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Purpose This pilot study of a culturally adapted online mental health literacy (MHL) program called ‘Tara, Usap Tayo!’ (C’mon, Let’s Talk) aims to assess the acceptability, appropriateness, feasibility, and potential effectiveness in improving the help-seeking behavior of Filipino migrant domestic workers in the United Kingdom (UK). Methods Using mixed methods, we conducted a non-randomized single-group study of the online MHL program with 21 participants. The development of this intervention was guided by the Medical Research Council Framework for developing complex interventions and utilized Heim & Kohrt’s (2019) framework for cultural adaptation. Content materials from the WHO Mental Health Gap Action Program (mhGAP), WHO Problem Management Plus (PM +) and Adult Improving Access to Psychological Therapies (IAPT) were modified and translated into the Filipino language. The MHL program was delivered online in three sessions for two hours each session. Data were collected at three time points: (T1) pretest; (T2) posttest; and (3) follow-up test. Quantitative data on participants’ attitudes towards help-seeking and level of mental health literacy as outcome measures of potential intervention effectiveness were collected at T1, T2 and T3, while focus group discussions (FGDs) to assess participants’ feedback on the acceptability, feasibility, and appropriateness of the online MHL program were conducted immediately at T2. Data analysis was done using a thematic approach for qualitative data from the FGDs and descriptive statistics and repeated-measures ANOVA were used to assess the difference in the T1, T2, and T3 tests . Both quantitative and qualitative results were then integrated and triangulated to answer the research questions. Results The online MHL program is generally acceptable, appropriate, and feasible for use among Filipino migrant domestic workers. Preliminary findings lend support for its possible effectiveness in improving mental health literacy and help-seeking propensity. The cultural adaptation made in the content, form, and delivery methods of the intervention was acceptable and feasible for this target subcultural group. Conclusion By improving their mental health literacy and help-seeking propensity, this online MHL program has the potential to provide support to the mental health and well-being of Filipino migrant domestic workers in the UK. Further feasibility study or large-scale randomized controlled trial is needed to confirm the preliminary findings of this study.

PurposeThis systematic review aims to synthesise the evidence on behavioural and attitudinal patterns as well as barriers and enablers in Filipino formal help-seeking.MethodsUsing PRISMA framework, 15 studies conducted in 7 countries on Filipino help-seeking were appraised through narrative synthesis.ResultsFilipinos across the world have general reluctance and unfavourable attitude towards formal help-seeking despite high rates of psychological distress. They prefer seeking help from close family and friends. Barriers cited by Filipinos living in the Philippines include financial constraints and inaccessibility of services, whereas overseas Filipinos were hampered by immigration status, lack of health insurance, language difficulty, experience of discrimination and lack of acculturation to host culture. Both groups were hindered by self and social stigma attached to mental disorder, and by concern for loss of face, sense of shame, and adherence to Asian values of conformity to norms where mental illness is considered unacceptable. Filipinos are also prevented from seeking help by their sense of resilience and self-reliance, but this is explored only in qualitative studies. They utilize special mental health care only as the last resort or when problems become severe. Other prominent facilitators include perception of distress, influence of social support, financial capacity and previous positive experience in formal help.ConclusionWe confirmed the low utilization of mental health services among Filipinos regardless of their locations, with mental health stigma as primary barrier, while resilience and self-reliance as coping strategies were cited in qualitative studies. Social support and problem severity were cited as prominent facilitators.

