Mortality in Western Australian psychiatric patients

  Background: The aim was to examine mortality in psychiatric patients in Western Australia (WA), over a time period of considerable change in the delivery of mental health services. Methods: A population-based record linkage analysis was undertaken to quantify mortality among people with mental illness in WA. Mortality rates were calculated in users of mental health services and compared with rates in the whole population of WA. Trends in mortality were also examined using relative survival analysis, and proportional hazards regression. Results: The overall mortality rate ratio was 2.57 in males (95% CI: 2.51–2.64), and 2.18 in females (2.12–2.24). The highest cause-specific mortality rate ratio was for deaths due to suicide [RR: 7.37 in males (95% CI: 6.74–8.05) and 8.38 in females (95% CI: 7.11–9.89)], with mortality rate ratios being significantly greater than 1 for all other major causes of death. A relative survival analysis found that the excess mortality risk was concentrated in the first few years after first contact with mental health services. Proportional hazards regression analysis found a slight elevation of mortality rates over time. Conclusions: Mortality among psychiatric patients remains high and appears to be increasing. Highest excess mortality rate is associated with suicide, but mortality rates are significantly elevated for all major causes of death. Accepted: 10 April 2000     

Body mass index in relation to ovarian cancer survival.

Evidence for an association between indicators of adiposity and survival after ovarian cancer has been inconsistent. A prospective cohort study was conducted in China to examine the relationship between ovarian cancer survival and body mass index (BMI). From the 214 patients recruited in 1999 to 2000 with histopathologically confirmed invasive epithelial ovarian cancer, 207 patients or their close relatives (96.7% of cases) were traced and followed to 2003. Deaths were recorded and Cox proportional hazards regression was used to obtain hazard ratios (HR) and 95% confidence intervals (95% CI) from multivariate models. Reduced survival was observed among patients with BMI > or = 25 kg/m(2) at 5 years before diagnosis (P = 0.001). There were 98 (59.8%) of 164 patients with BMI <25 kg/m(2) survived to the time of interview compared with only 15 women (34.9%) among the 43 patients whose BMI was > or =25 kg/m(2). The HRs significantly increased with higher BMI at 5 years before diagnosis but not at diagnosis nor at age 21 years. The adjusted HR was 2.33 (95% CI, 1.12-4.87) for BMI of > or =25 versus <20 kg/m(2), with a significant dose-response relationship. The HR was 3.31 (95% CI, 1.26-8.73) among patients who had been overweight or obese at age 21 years, but a linear dose-response was not found. We conclude that premorbid BMI may have independent prognostic significance in ovarian cancer.     

Percutaneous nephropexy

OBJECTIVE: The authors present a 12-year (1986-98) study of a new procedure called percutaneous nephropexy (PCNP). This procedure was performed on 51 renal ptosis patients at two urological departments (in Pakistan and Hungary) with satisfactory results. The idea for PCNP was adapted from the observation that after drain insertion following nephrostomy a scar is quite sufficient to hold the kidney in place. That idea was used to fix the kidney at the required level. MATERIAL AND METHODS: Thirteen patients complained of a palpable mobile mass in the abdomen while others suffered from pain in their affected flank with recurrent attacks of urinary tract infection. On ultrasonic examination the kidney was found to be lower than the normal position. This observation was confirmed by a standing intravenous urography (IVU) examination that also showed a tortuous ureter. Nine patients also had a stone in the affected kidney. The operation involved puncture and dilatation of a channel through the lower calyx. RESULTS: Control IVU examination was performed after wound healing and was repeated 2 months after the operation, followed by consecutive ultrasonic examinations. Standing X-ray films obtained after contrast material injection showed the kidney to be at a higher level with a straight ureter. Forty-five patients (88.2%) recovered completely. CONCLUSION: In the authors' opinion PCNP is a good alternative to open nephropexy operations in renal ptosis cases, particularly when laparoscopic surgery facilities are not available. Although PCNP was developed in circumstances in which the availability of equipment was restricted, in terms of benefits it is comparable with laparoscopic nephropexy.     

Human carcinogenic risk evaluation, Part III: Assessing cancer hazard and risk in human drug development.

Assessing cancer risk for human pharmaceuticals is important because drugs are taken at pharmacologically active doses and often on a chronic basis. Epidemiologic studies on patient populations have limited value because of the long latency period for most cancers and because these studies lack sensitivity. The Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration relies on short-term surrogate assays (genetic toxicology studies) to assess risk to patients involved in clinical trials and on rodent carcinogenicity studies to assess cancer risk for drug approval. Unlike some other agencies that typically perform quantitative risk assessments on chemical pollutants or pesticide products, CDER does not perform such quantitative extrapolations. Rather, the evaluation of risk is the result of an integrated assessment of what is known about the drug, and risk is considered in the context of the clinical benefit. Mode of action of carcinogenesis and thresholds for effects are important considerations. The results of carcinogenicity studies of approved products are published in the drug labeling and individual clinicians balance risk and benefit in making prescribing decisions.     

