and child health services. This study examined the extent of dropout as well as factors associated with retention across the MNCH continuum from antenatal care (ANC), through skilled birth attendance (SBA), to postnatal care (PNC).We analyzed data from 1931 women who delivered in the preceding 2-14 months, from a two-stage cluster sampling household survey in four districts of Tanzania's Morogoro region. The survey was conducted in 2011 as a part of a baseline for an independent evaluation of a maternal health program. Using the Anderson model of health care seeking, we fitted logistic models for three transition stages in the continuum.Only 10% of women received the 'recommended' care package (4+ ANC visits, SBA, and 1+ PNC visit), while 1% reported not having care at any stage. Receipt of four ANC visits was positively associated with women being older in age (age 20-34 years-OR: 1.77, 95%CI: 1.22-2.56; age 35-49 years-2.03, 1.29-3.2), and knowledge of danger signs (1.75, 1.39 -2.1). A pro-rich bias was observed in facility-based deliveries (proxy for SBA), with women from the fourth (1.66, 1.12-2.47) and highest quintiles of household wealth (3.4, 2.04-5.66) and the top tertile of communities by wealth (2.9, 1.14-7.4). Higher rates of facility deliveries were also reported with antenatal complications (1.37, 1.05-1.79), and 4+ ANC visits (1.55, 1.14-2.09). Returning for PNC was highest among the wealthiest communities (2.25, 1.21-4.44); catchment areas of a new PNC program (1.89, 1.03-3.45); knowledge of danger signs (1.78, 1.13-2.83); community health worker counselling (4.22, 1.97-9.05); complicated delivery (3.25, 1.84-5.73); and previous health provider counselling on family planning (2.39, 1.71-3.35).Dropout from maternal care continuum is high, especially for the poorest, in rural Tanzania. Interactions with formal health system and perceived need for future services appear to be important factors for retention., (© The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Global health practitioners are increasingly advocating for the integration of community-based health-care platforms as a strategy for increasing the coverage of programs, encouraging program efficiency, and promoting universal health-care goals. To leverage the strengths of compatible programs and avoid geographic and temporal duplications in efforts, the Tanzanian Ministry of Health and Social Welfare coordinated immunization and neglected tropical disease programs for the first time in 2014. Specifically, a measles and rubella supplementary vaccine campaign, mass drug administration (MDA) of ivermectin and albendazole, and Vitamin A were provisionally integrated into a shared community-based delivery platform. Over 21 million people were targeted by the integrated campaign, with the immunization program and MDA program reaching 97% and 93% of targeted individuals, respectively. The purpose of this short report is to share the Tanzanian experience of launching and managing this integrated campaign with key stakeholders., (© The American Society of Tropical Medicine and Hygiene.)

