Metformin therapy in COVID-19: inhibition of NETosis

Journal of Thrombosis and Thrombolysis -     

Effects of aquatic physical exercise on neuropsychological factors in older people: A systematic review

Background. There is a lack of standardized protocols and clinical trials for older adults involving neuropsychological factors in the literature. Furthermore, no systematic review has been published investigating this theme.Purpose. The purpose of this systematic review was to analyze the effects of aquatic physical exercise on neuropsychological factors in older adults.Methods. A systematic review (CRD42020176899) was conducted, using articles from Pubmed, Web of Science, Scopus, Cochrane Library, Science Direct and Medline published until March 2020 (without limit of previous year). Eligibility criteria for selecting studies were: clinical trials; samples with a mean age of 65 years old and over; articles involving aquatic physical exercise; and presenting neuropsychological outcomes (behavior, cognition, psychological, mental health).Results and discussion. The search yielded 801 records and 16 studies were included, totaling: 1707 older adults, with a mean age of 71.3 years old (range of mean ages in the studies: 65.3 to 88.4 years old) and a predominance of women. Aquatic physical exercise showed positive results in the mental component of quality of life, fear of falling, mood, anxiety and internal health locus of control in healthy sedentary older adults. Only one study out of 5 carried out with older adults with osteoarthritis showed improvements in psychological well-being after aquatic intervention. Older women with osteopenia or osteoporosis showed improvements in the mental component of quality of life. Studies on dementia showed a significant improvement in behavioral and psychological symptoms after aquatic intervention and no effect on depressive symptoms.Conclusion. Based on the results of this systematic review, aquatic physical exercise has positive effects on quality of life, fear of falling, cognitive functions, mood, anxiety and internal health locus of control in sedentary community-dwelling older people. It can be a great resource for carrying out physical activities in this population.     

Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.     

The impact of the housing status on clinical outcomes and health care utilization among individuals living with HIV

ABSTRACT

The lack of stable housing can impair access and continuity of care for patients living with human immunodeficiency virus (HIV). This study investigated the relationship between housing status assessed at multiple time points and several core HIV-related outcomes within the same group of HIV patients experiencing homelessness. Patients with consistently stable housing (CSH) during the year were compared to patients who lacked CSH (non-CSH group). The study outcomes included HIV viral load (VL), CD4 counts, and health care utilization. Multivariable and propensity weighted analyses were used to assess outcomes adjusting for potential group differences. Of 208 patients, 88 (42%) had CSH and 120 (58%) were non-CSH. Patients with CSH had significantly higher proportion of VL suppression and higher mean CD4 counts. The frequency of nurse visits in the CSH group was less than a half of that in the non-CSH group. Patients with CSH were less likely to be admitted to the medical respite facility, and if admitted, their length of stay was about a half of that for the non-CSH group. Our study findings show that patients with CSH had significantly better HIV virologic control and immune status as well as improved health care utilization.     

Lipids,Lipid-Lowering Therapy,and Neuropathy: A Narrative Review

Statins, or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are the mainstay of treatment for hypercholesterolemia as they effectively reduce LDL-C levels and risk of atherosclerotic cardiovascular disease. Apart from hyperglycemia, dyslipidemia and HDL dysfunction are known risk factors for neuropathy in people with obesity and diabetes. Although there are case reports of statin-induced neuropathy, ad hoc analyses of clinical trials and observational studies have shown that statins may improve peripheral neuropathy. However, large randomized controlled trials and meta-analyses of cardiovascular outcome trials with statins and other lipid-lowering drugs have not reported on neuropathy outcomes. Because neuropathy was not a prespecified outcome in major cardiovascular trials, one cannot conclude whether statins or other lipid-lowering therapies increase or decrease the risk of neuropathy. The aim of this review was to assess if statins have beneficial or detrimental effects on neuropathy and whether there is a need for large well-powered interventional studies using objective neuropathy end points.     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.