Reflections of Moral Suffering,Resilience, and Wisdom of Pediatric Oncology Social Workers during the COVID-19 Pandemic

Background: The COVID-19 pandemic has significantly altered the lives of pediatric oncology social workers. Challenges include difficulty building rapport with the use of telephone/computers, lack of clarity around who is designated as “essential”, structural challenges, isolation, and witnessing distress. This study aimed to describe the ways that the pandemic has personally impacted pediatric oncology social workers. Methods: Participants were recruited through the Association of Pediatric Oncology Social Workers (APOSW) listserv. In total, 101 participants from 31 states and the District of Columbia completed an online survey containing quantitative and open-ended questions. Qualitative data analysis included thematic analysis of participants’ optional survey responses to three open-ended questions. Results: Fifty-seven of the participants provided responses that revealed 3 first level codes and 11 second level codes. First level codes were developed a priori from the questions: Experiences that stay with you, Wisdom gained and Impact on your work. Pandemic-related challenges caused moral suffering and professional challenges for participants but also created opportunities to find meaning in their work. Conclusion: Data illuminated moral suffering, unrecognized resilience, new ways of maintaining self-and family care, and creative approaches to care of children with cancer and their families at diagnosis, during treatments and at the end of life.     

Moderate Colitis Not Requiring Intravenous Steroids Is Associated with Improved Survival in Stage IV Melanoma after Anti-CTLA4 Monotherapy,But Not Combination Therapy

BackgroundFor patients with melanoma, gastrointestinal immune-related adverse events are common after receipt of anti-CTLA4 therapy. These present difficult decision points regarding whether to discontinue therapy. Detailing the situations in which colitis might predict for improved survival and how this is affected by discontinuation or resumption of therapy can help guide clinical decision-making.Materials and MethodsPatients with stage IV melanoma receiving anti-CTLA4 therapy from 2008 to 2019 were analyzed. Immune-related colitis treated with ≥50 mg prednisone or equivalent daily or secondary immunosuppression was included. Moderate colitis was defined as receipt of oral glucocorticoids only; severe colitis was defined as requiring intravenous glucocorticoids or secondary immunosuppression. The primary outcome was overall survival (OS).ResultsIn total, 171 patients received monotherapy, and 91 received dual checkpoint therapy. In the monotherapy group, 25 patients developed colitis and a nonsignificant trend toward improved OS was observed in this group. Notably, when colitis was categorized as none, moderate or severe, OS was significantly improved for moderate colitis only. This survival difference was not present after dual checkpoint therapy. There were no differences in known prognostic variables between groups, and on multivariable analysis neither completion of all ipilimumab cycles nor resumption of immunotherapy correlated with OS, while the development of moderate colitis did significantly affect OS.ConclusionThis single-institution retrospective series suggests moderate colitis correlates with improved OS for patients with stage IV melanoma treated with single-agent anti-CTLA4, but not dual agent, and that this is true regardless of whether the immune-checkpoint blockade is permanently discontinued.     

Assessment of Objective and Subjective Cognitive Function in Patients With Treatment-Resistant Depression Undergoing Repeated Ketamine Infusions

BackgroundSubanesthetic ketamine infusions can elicit rapid and sustained antidepressant effects, yet the potential cognitive impact of ketamine has not been thoroughly examined. This study measured changes in objective and subjective cognitive function following repeated ketamine treatment.MethodsThirty-eight patients with treatment-resistant depression were administered cognitive assessments before and after undergoing 7 i.v. ketamine infusions (0.5 mg/kg over 40 minutes) within a clinical trial examining the efficacy of single and repeated administrations. Depression severity and perceived concentration were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms Self-Report.ResultsTwenty-three participants (60.5%) responded after repeated infusions (≥50% decrease in MADRS total scores). We measured significant improvements in several cognitive domains, including attention, working memory, verbal, and visuospatial memory (effect sizes ranging from Cohen d = 0.37–0.79). Cognitive changes were attributed to reduction in depressive symptoms except for improvement in verbal memory, which remained significant after adjustment for change in MADRS total score (P = .029, η _p²=0.13). Only responders reported improvement in subjective cognitive function with repeated ketamine administration (MADRS item 6, P < .001, d = 2.00; Quick Inventory of Depressive Symptoms Self-Report item 10, P < .001, d = 1.36).ConclusionA short course of repeated ketamine infusions did not impair neurocognitive function in patients with treatment-resistant depression. Further research is required to understand the potential mediating role of response and remission on improved cognitive function accompanying ketamine treatment as well as to examine longer-term safety outcomes. ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01945047","term_id":"NCT01945047"}}NCT01945047     

Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches : A workshop report

Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives.