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Abstract Background There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder. Methods This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18–65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles. Discussion This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

Abstract Background HIV burden in the US among people who inject drugs (PWID) is driven by overlapping syndemic factors such as co-occurring health needs and environmental factors that synergize to produce worse health outcomes among PWID. This includes stigma, poverty, and limited healthcare access (e.g. medication to treat/prevent HIV and for opioid use disorder [MOUD]). Health services to address these complex needs, when they exist, are rarely located in proximity to each other or to the PWID who need them. Given the shifting drug use landscapes and geographic heterogeneity in the US, we evaluate a data-driven approach to guide the delivery of such services to PWID in local communities. Methods We used a hybrid, type I, embedded, mixed method, data-driven approach to identify and characterize viable implementation neighborhoods for the HPTN 094 complex intervention, delivering integrated MOUD and HIV treatment/prevention through a mobile unit to PWID across five US cities. Applying the PRISM framework, we triangulated geographic and observational pre-implementation phase data (epidemiological overdose and HIV surveillance data) with two years of implementation phase data (weekly ecological assessments, study protocol meetings) to characterize environmental factors that affected the viability of implementation neighborhoods over time and across diverse settings. Results Neighborhood-level drug use and geographic diversity alongside shifting socio-political factors (policing, surveillance, gentrification) differentially affected the utility of epidemiological data in identifying viable implementation neighborhoods across sites. In sites where PWID are more geographically dispersed, proximity to structural factors such as public transportation and spaces where PWID reside played a role in determining suitable implementation sites. The utility of leveraging additional data from local overdose and housing response systems to identify viable implementation neighborhoods was mixed. Conclusions Our findings suggest that data-driven approaches provide a contextually relevant pragmatic strategy to guide the real-time implementation of integrated care models to better meet the needs of PWID and help inform the scale-up of such complex interventions. This work highlights the utility of implementation science methods that attend to the impact of local community environmental factors on the implementation of complex interventions to PWID across diverse drug use, sociopolitical, and geographic landscapes in the US. Trial registration ClincalTrials.gov, Registration Number: NCT04804072 . Registered 18 February 2021.

Abstract Objectives Phenobarbital (PB) is a long‐acting GABA A‐agonist with favorable pharmacokinetics (long half‐life and duration of effect) that allows effective treatment of alcohol withdrawal (AW) after administration of a single loading dose. Current evidence suggests that in the setting of AW, PB administration may be associated with decreased hospital admissions and hospital length of stay. The aim of this study was to evaluate the safety outcomes of AW patients who were treated and discharged from the emergency department (ED) after receiving PB for AW. Methods This retrospective chart review included a convenience sample of 33 AW patients who presented to four EDs within an 18‐month span. Descriptive statistics (frequencies and percentages) were used to describe demographics, distribution of resources and referrals, and the safety outcomes of PB administration for low‐risk AW patients. Patients were selected for inclusion in consultation with a medical toxicologist, treated with PB, and discharged from the ED. Electronic medical records were utilized to gather information on the patient cohort. Results All patients were treated with at least a single loading dose of 5‒10 mg/kg (ideal body weight) of intravenous or per os PB during their ED stay. Only one patient had an unanticipated event after discharge, which was related to driving against advice. Two additional patients had ED revisits for recurrent alcohol use within 72 h, and 16 patients had recurrent alcohol use within 30 days. All 33 patients were provided with resources for linkage to treatment. None required hospital admission. Conclusion ED PB “load and go” may be a safe, effective AW treatment that could help treat AW, facilitate linkage to specific rehabilitation treatments, and decrease hospital admissions.

Abstract Background Persons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, “whole-person” strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit (“mobile unit”) with peer navigation compared to peer navigation alone to access these services at brick and mortar locations. Methods HPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of “one-stop” integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization. Discussion This trial responds to a need for evidence on using a “whole-person” strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care. Trial registration ClinicalTrials.gov NCT04804072 . Registered on 18 March 2021.

