Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment.

OBJECTIVES: To report the impact of continued burosumab treatment on clinical laboratory tests of efficacy, patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia who continued from a 96-week phase 3 study into a 48-week open-label extension. METHODS: Eligible participants from the phase 3 study continued on the burosumab regimen received at the end of the phase 3 study for a further 48 weeks (n=31). Some (not all) received compassionate burosumab treatment between the two studies (a period of 6-18 months). The primary efficacy outcome was fasting serum phosphate concentration; secondary outcomes were serum 1,25 dihydroxyvitamin D concentration, renal phosphate reabsorption, PROs and ambulatory function. RESULTS: Improvements in fasting serum phosphate, serum 1,25 dihydroxyvitamin D and renal phosphate reabsorption at 96 weeks were maintained through the 48-week extension. Improvements were also maintained in stiffness and physical function measured using the Western Ontario and McMaster Universities Osteoarthritis Index, pain and fatigue endpoints measuring using the Brief Pain Inventory short-form and Brief Pain Inventory, respectively, and in ambulatory function (6-Minute Walk Test).A post-hoc exploratory analysis exploring outcomes in participants who discontinued burosumab treatment between the studies (n=7) and those who received at least one dose (n=23) indicated that the benefits of burosumab on clinical laboratory tests of efficacy, PROs and ambulatory function may be lost when treatment is interrupted but recover over time when treatment is reinstated. CONCLUSION: Continued treatment with burosumab appears necessary for sustained clinical benefit. TRIAL REGISTRATION NUMBERS: Phase 3: NCT02526160; open-label extension: NCT03920072.

The COVID-19, racism, and violence syndemic: Evidence from a qualitative study with Black residents of Chicago.

The COVID-19 pandemic emerged in the United States in the shadows of a vast history of structural racism and community and police violence that disproportionately affect Black communities. Collectively, they have created a syndemic, wherein COVID-19, racism, and violence are mutually reinforcing to produce adverse health outcomes. The purpose of this study was to understand the COVID-19, racism, and violence syndemic and examine how structural racism and violence contributed to the disproportionate impact of COVID-19 on Black communities. In early 2021, we conducted phenomenological qualitative interviews with 50 Black residents of Chicago. Interview transcripts were coded and analyzed using thematic analysis. We identified four primary themes in our analyses: 1) the intersection of racism and violence in Chicago; 2) longstanding inequities were laid bare by COVID-19; 3) the pervasiveness of racism and violence contributes to poor mental health; 4) and COVID-19, racism and violence emerged as a syndemic. Our findings underscore the importance of addressing social and structural factors in remediating the health and social consequences brought about by COVID-19.

Sexually Transmitted Infections Diagnosed Among Sexual and Gender Minority Communities During the First 11 Months of the COVID-19 Pandemic in Midwest and Southern Cities in the United States.

BACKGROUND: The COVID-19 pandemic adversely affected sexual health services. Given the burden of sexually transmitted infections (STIs) on sexual and gender minorities (SGMs), we estimated incidence of self-reported STI diagnoses and factors associated with STI diagnoses among SGMs during the pandemic's first year. METHODS: A cohort of 426 SGM persons, 25 years or older, recruited in Chicago, Milwaukee, Detroit, Minneapolis, and Houston completed 5 online surveys from April 2020 to February 2021. Persons self-reported on each survey all health care provider STI diagnoses. Kaplan-Meier was used to estimate the cumulative risk of STI diagnoses, stratified by human immunodeficiency virus (HIV) status. Factors associated with STI diagnoses were assessed with a longitudinal negative binomial regression. RESULTS: Median age was 37 years, and 27.0% were persons living with HIV (PLH). Participants reported 63 STIs for a cumulative incidence for PLH and HIV-negative persons of 0.19 (95% confidence interval [CI], 0.13-0.29) and 0.12 (95% CI, 0.09-0.17), respectively. Regardless of HIV, a younger age and changes in health care use were associated with STI diagnoses. Among HIV-negative persons, the rate of STI diagnoses was higher in Houston than the Midwest cities (adjusted relative risk, 2.37; 95% CI, 1.08-5.20). Among PLH, a decrease in health care use was also associated with STI diagnoses (adjusted relative risk, 3.53; 95% CI, 1.01-12.32 vs no change in health care services), as was Hispanic ethnicity and using a dating app to meet a sex partner. CONCLUSIONS: Factors associated with STI diagnoses during the COVID-19 pandemic generally reflected factors associated with STI incidence before the pandemic like geography, HIV, age, and ethnicity.

