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We multiply ascertained the BRCA1 pathogenic missense variant c.5207T > C; p.Val1736Ala (V1736A) in clinical investigation of breast and ovarian cancer families from Orkney in the Northern Isles of Scotland, UK. We sought to investigate the frequency and clinical relevance of this variant in those of Orcadian ancestry as an exemplar of the value of population cohorts in clinical care, especially in isolated populations. Oral history and birth, marriage and death registrations indicated genealogical linkage of the clinical cases to ancestors from the Isle of Westray, Orkney. Further clinical cases were identified through targeted testing for V1736A in women of Orcadian ancestry attending National Health Service (NHS) genetic clinics for breast and ovarian cancer family risk assessments. The variant segregates with female breast and ovarian cancer in clinically ascertained cases. Separately, exome sequence data from 2088 volunteer participants with three or more Orcadian grandparents, in the ORCADES research cohort, was interrogated to estimate the population prevalence of V1736A in Orcadians. The effects of the variant were assessed using Electronic Health Record (EHR) linkage. Twenty out of 2088 ORCADES research volunteers (~1%) carry V1736A, with a common haplotype around the variant. This allele frequency is ~480-fold higher than in UK Biobank participants. Cost-effectiveness of population screening for BRCA1 founder pathogenic variants has been demonstrated at a carrier frequency below the ~1% observed here. Thus we suggest that Orcadian women should be offered testing for the BRCA1 V1736A founder pathogenic variant, starting with those with known Westray ancestry.

Troy J. Bassett, The Rise and Fall of the Victorian Three-Volume Novel, New Directions in Book History (Cham, Switzerland: Palgrave Macmillan, 2020), xvii, 256 pp., ISBN 978-3-030-31925-0 (hardcover), ISBN 978-3-030-31926-7 (e-book)

The BRCA1 pathogenic missense variant c.5207T>C; p.Val1736Ala (V1736A) was multiply ascertained in the clinical investigation of breast and ovarian cancer families from Orkney in the Northern Isles of Scotland, UK. Oral history and birth, marriage and death registrations indicated genealogical linkage of the clinical cases to ancestors from the Isle of Westray, Orkney. Further clinical cases were identified through targeted testing for V1736A in women of Orcadian ancestry attending National Health Service (NHS) genetic clinics for breast and ovarian cancer family risk assessments. Fourteen mutation carriers were identified from predictive tests in relatives of affected members of the index kindred, nine more from NHS diagnostic testing plus a further six obligate carrier females. The variant segregates with female breast and ovarian cancer in clinically ascertained cases. Separately, exome sequence data from 2,090 volunteer participants with three or more Orcadian grandparents, in the ORCADES research cohort, was interrogated to estimate the population prevalence of V1736A in Orcadians. The effects of the variant were assessed using Electronic Health Record (EHR) linkage. Twenty out of 2,090 ORCADES research volunteers (∼1%) carry V1736A, with a common haplotype around the variant. This allele frequency is ∼480-fold higher than in UK Biobank participants. Cost-effectiveness of population screening for a single BRCA1 founder mutation has been demonstrated at a carrier frequency below the ∼1% observed here. Thus we suggest that Orcadian women should be offered testing for the BRCA1 V1736A founder mutation, starting with those with ancestry from Westray.

