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Background: Multi-arm multi-stage trials are an efficient, adaptive approach for testing many treatments simultaneously within one protocol. In settings where numbers of patients available to be entered into trials and resources might be limited, such as primary postpartum haemorrhage, it may be necessary to select a pre-specified subset of arms at interim stages even if they are all showing some promise against the control arm. This will put a limit on the maximum number of patients required and reduce the associated costs. Motivated by the World Health Organization Refractory HaEmorrhage Devices trial in postpartum haemorrhage, we explored the properties of such a selection design in a randomised phase III setting and compared it with other alternatives. The objectives are: (1) to investigate how the timing of treatment selection affects the operating characteristics; (2) to explore the use of an information-rich (continuous) intermediate outcome to select the best-performing arm, out of four treatment arms, compared with using the primary (binary) outcome for selection at the interim stage; and (3) to identify factors that can affect the efficiency of the design. Methods: We conducted simulations based on the refractory haemorrhage devices multi-arm multi-stage selection trial to investigate the impact of the timing of treatment selection and applying an adaptive allocation ratio on the probability of correct selection, overall power and familywise type I error rate. Simulations were also conducted to explore how other design parameters will affect both the maximum sample size and trial timelines. Results: The results indicate that the overall power of the trial is bounded by the probability of ‘correct’ selection at the selection stage. The results showed that good operating characteristics are achieved if the treatment selection is conducted at around 17% of information time. Our results also showed that although randomising more patients to research arms before selection will increase the probability of selecting correctly, this will not increase the overall efficiency of the (selection) design compared with the fixed allocation ratio of 1:1 to all arms throughout. Conclusions: Multi-arm multi-stage selection designs are efficient and flexible with desirable operating characteristics. We give guidance on many aspects of these designs including selecting the intermediate outcome measure, the timing of treatment selection, and choosing the operating characteristics.

Objective: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. Data sources: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. Study eligibility criteria: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. Methods: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. Results: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). Conclusion: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

Background Violence against women is a serious public health concern, and is highly prevalent globally, including in India. Health-care providers [HCPs] can play an important role in addressing and reducing negative consequences of violence against women. We implemented a pre-post intervention study of HCP training in three tertiary care facilities in Maharashtra, India. Methods The study used a pre-post intervention design with assessment of HCPs’ (n = 201) knowledge, attitudes, perceived preparedness and practice at three time points: before training, after training and at 6 months follow- up. Results Total median score of knowledge about common signs and symptoms of violence (8.89 vs, 10.00), attitudes towards acceptability of violence (9.05 vs. 10.00), individual (6.74 vs. 10.00) and system level preparedness (6.11 vs. 8.14) improved from pre to post- training. The generalized estimating equation [GEE] model, adjusted for age, sex, site and department, showed an improvement in knowledge, attitudes and preparedness post- training. The change from pre to 6 months follow- up was not significant for attitude. Conclusions This package of interventions, including training of HCPs, improved HCPs’ knowledge, attitudes and practices, yet changes in attitudes and preparedness did not sustain over time. This study indicates feasibility and positive influence of a multi-component intervention to improve HCP readiness to respond to violence against women in a low-resource setting. Future phases of intervention development include adapting this intervention package for primary and secondary health facilities in this context, and future research should assess these interventions using a rigorous experimental design. Finally, these results can be used to advocate for multi-layered, systems-based approaches to strengthening health response to violence against women.

The authors have requested that this preprint be removed from Research Square.

IntroductionCOVID-19 has led to an unprecedented increase in demand on health systems to care for people infected, necessitating the allocation of significant resources, especially medical resources, towards the response. This, compounded by the restrictions on movement instituted may have led to disruptions in the provision of essential services, including sexual and reproductive health (SRH) services. This study aims to assess the availability of contraception, comprehensive abortion care, sexually transmitted infection prevention and treatment and sexual and gender-based violence care and support services in local health facilities during COVID-19 pandemic. This is a standardised generic protocol designed for use across different global settings.Methods and analysisThis study adopts both quantitative and qualitative methods to assess health facilities’ SRH service availability and readiness, and clients’ and providers’ perceptions of the availability and readiness of these services in COVID-19-affected areas. The study has two levels: (1) perceptions of clients (and the partners) and healthcare providers, using qualitative methods, and (2) assessment of infrastructure availability and readiness to provide SRH services through reviews, facility service statistics for clients and a qualitative survey for healthcare provider perspectives. The health system assessment will use a cross-sectional panel survey design with two data collection points to capture changes in SRH services availability as a result of the COVID-19 epidemic. Data will be collected using focus group discussions, in-depth interviews and a health facility assessment survey.Ethics and disseminationEthical approval for this study was obtained from the WHO Scientific and Ethics Review Committee (protocol ID CERC.0103). Each study site is required to obtain the necessary ethical and regulatory approvals that are required in each specific country.

An interrupted time series with a parallel control group (ITS-CG) design is a powerful quasi-experimental design commonly used to evaluate the effectiveness of an intervention, on accelerating uptake of useful public health products, and can be used in the presence of regularly collected data. This paper illustrates how a segmented Poisson model that utilizes general estimating equations (GEE) can be used for the ITS-CG study design to evaluate the effectiveness of a complex social accountability intervention on the level and rate of uptake of modern contraception. The intervention was gradually rolled-out over time to targeted intervention communities in Ghana and Tanzania, with control communities receiving standard of care, as per national guidelines. Two ITS GEE segmented regression models are proposed for evaluating of the uptake. The first, a two-segmented model, fits the data collected during pre-intervention and post-intervention excluding that collected during intervention roll-out. The second, a three-segmented model, fits all data including that collected during the roll-out. A much simpler difference-in-difference (DID) GEE Poisson regression model is also illustrated. Mathematical formulation of both ITS-segmented Poisson models and that of the DID Poisson model, interpretation and significance of resulting regression parameters, and accounting for different sources of variation and lags in intervention effect are respectively discussed. Strengths and limitations of these models are highlighted. Segmented ITS modelling remains valuable for studying the effect of intervention interruptions whether gradual changes, over time, in the level or trend in uptake of public health practices are attributed by the introduced intervention.Trial Registration: The Australian New Zealand Clinical Trials registry.Trial registration number: ACTRN12619000378123.Trial Registration date: 11-March-2019.