Background: Tanzania is on track to meet Millennium Development Goal (MDG) 4 for child survival, but is making insufficient progress for newborn survival and maternal health (MDG 5) and family planning. To understand this mixed progress and to identify priorities for the post-2015 era, Tanzania was selected as a Countdown to 2015 case study., Methods: We analysed progress made in Tanzania between 1990 and 2014 in maternal, newborn, and child mortality, and unmet need for family planning, in which we used a health systems evaluation framework to assess coverage and equity of interventions along the continuum of care, health systems, policies and investments, while also considering contextual change (eg, economic and educational). We had five objectives, which assessed each level of the health systems evaluation framework. We used the Lives Saved Tool (LiST) and did multiple linear regression analyses to explain the reduction in child mortality in Tanzania. We analysed the reasons for the slower changes in maternal and newborn survival and family planning, to inform priorities to end preventable maternal, newborn, and child deaths by 2030., Findings: In the past two decades, Tanzania's population has doubled in size, necessitating a doubling of health and social services to maintain coverage. Total health-care financing also doubled, with donor funding for child health and HIV/AIDS more than tripling. Trends along the continuum of care varied, with preventive child health services reaching high coverage (≥85%) and equity (socioeconomic status difference 13-14%), but lower coverage and wider inequities for child curative services (71% coverage, socioeconomic status difference 36%), facility delivery (52% coverage, socioeconomic status difference 56%), and family planning (46% coverage, socioeconomic status difference 22%). The LiST analysis suggested that around 39% of child mortality reduction was linked to increases in coverage of interventions, especially of immunisation and insecticide-treated bednets. Economic growth was also associated with reductions in child mortality. Child health programmes focused on selected high-impact interventions at lower levels of the health system (eg, the community and dispensary levels). Despite its high priority, implementation of maternal health care has been intermittent. Newborn survival has gained attention only since 2005, but high-impact interventions are already being implemented. Family planning had consistent policies but only recent reinvestment in implementation., Interpretation: Mixed progress in reproductive, maternal, newborn, and child health in Tanzania indicates a complex interplay of political prioritisation, health financing, and consistent implementation. Post-2015 priorities for Tanzania should focus on the unmet need for family planning, especially in the Western and Lake regions; addressing gaps for coverage and quality of care at birth, especially in rural areas; and continuation of progress for child health., Funding: Government of Canada, Foreign Affairs, Trade, and Development; US Fund for UNICEF; and the Bill & Melinda Gates Foundation., (Copyright © 2015 Afnan-Holmes et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine whether specific medical conditions and/or fetal compromise during labor are associated with fresh stillbirth (FSB), and whether absent fetal heart rate (FHR) before delivery can increase risk of FSB., Methods: An observational cohort study was conducted at three university referral hospitals in Tanzania between January and September 2013. Maternal, labor, and neonatal characteristics were recorded for all deliveries. FSB was defined as an Apgar score of 0 at 1 and 5minutes, with intact skin and suspected death during labor or delivery., Results: Among 15 305 deliveries, there were 499 stillbirths (243 FSBs and 256 macerated stillbirths). Stillbirth was significantly more likely than a live birth after maternal transfer (odds ratio [OR] 3.27; 95% confidence interval [CI] 2.73-3.92; P<0.001) and when FHR was absent (OR 996.29; 95% CI 632.19-1570.09; P<0.001). Risk of stillbirth increased with uterine rupture (OR 138.62; 95% CI 60.73-316.44), placental abruption (OR 40.96; 95% CI 28.97-57.91), cord prolapse (OR 13.49; 95% CI 6.97-26.11), and prematurity (OR 6.87; 95% CI 4.71-10.03; P<0.001 for all)., Conclusion: In low-resource settings, FSB may be prevented by using a combined strategy of clinical risk identification, early detection of abnormal FHR, and expedited delivery., (Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: In 2009, a project was implemented in 8 primary health clinics throughout Tanzania to explore the feasibility of integrating pediatric HIV prevention services with routine infant immunization visits., Methods: We conducted interviews with 64 conveniently sampled mothers of infants who had received integrated HIV and immunization services and 16 providers who delivered the integrated services to qualitatively identify benefits and challenges of the intervention midway through project implementation., Findings: Mothers' perceived benefits of the integrated services included time savings, opportunity to learn their child's HIV status and receive HIV treatment, if necessary. Providers' perceived benefits included reaching mothers who usually would not come for only HIV testing. Mothers and providers reported similar challenges, including mothers' fear of HIV testing, poor spousal support, perceived mandatory HIV testing, poor patient flow affecting confidentiality of service delivery, heavier provider workloads, and community stigma against HIV-infected persons; the latter a more frequent theme in rural compared with urban locations., Interpretation: Future scale-up should ensure privacy of these integrated services received at clinics and community outreach to address stigma and perceived mandatory testing. Increasing human resources for health to address higher workloads and longer waiting times for proper patient flow is necessary in the long term.

Background: Early neonatal mortality has remained high and unchanged for many years in Tanzania, a resource-limited country. Helping Babies Breathe (HBB), a novel educational program using basic interventions to enhance delivery room stabilization/resuscitation, has been developed to reduce the number of these deaths., Methods: Master trainers from the 3 major referral hospitals, 4 associated regional hospitals, and 1 district hospital were trained in the HBB program to serve as trainers for national dissemination. A before (n = 8124) and after (n = 78 500) design was used for implementation. The primary outcomes were a reduction in early neonatal deaths within 24 hours and rates of fresh stillbirths (FSB)., Results: Implementation was associated with a significant reduction in neonatal deaths (relative risk [RR] with training 0.53; 95% confidence interval [CI] 0.43-0.65; P ≤ .0001) and rates of FSB (RR with training 0.76; 95% CI 0.64-0.90; P = .001). The use of stimulation increased from 47% to 88% (RR 1.87; 95% CI 1.82-1.90; P ≤ .0001) and suctioning from 15% to 22% (RR 1.40; 95% CI 1.33-1.46; P ≤ .0001) whereas face mask ventilation decreased from 8.2% to 5.2% (RR 0.65; 95% CI 0.60-0.72; P ≤ .0001)., Conclusions: HBB implementation was associated with a significant reduction in both early neonatal deaths within 24 hours and rates of FSB. HBB uses a basic intervention approach readily applicable at all deliveries. These findings should serve as a call to action for other resource-limited countries striving to meet Millennium Development Goal 4.

Minimizing the time between efficacy studies and public health action is important to maximize health gains. We report the rationale, development and implementation of a district-based strategy for the implementation of intermittent preventive treatment in infants (IPTi) for malaria and anaemia control in Tanzania. From the outset, a research team worked with staff from all levels of the health system to develop a public-health strategy that could continue to function once the research team withdrew. The IPTi strategy was then implemented by routine health services to ensure that IPTi behaviour-change communication materials were available in health facilities, that health workers were trained to administer and to document doses of IPTi, that the necessary drugs were available in facilities and that systems were in place for stock management and supervision. The strategy was integrated into existing systems as far as possible and well accepted by health staff. Time-and-motion studies documented that IPTi implementation took a median of 12.4 min (range 1.6-28.9) per nurse per vaccination clinic. The collaborative approach between researchers and health staff effectively translated research findings into a strategy fit for public health implementation.