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Food biodiversity and total and cause-specific mortality in 9 European countries: An analysis of a prospective cohort study

Lun, 18/10/2021 - 15:00

by Giles T. Hanley-Cook, Inge Huybrechts, Carine Biessy, Roseline Remans, Gina Kennedy, Mélanie Deschasaux-Tanguy, Kris A. Murray, Mathilde Touvier, Guri Skeie, Emmanuelle Kesse-Guyot, Alemayehu Argaw, Corinne Casagrande, Geneviève Nicolas, Paolo Vineis, Christopher J. Millett, Elisabete Weiderpass, Pietro Ferrari, Christina C. Dahm, H. Bas Bueno-de-Mesquita, Torkjel M. Sandanger, Daniel B. Ibsen, Heinz Freisling, Stina Ramne, Franziska Jannasch, Yvonne T. van der Schouw, Matthias B. Schulze, Konstantinos K. Tsilidis, Anne Tjønneland, Eva Ardanaz, Stina Bodén, Lluís Cirera, Giuliana Gargano, Jytte Halkjær, Paula Jakszyn, Ingegerd Johansson, Verena Katzke, Giovanna Masala, Salvatore Panico, Miguel Rodriguez-Barranco, Carlotta Sacerdote, Bernard Srour, Rosario Tumino, Elio Riboli, Marc J. Gunter, Andrew D. Jones, Carl Lachat

Background

Food biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population.

Methods and findings

We examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual’s yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P10–P90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total mortality in the second, third, fourth, and fifth (highest) quintiles (Qs) of DSR to the first (lowest) Q indicate significant inverse associations, after stratification by sex, age, and study center and adjustment for smoking status, educational level, marital status, physical activity, alcohol intake, and total energy intake, Mediterranean diet score, red and processed meat intake, and fiber intake [HR (95% CI): 0.91 (0.88 to 0.94), 0.80 (0.76 to 0.83), 0.69 (0.66 to 0.72), and 0.63 (0.59 to 0.66), respectively; PWald < 0.001 for trend]. Absolute death rates among participants in the highest and lowest fifth of DSR were 65.4 and 69.3 cases/10,000 person-years, respectively. Significant inverse associations were also observed between DSR and deaths due to cancer, heart disease, digestive disease, and respiratory disease. An important study limitation is that our findings were based on an observational cohort using self-reported dietary data obtained through single baseline food frequency questionnaires (FFQs); thus, exposure misclassification and residual confounding cannot be ruled out.

Conclusions

In this large Pan-European cohort, higher DSR was inversely associated with total and cause-specific mortality, independent of sociodemographic, lifestyle, and other known dietary risk factors. Our findings support the potential of food (species) biodiversity as a guiding principle of sustainable dietary recommendations and food-based dietary guidelines.

Modeling the epidemiological impact of the UNAIDS 2025 targets to end AIDS as a public health threat by 2030

Lun, 18/10/2021 - 15:00

by John Stover, Robert Glaubius, Yu Teng, Sherrie Kelly, Tim Brown, Timothy B. Hallett, Paul Revill, Till Bärnighausen, Andrew N. Phillips, Christopher Fontaine, Luisa Frescura, Jose Antonio Izazola-Licea, Iris Semini, Peter Godfrey-Faussett, Paul R. De Lay, Adèle Schwartz Benzaken, Peter D. Ghys

Background

UNAIDS has established new program targets for 2025 to achieve the goal of eliminating AIDS as a public health threat by 2030. This study reports on efforts to use mathematical models to estimate the impact of achieving those targets.

Methods and findings

We simulated the impact of achieving the targets at country level using the Goals model, a mathematical simulation model of HIV epidemic dynamics that includes the impact of prevention and treatment interventions. For 77 high-burden countries, we fit the model to surveillance and survey data for 1970 to 2020 and then projected the impact of achieving the targets for the period 2019 to 2030. Results from these 77 countries were extrapolated to produce estimates for 96 others. Goals model results were checked by comparing against projections done with the Optima HIV model and the AIDS Epidemic Model (AEM) for selected countries. We included estimates of the impact of societal enablers (access to justice and law reform, stigma and discrimination elimination, and gender equality) and the impact of Coronavirus Disease 2019 (COVID-19). Results show that achieving the 2025 targets would reduce new annual infections by 83% (71% to 86% across regions) and AIDS-related deaths by 78% (67% to 81% across regions) by 2025 compared to 2010. Lack of progress on societal enablers could endanger these achievements and result in as many as 2.6 million (44%) cumulative additional new HIV infections and 440,000 (54%) more AIDS-related deaths between 2020 and 2030 compared to full achievement of all targets. COVID-19–related disruptions could increase new HIV infections and AIDS-related deaths by 10% in the next 2 years, but targets could still be achieved by 2025. Study limitations include the reliance on self-reports for most data on behaviors, the use of intervention effect sizes from published studies that may overstate intervention impacts outside of controlled study settings, and the use of proxy countries to estimate the impact in countries with fewer than 4,000 annual HIV infections.