Background Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. Methods This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be randomized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by six months will be considered as having an adequate or curative treatment response. Discussion Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. Trial registration Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

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WHO has established a Global Clinical Platform for the clinical characterisation of COVID-19 among hospitalised individuals. We assessed whether people living with HIV hospitalised with COVID-19 had increased odds of severe presentation and of in-hospital mortality compared with individuals who were HIV-negative and associated risk factors.Between Jan 1, 2020, and July 1, 2021, anonymised individual-level data from 338 566 patients in 38 countries were reported to WHO. Using the Platform pooled dataset, we performed descriptive statistics and regression analyses to compare outcomes in the two populations and identify risk factors.Of 197 479 patients reporting HIV status, 16 955 (8·6%) were people living with HIV. 16 283 (96.0%) of the 16 955 people living with HIV were from Africa; 10 603 (62·9%) were female and 6271 (37·1%) were male; the mean age was 45·5 years (SD 13·7); 6339 (38·3%) were admitted to hospital with severe illness; and 3913 (24·3%) died in hospital. Of the 10 166 people living with HIV with known antiretroviral therapy (ART) status, 9302 (91·5%) were on ART. Compared with individuals without HIV, people living with HIV had 15% increased odds of severe presentation with COVID-19 (aOR 1·15, 95% CI 1·10-1·20) and were 38% more likely to die in hospital (aHR 1·38, 1·34-1·41). Among people living with HIV, male sex, age 45-75 years, and having chronic cardiac disease or hypertension increased the odds of severe COVID-19; male sex, age older than 18 years, having diabetes, hypertension, malignancy, tuberculosis, or chronic kidney disease increased the risk of in-hospital mortality. The use of ART or viral load suppression were associated with a reduced risk of poor outcomes; however, HIV infection remained a risk factor for severity and mortality regardless of ART and viral load suppression status.In this sample of hospitalised people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was an independent risk factor for both severe COVID-19 at admission and in-hospital mortality. These findings have informed WHO immunisation policy that prioritises vaccination for people living with HIV. As the results mostly reflect the data contribution from Africa, this analysis will be updated as more data from other regions become available.None.For the French translation of the abstract see Supplementary Materials section.

Summary Background Women across the world are mistreated during childbirth. We aimed to develop and implement evidence-informed, validated tools to measure mistreatment during childbirth, and report results from a cross-sectional study in four low-income and middle-income countries. Methods We prospectively recruited women aged at least 15 years in twelve health facilities (three per country) in Ghana, Guinea, Myanmar, and Nigeria between Sept 19, 2016, and Jan 18, 2018. Continuous observations of labour and childbirth were done from admission up to 2 h post partum. Surveys were administered by interviewers in the community to women up to 8 weeks post partum. Labour observations were not done in Myanmar. Data were collected on sociodemographics, obstetric history, and experiences of mistreatment. Findings 2016 labour observations and 2672 surveys were done. 838 (41·6%) of 2016 observed women and 945 (35·4%) of 2672 surveyed women experienced physical or verbal abuse, or stigma or discrimination. Physical and verbal abuse peaked 30 min before birth until 15 min after birth (observation). Many women did not consent for episiotomy (observation: 190 [75·1%] of 253; survey: 295 [56·1%] of 526) or caesarean section (observation: 35 [13·4%] of 261; survey: 52 [10·8%] of 483), despite receiving these procedures. 133 (5·0%) of 2672 women or their babies were detained in the facility because they were unable to pay the bill (survey). Younger age (15–19 years) and lack of education were the primary determinants of mistreatment (survey). For example, younger women with no education (odds ratio [OR] 3·6, 95% CI 1·6–8·0) and younger women with some education (OR 1·6, 1·1–2·3) were more likely to experience verbal abuse, compared with older women (≥30 years), adjusting for marital status and parity. Interpretation More than a third of women experienced mistreatment and were particularly vulnerable around the time of birth. Women who were younger and less educated were most at risk, suggesting inequalities in how women are treated during childbirth. Understanding drivers and structural dimensions of mistreatment, including gender and social inequalities, is essential to ensure that interventions adequately account for the broader context. Funding United States Agency for International Development and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO.

Inclusion of pregnant women in COVID-19 clinical trials would allow evaluation of effective therapies that might improve maternal health, pregnancy, and birth outcomes, and avoid the delay of developing treatment recommendations for pregnant women. We explored the inclusion of pregnant women in treatment trials of COVID-19 by reviewing ten international clinical trial registries at two timepoints in 2020. We identified 155 COVID-19 treatment studies of non-biological drugs for the April 7-10, 2020 timepoint, of which 124 (80%) specifically excluded pregnant women. The same registry search for the July 10-15, 2020 timepoint, yielded 722 treatment studies, of which 538 (75%) specifically excluded pregnant women. We then focused on studies that included at least one of six drugs (remdesivir, lopinavir-ritonavir, interferon beta, corticosteroids, chloroquine and hydroxychloroquine, and ivermectin) under evaluation for COVID-19. Of 176 such studies, 130 (74%) listed pregnancy as an exclusion criterion. Of 35 studies that evaluated high-dose vitamin treatment for COVID-19, 27 (77%) excluded pregnant women. Despite the surge in treatment studies for COVID-19, the proportion excluding pregnant women remains consistent. Exclusion was not well justified as many of the treatments being evaluated have no or low safety concerns during pregnancy. Inclusion of pregnant women in clinical treatment trials is urgently needed to identify effective COVID-19 treatment for this population.

