Protocol: inspiratory muscle training for promoting recovery and outcomes in ventilated patients (IMPROVe): a randomised controlled trial

Introduction: Inspiratory muscle weakness is a known consequence of mechanical ventilation and a potential contributor to difficulty in weaning from ventilatory support. Inspiratory muscle training (IMT) reduces the weaning period and increases the likelihood of successful weaning in some patients. However, it is not known how this training affects the residual inspiratory muscle fatigability following successful weaning nor patients' quality of life or functional outcomes. Methods and analysis: This dual centre study includes two concurrent randomised controlled trials of IMT in adult patients who are either currently ventilator-dependent (>7 days) (n=70) or have been recently weaned from mechanical ventilation (>7 days) in the past week (n=70). Subjects will be stable, alert and able to actively participate and provide consent. There will be concealed allocation to either treatment (IMT) or usual physiotherapy (including deep breathing exercises without a resistance device). Primary outcomes are inspiratory muscle fatigue resistance and maximum inspiratory pressures. Secondary outcomes are quality of life (Short Form-36v2, EQ-5D), functional status (Acute Care Index of Function), rate of perceived exertion (Borg Scale), intensive care length of stay (days), post intensive care length of stay (days), rate of reintubation (%) and duration of ventilation (days). Ethics and dissemination: Ethics approval has been obtained from relevant institutions, and results will be published with a view to influencing physiotherapy practice in the management of long-term ventilator-dependent patients to accelerate weaning and optimise rehabilitation outcomes

A Comparison of Miltefosine and Sodium Stibogluconate for Treatment of Visceral Leishmaniasis in an Ethiopian Population with High Prevalence of HIV Infection.

BACKGROUND: Antimonials are the mainstay of visceral leishmaniasis (VL) treatment in Africa. The increasing incidence of human immunodeficiency virus (HIV) coinfection requires alternative safe and effective drug regimens. Oral miltefosine has been proven to be safe and effective in the treatment of Indian VL but has not been studied in Africa or in persons with HIV and VL coinfection. METHODS: We compared the efficacy of miltefosine and sodium stibogluconate (SSG) in the treatment of VL in persons in Ethiopia. A total of 580 men with parasitologically and/or serologically confirmed VL were randomized to receive either oral miltefosine (100 mg per day for 28 days) or intramuscular SSG (20 mg/kg per day for 30 days). RESULTS: The initial cure rate was 88% in both treatment groups. Mortality during treatment was 2% in the miltefosine group, compared with 10% in the SSG group. Initial treatment failure was 8% in the miltefosine group, compared with 1% in the SSG group. Among the 375 patients (65%) who agreed to HIV testing, HIV seroprevalence was 29%. Among patients not infected with HIV, initial cure, mortality, and initial treatment failure rates were not significantly different (94% vs. 95%, 1% vs. 3%, and 5% vs. 1% for the miltefosine and SSG groups, respectively). Initial treatment failure with miltefosine occurred in 18% of HIV-coinfected patients, compared with treatment failure in 5% of non-HIV-infected patients. At 6 months after treatment, 174 (60%) of the 290 miltefosine recipients and 189 (65%) of the 290 SSG recipients experienced cure; 30 (10%) of 290 in the miltefosine group and 7 (2%) of 290 in the SSG group experienced relapse, and the mortality rate was 6% in the miltefosine group, compared with 12% in the SSG group. HIV-infected patients had higher rates of relapse (16 [25%] of 63 patients), compared with non-HIV-infected patients (5 [5%] of 131). CONCLUSIONS: Treatment with miltefosine is equally effective as standard SSG treatment in non-HIV-infected men with VL. Among HIV-coinfected patients, miltefosine is safer but less effective than SSG

SARS‐CoV‐2 receptor ACE 2 and TMPRSS 2 are primarily expressed in bronchial transient secretory cells

The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis

Keeping Data Science Broad: Negotiating the Digital and Data Divide Among Higher Education Institutions

The goal of the “Keeping Data Science Broad” series of webinars and workshops was to garner community input into pathways for keeping data science education broadly inclusive across sectors, institutions, and populations. Input was collected from data science programs across the nation, either traditional or alternative, and from a range of institution types including community colleges, minority-led and minority-serving institutions, liberal arts colleges, tribal colleges, universities, and industry partners. The series consisted of two webinars (August 2017 and September 2017) leading up to a workshop (November 2017) exploring the future of data science education and workforce at institutions of higher learning that are primarily teaching-focused. A third follow-up webinar was held after the workshop (January 2018) to report on outcomes and next steps. Program committee members were chosen to represent a broad spectrum of communities with a diversity of geography (West, Northeast, Midwest, and South), discipline (Computer Science, Math, Statistics, and Domains), as well as institution type (Historically Black Colleges and Universities (HBCU’s), Hispanic-Serving Institutions (HSI’s), other Minority-Serving Institutions (MSI\u27s), Community College\u27s (CC’s), 4-year colleges, Tribal Colleges, R1 Universities, Government and Industry Partners)

Keeping Data Science Broad: Negotiating the Digital and Data Divide Among Higher Education Institutions

The goal of the “Keeping Data Science Broad” series of webinars and workshops was to garner community input into pathways for keeping data science education broadly inclusive across sectors, institutions, and populations. Input was collected from data science programs across the nation, either traditional or alternative, and from a range of institution types including community colleges, minority-led and minority-serving institutions, liberal arts colleges, tribal colleges, universities, and industry partners. The series consisted of two webinars (August 2017 and September 2017) leading up to a workshop (November 2017) exploring the future of data science education and workforce at institutions of higher learning that are primarily teaching-focused. A third follow-up webinar was held after the workshop (January 2018) to report on outcomes and next steps. Program committee members were chosen to represent a broad spectrum of communities with a diversity of geography (West, Northeast, Midwest, and South), discipline (Computer Science, Math, Statistics, and Domains), as well as institution type (Historically Black Colleges and Universities (HBCU’s), Hispanic-Serving Institutions (HSI’s), other Minority-Serving Institutions (MSI\u27s), Community College\u27s (CC’s), 4-year colleges, Tribal Colleges, R1 Universities, Government and Industry Partners)

Stimulation programs for pediatric drug research – do children really benefit?

Most drugs that are currently prescribed in pediatrics have not been tested in children. Pediatric drug studies are stimulated in the USA by the pediatric exclusivity provision under the Food and Drug Administration Modernization Act (FDAMA) that grants patent extensions when pediatric labeling is provided. We investigated the effectiveness of these programs in stimulating drug research in children, thereby increasing the evidence for safe and effective drug use in the pediatric population. All drugs granted pediatric exclusivity under the FDAMA were analyzed by studying the relevant summaries of medical and clinical pharmacology reviews of the pediatric studies or, if these were unavailable, the labeling information as provided by the manufacturer. A systematic search of the literature was performed to identify drug utilization patterns in children. From July 1998 to August 2006, 135 drug entities were granted pediatric exclusivity. Most frequent drug groups were anti-depressants and mood stabilizers, ACE inhibitors, lipid-lowering preparations, HIV antivirals, and non-steroidal anti-inflammatory and anti-rheumatic drugs. The distribution of the different drugs closely matched the distribution of these drugs over the adult market, and not the drug utilization by children