Introduction: Despite national goals to eliminate Hepatitis C (HCV) and the advancement of curative, well-tolerated direct-acting antiviral (DAAs) regimens, rates of HCV treatment have declined nationally since 2015. Current HCV guidelines encourage treatment of HCV by primary care providers (PCPs). Payors have reduced restrictions to access DAAs nationally and in California however it remains unclear if the removal of these restrictions has impacted the proportion of PCPs prescribing DAAs at a health system level. Our objective was to examine the proportion of DAAs prescribed by PCPs and specialists and to describe the population receiving treatment in a single health system from 2015 to 2022. Methods: We examined the proportion of DAAs prescribed by PCPs and specialists and the population receiving treatment through a retrospective analysis of claims data in the University of California, Los Angeles (UCLA) Health System from 2015 to 2022. We described number of prescriptions for HCV medication prescribed by PCPs and specialists by year, medication type, and physician specialty. We also described numbers of prescriptions by patient demographics and comorbidities. Results: A total of 1515 adult patients received a prescription for HCV medication through the UCLA Health System between 2015 and 2022. The proportion of patients receiving prescriptions for PCPs peaked at 19% in 2016, yet decreased to 5.7% in 2022, an average of 13% across all years. Median age of patients receiving treatment was 60 years old, and 56% of patients receiving HCV treatment had commercial insurance as their primary payer. Conclusions: HCV treatment declined from 2015 to 2022 among specialists and PCPs in our health system. Older patients comprised the majority of patients receiving treatment, suggesting a need for novel approaches to reach patients under 40, an age group with significant increases in HCV transmission.

Abstract Background Research on women who inject drugs is scarce in low- and middle-income countries. Women experience unique harms such as sexism and sexual violence which translate into negative health outcomes. The present work aims to provide insight into the experiences of women who inject drugs at the US–Mexico border to identify social and health-related risk factors for overdose to guide harm reduction interventions across the Global South. Methods We recruited 25 women ≥ 18 years of age accessing harm reduction and sexual health services at a non-governmental harm reduction organization, “Verter”, in Mexicali, Mexico. We employed purposeful sampling to recruit women who inject drugs who met eligibility criteria. We collected quantitative survey data and in-depth interview data. Analyses of both data sources involved the examination of descriptive statistics and thematic analysis, respectively, and were guided by the syndemic and continuum of overdose risk frameworks. Results Survey data demonstrated reports of initiating injection drug use at a young age, experiencing homelessness, engaging in sex work, being rejected by family members, experiencing physical violence, injecting in public spaces, and experiencing repeated overdose events. Interview data provided evidence of stigma and discrimination toward women, a lack of safe spaces and support systems, risk of overdose-related harms, sexual violence, and the overall need for harm reduction services. Conclusion Women who inject drugs in Mexicali describe experiences of violence, overdose, and public injecting. Women are particularly vulnerable in the Mexicali context, as this area faces a noticeable lack of health and social services. Evidenced-based harm reduction strategies such as safe consumption sites and overdose prevention strategies (e.g., naloxone distribution and training) may benefit this population. Evidence from local organizations could help close the gap in service provision in low-resource settings like Mexico, where government action is almost nonexistent.

Summary: The public health crisis due to opioid overdose is worsening in Mexico’s northern region due to the introduction of illicitly manufactured fentanyl into the local drug supply. Though there is an increase in overdose deaths, there is no accurate report of overdoses by Mexican government agencies and no comprehensive opioid overdose prevention strategy. There is currently only an anti-drug marketing strategy which is likely insufficient to mitigate the growing epidemic. In order to address the growing opioid overdose crisis in the country, it is necessary to create and implement a decentralized prevention strategy, that includes naloxone distribution, expanded treatment services in regions most in need, and create active dialogue with community organisations already implementing harm reduction actions. Decisive action must be taken by the Mexican government to ensure the health and wellbeing of the Mexican citizens, especially those at high risk for opioid overdose.