Summary: Background: Amid efforts to improve the quality of care for women and neonates during childbirth, there is growing interest in the experience of care, including respectful care practices. However, there is little research on the prevalence of practices that might constitute mistreatment of neonates. This study aims to describe the care received by neonates up to 2 h after birth in a sample of three countries in west Africa. Methods: Data from this multicountry, facility-based, observational study were collected on 15 neonatal care practices across nine facilities in Ghana, Guinea, and Nigeria, as part of WHO's wider multicountry study on how women are treated during childbirth. Women were eligible if they were admitted to the participating health facilities for childbirth, in early established labour or active labour, aged 15 years or older, and provided written informed consent on behalf of themselves and their neonate. All labour observations were continuous, one-to-one observations of women and neonates by independent data collectors. Descriptive statistics and multivariate logistic regressions were used to examine associations between these neonatal care practices, maternal and neonate characteristics, and maternal mistreatment. Early neonate deaths, stillbirths, and higher order multiple births were excluded from analysis. Findings: Data collection took place from Sept 19, 2016, to Feb 26, 2017, in Nigeria; from Aug 1, 2017, to Jan 18, 2018, in Ghana; and from July 1 to Oct 30, 2017, in Guinea. We included data for 362 women–neonate dyads (356 [98%] with available data for neonatal care practices) in Nigeria, 760 (749 [99%]) in Ghana, and 558 (522 [94%]) in Guinea. Delayed cord clamping was done for most neonates (1493 [91·8%] of 1627); other practices, such as skin-to-skin contact, were less commonly done (1048 [64·4%]). During the first 2 h after birth, separation of the mother and neonate occurred in 844 (51·9%) of 1627 cases; and was more common for mothers who were single (adjusted odds ratio [AOR; adjusting for country, maternal age, education, marital status, neonate weight at birth, and neonate sex] 1·8, 95% CI 1·3–2·6) than those who were married or cohabiting. Lack of maternal education was associated with increased likelihood of neonates not receiving recommended breastfeeding practices. Neonates with a low birthweight (

IntroductionComplications due to unsafe abortions are an important cause of morbidity and mortality in many sub-Saharan African countries. We aimed to characterise abortion-related complication severity, describe their management, and to report women’s experience of abortion care in Africa.MethodsA cross-sectional study was implemented in 210 health facilities across 11 sub-Saharan African countries. Data were collected on women’s characteristics, clinical information and women’s experience of abortion care (using the audio computer-assisted self-interviewing (ACASI) system). Severity of abortion complications were organised in five hierarchical mutually exclusive categories based on indicators present at assessment. Descriptive bivariate analysis was performed for women’s characteristics, management of complications and reported experiences of abortion care by severity. Generalised linear estimation models were used to assess the association between women’s characteristics and severity of complications.ResultsThere were 13 657 women who had an abortion-related complication: 323 (2.4%) women were classified with severe maternal outcomes, 957 (7.0%) had potentially life-threatening complications, 7953 (58.2%) had moderate complications and 4424 (32.4%) women had mild complications. Women who were single, multiparous, presenting ≥13 weeks of gestational age and where expulsion of products of conception occurred prior to arrival to facility were more likely to experience severe complications. For management, the commonly used mechanical methods of uterine evacuation were manual vacuum aspiration (76.9%), followed by dilation and curettage (D&C) (20.1%). Most frequently used uterotonics were oxytocin (50∙9%) and misoprostol (22.7%). Via ACASI, 602 (19.5%) women reported having an induced abortion. Of those, misoprostol was the most commonly reported method (54.3%).ConclusionThere is a critical need to increase access to and quality of evidence-based safe abortion, postabortion care and to improve understanding around women’s experiences of abortion care.

BackgroundEvidence has shown the benefits of labour companions during childbirth. Few studies have documented the relationship between the absence of labour companions and mistreatment of women during childbirth in low-income and middle-income countries using a standardised tool.MethodsWe conducted a secondary analysis of the WHO multi-country study on how women are treated during childbirth, where a cross-sectional community survey was conducted with women up to 8 weeks after childbirth in Ghana, Guinea, Nigeria and Myanmar. Descriptive analysis and multivariable logistic regression were used to examine whether labour companionship was associated with various types of mistreatment.ResultsOf 2672 women, about half (50.4%) reported the presence of a labour companion. Approximately half (49.6%) of these women reported that the timing of support was during labour and after childbirth and most of the labour companions (47.0%) were their family members. Across Ghana, Guinea and Nigeria, women without a labour companion were more likely to report physical abuse, non-consented medical procedures and poor communication compared with women with a labour companion. However, there were country-level variations. In Guinea, the absence of labour companionship was associated with any physical abuse, verbal abuse, or stigma or discrimination (adjusted OR (AOR) 3.6, 1.9–6.9) and non-consented vaginal examinations (AOR 3.2, 1.6–6.4). In Ghana, it was associated with non-consented vaginal examinations (AOR 2.3, 1.7–3.1) and poor communication (AOR 2.0, 1.3–3.2). In Nigeria, it was associated with longer wait times (AOR 0.6, 0.3–0.9).ConclusionLabour companionship is associated with lower levels of some forms of mistreatment that women experience during childbirth, depending on the setting. Further work is needed to ascertain how best to implement context-specific labour companionship to ensure benefits while maintaining women’s choices and autonomy.

