Outcome of Nephrectomies in Malta since 2000

Aim: To audit the oncological results and perioperative surgical outcome of nephrectomies performed in Malta since year 2000. Method: A retrospective index case list of all nephrectomies carried out by three urological surgeons at St Luke’s and Mater Dei Hospitals from 1st September 2000 to 31st March 2012 was compiled from departmental data. Clinical, radiological and histological data were compiled from the case notes and hospital intranet computerised investigation results. Clinical staging of all patients was revised using the Union Internationale Contre le Cancer TNM staging 2009. All the patients who underwent nephrectomy for clear cell renal cell carcinoma were stratified according to individual predicted prognosis based on the SSIGN score developed by the Mayo clinic. Results: Between September 2000 and March 2012, 319 nephrectomies were carried out at the Urology Unit, of these 288 were carried out for malignancy, 218 of which were clear cell renal cell carcinoma (RCC). 112 complications were recorded for the whole cohort; two patients died from perioperative complications. 80 patients passed away, 51 of these as a direct consequence of their renal cell cancer. Median duration of follow up was 42.7 months. A Cox model reveals that a SSIGN score greater than 6 significantly worsens survival rate for RCC (p<<0.001). Conclusion: Morbidity following surgery, mortality rates, and oncological results in our single centre study are acceptable when compared to larger series.peer-reviewe

Local survival outcomes in metastatic renal cell carcinoma

A quarter of patients who develop renal cell carcinoma will have metastatic disease at presentation. The role of cytoreductive surgery in these patients is a topic of debate. The aim of this study was to analyse survival outcomes of patients treated in Malta who did and did not receive a nephrectomy. Data was gathered retrospectively from the Malta Cancer Registry and Mortality Data at the Department of Health Information, records of multidisciplinary team meetings held within the urology department at Mater Dei Hospital, hospital imaging and patient records. Data gathered included: patient demographics, date of diagnosis, TNM staging, tumour histology, Fuhrman grade, time to treatment and modality of treatment. Exclusions included: • Localized disease relapsing after surgery • Non-renal cell histological subtypes • Presence of metastasis at diagnosis not certain • Concomitant primary tumours 77 patients diagnosed over 5 years between 04.03.2005 and 13.2.2009 were included. The age at presentation ranged from 30 to 88 years, with a median age of 67 years. 11 were incidental findings and 47 were symptomatic. The most prevalent symptoms were abdominal pain and gross haematuria. Five-year cancer specific survival in patients who received a nephrectomy was significantly better at 65%, compared to patients who did not undergo surgery (32%) P value <0.05, CI 95%. These results where compared favourably with SEER data outcomespeer-reviewe

Does Birth Weight Influence Physical Activity in Youth? A Combined Analysis of Four Studies Using Objectively Measured Physical Activity

Animal models suggest growth restriction in utero leads to lower levels of motor activity. Furthermore, individuals with very low birth weight report lower levels of physical activity as adults. The aim of this study was to examine whether birth weight acts as a biological determinant of physical activity and sedentary time. This study uses combined analysis of three European cohorts and one from South America (n = 4,170). Birth weight was measured or parentally reported. Height and weight were measured and used to calculate Body Mass Index (BMI). PA was objectively measured using accelerometry for ≥3 days, ≥10 hours day. Data was standardized to allow comparisons between different monitors. Total physical activity was assessed as counts per minute (cpm), with time spent above moderate activity (MVPA) >2,000 counts and time spent sedentary (<100 counts). There was no evidence for an association between birth weight and total physical activity (p = 0.9) or MVPA (p = 0.7). Overall there was no evidence for an association between birth weight and sedentary time (p = 0.8). However in the Pelotas study we did find an association between higher birth weight (kg) and lower overall physical activity (cpm) (β = −31, 95%CI: −58, −46, p = 0.03) and higher birth weight and greater sedentary time (mins/day) (β = 16.4, 95%CI: 5.3, 27.5, p = 0.004), although this was attenuated and no longer significant with further adjustment for gestational age. Overall this combined analysis suggests that birth weight may not be an important biological determinant of habitual physical activity or sedentary behaviour in children and adolescents