Scarce data are available on what variables affect the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of symptomatic COVID-19, and, particularly, the relationship with viral load. We aimed to analyse data from linked index cases of COVID-19 and their contacts to explore factors associated with transmission of SARS-CoV-2. In this cohort study, patients were recruited as part of a randomised controlled trial done between March 17 and April 28, 2020, that aimed to assess if hydroxychloroquine reduced transmission of SARS-CoV-2. Patients with COVID-19 and their contacts were identified by use of the electronic registry of the Epidemiological Surveillance Emergency Service of Catalonia (Spain). Patients with COVID-19 included in our analysis were aged 18 years or older, not hospitalised, had quantitative PCR results available at baseline, had mild symptom onset within 5 days before enrolment, and had no reported symptoms of SARS-CoV-2 infections in their accommodation or workplace within the 14 days before enrolment. Contacts included were adults with a recent history of exposure and absence of COVID-19-like symptoms within the 7 days preceding enrolment. Viral load of contacts, measured by quantitative PCR from a nasopharyngeal swab, was assessed at enrolment, at day 14, and whenever the participant reported COVID-19-like symptoms. We assessed risk of transmission and developing symptomatic disease and incubation dynamics using regression analysis. We assessed the relationship of viral load and characteristics of cases (age, sex, number of days from reported symptom onset, and presence or absence of fever, cough, dyspnoea, rhinitis, and anosmia) and associations between risk of transmission and characteristics of the index case and contacts. We identified 314 patients with COVID-19, with 282 (90%) having at least one contact (753 contacts in total), resulting in 282 clusters. 90 (32%) of 282 clusters had at least one transmission event. The secondary attack rate was 17% (125 of 753 contacts), with a variation from 12% when the index case had a viral load lower than 1 × 106 copies per mL to 24% when the index case had a viral load of 1 × 1010 copies per mL or higher (adjusted odds ratio per log10 increase in viral load 1·3, 95% CI 1·1–1·5). Increased risk of transmission was also associated with household contact (3·0, 1·59–5·65) and age of the contact (per year: 1·02, 1·01–1·04). 449 contacts had a positive PCR result at baseline. 28 (6%) of 449 contacts had symptoms at the first visit. Of 421 contacts who were asymptomatic at the first visit, 181 (43%) developed symptomatic COVID-19, with a variation from approximately 38% in contacts with an initial viral load lower than 1 × 107 copies per mL to greater than 66% for those with an initial viral load of 1 × 1010 copies per mL or higher (hazard ratio per log10 increase in viral load 1·12, 95% CI 1·05–1·20; p=0·0006). Time to onset of symptomatic disease decreased from a median of 7 days (IQR 5–10) for individuals with an initial viral load lower than 1 × 107 copies per mL to 6 days (4–8) for those with an initial viral load between 1 × 107 and 1 × 109 copies per mL, and 5 days (3–8) for those with an initial viral load higher than 1 × 109 copies per mL. In our study, the viral load of index cases was a leading driver of SARS-CoV-2 transmission. The risk of symptomatic COVID-19 was strongly associated with the viral load of contacts at baseline and shortened the incubation time of COVID-19 in a dose-dependent manner. YoMeCorono, Generalitat de Catalunya. For the Catalan translation of the abstract see Supplementary Materials section.

BACKGROUNDWeeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called multisystem inflammatory syndrome in children (MIS-C). Gastrointestinal (GI) symptoms are common in patients with MIS-C, and a severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not been identified to date.METHODSHere, we analyzed biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. Stools were assessed for SARS-CoV-2 by reverse transcription PCR (RT-PCR), and plasma was examined for markers of breakdown of mucosal barrier integrity, including zonulin. Ultrasensitive antigen detection was used to probe for SARS-CoV-2 antigenemia in plasma, and immune responses were characterized. As a proof of concept, we treated a patient with MIS-C with larazotide, a zonulin antagonist, and monitored the effect on antigenemia and the patient's clinical response.RESULTSWe showed that in children with MIS-C, a prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. The patient with MIS-C treated with larazotide had a coinciding decrease in plasma SARS-CoV-2 spike antigen levels and inflammatory markers and a resultant clinical improvement above that achieved with currently available treatments.CONCLUSIONThese mechanistic data on MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19-related disease in children.