The novel coronavirus disease (COVID-19) outbreak was first declared in China in December 2019, and WHO declared the pandemic on 11 March 2020. A fast-rising number of confirmed cases has been observed in all continents, with Europe at the epicentre of the outbreak at this moment.Sexual and reproductive health (SRH) and rights is a significant public health issue during the epidemics. The novel coronavirus (SARS-CoV-2) is new to humans, and only limited scientific evidence is available to identify the impact of the disease COVID-19 on SRH, including clinical presentation and outcomes of the infection during pregnancy, or for persons with STI/HIV-related immunosuppression. Beyond the clinical scope of SRH, we should not neglect the impacts at the health system level and disruptions or interruptions in regular provision of SRH services, such as pre- and postnatal checks, safe abortion, contraception, HIV/AIDS and sexually transmitted infections. Furthermore, other aspects merit attention such as the potential increase of gender-based violence and domestic abuse, and effects of stigma and discrimination associated with COVID-19 and their effects on SRH clients and health care providers. Therefore, there is an urgent need for the scientific community to generate sound clinical, epidemiological, and psycho-social behavioral links between COVID-19 and SRH and rights outcomes.

Background In 2016, WHO launched the Global Health Sector Strategy on STIs, 2016–2021 (GHSS) to provide guidance and benchmarks for country achievement by 2020 and four global targets for achievement by 2030. Methods A country survey jointly developed by experienced technical personnel at WHO Headquarters (HQ) and WHO regional offices was reviewed and distributed by WHO regional advisors to 194 WHO Member States in September-March 2020. The survey sought to assess implementation and prioritization of STI policy, surveillance, service delivery, commodity availability, and surveillance based on targets of the GHSS. Results A majority (58%, 112/194) of countries returned a completed survey reflecting current (2019) STI activities. The regions with the highest survey completion rates were South-East Asia Region (91%, 10/11), Region of the Americas (71%, 25/35) and Western Pacific Region (67%, 18/27). Having a national STI strategy was reported by 64% (72/112) and performing STI surveillance activities by 88% (97/110) of reporting countries. Availability of STI services within primary health clinics was reported by 88% of countries (99/112); within HIV clinics by 92% (103/112), and within reproductive health services by 85% (95/112). Existence of a national strategy to eliminate mother-to-child transmission of HIV and syphilis (EMTCT) was reported by 70% of countries (78/112). Antimicrobial resistance (AMR) monitoring for gonococcal infection (gonorrhoea) was reported by 64% (57/89) of reporting countries with this laboratory capacity. Inclusion of HPV vaccine for young women in the national immunization schedule was reported by 59% (65/110) and availability of cervical cancer screening was reported by 91% (95/104). Stockouts of STI medicines, primarily benzathine penicillin, within the prior four years were reported by 34% (37/110) of countries. Conclusions Mechanisms to support improvements to STI service delivery through national-level policy, commitment, programming and surveillance are needed to operationalize, accelerate and monitor progress towards achievement of the 2030 global STI strategy targets.

Importance Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression. Objective To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event. Design, Setting, and Participants This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019. Interventions Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo. Main Outcomes and Measures Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide. Results The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group. Conclusions and Relevance In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities. Trial Registration ClinicalTrials.gov Identifier:NCT01928446

Background The estimation of an effect size is an important step in designing an adequately powered, feasible clinical trial intended to change clinical practice. During the planning phase of VA Cooperative Study #590, “Double-Blind Placebo-Controlled Study of Lithium for Preventing Repeated Suicidal Self-Directed Violence in Patients with Depression or Bipolar Disorder (Li+),” it was not clear what effect size would be considered large enough to influence prescribing behavior among practicing clinicians. Methods We conducted an online survey of VA psychiatrists to assess their interest in the study question, their clinical experience with lithium, and their opinion about what suicide reduction rate would change their prescribing habits. The 9-item survey was hosted on SurveyMonkey© and VA psychiatrists were individually emailed an invitation to complete an anonymous online survey. Three email waves were sent over three weeks. Results Overall, 862 of 2713 VA psychiatrists (response rate = 31.8%) responded to the anonymous survey. 74% of the respondents would refer a patient to the proposed trial, 9% would not, and 17% were unsure. Presented with suicide reduction rates in 10% increments ranging from 10 to 100%, 61% of respondents indicated that they would use lithium if suicide attempts were reduced by at least 40%; 83% would use lithium if it reduced attempts by at least 50%. Conclusions Even with the limitations of response bias and the reliability of responses on future prescribing behavior, a survey of potential users of a clinical trial's results offers a convenient, empirical method for determining and justifying clinically relevant effect sizes.

Importance Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. Objective To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. Design, Setting, and Participants The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Interventions Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Main Outcomes and Measures Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Results Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed. Conclusions and Relevance A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma. Trial Registration clinicaltrials.gov Identifier:NCT00847912

Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy.Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point.The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury.Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466 .).