Abstract Objectives To investigate the impact of the COVID-19 pandemic along the U.S.-Mexico border region and evaluate the relationship of COVID-19 related mortality, socioeconomic status, and vaccination. Methods We used indirect standardization to age-adjust mortality rates and calculate standardized mortality ratios [SMR] in both countries. To examine the impact of socioeconomic factors, we calculated the Human Development Index (HDI) by county/municipality. We performed linear regression to understand the relationship between mortality, vaccination, and HDI. We used choropleth maps to visualize the trends seen in the region. Results Between January 22nd, 2020 and December 1st, 2021, surges of cases and deaths were similar in dyad cities along the U.S.-Mexico border visualizing the interconnectedness of the region. Mortality was higher in U.S. counties along the border compared to the national average (SMR 1.17, 95% CI 1.15–1.19). In Mexico, border counties had a slightly lower mortality to the national average (SMR 0.94, 95% CI 0.93–0.95). In U.S. border states, SMR was shown to negatively correlate with human development index (HDI), a socioeconomic proxy, resulting in a higher SMR in the border region compared to the rest of the counties. Conversely in Mexican border states, there was no association between SMR and HDI. Related to vaccination, U.S. counties along the border were vaccinated at a greater percentage than non-border counties and vaccination was negatively correlated with HDI. In Mexico, states along the border had a higher ratio of vaccinations per person than non-border states. Conclusions The U.S.-Mexico border is a divide of incredible importance not only to immigration but as a region with unique social, economic, environmental, and epidemiological factors that impact disease transmission. We investigated how the COVID-19 pandemic followed trends of previously studied diseases in the corridor such as tuberculosis, HIV, and influenza H1N1. These data state how targeted intervention along the U.S.-Mexico border region is a necessity when confronting COVID-19 and have implications for future control of infectious diseases in the region.

Background. Delayed graft function (DGF) is a major complication of deceased donor kidney transplantation. Saline (0.9% sodium chloride) is a commonly used intravenous fluid in transplantation but may increase the risk of DGF because of its high chloride content. Better Evidence for Selecting Transplant Fluids (BEST-Fluids), a pragmatic, registry-based, double-blind, randomized trial, sought to determine whether using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce DGF. We sought to evaluate the generalizability of the trial cohort by reporting the baseline characteristics and representativeness of the trial participants in detail. Methods. We compared the characteristics of BEST-Fluids participants with those of a contemporary cohort of deceased donor kidney transplant recipients in Australia and New Zealand using data from the Australia and New Zealand Dialysis and Transplant Registry. To explore potential international differences, we compared trial participants with a cohort of transplant recipients in the United States using data from the Scientific Registry of Transplant Recipients. Results. During the trial recruitment period, 2373 deceased donor kidney transplants were performed in Australia and New Zealand; 2178 were eligible‚ and 808 were enrolled in BEST-Fluids. Overall, trial participants and nonparticipants were similar at baseline. Trial participants had more coronary artery disease (standardized difference [d] = 0.09; P = 0.03), longer dialysis duration (d = 0.18, P < 0.001), and fewer hypertensive (d = −0.11, P = 0.03) and circulatory death (d = −0.14, P < 0.01) donors than nonparticipants. Most key characteristics were similar between trial participants and US recipients, with moderate differences (|d| ≥ 0.2; all P < 0.001) in kidney failure cause, diabetes, dialysis duration, ischemic time, and several donor risk predictors, likely reflecting underlying population differences. Conclusions. BEST-Fluids participants had more comorbidities and received slightly fewer high-risk deceased donor kidneys but were otherwise representative of Australian and New Zealand transplant recipients and were generally similar to US recipients. The trial results should be broadly applicable to deceased donor kidney transplantation practice worldwide.

Background: Drug overdoses are prevalent in low- and middle-income countries but are scarcely reported in the literature. We report on an opioid overdose reversal and naloxone distribution program that was instituted at the first safe consumption site in Latin America. Methods: A cross-sectional analysis of witnessed drug overdoses and naloxone distribution between 1 June 2019 and 31 May 2021 in Mexicali, Mexico. Case report forms were entered in an electronic database. Trends in overdose and naloxone distribution were described. Comparisons were made before and after the COVID-19 pandemic was declared in the city. Maps were created to represent the geographic distribution of overdose in the city. Results: During the study period 1,534 doses of naloxone were distributed throughout the community. In addition, there were 464 overdoses reported during this period, of which 4 were fatal. There was a 30% increase in reported overdoses from the period before the COVID-19 pandemic to the period after the pandemic was declared (p = 0.03). Most common substance reported included heroin (93%), sedatives (21%), methamphetamine (16%) and fentanyl (14%). Naloxone was given in 96% of cases (median 1 dose, IQR 1–2 doses) and emergency services were called in 20% of cases. Conclusions: An opioid overdose reversal program in Mexicali, Mexico was able to distribute naloxone and register drug overdoses between 2019 and 2021 as a harm reduction strategy. This adds to the growing body of literature on the impact of community-based programs on preventing fatal overdoses and the potential for implementation in low-resource settings.