1000 Hometown Heroes: Mobilising community social influencers for COVID-19 prevention, care and coping.

Coronavirus disease 2019 (COVID-19) created life-disrupting stressors that disproportionately burden disadvantaged communities with devastating impacts that extend far beyond the burden of the disease itself, including joblessness, housing and food insecurity, educational system upheavals, isolation due to disrupted relationships, worsened mental health and substance use and violence. Socially interconnected community members are resources whose efforts can be mobilised to improve COVID-19 coping within their social networks. This research examined the feasibility, acceptability, and reach of a social media-based peer influencer intervention for COVID-19 coping. Over a 9-month period in 2020, the project enrolled 1253 social influencers in Milwaukee-primarily ethnic and racial minorities-who regularly received and passed along messages to members of their social networks that provided advice about COVID-19 pandemic coping, economic survival, health protection, mental health, family needs, social justice and other impacts. Messages were shared by influencers with others over social media and also text messages, phone calls and conversations. Facebook social media tracking metrics objectively measured the community reach of social influencers' messages. Quantitative surveys and qualitative follow-up interviews with a subset of influencers also measured the feasibility and acceptability of the intervention. Social media monitoring metrics showed that, by the end of the project, influencers' messages reached an average of 7978 unique individuals per week and had an average of 13,894 total views per week, with more than 140,000 total cumulative organic impressions. More than half of social influencers indicated that-beyond Facebook message sharing-they shared COVID-19 prevention, care, and coping messages with social network members in conversations, phone calls and text messages. Social influencers reported that they valued having the opportunity to help community members to cope with pandemic stressors by conveying practical COVID-19 coping advice.

Clinical Outcomes Following a Change in Gestational Diabetes Mellitus Diagnostic Criteria Due to the COVID-19 Pandemic: A Case-Control Study.

BACKGROUND: Due to COVID-19, many centres adopted a change to the diagnosis of GDM. METHODS: A case-control study of antenatal patients between 1 April and 30 June in 2019 and 2020 looking at detection rates of GDM, use of medication, obstetric, and fetal outcomes. RESULTS: During COVID-19, the rate of positive GDM tests approximately halved (20% (42/210) in 2020 vs. 42.2% (92/218) in 2019, (p < 0.01)) with higher rates of requirement for insulin at diagnosis (21.4% (2020) vs. 2.2% (2019); p < 0.01), and at term (31% (2020) vs. 5.4% (2019); p < 0.01). and metformin at diagnosis (4.8% (2020) vs. 1.1% (2019); p < 0.01), and at term (14.3% (2020) vs. 7.6% (2019) p < 0.01), with no differences in birth outcomes. CONCLUSIONS: There was likely an underdiagnosis of GDM while women at a higher risk of hyperglycaemia were correctly identified. The GTT should be maintained as the gold-standard test where possible, with provisions made for social distancing during testing if required.

Immunological assessment of SARS-CoV-2 infection in pregnancy from diagnosis to delivery: A multicentre prospective study.

BACKGROUND: Background Population-based data on SARS-CoV-2 infection in pregnancy and assessment of passive immunity to the neonate, is lacking. We profiled the maternal and fetal response using a combination of viral RNA from naso-pharyngeal swabs and serological assessment of antibodies against SARS-CoV-2. METHODS: This multicentre prospective observational study was conducted between March 24th and August 31st 2020. Two independent cohorts were established, a symptomatic SARS-CoV-2 cohort and a cohort of asymptomatic pregnant women attending two of the largest maternity hospitals in Europe. Symptomatic women were invited to provide a serum sample to assess antibody responses. Asymptomatic pregnant women provided a nasopharyngeal swab and serum sample. RT-PCR for viral RNA was performed using the Cobas SARS-CoV-2 6800 platform (Roche). Umbilical cord bloods were obtained at delivery. Maternal and fetal serological response was measured using both the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche), Abbott SARS-CoV-2 IgG Assay and the IgM Architect assay. Informed written consent was obtained from all participants. RESULTS: Ten of twenty three symptomatic women had SARS-CoV-2 RNA detected on nasopharyngeal swabs. Five (5/23, 21.7%) demonstrated serological evidence of anti-SARS-CoV-2 IgG antibodies and seven (30.4%, 7/23) were positive for IgM antibodies. In the asymptomatic cohort, the prevalence of SARS-CoV-2 infection in RNA was 0.16% (1/608). IgG SARS-CoV-2 antibodies were detected in 1·67% (10/598, 95% CI 0·8%-3·1%) and IgM in 3·51% (21/598, 95% CI 2·3-5·5%). Nine women had repeat testing post the baseline test. Four (4/9, 44%) remained IgM positive and one remained IgG positive. 3 IgG anti-SARS-CoV-2 antibodies were detectable in cord bloods from babies born to five seropositive women who delivered during the study. The mean gestation at serological test was 34 weeks. The mean time between maternal serologic positivity and detection in umbilical cord samples was 28 days. CONCLUSION: Using two independent serological assays, we present a comprehensive illustration of the antibody response to SARS-CoV-2 in pregnancy, and show a low prevalence of asymptomatic SARS-CoV2. Transplacental migration of anti-SARS-CoV-2 antibodies was identified in cord blood of women who demonstrated antenatal anti-SARS-CoV-2 antibodies, raising the possibility of passive immunity.