Background The call for women-centred approaches to reduce labour interventions, particularly primary caesarean section, has renewed an interest in gaining a better understanding of natural labour progression. Objective To synthesise available data on the cervical dilatation patterns during spontaneous labour of ‘low-risk’ women with normal perinatal outcomes. Search strategy PubMed, EMBASE, CINAHL, POPLINE, Global Health Library, and reference lists of eligible studies. Selection criteria Observational studies and other study designs. Data collection and analysis Two authors extracted data on: maternal characteristics; labour interventions; the duration of labour centimetre by centimetre; and the duration of labour from dilatation at admission through to 10 cm. We pooled data across studies using weighted medians and employed the Bootstrap-t method to generate the corresponding confidence bounds. Main results Seven observational studies describing labour patterns for 99 971 women met our inclusion criteria. The median time to advance by 1 cm in nulliparous women was longer than 1 hour until a dilatation of 5 cm was reached, with markedly rapid progress after 6 cm. Similar labour progression patterns were observed in parous women. The 95th percentiles for both parity groups suggest that it was not uncommon for some women to reach 10 cm, despite dilatation rates that were much slower than the 1-cm/hour threshold for most part of their first stage of labours. Conclusion An expectation of a minimum cervical dilatation threshold of 1 cm/hour throughout the first stage of labour is unrealistic for most healthy nulliparous and parous women. Our findings call into question the universal application of clinical standards that are conceptually based on an expectation of linear labour progress in all women. Funding UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research, World Health Organization, and the United States Agency for International Development (USAID). Tweetable abstract Cervical dilatation threshold of 1 cm/hour throughout labour is unrealistic for most women, regardless of parity.