The effect of continuous positive airway pressure (CPAP) on mediators of cardiovascular disease and depression in women with obstructive sleep apnea (OSA) is unknown. We aimed to assess the effect of CPAP therapy on a variety of biomarkers of inflammation, antioxidant activity, and depression in women with OSA. We conducted a multicenter, randomized controlled trial in 247 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI] ≥ 15). Women were randomized to CPAP (n = 120) or conservative treatment (n = 127) for 12 weeks. Changes in tumor necrosis factor α (TNFα), interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), catalase (CAT), superoxide dismutase (SOD), and brain-derived neurotrophic factor (BDNF) were assessed. Additional analyses were conducted in subgroups of clinical interest. Women had a median (25th-75th percentiles) age of 58 (51-65) years, body mass index 33.5 (29.0-38.3) kg/m2, and AHI 33.3 (22.8-49.3). No differences were found between groups in the baseline levels of the biomarkers. After 12 weeks of follow-up, there were no changes between groups in any of the biomarkers assessed. These results did not change when the analyses were restricted to sleepy women or to those with severe OSA. In women with CPAP use at least 5 hours per night, only TNFα levels decreased compared to the control group (-0.29 ± 1.1 vs -0.06 ± 0.53, intergroup difference -0.23 [95% CI = -0.03 to -0.50]; p = 0.043). Twelve weeks of CPAP therapy does not improve biomarkers of inflammation, antioxidant activity, or depression compared to conservative treatment in women with moderate-to-severe OSA. NCT02047071.

This study was funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393; J.R.R.) and PTA-12264I, Retos de la Sociedad (DEP2016-79512-R; J.R.R.) and European Regional Development Funds (ERDF; J.R.R.), the Spanish Ministry of Education (FPU13/04365 (G.S.D.), FPU14/04172 (F.A.G.), FPU15/04059 (J.M.A.), FPU16/03653 (A.M.G.), FPU16/02828 (F.J.O.P.), FPU16/05159 (H.X.), FPU17/01523 (L.O.A.), FPU19/01609 (L.J.F.)), International Doctoral Studies Scholarship no. 440575 from the Mexican National Council of Science and Technology (CONACYT; WDMA), the Fundación Iberoamericana de Nutrición (FINUT; JRR), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022; J.R.R.), the AstraZeneca HealthCare Foundation (J.R.R.), the University of Granada Plan Propio de Investigación 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES) (J.R.R.)- and Plan Propio de Investigación 2018 - Programa Contratos-Puente and Programa Perfecionamiento de Doctores (G.S.D.), the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF; ref. SOMM17/6107/UGR; JRR), the Junta de Andalucía, Consejería de Economía, Conocimiento, Empresas y Universidad (ref. P18-RT-4455; J.R.R.), the Fundación Alfonso Martín Escudero (B.M.T. and G.S.D.), the Maria Zambrano fellowship by the Ministerio de Universidades y la Unión Europea NextGenerationEU (RR_C_2021_04; B.M.T.), and the Novo Nordisk Foundation (NNF18OC0032394; M.S.).