The Southern Ocean plays a fundamental role in in the global carbon cycle and is estimated to absorb ~40% of anthropogenic carbon-dioxide (CO2) emissions. Recent studies have highlighted the potentially large decadal variability of this uptake, and the uncertainties associated with estimates derived from different ocean carbon measurement technologies. The majority of these estimates of Southern Ocean CO2 uptake are commonly derived from ‘bottom-up’ analyses of oceanic carbon measurements. An independent means of estimating air-sea CO2 fluxes is provided by ‘top-down’ analyses, which employ inverse methods or data assimilation techniques combining atmospheric CO2 measurements with numerical transport model analyses. Robust regional flux estimates from such top-down methods require an atmospheric observational network with sufficient spatial coverage. At present, however, long-term measurements of atmospheric CO2 are only available at a limited number of sites in the Southern Ocean region. Given this sparse atmospheric sampling there is an urgent need for expansion of the current Southern Ocean atmospheric CO2 measurement network.The British Antarctic Survey has identified a number of locations (including the sub-Antarctic and South Atlantic Islands of Tristan da Cunha, South Georgia and the Falklands) where new systems for long-term observations of CO2 could be established. In this analysis we present results from a set of Observing System Sampling Experiments (OSSEs) using the GEOS-Chem atmospheric transport model, in combination with the Local Ensemble Transform Kalman Filter method (Chen et al. 2021) to identify the effectiveness of these locations towards providing improved constraints on Southern Ocean air-sea fluxes. Our assessment of potential sampling sites is derived from metrics quantifying the uncertainty reduction of regional oceanic CO2 flux estimates.ReferencesChen et al. (2021) Variability of North Atlantic CO2 fluxes for the 2000–2017 period estimated from atmospheric inverse analyses. Biogeosciences, 18 (15). pp. 4549-4570. ISSN 1726-4189.

IntroductionThe purpose of VIKING II is to create an observational cohort of volunteers with ancestry from the Northern Isles of Scotland, primarily for identifying genetic variants influencing disease. The new online protocol is separate to, but follows on from, earlier genetic epidemiological clinic-based studies in the isolated populations of Orkney and Shetland. These populations are favourable for the study of rarer genetic variants due to genetic drift, the large number of relatives, and availability of pedigree information.Methods and AnalysisOnline methods are being used to recruit ∼4,000 people who have Northern Isles ancestry, living anywhere in the world. The option for participants to have actionable genetic results returned is offered. Broad consent will be taken electronically. Data will be collected at baseline through an online questionnaire and longitudinally through linkage to NHS data in the electronic health record. The questionnaire collects a variety of phenotypes including personal and family health. DNA will be extracted from saliva samples then genome-wide genotyped and exome sequenced. VIKING II aims to capitalise on the special features of the Northern Isles populations to create a research cohort that will facilitate the analysis of genetic variants associated with a broad range of traits and disease endpoints.Ethics and DisseminationThe South East Scotland Research Ethics Committee gave the study a favourable opinion. VIKING II is sponsored by the University of Edinburgh and NHS Lothian. Summary research findings will be disseminated to participants and funding bodies, presented at conferences and reported in peer-reviewed publications.Article SummaryStrengths and limitations of this studyDetailed data and biological sample collection of research volunteers with unique ancestry.Consent for access to routinely collected clinical EHR data and for future re-contact, providing a longitudinal component.Optional consent for return of actionable genetic results.4,000 participants is a relatively small number for certain types of genetic analyses, so the cohort is underpowered on its own, in some study designs.Resources to maintain the cohort, and to store data and DNA samples, are significant, with sustainability dependent on infrastructure support and continued funding.

The purpose of this phronetic/pragmatic, mixed-methods study was to integrate quantitative data with qualitative data in examining the complex relations among depression, exercise, screen-viewing time, and life plans among 14 socioeconomically disadvantaged African American young adults. Based on the thematic analysis, the two emerging themes were as follows: life priorities (passing the General Educational Development [GED] test, pursuing profession/career, and being dedicated to church/ministry) and challenges in passing GED examination (e.g., difficulties with the GED test, high stress and low confidence, low interest in studying, health issues, and feelings of rejection/isolation). Based on cross tabulation, depression was highly associated with aerobic exercise and screen-viewing time (Cramer’s V = .44 and .42, respectively). Participants’ life challenges diminished the antidepressant effect of exercise and were linked to depression and excessive screen use. Two active men and a somewhat active woman experienced educational or health-related struggles, heavy screen watching, and severe depression. All three active men experienced educational challenges and severe depression. Two inactive participants reported limited screen use and limited depression, possibly because of their valued life goals (e.g., writing poetry and spiritually helping others). Contrary to the dominant cultural stereotype about African Americans being lazy, the study results show that the participants had highly similar career goals to the majority population yet faced many, significant structural barriers that interfered with their progress and thus sapped their motivation in achieving their life plans. Policy change is needed to reduce social structural barriers and racial systems of oppression in order to decrease poverty and depression.