To generate estimates of the global prevalence and incidence of urogenital infection with chlamydia, gonorrhoea, trichomoniasis and syphilis in women and men, aged 15-49 years, in 2016.For chlamydia, gonorrhoea and trichomoniasis, we systematically searched for studies conducted between 2009 and 2016 reporting prevalence. We also consulted regional experts. To generate estimates, we used Bayesian meta-analysis. For syphilis, we aggregated the national estimates generated by using Spectrum-STI.For chlamydia, gonorrhoea and/or trichomoniasis, 130 studies were eligible. For syphilis, the Spectrum-STI database contained 978 data points for the same period. The 2016 global prevalence estimates in women were: chlamydia 3.8% (95% uncertainty interval, UI: 3.3-4.5); gonorrhoea 0.9% (95% UI: 0.7-1.1); trichomoniasis 5.3% (95% UI:4.0-7.2); and syphilis 0.5% (95% UI: 0.4-0.6). In men prevalence estimates were: chlamydia 2.7% (95% UI: 1.9-3.7); gonorrhoea 0.7% (95% UI: 0.5-1.1); trichomoniasis 0.6% (95% UI: 0.4-0.9); and syphilis 0.5% (95% UI: 0.4-0.6). Total estimated incident cases were 376.4 million: 127.2 million (95% UI: 95.1-165.9 million) chlamydia cases; 86.9 million (95% UI: 58.6-123.4 million) gonorrhoea cases; 156.0 million (95% UI: 103.4-231.2 million) trichomoniasis cases; and 6.3 million (95% UI: 5.5-7.1 million) syphilis cases.Global estimates of prevalence and incidence of these four curable sexually transmitted infections remain high. The study highlights the need to expand data collection efforts at country level and provides an initial baseline for monitoring progress of theProduire des estimations de la prévalence et de l'incidence mondiales des infections urogénitales dues à la chlamydiose, à la gonorrhée, à la trichomonase et à la syphilis chez les femmes et les hommes de 15 à 49 ans, en 2016.Pour la chlamydiose, la gonorrhée et la trichomonase, nous avons systématiquement recherché les études menées entre 2009 et 2016 qui s’intéressaient à la prévalence. Nous avons également consulté des experts régionaux. Pour produire des estimations, nous avons eu recours à une méta-analyse bayésienne. Pour la syphilis, nous avons regroupé les estimations nationales obtenues à l'aide de Spectrum-STI.Pour la chlamydiose, la gonorrhée et/ou la trichomonase, 130 études étaient éligibles. Pour la syphilis, la base de données de Spectrum-STI contenait 978 points de données pour la période considérée. Les estimations de la prévalence mondiale en 2016 chez les femmes étaient les suivantes: chlamydiose 3,8% (intervalle d'incertitude de 95%, II: 3,3–4,5); gonorrhée 0,9% (II 95%: 0,7–1,1); trichomonase 5,3% (II 95%: 4,0–7,2); et syphilis 0,5% (II 95%: 0,4–0,6). Chez les hommes, les estimations de la prévalence étaient les suivantes: chlamydiose 2,7% (II 95%: 1,9-3,7); gonorrhée 0,7% (II 95%: 0,5-1,1); trichomonase 0,6% (II 95%: 0,4-0,9); et syphilis 0,5% (II 95%: 0,4–0,6). L'incidence totale estimée était de 376,4 millions de cas: 127,2 millions (II 95%: 95,1–165,9 millions) de cas de chlamydiose; 86,9 millions (II 95%: 58,6-123,4 millions) de cas de gonorrhée; 156,0 millions (II 95%: 103,4-231,2 millions) de cas de trichomonase; et 6,3 millions (II 95%: 5,5–7,1 millions) de cas de syphilis.Les estimations mondiales de la prévalence et de l'incidence de ces quatre infections sexuellement transmissibles guérissables restent élevées. Cette étude souligne la nécessité d'amplifier les efforts de collecte de données au niveau des pays et offre un point de référence pour suivre la progression de laGenerar estimaciones de la prevalencia y la incidencia mundiales de la infección urogenital por clamidia, gonorrea, tricomoniasis y sífilis en mujeres y hombres de 15 a 49 años de edad en 2016.Para la clamidia, la gonorrea y la tricomoniasis, se realizaron búsquedas sistemáticas de estudios realizados entre 2009 y 2016 que registrasen la prevalencia. También se consultó a expertos regionales. Para generar estimaciones, se utilizó el metanálisis bayesiano. Para la sífilis, se añadieron las estimaciones nacionales generadas por el uso de Spectrum-STI.Para la clamidia, la gonorrea y/o la tricomoniasis, hubo 130 estudios que cumplían los criterios. Para la sífilis, la base de datos Spectrum-STI contenía 978 puntos de datos para el mismo periodo. Las estimaciones de prevalencia mundial en mujeres en 2016 fueron: clamidia 3,8 % (intervalo de incertidumbre, II, del 95 %: 3,3-4,5); gonorrea 0,9 % (II del 95 %: 0,7-1,1); tricomoniasis 5,3 % (II del 95 %: 4,0-7,2); y sífilis 0,5 % (II del 95 %: 0,4-0,6). Las estimaciones de prevalencia en hombres fueron: clamidia 2,7 % (intervalo de incertidumbre, II, del 95 %: 1,9-3,7); gonorrea 0,7 % (II del 95 %: 0,5-1,1); tricomoniasis 0,6 % (II del 95 %: 0,4-0,9); y sífilis 0,5 % (II del 95 %: 0,4-0,6). El total estimado de casos incidentes fue de 376,4 millones: 127,2 millones (II del 95 %: 95,1-165,9 millones) de casos de clamidia; 86,9 millones (II del 95 %: 58,6-123,4 millones) de casos de gonorrea; 156,0 millones (II del 95 %: 103,4-231,2 millones) de casos de tricomoniasis; y 6,3 millones (II del 95 %: 5,5-7,1 millones) de casos de sífilis.Las estimaciones mundiales de la prevalencia y la incidencia de estas cuatro enfermedades de transmisión sexual curables siguen siendo elevadas. El estudio destaca la necesidad de ampliar los esfuerzos de recopilación de datos a nivel nacional y proporciona una base inicial para el seguimiento de los progresos de laوضع تقديرات للانتشار والإصابة العالمية لعدوى الجهاز البولي التناسلي، وأمراض الكلاميديا، والسيلان، وداء المشعرات، والزهري لدى النساء والرجال، الذين تتراوح أعمارهم بين 15 و49 سنة، في عام 2016.بالنسبة للكلاميديا، والسيلان، وداء المشعرات، فقد قمنا بالبحث بشكل منهجي عن الدراسات التي تمت خلال الفترة من 2009 إلى 2016 والتي توضح مدى الانتشار. كما قمنا باستشارة خبراء إقليميين. ولوضع التقديرات، قمنا باستخدام التحليل التلوي Bayesian. بالنسبة لمرض الزهري، قمنا بتجميع التقديرات الوطنية الناتجة عن استخدام Spectrum-STI.بالنسبة لأمراض الكلاميديا، والسيلان، وداء المشعرات، كانت هناك 130 دراسة مؤهلة. وبالنسبة لمرض الزهري، احتوت قادة بيانات Spectrum-STI على 978 نقطة بيانات لنفس الفترة. كانت تقديرات الانتشار العالمي في عام 2016 في النساء: الكلاميديا 3.8% (فاصل عدم الثقة 95%: 3.3 إلى 4.5)، والسيلان 0.9% (فاصل عدم الثقة 95%: 0.7 إلى 1.1)، وداء المشعرات 5.3% (فاصل عدم الثقة 95%: 4.0 إلى 7.2)؛ والزهري 0.5% (فاصل عدم الثقة 95%: 0.4 إلى 0.6). كانت تقديرات الانتشار في عام 2016 في الرجال: الكلاميديا 2.7% (فاصل عدم الثقة 95%: 1.9 إلى 3.7)، والسيلان 0.7% (فاصل عدم الثقة 95%: 0.5 إلى 1.1)، وداء المشعرات 0.6% (فاصل عدم الثقة 95%: 0.4 إلى 0.9)، والزهري 0.5% (فاصل عدم الثقة 95%: 0.4–0.6). بلغ مجموع حالات الإصابة التقديري 376.4 مليون حالة: 127.2 مليون (فاصل عدم الثقة 95%: 95.1 إلى 165.9 مليون) حالات الكلاميديا؛ 86.9 مليون (فاصل عدم الثقة 95%: 58.6 إلى 123.4 مليون) حالات السيلان؛ 156.0 مليون (فاصل عدم الثقة 95%: 103.4 إلى 231.2 مليون) حالات داء المشعرات؛ 6.3 مليون (فاصل عدم الثقة 95%: 5.5 إلى 7.1 مليون) حالات الزهري.لا تزال التقديرات العالمية عالية لانتشار والإصابة بهذه الأمراض الأربعة المنقولة جنسياً والعلاج منها. تسلط الدراسة الضوء على الحاجة إلى توسيع جهود جمع البيانات على مستوى الدول، وتوفر خط أساس أولي لمراقبة التقدم المحرز في إستراتيجية قطاع الصحة العالمية التابع لمنظمة الصحة العالمية بشأن الأمراض المنقولة جنسياً خلال الفترة من 2016 إلى 2021.旨在估计 2016 年 15-49 岁男女泌尿生殖系统感染衣原体病、淋病、滴虫病和梅毒的全球患病率和发病率。.对于衣原体病、淋病和滴虫病,我们系统搜索了 2009 年至 2016 年间的患病率报告研究。我们还咨询了区域专家。为了生成估计值,我们使用了贝叶斯荟萃分析。对于梅毒,我们汇总分析了使用 Spectrum-STI 生成的全国估计值。.对于衣原体病、淋病和/或滴虫病,符合要求的有 130 项研究。对于梅毒, Spectrum-STI 数据库包含了同一时期的 978 个数据点。2016 年,全球女性患病率估计值为:衣原体病 3.8%(95% 不确定区间,UI:3.3-4.5);淋病 0.9%(95% UI:0.7–1.1);滴虫病 5.3%(95% UI:4.0–7.2)和梅毒 0.5%(95% UI:0.4-0.6)。全球男性患病率估计值为:衣原体病 2.7%(95% UI:1.9-3.7);淋病 0.7%(95% UI:0.5-1.1);滴虫病 0.6%(95% UI:0.4-0.9);梅毒 0.5%(95% UI:0.4-0.6)。预计病例总数为 3.764 亿:1.272 亿(95% UI:9510-16590 万)衣原体病病例;8690 万(95% UI:5860-12340 万)淋病病例;15600 万(95% UI:10340-23120 万)滴虫病病例;630 万(95% UI:550-710 万)梅毒病例。.对这四种可治愈的性传播疾病的患病率和发病率的全球估计值仍然很高。该研究强调了扩大国家级数据收集工作的必要性,并为监测 2016 至 2021 年世卫组织全球卫生部门性传播疾病战略的进展提供了初始基线。.Оценить распространенность в мировом масштабе и частоту урогенитальных инфекций, вызываемых хламидией, а также гонореи, трихомониаза и сифилиса у мужчин и женщин в возрасте от 15 до 49 лет по состоянию на 2016 год.Для хламидиоза, гонореи и трихомониаза авторы провели систематический поиск исследований, выполненных в период с 2009 по 2016 год, в которых приводились данные по распространенности заболеваний. Авторы также консультировались с международными специалистами. Для оценки использовался байесовский метаанализ. Для исследования сифилиса нами были объединены национальные оценки, созданные с использованием методики Spectrum-STI.Было обнаружено 130 исследований на тему хламидийной инфекции, гонореи и (или) трихомониаза. Что касается сифилиса, база данных Spectrum-STI за тот же период содержала 978 источников данных. По состоянию на 2016 год распространенность изучаемых заболеваний в мире среди женщин составляла: хламидиоз 3,8% (95%-й интервал неопределенности, ИН: 3,3–4,5), гонорея 0,9% (95%-й ИН: 0,7–1,1), трихомониаз 5,3% (95%-й ИН: 4,0–7,2) и сифилис 0,5% (95%-й ИН: 0,4–0,6). У мужчин распространенность хламидиоза составила 2,7% (95%-й ИН: 1,9–3,7), гонореи 0,7% (95%-й ИН: 0,5–1,1), трихомониаза 0,6% (95%-й ИН: 0,4–0,9) и сифилиса 0,5% (95%-й ИН: 0,4–0,6). Общее приблизительное количество случаев заболевания составило 376,4 млн человек: 127,2 млн (95 %-й ИН: 95,1–165,9 млн) случаев хламидийной инфекции, 86,9 млн (95%-й ИН: 58,6–123,4 млн) случаев гонореи, 156,0 млн (95%-й ИН: 103,4–231,2 млн) случаев трихомониаза и 6,3 млн (95%-й ИН: 5,5–7,1 млн) случаев сифилиса.Оценки мировой распространенности и частоты этих четырех излечимых инфекций, передаваемых половым путем (ИППП), остаются высокими. Исследование показывает необходимость предпринимать дальнейшие усилия по сбору данных на уровне каждой страны и может служить источником базовых значений для мониторинга прогресса в исполнении глобальных стратегий ВОЗ в секторе здравоохранения относительно ИППП на период 2016–2021 гг.