Several de-escalation approaches are under investigation in patients with HER2-positive, early-stage breast cancer. We assessed early metabolic responses to neoadjuvant trastuzumab and pertuzumab using 18F-fluorodeoxyglucose (18F-FDG)-PET (18F-FDG-PET) and the possibility of chemotherapy de-escalation using a pathological response-adapted strategy. We did a multicentre, randomised, open-label, non-comparative, phase 2 trial in 45 hospitals in Spain, France, Belgium, Germany, the UK, Italy, and Portugal. Eligible participants were women aged 18 years or older with centrally confirmed, HER2-positive, stage I–IIIA, invasive, operable breast cancer (≥1·5 cm tumour size) with at least one breast lesion evaluable by 18F-FDG-PET, an Eastern Cooperative Oncology Group performance status of 0 or 1, and a baseline left ventricular ejection fraction of at least 55%. We randomly assigned participants (1:4), via an interactive response system using central block randomisation with block sizes of five, stratified by hormone receptor status, to either docetaxel (75 mg/m2 intravenous), carboplatin (area under the concentration–time curve 6 mg/mL  per  min intravenous), trastuzumab (subcutaneous 600 mg fixed dose), and pertuzumab (intravenous 840 mg loading dose, 420 mg maintenance doses; group A); or trastuzumab and pertuzumab (group B). Hormone receptor-positive patients allocated to group B were additionally given letrozole if postmenopausal (2·5 mg/day orally) or tamoxifen if premenopausal (20 mg/day orally). Centrally reviewed 18F-FDG-PET scans were done before randomisation and after two treatment cycles. Patients assigned to group A completed six cycles of treatment (every 3 weeks) regardless of 18F-FDG-PET results. All patients assigned to group B initially received two cycles of trastuzumab and pertuzumab. 18F-FDG-PET responders in group B continued this treatment for six further cycles; 18F-FDG-PET non-responders in this group were switched to six cycles of docetaxel, carboplatin, trastuzumab, and pertuzumab. Surgery was done 2–6 weeks after the last dose of study treatment. Adjuvant treatment was selected according to the neoadjuvant treatment administered, pathological response, hormone receptor status, and clinical stage at diagnosis. The coprimary endpoints were the proportion of 18F-FDG-PET responders in group B with a pathological complete response in the breast and axilla (ypT0/is ypN0) as determined by a local pathologist after surgery after eight cycles of treatment, and 3-year invasive disease-free survival of patients in group B, both assessed by intention to treat. The definitive assessment of pathological complete response was done at this primary analysis; follow-up to assess invasive disease-free survival is continuing, hence these data are not included in this Article. Safety was assessed in all participants who received at least one dose of study drug. Health-related quality-of-life was assessed with EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline, after two cycles of treatment, and before surgery. This trial is registered with EudraCT (2016-002676-27) and ClinicalTrials.gov (NCT03161353), and is ongoing. Between June 26, 2017, and April 24, 2019, we randomly assigned 71 patients to group A and 285 to group B. Median follow-up was 5·7 months (IQR 5·3–6·0). 227 (80%) of 285 patients in group B were 18F-FDG-PET responders, of whom 86 (37·9%, 95% CI 31·6–44·5; p<0·0001 compared with the historical rate) of 227 had a pathological complete response. The most common haematological grade 3–4 adverse events were anaemia (six [9%] of 68 patients in group A vs four [1%] of 283 patients in group B), neutropenia (16 [24%] vs ten [4%]), and febrile neutropenia (14 [21%] vs 11 [4%]). Serious adverse events occurred in 20 (29%) of 68 patients in group A versus 13 (5%) of 283 patients in group B. No deaths were reported during neoadjuvant treatment. Global health status declined by at least 10% in 65·0% (95% CI 46·5–72·4) and 35·5% (29·7–41·7) of patients in groups A and B, respectively 18F-FDG-PET identified patients with HER2-positive, early-stage breast cancer who were likely to benefit from chemotherapy-free dual HER2 blockade with trastuzumab and pertuzumab, and a reduced impact on global health status. Depending on the forthcoming results for the 3-year invasive disease-free survival endpoint, this strategy might be a valid approach to select patients not requiring chemotherapy. F Hoffmann-La Roche.

The Moderna mRNA-1273 vaccine, which elicited antibodies and T cells specific for the Covid-19 virus in adults 55 years of age or younger, elicited similarly high levels of neutralizing-antibody and CD4 T-cell responses in a small group of older adults, including those 71 years of age or older.

Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele human leukocyte antigen (HLA)-B*5701, whereas a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated two genes, one of which encodes an RNA polymerase I subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.

This study investigated the effects of a multicomponent exercise intervention on muscle strength, incidence of falls and functional outcomes in frail elderly patients with dementia after long-term physical restraint, followed by 24 weeks of training cessation. Eighteen frail elderly patients with mild dementia (88.1 ± 5.1 years) performed a multicomponent exercise program, which consisted of 4 weeks of walking, balance and cognitive exercises, followed by 4 weeks of resistance exercise performed twice weekly [8–12 repetitions at 20–50 % of the one-repetition maximum (1RM)], combined with walking, balance and cognitive exercises. Before and after training, as well as after 24 weeks of training cessation, strength outcomes, Barthel Index, balance, gait ability, rise from a chair ability, dual task performance, incidence of falls and Mini-Mental State Examination were assessed. After the first 4 weeks of training, there was a significant improvement only in the balance test, whereas no additional changes were observed. However, after the second part of the training, the participants required significantly less time for the time-up-and-go test ( P  < 0.05), and improved the isometric hand grip, hip flexion and knee extension strength, as well as the leg press 1RM ( P  < 0.01). A significant reduction was also observed in the incidence of falls ( P  < 0.01). After 24 weeks of training cessation, abrupt decreases were observed in nearly all of the physical outcomes ( P  < 0.05). The exercise intervention improved strength, balance and gait ability in frail elderly patients with dementia after long-term physical restraint, and these benefits were lost after training cessation.