Objective: To determine the diagnostic yield of repeat testing for SARS-CoV-2. Methods: A retrospective analysis was performed of all SARS-CoV-2 test results within the UCLA Health System between March 9th and April 29th, 2020. All patients with repeat test results were identified, and those with discordant results were reviewed. Results: Between March 9th and April 29th, there were 10,165 SARS-CoV-2 test results, of which 630 (6.2%) were positive. Among the 904 patients with repeat test results, 808 (89.4%) were initially negative, and 96 (10.6%) were initially positive. Among the 808 patients with an initial negative test, 15 (1.9%) subsequently tested positive. Eleven cases with an initial negative SARS-CoV-2 test and without a known prior positive SARS-CoV-2 test were reviewed; 6 were employed as healthcare workers, and 10 were positive on the second test. Conclusions: We found a low diagnostic yield of repeat testing for SARS-CoV-2 in our health system. Repeat testing might prove useful in certain clinical scenarios, such as in healthcare workers, when symptoms develop after a negative test, and in hospitalized patients with a high clinical suspicion of COVID-19.

In Ghana, the high-risk obstetric referral system is inadequate. Delay is common and patients often arrive to receiving hospitals in compromised states. An effective referral system should include an adequately resourced referral hospital, communication across sectors, accountability, transport, monitoring capability and policy support, which are currently lacking. A pilot program was undertaken to facilitate communication between hospital staffs. Additionally, data was collected to better understand and characterize obstetric referrals in Accra. Thirteen institutions were selected based on referral volume to implement the use of pre-referral treatment guidelines and WhatsApp as a mobile technology communication platform (Platform). Participants included healthcare workers from 8 health centers, 4 district hospitals, the Greater Accra Regional Hospital (GARH), administrators, doctors from other tertiary hospitals in Accra and medical consultants abroad. Facilities were provided smartphones and guidelines on using WhatsApp for advice on patient care or referral. Data were collected on WhatsApp communications among participants (March-August 2017). During this period, 618 cases were posted on the Platform and users increased from 69 to 81. The median response time was 17 min, a receiving hospital was identified 511 (82.7%) times and pre-referral treatment was initiated in 341 (55.2%). Subsequently, data collected on 597 referrals to GARH (September-November 2017) included 319 (53.4%) from Platform and 278 (46.6%) from non-Platform hospitals. Of these, 515 (86.3%) were urgent referrals; the median (interquartile range) referral to arrival time was 293 (111-1887) minutes without variation by facility grouping. Taxis were utilized for transportation in 80.2%; however, referral time shortened when patients arrived by ambulance and with a midwife. Only 23.5% of urgent referrals arrived within two hours. This project demonstrates that WhatsApp can be used as a communication tool for high-risk obstetric referrals and highlights the need to continue to improve urban referral processes due to identified delays which may contribute to poor outcomes.