Objectives: To examine the effect of breast cancer and its treatment on fracture risk in older breast cancer survivors. Design: A 10-year prospective cohort study beginning 5 years after a diagnosis of breast cancer for survivors and match date for comparison women. Setting: Six integrated healthcare systems. Participants: Women aged 65 and older (1,286 survivors, 1,286 comparison women, mean age 77.7 in both groups, white, non-Hispanic: survivors, 81.6%; comparison women, 85.2%) who were alive and recurrence free 5 years after a diagnosis of early-stage breast cancer and matched on age, study site, and enrollment year to a comparison cohort without breast cancer. Measurements: Cox proportional hazards models were used to estimate the association between fracture risk and survivor-comparison status, adjusting for drugs and risk factors associated with bone health. A subanalysis was used to evaluate the association between tamoxifen exposure and fracture risk. Results: No difference was observed in fracture rates between groups (hazard ratio (HR) = 1.1, 95% confidence interval (CI) = 0.9�1.3). The protective effect of tamoxifen was not statistically significant (HR = 0.9, 95% CI = 0.6�1.2). Conclusion: Long-term survivors of early-stage breast cancer diagnosed at age 65 and older are not at greater risk of osteoporotic fractures than age-matched women without breast cancer. There appears to be no long-term protection from fractures with tamoxifen use.

BACKGROUND Of the approximately 2.4 million American women with a history of breast cancer, 43% are aged ≥ 65 years and are at risk for developing subsequent malignancies. METHODS Women from 6 geographically diverse sites included 5-year breast cancer survivors (N = 1361) who were diagnosed between 1990 and 1994 at age ≥ 65 years with stage I or II disease and a comparison group of women without breast cancer (N = 1361). Women in the comparison group were age-matched and site-matched to breast cancer survivors on the date of breast cancer diagnosis. Follow-up began 5 years after the index date (survivor diagnosis date or comparison enrollment date) until death, disenrollment, or through 15 years after the index date. Data were collected from medical records and electronic sources (cancer registry, administrative, clinical, National Death Index). Analyses included descriptive statistics, crude incidence rates, and Cox proportional hazards regression models for estimating the risk of incident malignancy and were adjusted for death as a competing risk. RESULTS Survivors and women in the comparison group were similar: >82% were white, 55% had a Charlson Comorbidity Index of 0, and ≥ 73% had a body mass index ≤ 30 kg/m(2) . Of all 306 women (N = 160 in the survivor group, N = 146 in the comparison group) who developed a first incident malignancy during follow-up, the mean time to malignancy was similar (4.37 ± 2.81 years vs 4.03 ± 2.76 years, respectively; P = .28), whereas unadjusted incidence rates were slightly higher in survivors (1882 vs 1620 per 100,000 person years). The adjusted hazard of developing a first incident malignancy was slightly elevated in survivors in relation to women in the comparison group, but it was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.94-1.47). CONCLUSIONS Older women who survived 5 years after an early stage breast cancer diagnosis were not at an elevated risk for developing subsequent incident malignancies up to 15 years after their breast cancer diagnosis.