PrEP Use and Persistence Among Young Sexual Minority Men 17-24 Years Old During the COVID-19 Pandemic.

The COVID-19 pandemic has caused disruptions to health care access for sexual and gender minorities in the U.S. We sought to explore the impact of COVID-19 on HIV pre-exposure prophylaxis (PrEP) use and sexual health services by assessing PrEP eligibility and use, changes in sexual behaviors, and HIV/STI testing during the COVID-19 pandemic. We surveyed 239 young sexual minority men (YSMM) 17-24 years old between April and September 2020 in the U.S. One-in-seven YSMM PrEP users discontinued use during the pandemic, and all those who discontinued PrEP reported a decrease in sexual activity. Twenty percent reported difficulty getting prescriptions and medications from their doctors or pharmacies, and more than 10% reported challenges accessing HIV/STI testing. Among those who met Centers for Disease Control and Prevention criteria for PrEP (n = 104), 86.5% were not currently using PrEP. Among those surveyed 3 months or later after the start of major COVID-19 stay-at-home measures (n = 165), 35.8% reported CAS with a causal partner within the past 3 months during the COVID-19 pandemic. Seeking HIV testing was associated with reporting condomless anal sex in the previous 3 months, indicating the necessity for ensuring continuity of basic sexual health services for YSMM. Failure to adequately adjust HIV prevention services and intervention in the face of pandemic-related adversity undermines efforts to end the HIV epidemic in the U.S.

RESUMEN: La pandemia de COVID-19 ha causado interrupciones en el acceso a la atención médica para las minorías sexuales y de género en los EE. UU. Buscamos explorar el impacto de COVID-19 en el uso de la profilaxis de preexposición al VIH (PrEP) y los servicios de salud sexual mediante la evaluación de la elegibilidad y el uso de PrEP, los cambios en los comportamientos sexuales y las pruebas de VIH/ITS durante la pandemia de COVID-19. Encuestamos a 239 hombres jóvenes de minorías sexuales (YSMM) de 17 a 24 años entre abril y septiembre de 2020 en los EE. UU. Uno de cada siete usuarios de PrEP YSMM interrumpió su uso durante la pandemia, y todos los que interrumpieron la PrEP informaron una disminución en la actividad sexual. El veinte por ciento informó tener dificultades para obtener recetas y medicamentos de sus médicos o farmacias, y más del 10% informó tener dificultades para acceder a las pruebas de VIH/ITS. Entre los que cumplieron con los criterios de los Centros para el Control y la Prevención de Enfermedades para la PrEP (n = 104), el 86,5% no estaba usando PrEP actualmente. Entre los encuestados 3 meses o más después del inicio de las principales medidas de COVID-19 para quedarse en casa (n = 165), el 35,8% informó CAS con una pareja causal en los últimos 3 meses durante la pandemia de COVID-19. La búsqueda de la prueba del VIH se asoció con la notificación de sexo anal sin condón en los 3 meses anteriores, lo que indica la necesidad de garantizar la continuidad de los servicios básicos de salud sexual para YSMM. No ajustar adecuadamente los servicios de prevención del VIH y la intervención frente a la adversidad relacionada con la pandemia socava los esfuerzos para poner fin a la epidemia del VIH en los EE. UU.

Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial.

Importance: Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk. Objective: To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants. Interventions: Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks. Main Outcomes and Measures: The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2-positive participants. Results: Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, -9 to 17; vs placebo: 3 milliseconds; 95% CI, -5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered. Conclusions and Relevance: In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04329923.

"I Feel Almost as Though I've Lived This Before": Insights from Sexual and Gender Minority Men on Coping with COVID-19.

As communities struggle with how to cope with the health and social consequences of coronavirus disease 2019 (COVID-19), sexual and gender minority men living with or affected by the HIV/AIDS epidemic have important insights into how to cope with uncertainty, public health protocols, and grief. We recruited sexual and gender minority men using online networking apps from April 18-24, 2020 to enroll a longitudinal cohort. We analyzed baseline qualitative data from open-ended responses using content analysis to examine how the HIV/AIDS epidemic has helped sexual minority men with the current COVID-19 pandemic. Of the 437 participants who completed the survey, 155 (35%) indicated that HIV/AIDS had helped them cope with COVID-19. Free-response data from those 135 of those participants clustered around four themes: (1) experience having lived through a pandemic, (2) experience coping with stigma, (3) familiarity with public health protocols, and (4) belief in collective action. Based on the experiences of these men, public health approaches centered on resilience and collective action could be particularly helpful in responding and coping with COVID-19-especially if the pandemic persists over longer periods of time.