Involuntary civil commitment (ICC) to treatment for opioid use disorder (OUD) prevents imminent overdose, but also restricts autonomy and raises other ethical concerns. Using the Kass Public Health Ethics Framework, we identified ICC benefits and harms. Benefits include: protection of vulnerable, underserved patients; reduced legal consequences; resources for families; and “on-demand” treatment access. Harms include: stigmatizing and punitive experiences; heightened family conflict and social isolation; eroded patient self-determination; limited or no provision of OUD medications; and long-term overdose risk. To use ICC ethically, it should be recognized as comprising vulnerable patients worthy of added protections; be a last resort option; utilize consensual, humanizing processes; provide medications and other evidence-based-treatment; integrate with existing healthcare systems; and demonstrate effective outcomes before diffusion. ICC to OUD treatment carries significant potential harms that, if unaddressed, may outweigh its benefits. Findings can inform innovations for ensuring that ICC is used in an ethically responsible way.

SummaryAlthough progress has been made in reducing disparities in life expectancy, addressing the persistence of health inequities by race remains a high priority for public health professionals. The purpose of this research was to refine a minority stress model (MSM) by identifying previously unrecognized factors contributing to stress and chronic disease health disparities among low-income middle-aged African-American men. Using a Community-Based Participatory Research approach, we conducted semi-structured individual health interviews with 42 low-income middle-aged African-American men in a mid-size New England city. The interviews focused on the participants’ perceptions of the causes of health disparities. Four major themes emerged from the analysis: the positive aspects of work, both financial and symbolic; and the negative repercussions of not working, both financial and symbolic in terms of a sense of self-respect. On an instrumental level, working men can support their family, be physically active and find social support. Symbolically, work provides a positive sense of identity as a man; it offers both social- and self-respect; it provides discipline and a sense of gratitude. Conversely, the lack of work is a significant source of stress, stemming both from the inability to support one’s family and from having nothing to do, which lead to depression, low self-esteem, suicidal ideation and anger. With no perceived viable routes to socially approved roles, many low-income men of color succumb to internalizing a negative identity. This research demonstrates a clear link between structural problems with the US economy and harms to sense of identity among low-income, middle-aged African-American men.

Precarious work has steadily grown in the United States since the rise of neoliberal policies. The continued expansion of this type of work has led to precarious employment as a recognized category within social determinants of health work and to a growing literature within public health research. African-American men are disproportionately vulnerable to precarious work, which in turn contributes to adverse health effects. Nevertheless, African-American men’s experiences of employment and the perceived impact on their well-being remain underexplored. This study was part of the formative exploratory phase of a 5-year community-based participatory research project to examine the biopsychosocial determinants of stress among low/no-income, African-American men. Through thematic analysis of 42 semi-structured interviews, 3 themes emerged: ( a) occupational hazards and health, ( b) internalization of neoliberal ideology, and ( c) constraints of structural factors. Neoliberal economic policies cause material deprivation and exacerbate systemic injustices that disproportionately affect communities of color. The accompanying neoliberal ideology of personal responsibility shapes men’s perceptions of success and failure. Public health research must continue to push against health promotion practices that predominantly focus on individual behavior. Rather than exploring only the granularities of individual behaviors, health problems must be examined through prolonged historical, political, economic, and social disenfranchisement.

OBJECTIVE: We determined the prevalence and correlates of cannabis use in Massachusetts after recreational use was passed, but before recreational cannabis stores opened. METHOD: A cross-sectional, population-based survey of Massachusetts adults, age 18 years or older, (n=3,022) was conducted in November–December, 2017. We estimated population-level prevalence and correlates of past 30-day cannabis use. RESULTS: 21.1% [95% CI: 18.6, 23.6] of Massachusetts adults reported past 30-day cannabis use. Among cannabis users, 56.0% [49.1, 62.9] reported non-medical cannabis use, 15.5% [12.1, 18.9] reported medical cannabis use, and 28.5% [22.3, 34.8] reported both types of use. Men were more likely than women to use cannabis (Risk Ratio: 1.3 [1.1, 1.6]), as were young adults (18–25 years old), those with lower socioeconomic status, non-parenting individuals, those who used alcohol (1.9 [1.4, 2.6]) or other substances (1.7 [1.3, 2.4]), and residents of Western Massachusetts (2.0 [1.3, 3.0]; ref: Boston area), the Northeast (1.8 [1.2, 2.7]), and the Southeast (1.8 [1.1, 2.7]). CONCLUSIONS: Cannabis is widely used in Massachusetts, with varying prevalence rates by gender, age, socioeconomic status, poly-substance use, and region. Findings may inform public health efforts and serve as a baseline for measuring health and social impacts of opening retail cannabis stores.

Continuous Glucose Monitoring (CGM) data play an increasing role in clinical practice as they provide detailed quantification of blood glucose levels during the entire 24-hour period. The R package iglu implements a wide range of CGM-derived metrics for measuring glucose control and glucose variability. The package also allows one to visualize CGM data using time-series and lasagna plots. A distinct advantage of iglu is that it comes with a point-and-click graphical user interface (GUI) which makes the package widely accessible to users regardless of their programming experience. Thus, the open-source and easy to use iglu package will help advance CGM research and CGM data analyses. R package iglu is publicly available on CRAN and at https://github.com/irinagain/iglu.

Low/no-income, African American men are disproportionally burdened by chronic disease resulting from a complex interplay of systemic, sociocultural, and individual factors. These disparities are related to poverty, racism, gender role strain, high levels of stress, low levels of physical activity, and malnutritious diet. Men of Color Health Awareness (MOCHA) is a community-driven movement to address the physical, mental, social, and spiritual needs of men of color. As part of ongoing programming, the MOCHA Standard intervention consists of a 10-week program including: (1) small group discussions of issues particularly relevant to men of color, (2) classes on health topics focusing on chronic disease control, such as nutrition, obesity, high blood pressure, fitness, and the social determinants of health; and (3) 60-min of moderately intensive aerobic exercise twice a week. While the MOCHA Standard intervention has yielded positive results, feedback from previous participants warranted an in-depth sociocultural tailoring of the curriculum to improve community receptiveness, in particular, revising the sessions to "narrativize" the materials to strengthen their potential effectiveness. This manuscript describes the novel recruitment strategies; the development of an enhanced MOCHA+ Stories Matter program that uses narrative communication strategies; and the methodology used to assess the comparative effectiveness of the MOCHA Standard relative to MOCHA+ Stories Matter program in lowering stress and risk of chronic diseases in a randomized controlled trial. The results of this research will contribute to the identification of effective interventions to address health disparities in low-income African-American men and the dissemination of effective chronic disease prevention programming.

Background: Despite widespread adoption of health information technology, U.S. providers face persistent barriers to coordination of care. We sought to develop and implement a patient-centered smartphone app that facilitates care coordination when patients receive care at any hospital in a region. Materials and Methods: Partnering with patients and primary care teams at a federally qualified health center (FQHC), we developed an app that (1) used real-time location data to identify encounters at 41 regional hospitals; (2) sent notifications to users' phones, asking them to confirm hospital arrival/discharge, and; (3) sent automated messages to primary care teams about confirmed hospital encounters. App design included multiple, successive rounds of active patient participation. In a small beta test of the initial version of the app, high-risk, low-income FQHC patients ran the app on their phone for 3 months. A formative mixed methods evaluation examined the app's technical performance and user experience. Results: Twelve patients enrolled in the beta test and provided follow-up data; 11 (92%) were racial/ethnic minorities. Participants obtained emergency or inpatient care at four regional hospitals. The app had 75% sensitivity to detect events when notifications should have fired, and 90% positive predictive value (PPV) of events when notifications fired. Barriers to implementation related to the app's user interface and the performance of its location tracking algorithm. Conclusions: We partnered with patients from a traditionally underserved population to develop a new smartphone-based approach to regional care coordination. The app had moderate sensitivity and high PPV for identifying regional hospital visits.

Purpose: To examine whether food insecurity longitudinally affects smoking status. Design: Population-based prospective study Setting: Data from the 2003 and 2015 Panel Study of Income Dynamics (PSID). Participants: Four thousand five hundred sixty-three adults who were smokers and nonsmokers, participating in the 2003 (current study baseline) and 2015 (current study follow-up) waves of PSID. Measures: Based on self-reported smoking status at baseline and follow-up, respondents were categorized as continued smoking, stopped smoking, started smoking, and continued nonsmoking. Similarly, respondents were categorized as stayed food secure, stayed food insecure, became food insecure, and became food secure based on responses to the Food Security Survey at baseline and follow-up. Analysis: Two logistic regression analyses to examine (1) among smokers at baseline the odds of stopping versus continuing smoking by follow-up and (2) among nonsmokers at baseline the odds of starting versus continuing nonsmoking by follow-up. In both models, change in food insecurity status was the primary independent variable, controlling for demographics including poverty. Results: Among smokers at baseline, becoming food insecure (vs staying food secure) was independently associated with lower likelihood of stopping smoking by follow-up (odds ratio [OR] = 0.66). Among nonsmokers at baseline, becoming food insecure (vs staying food secure) was independently associated with higher likelihood of starting smoking by follow-up (OR = 3.77). Conclusions: Food insecurity is a risk factor for smoking, which has significant implications for developing interventions to reduce smoking prevalence, especially among low-income groups.

Given the rise in obesity and the positive exercise effects in curbing obesity levels, exercise promoters are expected to use technological applications—social media and fitness applications—in their exercise motivational programs. The purpose of this article is to critique the use of social media and fitness apps as both ineffective and potentially harmful. An alternative approach is proposed where phronesis (practical wisdom) in exercise participation can be achieved via physical and cognitive mastery of the action for its own sake (real techne-art, embodiment). Emphasizing exercise outcomes (e.g., energy expenditure) captured by external devices distracts from embodied and phronetic action. Drawing on the philosophies of phronesis, techne, and embodiment, exercise promoters should emphasize embodied exercise experiences via mastery of action, social interactions, and connectedness to nature. They should target real action in real communities, and not emotionless and meaningless online forums ab...

Background: Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy.Methods: RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627.Findings: Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08–1·13] vs 0·77 [0·13–4·61]; pinteraction=0·41), cerebral microbleed number 0–1 versus 2–4 versus 5 or more (HR 0·77 [0·13–4·62] vs 0·32 [0·03–3·66] vs 0·33 [0·07–1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004–6·79] vs 0·37 [0·09–1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05).Interpretation: Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision.Funding: British Heart Foundation.

Objectives: Launched in 1989, the Scottish Motor Neuron Disease Register (SMNDR) has provided a resource for prospective clinical data collection. However, in 2015 we aimed to evolve a system to al...

The conduct of community-based participatory research (CBPR) is a recent innovation in research designs aimed at identifying effective public health interventions. CBPR aims to maximize participation of affected populations in all phases of the research to fulfill three purposes: it is (1) a method for developing innovative interventions, (2) an intervention itself intended to change the respective partners positively as a result of their participation, and (3) a means to fulfill an ethical obligation. CBPR is most ethically significant for respecting community autonomy and providing protections from community-level harms, such as stigmatization of identifiable social groups, lost opportunity costs, and overcoming mistrust, which may lead to reluctance to participate in research and, hence, a lack of empirical data on potential adverse effects or benefits for certain social groups. Key unresolved issues include procedures for enlisting legitimate community representatives and the scope of their authority over the conduct of the research.

Background: High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset.Methods: We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK-based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053.Findings: Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants' systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (pvs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups.Interpretation: Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultra-acute prehospital setting.Funding: British Heart Foundation.

Public health interventions present distinct ethical challenges relative to clinical medical interventions, primarily because of their focus on prevention (rather than treatment) and their intended impact on the health of a population as a whole (rather than the individual). Public health interventions can be broadly categorized as falling into two main types: educational and environmental. Educational interventions aim to change individual behaviors, whereas environmental interventions seek to change the social and environmental conditions that encourage, require, or reinforce behaviors that are either beneficial or harmful to health. Public health interventions raise normative concerns with respect to three key ethical principles: the potential for harm (including stigmatization, lost opportunity costs, and threats to autonomy), justice, and social solidarity, particularly with respect to the problem of free riders. The high value placed on individual liberty in the modern era makes the task of asking individuals to give up freedoms to protect and promote population health increasingly difficult.

Background: Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.Methods: FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.Findings: Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.Interpretation: Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.Funding: UK Stroke Association and NIHR Health Technology Assessment Programme.

Background : Lack of early initiation of antiretroviral therapy (ART) remains a major health concern due to increased risk of premature mortality and further HIV transmission. This study explored CD4+ cell count monitoring in relation to delays in ART initiation among HIV-positive individuals in the Kathmandu Valley, Nepal, where ART coverage was only 23.7% in 2011. Design : We recruited a total of 87 ART-naive, HIV-positive individuals aged 18 to 60 years through the networks of five non-government organizations working with HIV-positive individuals. We collected data on the history of ART initiation, CD4+ cell count monitoring, socio-demographic variables, perceived family support (measured with 10-item Nepali Family Support and Difficulty Scale), depression, and HIV symptom burden. Correlates of ART eligibility were examined using multivariable logistic regression analysis. Results : A total of 72 of the 87 ART-naive participants (82.8%) had monitored their CD4+ cell count in the past 6 months. Of these, 36 (50%) participants were eligible for ART initiation with CD4+ cell count

Fecal occult blood testing (FOBT) is a pragmatic screening option for many community health centers (CHCs), but FOBT screening programs will not reduce mortality if patients with positive results do not undergo diagnostic colonoscopy (DC). This study was conducted to investigate DC completion among CHC patients. This retrospective cohort study used data from three CHCs in the Midwest and Southwest. The primary study outcome was DC completion within 6 months of positive FOBT among adults age 50–75. Patient data was collected using automated electronic queries. Manual chart reviews were conducted if queries produced no evidence of DC. Poisson regression models described adjusted relative risks (RRs) of DC completion. The study included 308 patients; 63.3 % were female, 48.7 % were Spanish speakers and 35.7 % were uninsured. Based on combined query and chart review findings, 51.5 % completed DC. Spanish speakers were more likely than English speakers to complete DC [RR 1.19; 95 % confidence interval (CI) 1.04–1.36; P = 0.009], and DC completion was lower among patients with 0 visits than those with 1–2 visits (RR 2.81; 95% CI 1.83–4.33; P

Over the last several decades, consistent concerns have been raised about the quality of education and training provided to students in public health. In this article, we consider the implications of epidemiological transition—the decline of infectious diseases and rise of chronic diseases—for the types of education and training that would be most well suited for preparing students in health promotion to address the social and behavioral factors now associated with the leading causes of morbidity and mortality. As a result of this historic shift in disease etiology, the recommendation is to expand opportunities for applied experiential learning. Students need to become more adept at diagnosing the complex social, moral, and political dynamics that shape community priorities, perceptions of causes, and framing of health issues. The specific constellation of players, their history, relationships, and interpersonal dynamics are unique to each particular community setting, and hence, students need to become more sensitive to and proficient at picking up on the most significant influences and characteristics at work in the situation at hand. This type of “practical reasoning” stands in contrast to the perceived value of generalizable knowledge characteristic of models developed in the natural sciences. The ability to recognize and respond appropriately to the unique characteristics of a specific situation is best strengthened through extended practical experience.

Introduction Fecal immunochemical testing (FIT) is an attractive approach for colorectal cancer screening at community health centers. This budget impact analysis investigated benefits and costs of FIT outreach—with FIT kits mailed to patients, followed by reminders and phone calls—compared with point-of-care (POC) strategies. Methods Five screening and cost outcomes were simulated over 1 year at a “base case” community health center serving 1000 screening-eligible patients: (1) FIT completion among patients due for screening; (2) proportion up-to-date on screening; (3) cost per patient due for screening; (4) cost per completed FIT; and (5) total organizational cost. Uncertainty analysis investigated potential savings from optimizing staff workflows during FIT outreach. Data were collected in 2012–2014, with analysis conducted 2014–2015. Results Using POC strategies, 24.0% of patients due for screening completed FIT, versus 42.4% under outreach (18.4% absolute difference). When calculations included patients up-to-date on screening from prior colonoscopy, 41.7% were up-to-date via POC, versus 55.8% for outreach (14.1% absolute difference). POC cost $4.93 per patient, versus $30.43 for outreach ($25.50 difference). Cost per patient screened was $20.60 for POC and $71.84 for outreach ($51.24 difference). Total organizational cost was $3,779 for POC distribution and $23,315 for outreach ($19,536 difference). Outreach costs decreased by approximately one fourth under optimized workflows. Conclusions Outreach is an effective, practical, relatively low-cost strategy; costs could be reduced further by optimizing staff workflows. Despite its value, outreach costs more than POC distribution and may be difficult for community health centers to implement under current payment models.