Conclusions

The new targets for 2025 build on the progress made since 2010 and represent ambitious short-term goals. Achieving these targets would bring us close to the goals of reducing new HIV infections and AIDS-related deaths by 90% between 2010 and 2030. By 2025, global new infections and AIDS deaths would drop to 4.4 and 3.9 per 100,000 population, and the number of people living with HIV (PLHIV) would be declining. There would be 32 million people on treatment, and they would need continuing support for their lifetime. Incidence for the total global population would be below 0.15% everywhere. The number of PLHIV would start declining by 2023.

Evaluation of progress toward universal health coverage in Myanmar: A national and subnational analysis

Ven, 15/10/2021 - 15:00

by Zlatko Nikoloski, Alistair McGuire, Elias Mossialos

Background

Universal health coverage (UHC) encompasses 2 main components: access to essential healthcare services and protection from financial hardship when using healthcare. This study examines Myanmar’s efforts to achieve UHC on a national and subnational level. It is a primer of studying the concept of UHC on a subnational level, and it also establishes a baseline for assessing future progress toward reaching UHC in Myanmar.

Methods and findings

The study uses the Demographic and Health Survey (2015) and the Myanmar Living Conditions Survey (MLCS; 2017) and adapts a previously developed UHC index to provide insights into the main barriers preventing the country’s progress toward UHC. We find a negative correlation between the UHC index and the state/region poverty levels. The equity of access analysis reveals significant pro-rich inequity in access to all essential healthcare services. Socioeconomic status and limited availability of healthcare infrastructure are the main driving forces behind the unequal access to interventions that are crucial to achieving UHC by 2030. Finally, financial risk protection analysis shows that the poor are less likely to use healthcare services, and, once they do, they are at a greater risk of suffering financial catastrophe. Limitations of this study revolve around its correlational, rather than causal, nature.

Conclusions

We suggest a 2-pronged approach to help Myanmar achieve UHC: Government and state authorities should reduce the financial burden of seeking healthcare, and, coupled with this, significant investment in and expansion of health infrastructure and the health workforce should be made, particularly in the poorer and more remote states.

Correction: Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial

Ven, 15/10/2021 - 15:00

by Sheila Isanaka, Souna Garba, Brian Plikaytis, Monica Malone McNeal, Ousmane Guindo, Céline Langendorf, Eric Adehossi, Iza Ciglenecki, Rebecca F. Grais

HMG-CoA reductase inhibitors and COVID-19 mortality in Stockholm, Sweden: A registry-based cohort study

Gio, 14/10/2021 - 15:00

by Rita Bergqvist, Viktor H. Ahlqvist, Michael Lundberg, Maria-Pia Hergens, Johan Sundström, Max Bell, Cecilia Magnusson

Background

The relationship between statin treatment and Coronavirus Disease 2019 (COVID-19) mortality has been discussed due to the pleiotropic effects of statins on coagulation and immune mechanisms. However, available observational studies are hampered by study design flaws, resulting in substantial heterogeneity and ambiguities. Here, we aim to determine the relationship between statin treatment and COVID-19 mortality.