Long-acting injectable (LAI) antiretroviral therapy (ART) is a novel HIV treatment option for people with HIV. The first LAI ART regimen for HIV treatment received regulatory approval in the United States in January 2021. In February 2020, we collected qualitative data from 18 consumers and 23 clinical and non-clinical stakeholders to catalog anticipated individual-consumer, healthcare system, and structural levels barriers and facilitators to LAI ART implementation in Los Angeles County, California. Thematic analysis was guided by the CFIR implementation science model. CFIR constructs of intervention characteristics, individual characteristics, outer and inner setting, intervention characteristics, and implementation process emerged in analysis. Under intervention characteristics, anticipated facilitators included the relative advantage of LAI ART over pills for adherence and reduced treatment management burden and related anxiety; anticipated barriers included non-adherence to injection appointments, concerns of developing HIV resistance, discomfort with injection and cost. Anticipated facilitators based on individual characteristics included overall acceptability based on knowledge and positive beliefs about LAI ART. Participant noted several characteristics of the outer setting that could negatively impact implementation, such as medical mistrust, external policies, and LAI ART eligibility (i.e., to be virally suppressed prior to initiation). Participants were optimistic about the potential to decrease stigma but expressed that provider willingness for adoption could be hindered by challenges in organizational inner setting related to payment authorizations, increased staffing needs, medication procurement and storage, and provider and healthcare system readiness. Results from this pre-implementation study may inform rollout and scale-up of LAI ART in Los Angeles County.

Abstract Background Extra-gastric (particularly colonic) lymphoma of mucosa-associated lymphoid tissue in the immunosuppressed solid organ transplant recipient is rare. We report a case of low-volume mucosa-associated lymphoid tissue lymphoma with colonic and bone marrow involvement in a renal transplant recipient that has been managed conservatively. Case presentation A 62-year-old Caucasian man, 14 years after kidney transplantation, was diagnosed as having extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue with bone marrow and colonic involvement, after a colonoscopy identified mucosa-associated lymphoid tissue lymphoma in a sessile sigmoid polyp following surveillance fecal occult blood testing that returned a positive result. A gastric biopsy showed no evidence of Helicobacter pylori, but Helicobacter pylori immunoglobulin G was positive. He received Helicobacter pylori eradication treatment and is being managed expectantly. Immunosuppression was unchanged with prednisolone, mycophenolate mofetil, and cyclosporine A. Renal allograft function has remained stable. Conclusions This case highlights the unexpected occurrence of colonic mucosa-associated lymphoid tissue lymphoma in a kidney transplant recipient. The case emphasizes the importance of histopathological diagnosis of colonic lesions in this patient cohort because the unusual diagnosis of low-volume mucosa-associated lymphoid tissue lymphoma can be managed expectantly as it does not appear to be clinically aggressive in the immunosuppressed solid organ transplant.

Abstract Background In recent years, the number of infective endocarditis (IE) cases associated with injection drug use has increased. Clinical guidelines suggest deferring surgery for IE in people who inject drugs (PWID) due to a concern for worse outcomes in comparison to non-injectors (non-PWID). We performed a systematic review and meta-analysis of long-term outcomes in PWID who underwent cardiac surgery and compared these outcomes to non-PWID. Methods We systematically searched for studies reported between 1965 and 2018. We used an algorithm to estimate individual patient data (eIPD) from Kaplan-Meier (KM) curves and combined it with published individual patient data (IPD) to analyze long-term outcomes after cardiac surgery for IE in PWID. Our primary outcome was survival. Secondary outcomes were reoperation and mortality at 30-days, one-, five-, and 10-years. Random effects Cox regression was used for estimating survival. Results We included 27 studies in the systematic review and 19 provided data (KM or IPD) for the meta-analysis. PWID were younger and more likely to have S. aureus than non-PWID. Survival at 30-days, one-, five-, and 10-years was 94.3, 81.0, 62.1, and 56.6% in PWID, respectively; and 96.4, 85.0, 70.3, and 63.4% in non-PWID. PWID had 47% greater hazard of death (HR 1.47, 95% CI, 1.05–2.05) and more than twice the hazard of reoperation (HR 2.37, 95% CI, 1.25–4.50) than non-PWID. Conclusion PWID had shorter survival that non-PWID. Implementing evidence-based interventions and testing new modalities are urgently needed to improve outcomes in PWID after cardiac surgery.