The article examines the limitations of a strict scientific account of the causes of unhealthy behaviors, based on the standards promoted in evidence-based medicine, where randomized controlled trials are seen to provide the gold standard for establishing the validity of different explanations. The article critiques this account based on its disputed assumption that human free will does not exist, and thus, human autonomy and moral responsibility are an illusion. By denying human autonomy, the naturalistic paradigm also denies the possibility of human dignity. In contrast, the article describes and explains a humanistic account of human agency where human beings are characterized by the capacity to choose how to live their lives based on values that matter. Based on this humanistic framework, the article explains why dignity is an essential dimension of human health and well-being and describes key research challenges in moving the field of health promotion in a more humanistic direction. The article concludes with the recommendation to expand the goal of health promotion beyond physical fitness and to reorient the methods of research toward articulating values that matter and promoting human dignity.

Purpose: There is a dearth of effective, evidence-based programs to reduce chronic disease in low-income African-American men. We report on the results of formative research in the National Institutes of Health (NIH)-funded MOCHA Moving Forward project on factors identified by the participants to drive health disparities. Methods: Based on individual interviews with 42 middle-aged (40–65 years), low-income African-American men, three themes emerged. Results: First, the results indicate a hierarchy in the perceived relative influence of different factors, with poverty and unemployment perceived to have the most powerful affects. Second, results show that factors in different domains do not operate as discrete independent influences, but rather, interact synergistically. Finally, the findings show how perceived social structural constraints have produced deep cynicism about the future, with notably divergent reactions, producing a sense that there is almost nothing an individual can do, or paradoxically, a greater the sense of personal responsibility. Conclusion: The implications of addressing the cascade of social determinants to reduce chronic disease in African-American men are discussed.

Despite the proliferation of theory-based behavior-change programs to promote physical activity, obesity and diabetes rates continue to rise. Given the notable ineffective interventions, it is important to examine why these efforts have been largely unsuccessful and to consider potential alternatives. The purpose of this article is to consider the role of values in understanding decisions about physical activity and to outline a more appropriate framework for investigating them. Aristotle originally proposed that human behavior may be better understood in terms of phronesis (practical reasoning), aimed at realizing valued goals rather than as the product of antecedent causal determinants. Instead of relying exclusively on scientific methodologies, a more comprehensive approach to study physical activity participation would also incorporate analytical processes used in the humanities, especially with respect to conceptualizing the role of values in guiding human behavior. Therefore, revising and expanding ...

We evaluated the efficacy of a sexual risk reduction intervention utilizing protection motivation and social cognitive theories to address knowledge, threat and coping appraisals, and condom use intentions among HIV-positive individuals in Nepal. Using a quasi-experimental research design, we assigned 277 participants to intervention (n=146) and control (n=131) groups. The intervention group received six sessions on sexual risk reduction strategies and the control group six sessions on medication adherence, smoking, and mental health. Data were collected at baseline and immediately after the intervention. Results indicate that the sexual risk reduction intervention produced a significant increase in HIV transmission knowledge, perceived threat and coping appraisals, and intentions to use condoms with regular, HIV-positive, and HIV-negative partners. The positive effects of the intervention remained significant after adjusting for baseline scores and other potential confounders. In conclusion, our theory-based sexual risk reduction intervention was effective in improving HIV transmission knowledge, perceived threat and coping appraisals, and condom use intentions. Further studies are needed to evaluate the long-term efficacy of the intervention in increasing protection motivation and maintaining preventive behaviors.