Methods and findings

This cohort study included all Stockholm residents aged 45 or older (N = 963,876), followed up from 1 March 2020 until 11 November 2020. The exposure was statin treatment initiated before the COVID-19-pandemic, defined as recorded statin dispensation in the Swedish Prescribed Drug Register between 1 March 2019 and 29 February 2020. COVID-19-specific mortality was ascertained from the Swedish Cause of Death Registry. Hazard ratios (HRs) were calculated using multivariable Cox regression models. We further performed a target trial emulation restricted to initiators of statins.In the cohort (51.6% female), 169,642 individuals (17.6%) were statin users. Statin users were older (71.0 versus 58.0 years), more likely to be male (53.3% versus 46.7%), more often diagnosed with comorbidities (for example, ischemic heart disease 23.3% versus 1.6%), more frequently on anticoagulant and antihypertensive treatments, less likely to have a university-level education (34.5% versus 45.4%), and more likely to have a low disposable income (20.6% versus 25.2%), but less likely to reside in crowded housing (6.1% versus 10.3%).A total of 2,545 individuals died from COVID-19 during follow-up, including 765 (0.5%) of the statin users and 1,780 (0.2%) of the nonusers. Statin treatment was associated with a lowered COVID-19 mortality (adjusted HR, 0.88; 95% CI, 0.79 to 0.97, P = 0.01), and this association did not vary appreciably across age groups, sexes, or COVID-19 risk groups. The confounder adjusted HR for statin treatment initiators was 0.78 (95% CI, 0.59 to 1.05, P = 0.10) in the emulated target trial. Limitations of this study include the observational design, reliance on dispensation data, and the inability to study specific drug regimens.

Conclusions

Statin treatment had a modest negative association with COVID-19 mortality. While this finding needs confirmation from randomized clinical trials, it supports the continued use of statin treatment for medical prevention according to current recommendations also during the COVID-19 pandemic.

Transmission of community- and hospital-acquired SARS-CoV-2 in hospital settings in the UK: A cohort study

Mar, 12/10/2021 - 15:00

by Yin Mo, David W. Eyre, Sheila F. Lumley, Timothy M. Walker, Robert H. Shaw, Denise O’Donnell, Lisa Butcher, Katie Jeffery, Christl A. Donnelly, Oxford COVID infection review team , Ben S. Cooper

Background

Nosocomial spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been widely reported, but the transmission pathways among patients and healthcare workers (HCWs) are unclear. Identifying the risk factors and drivers for these nosocomial transmissions is critical for infection prevention and control interventions. The main aim of our study was to quantify the relative importance of different transmission pathways of SARS-CoV-2 in the hospital setting.

Methods and findings

This is an observational cohort study using data from 4 teaching hospitals in Oxfordshire, United Kingdom, from January to October 2020. Associations between infectious SARS-CoV-2 individuals and infection risk were quantified using logistic, generalised additive and linear mixed models. Cases were classified as community- or hospital-acquired using likely incubation periods of 3 to 7 days. Of 66,184 patients who were hospitalised during the study period, 920 had a positive SARS-CoV-2 PCR test within the same period (1.4%). The mean age was 67.9 (±20.7) years, 49.2% were females, and 68.5% were from the white ethnic group. Out of these, 571 patients had their first positive PCR tests while hospitalised (62.1%), and 97 of these occurred at least 7 days after admission (10.5%). Among the 5,596 HCWs, 615 (11.0%) tested positive during the study period using PCR or serological tests. The mean age was 39.5 (±11.1) years, 78.9% were females, and 49.8% were nurses. For susceptible patients, 1 day in the same ward with another patient with hospital-acquired SARS-CoV-2 was associated with an additional 7.5 infections per 1,000 susceptible patients (95% credible interval (CrI) 5.5 to 9.5/1,000 susceptible patients/day) per day. Exposure to an infectious patient with community-acquired Coronavirus Disease 2019 (COVID-19) or to an infectious HCW was associated with substantially lower infection risks (2.0/1,000 susceptible patients/day, 95% CrI 1.6 to 2.2). As for HCW infections, exposure to an infectious patient with hospital-acquired SARS-CoV-2 or to an infectious HCW were both associated with an additional 0.8 infection per 1,000 susceptible HCWs per day (95% CrI 0.3 to 1.6 and 0.6 to 1.0, respectively). Exposure to an infectious patient with community-acquired SARS-CoV-2 was associated with less than half this risk (0.2/1,000 susceptible HCWs/day, 95% CrI 0.2 to 0.2). These assumptions were tested in sensitivity analysis, which showed broadly similar results. The main limitations were that the symptom onset dates and HCW absence days were not available.

Conclusions

In this study, we observed that exposure to patients with hospital-acquired SARS-CoV-2 is associated with a substantial infection risk to both HCWs and other hospitalised patients. Infection control measures to limit nosocomial transmission must be optimised to protect both staff and patients from SARS-CoV-2 infection.

Cancer Special Issue: Early detection and minimal residual disease

Mar, 12/10/2021 - 15:00

by Beryne Odeny

Beryne Odeny discusses PLOS Medicine’s Special Issue on early cancer detection and minimal residual disease.

Cesarean section: More than a maternal health issue

Mar, 12/10/2021 - 15:00

by Marleen Temmerman, Abdu Mohiddin

A cesarean section (CS) can be a lifesaving intervention when medically indicated, but it may also lead to adverse short- and long-term health effects for women and children.

Associations between cesarean delivery and child mortality: A national record linkage longitudinal study of 17.8 million births in Brazil

Mar, 12/10/2021 - 15:00

by Enny S. Paixao, Christian Bottomley, Julia M. Pescarini, Kerry L. M. Wong, Luciana L. Cardim, Rita de Cássia Ribeiro Silva, Elizabeth B. Brickley, Laura C. Rodrigues, Flavia Jôse Oliveira Alves, Maria do Carmo Leal, Maria da Conceicao N. Costa, Maria Gloria Teixeira, Maria Yury Ichihara, Liam Smeeth, Mauricio L. Barreto, Oona M. R. Campbell

Background

There is an increasing use of cesarean delivery (CD) based on preference rather than on medical indication. However, the extent to which nonmedically indicated CD benefits or harms child survival remains unclear. Our hypothesis was that in groups with a low indication for CD, this procedure would be associated with higher child mortality and in groups with a clear medical indication CD would be associated with improved child survival chances.

Methods and findings

We conducted a population-based cohort study in Brazil by linking routine data on live births between January 1, 2012 and December 31, 2018 and assessing mortality up to 5 years of age. Women with a live birth who contributed records during this period were classified into one of 10 Robson groups based on their pregnancy and delivery characteristics. We used propensity scores to match CD with vaginal deliveries (1:1) and prelabor CD with unscheduled CD (1:1) and estimated associations with child mortality using Cox regressions. A total of 17,838,115 live births were analyzed. After propensity score matching (PSM), we found that live births to women in groups with low expected frequencies of CD (Robson groups 1 to 4) had a higher death rate up to age 5 years if they were born via CD compared with vaginal deliveries (HR = 1.25, 95% CI: 1.22 to 1.28; p < 0.001). The relative rate was greatest in the neonatal period (HR = 1.39, 95% CI: 1.34 to 1.45; p < 0.001). There was no difference in mortality rate when comparing offspring born by a prelabor CD to those born by unscheduled CD. For the live births to women with a CD in a prior pregnancy (Robson group 5), the relative rates for child mortality were similar for those born by CD compared with vaginal deliveries (HR = 1.05, 95% CI: 1.00 to 1.10; p = 0.024). In contrast, for live births to women in groups with high expected rates of CD (Robson groups 6 to 10), the child mortality rate was lower for CD than for vaginal deliveries (HR = 0.90, 95% CI: 0.89 to 0.91; p < 0.001), particularly in the neonatal period (HR = 0.84, 95% CI: 0.83 to 0.85; p < 0.001). Our results should be interpreted with caution in clinical practice, since relevant clinical data on CD indication were not available.

Conclusions

In this study, we observed that in Robson groups with low expected frequencies of CD, this procedure was associated with a 25% increase in child mortality. However, in groups with high expected frequencies of CD, the findings suggest that clinically indicated CD is associated with a reduction in child mortality.

Characterising the nationwide burden and predictors of unkept outpatient appointments in the National Health Service in England: A cohort study using a machine learning approach

Mar, 12/10/2021 - 15:00

by Sion Philpott-Morgan, Dixa B. Thakrar, Joshua Symons, Daniel Ray, Hutan Ashrafian, Ara Darzi

Background

Unkept outpatient hospital appointments cost the National Health Service £1 billion each year. Given the associated costs and morbidity of unkept appointments, this is an issue requiring urgent attention. We aimed to determine rates of unkept outpatient clinic appointments across hospital trusts in the England. In addition, we aimed to examine the predictors of unkept outpatient clinic appointments across specialties at Imperial College Healthcare NHS Trust (ICHT). Our final aim was to train machine learning models to determine the effectiveness of a potential intervention in reducing unkept appointments.

Methods and findings

UK Hospital Episode Statistics outpatient data from 2016 to 2018 were used for this study. Machine learning models were trained to determine predictors of unkept appointments and their relative importance. These models were gradient boosting machines. In 2017–2018 there were approximately 85 million outpatient appointments, with an unkept appointment rate of 5.7%. Within ICHT, there were almost 1 million appointments, with an unkept appointment rate of 11.2%. Hepatology had the highest rate of unkept appointments (17%), and medical oncology had the lowest (6%). The most important predictors of unkept appointments included the recency (25%) and frequency (13%) of previous unkept appointments and age at appointment (10%). A sensitivity of 0.287 was calculated overall for specialties with at least 10,000 appointments in 2016–2017 (after data cleaning). This suggests that 28.7% of patients who do miss their appointment would be successfully targeted if the top 10% least likely to attend received an intervention. As a result, an intervention targeting the top 10% of likely non-attenders, in the full population of patients, would be able to capture 28.7% of unkept appointments if successful. Study limitations include that some unkept appointments may have been missed from the analysis because recording of unkept appointments is not mandatory in England. Furthermore, results here are based on a single trust in England, hence may not be generalisable to other locations.

Conclusions

Unkept appointments remain an ongoing concern for healthcare systems internationally. Using machine learning, we can identify those most likely to miss their appointment and implement more targeted interventions to reduce unkept appointment rates.

Association of accelerometer-derived sleep measures with lifetime psychiatric diagnoses: A cross-sectional study of 89,205 participants from the UK Biobank

Mar, 12/10/2021 - 15:00

by Michael Wainberg, Samuel E. Jones, Lindsay Melhuish Beaupre, Sean L. Hill, Daniel Felsky, Manuel A. Rivas, Andrew S. P. Lim, Hanna M. Ollila, Shreejoy J. Tripathy

Background

Sleep problems are both symptoms of and modifiable risk factors for many psychiatric disorders. Wrist-worn accelerometers enable objective measurement of sleep at scale. Here, we aimed to examine the association of accelerometer-derived sleep measures with psychiatric diagnoses and polygenic risk scores in a large community-based cohort.

Methods and findings

In this post hoc cross-sectional analysis of the UK Biobank cohort, 10 interpretable sleep measures—bedtime, wake-up time, sleep duration, wake after sleep onset, sleep efficiency, number of awakenings, duration of longest sleep bout, number of naps, and variability in bedtime and sleep duration—were derived from 7-day accelerometry recordings across 89,205 participants (aged 43 to 79, 56% female, 97% self-reported white) taken between 2013 and 2015. These measures were examined for association with lifetime inpatient diagnoses of major depressive disorder, anxiety disorders, bipolar disorder/mania, and schizophrenia spectrum disorders from any time before the date of accelerometry, as well as polygenic risk scores for major depression, bipolar disorder, and schizophrenia. Covariates consisted of age and season at the time of the accelerometry recording, sex, Townsend deprivation index (an indicator of socioeconomic status), and the top 10 genotype principal components. We found that sleep pattern differences were ubiquitous across diagnoses: each diagnosis was associated with a median of 8.5 of the 10 accelerometer-derived sleep measures, with measures of sleep quality (for instance, sleep efficiency) generally more affected than mere sleep duration. Effect sizes were generally small: for instance, the largest magnitude effect size across the 4 diagnoses was β = −0.11 (95% confidence interval −0.13 to −0.10, p = 3 × 10−56, FDR = 6 × 10−55) for the association between lifetime inpatient major depressive disorder diagnosis and sleep efficiency. Associations largely replicated across ancestries and sexes, and accelerometry-derived measures were concordant with self-reported sleep properties. Limitations include the use of accelerometer-based sleep measurement and the time lag between psychiatric diagnoses and accelerometry.

Conclusions

In this study, we observed that sleep pattern differences are a transdiagnostic feature of individuals with lifetime mental illness, suggesting that they should be considered regardless of diagnosis. Accelerometry provides a scalable way to objectively measure sleep properties in psychiatric clinical research and practice, even across tens of thousands of individuals.

Behavioural activation to prevent depression and loneliness among socially isolated older people with long-term conditions: The BASIL COVID-19 pilot randomised controlled trial

Mar, 12/10/2021 - 15:00

by Simon Gilbody, Elizabeth Littlewood, Dean McMillan, Carolyn A. Chew-Graham, Della Bailey, Samantha Gascoyne, Claire Sloan, Lauren Burke, Peter Coventry, Suzanne Crosland, Caroline Fairhurst, Andrew Henry, Catherine Hewitt, Kalpita Joshi, Eloise Ryde, Leanne Shearsmith, Gemma Traviss-Turner, Rebecca Woodhouse, Andrew Clegg, Tom Gentry, Andrew J. Hill, Karina Lovell, Sarah Dexter Smith, Judith Webster, David Ekers

Background

Older adults, including those with long-term conditions (LTCs), are vulnerable to social isolation. They are likely to have become more socially isolated during the Coronavirus Disease 2019 (COVID-19) pandemic, often due to advice to “shield” to protect them from infection. This places them at particular risk of depression and loneliness. There is a need for brief scalable psychosocial interventions to mitigate the psychological impacts of social isolation. Behavioural activation (BA) is a credible candidate intervention, but a trial is needed.

Methods and findings

We undertook an external pilot parallel randomised trial (ISRCTN94091479) designed to test recruitment, retention and engagement with, and the acceptability and preliminary effects of the intervention. Participants aged ≥65 years with 2 or more LTCs were recruited in primary care and randomised by computer and with concealed allocation between June and October 2020. BA was offered to intervention participants (n = 47), and control participants received usual primary care (n = 49). Assessment of outcome was made blind to treatment allocation. The primary outcome was depression severity (measured using the Patient Health Questionnaire 9 (PHQ-9)). We also measured health-related quality of life (measured by the Short Form (SF)-12v2 mental component scale (MCS) and physical component scale (PCS)), anxiety (measured by the Generalised Anxiety Disorder 7 (GAD-7)), perceived social and emotional loneliness (measured by the De Jong Gierveld Scale: 11-item loneliness scale). Outcome was measured at 1 and 3 months. The mean age of participants was aged 74 years (standard deviation (SD) 5.5) and they were mostly White (n = 92, 95.8%), and approximately two-thirds of the sample were female (n = 59, 61.5%). Remote recruitment was possible, and 45/47 (95.7%) randomised to the intervention completed 1 or more sessions (median 6 sessions) out of 8. A total of 90 (93.8%) completed the 1-month follow-up, and 86 (89.6%) completed the 3-month follow-up, with similar rates for control (1 month: 45/49 and 3 months 44/49) and intervention (1 month: 45/47and 3 months: 42/47) follow-up. Between-group comparisons were made using a confidence interval (CI) approach, and by adjusting for the covariate of interest at baseline. At 1 month (the primary clinical outcome point), the median number of completed sessions for people receiving the BA intervention was 3, and almost all participants were still receiving the BA intervention. The between-group comparison for the primary clinical outcome at 1 month was an adjusted between-group mean difference of −0.50 PHQ-9 points (95% CI −2.01 to 1.01), but only a small number of participants had completed the intervention at this point. At 3 months, the PHQ-9 adjusted mean difference (AMD) was 0.19 (95% CI −1.36 to 1.75). When we examined loneliness, the adjusted between-group difference in the De Jong Gierveld Loneliness Scale at 1 month was 0.28 (95% CI −0.51 to 1.06) and at 3 months −0.87 (95% CI −1.56 to −0.18), suggesting evidence of benefit of the intervention at this time point. For anxiety, the GAD adjusted between-group difference at 1 month was 0.20 (−1.33, 1.73) and at 3 months 0.31 (−1.08, 1.70). For the SF-12 (physical component score), the adjusted between-group difference at 1 month was 0.34 (−4.17, 4.85) and at 3 months 0.11 (−4.46, 4.67). For the SF-12 (mental component score), the adjusted between-group difference at 1 month was 1.91 (−2.64, 5.15) and at 3 months 1.26 (−2.64, 5.15). Participants who withdrew had minimal depressive symptoms at entry. There were no adverse events. The Behavioural Activation in Social Isolation (BASIL) study had 2 main limitations. First, we found that the intervention was still being delivered at the prespecified primary outcome point, and this fed into the design of the main trial where a primary outcome of 3 months is now collected. Second, this was a pilot trial and was not designed to test between-group differences with high levels of statistical power. Type 2 errors are likely to have occurred, and a larger trial is now underway to test for robust effects and replicate signals of effectiveness in important secondary outcomes such as loneliness.