Summary: Background: In 2015, Mexico implemented regulatory changes and an electronic system to improve access to prescription opioids. We aimed to investigate trends in opioid dispensing after the implementation of these changes and assess how opioid dispensing varied geographically and by socioeconomic status. Methods: In this retrospective analysis of prescription medication surveillance data, we analysed dispensing data for group 1 medications (all opioids, including morphine, methadone, hydromorphone, oxycodone, tapentadol, fentanyl, sufentanil, and remifentanil) obtained from the Federal Commission for the Protection against Sanitary Risk database for 32 states and six large metropolitan areas in Mexico. We calculated crude annual opioid prescriptions per 10 000 people at the national, state, and municipal levels. Adapting methods from the report of the Lancet Commission on Palliative Care and Pain Relief, we calculated the need for palliative opioids by state, and then assessed the observed opioid dispensing rates as a percentage of expected need by geographical socioeconomic status. Within the six major metropolitan areas, we mapped the geocoded location of opioid prescriptions and assessed the association between opioid dispensing and socioeconomic status as well as the association between opioid dispensing and time to US border crossing for areas on the US–Mexico border. Findings: Between June 25, 2015, and Oct 7, 2019, opioid dispensing rates increased by an average of 13% (95% CI 6·8–19·6) per quarter (3 months). The overall national opioid dispensing rate during the study period was 26·3 prescriptions per 10 000 inhabitants. States with a higher socioeconomic status had higher opioid dispensing rates than states with lower socioeconomic status (rate ratio [RR] 1·88, 95% CI 1·33–2·58, p=0·00016) after controlling for the estimated opioid requirement per state, the presence of methadone clinics, and the presence of tertiary hospitals and cancer centres. The same association between opioid dispensing and socioeconomic status was observed in the metropolitan areas, and in those metropolitan areas on the US–Mexico border a 20% decrease (RR 0·80, 95% CI 0·75–0·86) in opioid dispensation was observed per each SD increase (SD 17·1 min) in travel time to the border. Interpretation: Measures introduced by the Mexican federal Government to increase opioid access for patients with palliative care needs were only marginally successful in raising opioid prescription rates. Opioid access should be improved for patients with palliative care needs who live in geographical areas of lower socioeconomic status. Funding: US National Institutes of Health.

The article asks why we cannot now more actively work to imagine and construct a transnational American studies that allows people to work from where they are. This has been a desirable goal for some time but the Covid crisis is an occasion to ask this question anew.

Worldwide, testing capacity for SARS-CoV-2 is limited and bottlenecks in the scale up of polymerase chain reaction (PCR-based testing exist. Our aim was to develop and evaluate a machine learning algorithm to diagnose COVID-19 in the inpatient setting. The algorithm was based on basic demographic and laboratory features to serve as a screening tool at hospitals where testing is scarce or unavailable. We used retrospectively collected data from the UCLA Health System in Los Angeles, California. We included all emergency room or inpatient cases receiving SARS-CoV-2 PCR testing who also had a set of ancillary laboratory features (n = 1,455) between 1 March 2020 and 24 May 2020. We tested seven machine learning models and used a combination of those models for the final diagnostic classification. In the test set (n = 392), our combined model had an area under the receiver operator curve of 0.91 (95% confidence interval 0.87-0.96). The model achieved a sensitivity of 0.93 (95% CI 0.85-0.98), specificity of 0.64 (95% CI 0.58-0.69). We found that our machine learning algorithm had excellent diagnostic metrics compared to SARS-CoV-2 PCR. This ensemble machine learning algorithm to diagnose COVID-19 has the potential to be used as a screening tool in hospital settings where PCR testing is scarce or unavailable.

PurposeTo describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV).Materials and methodsA retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV.ResultsOur cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis.ConclusionsObesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.