To examine five- and ten-year survival based on cancer-specific geriatric assessment (C-SGA) in older women with early stage breast cancer.We evaluated 660 women ≥65-years old diagnosed with stage I-IIIA primary breast cancer and attending physician permission to contact in four geographic regions in the United States of America (USA). Data were collected over ten-years of follow-up from consenting women's medical records, telephone interviews, National Death Index and Social Security Death Index. C-SGA was described by four domains using six measures: socio-demographic (financial resources); clinical (comorbidity, obesity); function (physical function limitations); and psychosocial (general mental health, social support). Survival from all-cause and breast-cancer-specific mortality and receipt of guideline-recommended therapy was assessed for different groups of subjects with C-SGA domain deficits (cut-off ≥3 deficits).The proportion of women with ≥3 C-SGA deficits surviving ten-years was consistently statistically significantly lower (all-cause 26% versus 46% and breast-cancer-specific 76% versus 89%, p≤0.04). The proportion significantly decreased as number of C-SGA deficits increased (linear trend p0.0001). Receipt of guideline-recommended therapy decreased with age but not consistently by number of C-SGA deficits. The all-cause and breast-cancer-specific death rate at five- and ten-years was consistently approximately two times higher in women with ≥3 C-SGA deficits even when fully adjusted for confounding factors (HR(5-yrAllCauseFullyAdjusted)=1.87 [1.36-2.57], HR(10-yrAllCauseFullyAdjusted)=1.74 [1.35-2.15], HR(5-yrBreastCancerFullyAdjusted)=1.95 [1.18-3.20], HR(10-yrBreastCancerFullyAdjusted)=1.99 [1.21-3.28]).Regardless of age and stage of disease, C-SGA predicts five- and ten-year all-cause and breast-cancer-specific survival in older women. Hence, C-SGA may provide an effective strategy to guide treatment decision-making and to identify risk factors for intervention.

OBJECTIVES To compare longitudinal patterns of health care utilization and quality of care for other health conditions between breast cancer-surviving older women and a matched cohort without breast cancer. DESIGN Prospective five-year longitudinal comparison of cases and matched controls. SUBJECTS Newly identified breast cancer patients recruited during 1997–1999 from four geographic regions (Los Angeles, CA; Minnesota; North Carolina; and Rhode Island; N = 422) were matched by age, race, baseline comorbidity and zip code location with up to four non-breast-cancer controls (N = 1,656). OUTCOMES Survival; numbers of hospitalized days and physician visits; total inpatient and outpatient Medicare payments; guideline monitoring for patients with cardiovascular disease and diabetes, and bone density testing and colorectal cancer screening. RESULTS Five-year survival was similar for cases and controls (80% and 82%, respectively; p = 0.18). In the first follow-up year, comorbidity burden and health care utilization were higher for cases (p

Purpose Some women with early-stage breast cancer are at higher risk of recurrence and can benefit from chemotherapy. We describe patterns of referral, receipt, and completion of chemotherapy among older women at high risk of recurrence. Patients and Methods A total of 2,124 women age 65 years or older who were diagnosed with early-stage breast cancer between 1990 and 1994 and 1996 to 1999 were included; 1,090 of these were at high risk of recurrence. We reviewed medical records to categorize chemotherapy outcomes as follows: did not discuss or were not referred to a medical oncologist (n = 133); discussed and/or referred to a medical oncologist but received no chemotherapy (n = 742); received an incomplete chemotherapy course (n = 29), or received a completed chemotherapy course (n = 186). Results Overall, 19.7% of high-risk women received any chemotherapy, and 86.5% of these women completed their chemotherapy courses. Just greater than 10% of high-risk women did not have a discussion about chemotherapy as part of breast cancer treatment documented in the medical record; these women also received fewer diagnostic assessments of their initial tumors. Conclusion Individuals who receive chemotherapy for early-stage breast cancer are a select subgroup of patients at high risk of recurrence. This study identifies characteristics of women who were referred for and who received chemotherapy, and this study plays an important role in understanding generalizability of studies that examine chemotherapy treatment effectiveness. Outcomes after breast cancer could continue to be improved with increased receipt of chemotherapy among older women at high risk of breast cancer recurrence.

The quality of medical record abstracts is often characterized in a reliability substudy. These results usually indicate agreement, but not the extent to which lack of agreement affects associations observed in the complete data. In this study, medical records were reviewed and abstracted for patients diagnosed with stage I or stage II breast cancer between 1990 and 1994 at one of six US Cancer Research Network sites. For a subsample, interrater reliability data were available. The authors calculated conventional hazard ratios and 95% confidence intervals for the association of demographic, tumor, and treatment characteristics with recurrence rate. These conventional estimates of effect were compared with three sets of estimates and 95% simulation intervals that took account of the uncertainty assessed by lack of agreement in the reliability substudy. The rate of recurrence was associated with increasing cancer stage and with treatment modality but not with demographic characteristics. The hazard ratios and simulation intervals that took account of the reliability data showed that the simulation interval grew wider as the sources of uncertainty taken into account grew more complete, but the associations expected a priori remained readily apparent. While many investigators use reliability data only as a metric for data quality, a more thorough approach can also quantitatively depict the uncertainty in the observed associations.