Conclusions

In this study, we observed that BA is a credible intervention to mitigate the psychological impacts of COVID-19 isolation for older adults. We demonstrated that it is feasible to undertake a trial of BA. The intervention can be delivered remotely and at scale, but should be reserved for older adults with evidence of depressive symptoms. The significant reduction in loneliness is unlikely to be a chance finding, and replication will be explored in a fully powered randomised controlled trial (RCT).

Trial registration

ISRCTN94091479.

ctDNA: An emerging neoadjuvant biomarker in resectable solid tumors

Mar, 12/10/2021 - 15:00

by Christopher Abbosh, Charles Swanton

Christopher Abbosh and Charles Swanton discuss circulating tumor DNA as a potential biomarker for neoadjuvant treatment response in solid tumors.

Clinical interventions for adults with comorbid alcohol use and depressive disorders: A systematic review and network meta-analysis

Ven, 08/10/2021 - 15:00

by Sean Grant, Gulrez Azhar, Eugeniu Han, Marika Booth, Aneesa Motala, Jody Larkin, Susanne Hempel

Background

Uncertainty remains regarding the effectiveness of treatments for patients diagnosed with both an alcohol use disorder (AUD) and depressive disorder. This study aimed to compare the effectiveness of clinical interventions for improving symptoms of adults with co-occurring AUDs and depressive disorders.

Methods and findings

We searched CINAHL, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Excerpta Medica Database, International Clinical Trials Registry Platform (ICTRP), PubMed, PsycINFO, and Web of Science from inception to December 2020. We included randomized controlled trials (RCTs) evaluating clinical interventions for adults with co-occurring AUDs and depressive disorders. Two independent reviewers extracted study-level information and outcome data. We assessed risk of bias using the Cochrane Risk of Bias tool, used frequentist random effects models for network meta-analyses, and rated our confidence in effect estimates using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Primary outcomes were remission from depression and alcohol use. Secondary outcomes were depressive symptoms, alcohol use, heavy drinking, health-related quality of life, functional status, and adverse events. We used standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes to estimate intervention effects. Overall, 36 RCTs with 2,729 participants evaluated 14 pharmacological and 4 psychological interventions adjunctive to treatment as usual (TAU). Studies were published from 1971 to 2019, conducted in 13 countries, and had a median sample size of 50 participants (range: 14 to 350 participants). We have very low confidence in all estimates of intervention effects on our primary outcomes (i.e., remission from depression and remission from alcohol use). We have moderate confidence that cognitive behavioral therapies (CBTs) demonstrated greater benefit than no additional treatment (SMD = −0.84; 95% confidence interval [CI], −1.05 to −0.63; p < 0.001) for depressive symptoms and low confidence (SMD = −0.25; 95% CI, −0.47 to −0.04; p = 0.021) for alcohol use. We have low confidence that tricyclic antidepressants (TCAs) demonstrated greater benefit than placebo (SMD = −0.37; 95% CI, −0.72 to −0.02, p = 0.038) for depressive symptoms. Compared with placebo, we have moderate confidence that selective serotonin reuptake inhibitors (SSRIs) demonstrated greater benefit for functional status (SMD = −0.92; 95% CI, −1.36 to −0.47, p < 0.001) and low confidence for alcohol use (SMD = −0.30; 95% CI, −0.59 to −0.02, p = 0.039). However, we have moderate confidence that patients receiving SSRIs also were more likely to experience an adverse event (OR = 2.20; 95% CI, 0.94 to 5.16, p = 0.07). We have very low confidence in all other effect estimates, and we did not have high confidence in any effect estimates. Limitations include the sparsity of evidence on intervention effects over the long term, risks of attrition bias, and heterogeneous definitions of adverse events in the evidence base.

Conclusions

We are very uncertain about the existence (or not) of any non-null effects for our primary outcomes of remission from depression and remission from alcohol use. The available evidence does suggest that CBTs likely reduced, and TCAs may have resulted in a slight reduction of depressive symptoms. SSRIs likely increased functional status, and SSRIs and CBTs may have resulted in a slight reduction of alcohol use. However, patients receiving SSRIs also likely had an increased risk of experiencing an adverse event. In addition, these conclusions only apply to postintervention and are not against active comparators, limiting the understanding of the efficacy of interventions in the long term as well as the comparative effectiveness of active treatments. As we did not have high confidence in any outcomes, additional studies are warranted to provide more conclusive evidence.