Abstract Background Mycophenolic acid (MPA), either given as an ester pro-drug or as an enteric-coated sodium salt, is the most commonly prescribed anti-proliferative immunosuppressive agent used following organ transplantation and widely applied in immune-mediated diseases. Clinicians are well aware of common adverse reactions related to MPA treatment, in particular diarrhea, leukopenia and infections. Here we report a case of severe, persistent ascites associated with MPA treatment. The otherwise unexplained and intractable ascites, requiring repeated paracenteses for more than 8 months, rapidly ceased with stopping the MPA treatment. To our knowledge this is the first case of severe ascites associated with MPA treatment reported in the scientific literature. Case Presentation A 45-year old female with type 1 diabetes mellitus received a simultaneous kidney-pancreas transplant. The surgery was uneventful. However, post-operatively she developed severe transudative ascites requiring in total more than 40 paracenteses treatments draining in the average 2.8 l of ascites fluid. The ascites formation persisted despite exclusion of a surgical complication, fully functioning kidney and pancreas allografts, lack of any significant proteinuria, normalization of circulating albumin levels, intensive use of diuretics and deliberate attempts to increase the intervals between the paracentesis treatments. Various differential diagnoses, including infectious, hepatic, vascular and cardiac causes were ruled out. Nine months after surgery enteric-coated mycophenolate sodium was switched to azathioprine after which ascites completely resolved. When mycophenolate was recommenced abdominal fullness and weight gain reoccurred. The patient had to be switched to long-term azathioprine treatment. More than 1 year post-conversion the patient remains free of ascites. Conclusion MPA is the most widely used antimetabolite immunosuppressive agent. We suggest to consider MPA treatment in the differential diagnosis of severe and unexplained ascites in transplant and non-transplant patients.

Background. This is an excerpt from chapter 4 of the annual registry report from the Australia and New Zealand islet and pancreas transplant registry. The full report is available at http://anziptr.org/reports/. Methods. We report data for all allogeneic islet isolation and transplant activity from 2002 to end 2017. Solid organ pancreas transplantation activity is reported separately. New Zealand does not have an islet transplant program. Data analysis was performed using Stata software version 14 (StataCorp, College Station, TX). Results. From 2002 to 2017, a total of 104 allogeneic islet transplants were performed in 62 recipients. Conclusions. The number of islet transplants performed in Australia was slightly lower in 2017 but continues to increase over time.

Condomless anal sex between male partners is the primary risk factor for HIV transmission among men who have sex with men (MSM). Correlates of condomless anal sex have been well-studied in developed countries, but they have received less attention in lower-to-middle income countries (LMIC), where MSM are often subject to stigma, discrimination, intolerance, and even the criminalization of same sex behavior. In Mexico, a LMIC where traditional views on homosexuality are common, HIV prevalence among MSM is high (16.9%), yet little research has been conducted on the correlates of condomless anal sex in this high-risk population. The present study examined correlates of condomless anal sex among 201 MSM recruited in Tijuana, Mexico, with a focus on the role of public sex venues in relation to sexual risk behavior. Eligibility requirements were: biologically male, 18 years of age or older, resident of Tijuana, and self-reported anal or oral sex with a male partner in the past year. Participants completed an interviewer-administered, demographic and psychosocial survey, and were tested for HIV and syphilis. A hierarchical multiple linear regression model was tested to identify correlates of condomless anal sex. Thirty-eight percent of participants (N = 76) reported condomless anal sex with a male partner in the past 2 months. Higher levels of condomless anal sex were associated with higher levels of depressive symptoms, greater sexual compulsivity, and more frequent seeking out of sex partners in a public venue in the past 2 months. In view of these findings, we recommend the development of multi-level, "combination" interventions, which in the Mexican context should include enhanced condom promotion and distribution, improved availability and access to mental health treatment and counseling services, and expanded HIV/STI testing in public venues.

94% of all birth defects (BD) and 95% of deaths due to the BD occur in low and middle income countries, many of which are preventable. In Tanzania, there is currently a paucity of BD data necessary to develop data informed prevention activities. Methods A cross-sectional analysis was conducted of deliveries identified with BD in the labor ward registers at four Dar es Salaam hospitals between October, 2011 and February, 2012. The birth prevalence of structural BD, case fatality proportion, and the distribution of structural defects associated deaths within total deaths were calculated. A total of 28 217 resident births were encountered during the study period. Overall birth prevalence of selected defects was 28.3/10 000 live births. Neural tube defects and indeterminate sex were the most and least common defects at birth (9.9 and 1.1/10 000 live births respectively). Among stillbirths (66.7%) and deaths that occurred within less than 5 days of an affected live birth (18.5%), neural tube defects were the most frequently associated structural defect. Structural BD is common and contributes to perinatal mortality in Dar es Salaam. More than half of perinatal deaths encountered among the studied selected external structural BD are associated with neural tube defects, a birth defect with well–established evidence based prevention interventions. By establishing a population–based BD surveillance program, Tanzania would have the information about neural tube defects and other major structural BD needed to develop and monitor prevention activities.