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

The association between HIV status and homelessness among Veterans in care

Veterans seeking care in the Department of Veterans Affairs Health Care System (VA) are more vulnerable to HIV infection and homelessness. However, there is little scholarship on the association between serostatus and homelessness among VA veterans. We examined this association in the Veterans Aging Cohort Study, a sample of 6,819 HIV-positive and HIV-negative veterans attending 8 VAs across the country. We utilized logistic models regressing shelter use in the last month on correlates. HIV and homelessness prevalence was higher than in general veteran populations. Being HIV-positive was protective against homelessness. Substance use, hazardous alcohol use, depression, schizophrenia, and being African American and male increased risk of homelessness. HIV-positive status reduced the homelessness risk posed by substance use, especially among African American substance users. However, women veterans with HIV were at higher risk of homelessness than noninfected women veterans. Implications for policies on veteran homelessness and housing for people with HIV are discussed

Diagnostic accuracy of loop mediated isothermal amplification coupled to nanopore sequencing (LamPORE) for the detection of SARS-CoV-2 infection at scale in symptomatic and asymptomatic populations.

OBJECTIVES Rapid, high throughput diagnostics are a valuable tool, allowing the detection of SARS-CoV-2 in populations, in order to identify and isolate people with asymptomatic and symptomatic infections. Reagent shortages and restricted access to high throughput testing solutions have limited the effectiveness of conventional assays such as reverse transcriptase quantitative PCR (RT-qPCR), particularly throughout the first months of the COVID-19 pandemic. We investigated the use of LamPORE, where loop mediated isothermal amplification (LAMP) is coupled to nanopore sequencing technology, for the detection of SARS-CoV-2 in symptomatic and asymptomatic populations. METHODS In an asymptomatic prospective cohort, for three weeks in September 2020 health care workers across four sites (Birmingham, Southampton, Basingstoke and Manchester) self-swabbed with nasopharyngeal swabs weekly and supplied a saliva specimen daily. These samples were tested for SARS-CoV-2 RNA using the Oxford Nanopore LamPORE system and a reference RT-qPCR assay on extracted sample RNA. A second retrospective cohort of 848 patients with influenza like illness from March 2020 - June 2020, were similarly tested from nasopharyngeal swabs. RESULTS In the asymptomatic cohort a total of 1200 participants supplied 23,427 samples (3,966 swab, 19,461 saliva) over a three-week period. The incidence of SARS-CoV-2 detection using LamPORE was 0.95%. Diagnostic sensitivity and specificity of LamPORE was >99.5% (reducing to ∼ 98% when clustered estimation was used) in both swab and saliva asymptomatic samples when compared to the reference RT-qPCR test. In the retrospective symptomatic cohort, the incidence was 13.4% and the sensitivity and specificity were 100%. CONCLUSIONS LamPORE is a highly accurate methodology for the detection of SARS-CoV-2 in both symptomatic and asymptomatic population settings and can be used as an alternative to RT-qPCR

Erectile Dysfunction Drug Receipt, Risky Sexual Behavior and Sexually Transmitted Diseases in HIV-infected and HIV-uninfected Men

BACKGROUND: Health care providers may be concerned that prescribing erectile dysfunction drugs (EDD) will contribute to risky sexual behavior. OBJECTIVES: To identify characteristics of men who received EDD prescriptions, determine whether EDD receipt is associated with risky sexual behavior and sexually transmitted diseases (STDs), and determine whether these relationships vary for certain sub-groups. DESIGN: Cross-sectional study. PARTICIPANTS: Two thousand seven hundred and eighty-seven sexually-active, HIV-infected and HIV-uninfected men recruited from eight Veterans Health Affairs outpatient clinics. Data were obtained from participant surveys, electronic medical records, and administrative pharmacy data. MEASURES: EDD receipt was defined as two or more prescriptions for an EDD, risky sex as having unprotected sex with a partner of serodiscordant or unknown HIV status, and STDs, according to self-report. RESULTS: Overall, 28% of men received EDD in the previous year. Eleven percent of men reported unprotected sex with a serodiscordant/unknown partner in the past year (HIV-infected 15%, HIV-uninfected 6%, P \u3c 0.001). Compared to men who did not receive EDD, men who received EDD were equally likely to report risky sexual behavior (11% vs. 10%, p = 0.9) and STDs (7% vs 7%, p = 0.7). In multivariate analyses, EDD receipt was not significantly associated with risky sexual behavior or STDs in the entire sample or in subgroups of substance users or men who had sex with men. CONCLUSION: EDD receipt was common but not associated with risky sexual behavior or STDs in this sample of HIV-infected and uninfected men. However, risky sexual behaviors persist in a minority of HIV-infected men, indicating ongoing need for prevention interventions