This paper focuses on code switching and transference as produced by one simultaneous and one sequential bilingual in order to better understand some aspects of bilingualism in children due to the important role that it plays on society. This research postulates that the degree of linguistic competence influences the choice of language selected by the child when communicating.Este estudio de investigación esta focalizado en code switching y transference producido por un bilingüe simultáneo y secuencial para entender mejor algunos aspectos del bilingüismo en los niños debido al papel importante que desempeñan en sociedad. Esta tesis postula que el grado de capacidad lingüística influencia la opción de la lengua seleccionada por el niño al comunicarse.

BACKGROUND:Many studies have measured the intensity of end of life care. However, no summary of the measures used in the field is currently available. OBJECTIVES:To summarise features, characteristics of use and reported validity of measures used for evaluating intensity of end of life care. METHODS:This was a systematic review according to PRISMA guidelines. We performed a comprehensive literature search in Ovid Medline, Embase, The Cochrane Library of Systematic Reviews and reference lists published between 1990-2014. Two reviewers independently screened titles, abstracts, full texts and extracted data. Studies were eligible if they used a measure of end of life care intensity, defined as all quantifiable measures describing the type and intensity of medical care administered during the last year of life. RESULTS:A total of 58 of 1590 potentially eligible studies met our inclusion criteria and were included. The most commonly reported measures were hospitalizations (n = 44), intensive care unit admissions (n = 39) and chemotherapy use (n = 27). Studies measured intensity of care in different timeframes ranging from 48 hours to 12 months. The majority of studies were conducted in cancer patients (n = 31). Only 4 studies included information on validation of the measures used. None evaluated construct validity, while 3 studies considered criterion and 1 study reported both content and criterion validity. CONCLUSIONS:This review provides a synthesis to aid in choosing intensity of end of life care measures based on their previous use but simultaneously highlights the crucial need for more validation studies and consensus in the field.

BackgroundInfections during pregnancy have the potential to adversely impact birth outcomes. We evaluated the association between receipt of inactivated influenza vaccine during pregnancy and prematurity and small for gestational age (SGA) births.Methods and findingsWe conducted a cohort analysis of surveillance data from the Georgia (United States) Pregnancy Risk Assessment Monitoring System. Among 4,326 live births between 1 June 2004 and 30 September 2006, maternal influenza vaccine information was available for 4,168 (96.3%). The primary intervention evaluated in this study was receipt of influenza vaccine during any trimester of pregnancy. The main outcome measures were prematurity (gestational age at birth ConclusionsThis study demonstrates an association between immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity during local, regional, and widespread influenza activity periods. However, no associations were found for the pre-influenza activity period. Moreover, during the period of widespread influenza activity there was an association between maternal receipt of influenza vaccine and reduced likelihood of SGA birth.

We have previously shown a reduction in anaemia and wasting malnutrition in infants

There are essentially three difficulties attending any search for cultural explanations of change in China: culture can be a broad and often a somewhat imprecise concept; the scale of China makes for difficulties in the unit of analysis; and the assumption of historical continuity may be somewhat attenuated. The antidote to essentialisation about Chinese culture is to approach explanation at a more local level. A recognition that there are local accounts of social and economic change that both help motivate behaviour and provide legitimation for specific forms of activity provides a more convincing framework for understanding the role of culture in both the evolution of the economic environment and business development. The evidence from an examination of town and village enterprises and their enterpreneurs in Taiyuan, provincial capital of Shanxi; of Islamic Salar entrepreneurs in Xunhua (Qinghai Province); and of women entrepreneurs in Qiongshan, Hainan, suggests that at the local level the state and economic interests have harnessed symbolic and representational forms of culture for particular interests and goals, including attempts to create a local competitive advantage for particular industries and social groups. In this process local cultural practice is used to underpin the manner of business development, including the structures of ownership, management and operation, as well as to some extent the kinds of economic activity that are developed.