Pioglitazone has a dubious bladder cancer risk but an undoubted cardiovascular benefit

On 8 April 2014, a US jury ordered Takeda and Eli Lilly to pay $9 bn in punitive damages after finding that they had concealed the cancer risks associated with pioglitazone. By contrast, on 28 August 2014, the long‐awaited outcome of the 10‐year Kaiser Permanente Northern California study was announced. That study was specifically designed to investigate whether patients exposed to pioglitazone were at an increased risk of bladder cancer and found no association; thus, at last, the controversial issue has been resolved. A review, in retrospect, of the story of the proposed link between pioglitazone and bladder cancer reveals flaws at every stage. In 2012, a BMJ editorial, in keeping with some other contemporary reports, stated ‘it can confidently be assumed that pioglitazone increases the risk of bladder cancer’. Examination of the information which led to such a statement shows that: 1) the pre‐clinical findings of bladder cancer in male rats is not indicative of human risk; 2) there is no association between bladder cancer and pioglitazone in randomized controlled trials, once cases that could not plausibly be related to treatment are removed; and 3) the observational studies that have suggested a link have over‐extrapolated from the data: pioglitazone‐treated patients had more risk factors for bladder cancer than those not treated with pioglitazone. Meanwhile careful study of randomized controlled trials shows evidence of cardiovascular benefit from pioglitazone in Type 2 diabetes, a condition which results, more than anything, in premature cardiovascular death and morbidity.     

The curvilinear relationship of early-life adversity and successful aging: the mediating role of mental health

Objectives: The steeling effect suggests that early-life adversity can have a beneficial impact later in life. However, little is known about its underlying mechanisms and long-term outcomes . The study aimed to examine the role of early-life adversity (ELA) on successful aging, and whether this relationship can be explained by mental and physical health.

Method: Socio-demographics, early-life adversity (ELA), individual quality of life (iQoL), and mental and physical health of 270 individuals (M_age = 66.82 years, 71.5% female) were assessed. Polynomial regressions and mediation analyses were conducted.

Results: Significant inverse U-shaped associations were found between ELA and iQoL (β = ?.59, p = .005) and between ELA and mental health (β = ?.64, p = .002), but not between ELA and physical health. Furthermore, mental health significantly mediated the relationship between ELA and iQoL (b = ?.84, BCa CI [?1.66, ?.27]).

Conclusion: Highest level of individual quality of life (i.e. successful aging) was related to a moderate amount of ELA. Additionally, mental health significantly mediated this relationship. These findings suggest that some amount of ELA could be beneficial for successful aging. Resource-focused interventions are needed to improve health and promote successful aging for an underdetected, at-risk subgroup with low early-life adversity.     

Accuracy and Precision of Acetabular Component Placement With Imageless Navigation in Obese Patients

Background

Obesity is a risk factor for acetabular component malposition when total hip arthroplasty is performed with manual techniques. The utility of imageless navigation in obese patients remains unknown. This study compared the accuracy and precision of imageless navigation for component orientation between obese and nonobese patients.

Increased hospital costs are associated with low skeletal muscle mass in patients undergoing elective open aortic surgery

Objective

Low psoas muscle area is shown to be an indicator for worse postoperative outcome in patients undergoing vascular surgical. Additionally, it has been associated with longer durations of hospital stay in patients with cancer who undergo surgery and subsequently greater health care costs in Europe and the United States. We sought to evaluate this effect on hospital expenditure for patients undergoing vascular repair in a health care system with universal access.

Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

Completeness and timeliness of diphtheria-tetanus-pertussis,measles-mumps-rubella,and polio vaccines in young children with chronic health conditions: A systematic review

Objective

To systematically review literature on uptake and timeliness of diphtheria-tetanus-pertussis, measles-mumps-rubella, and/or polio-containing vaccines in infants who were born preterm, with a low birth weight, and/or with chronic health conditions that were diagnosed within the first 6?months of life.

Attention,Externalizing, and Internalizing Problems of Youth Exposed to Parental Incarceration

Few studies have examined the effects of parental incarceration (PI) on outcomes above and beyond other risk and adverse childhood experiences (ACEs). The objectives of this study were to (1) the associations between PI and mental health problems (attention, externalizing, internalizing, and total behavioral problems) and (2) the mediating role of current socioeconomic status and cumulative ACEs. An observational and cross-sectional design was employed. Analyses included hierarchical multivariable linear regression modeling. The analytic sample included 613 adolescents (11–17?years). On average, youth exposed to PI experienced three times as many ACEs compared with youth unexposed. Youth exposed to PI were more likely to have behavioral problems than their unexposed peers. The main effect for all models was attenuated by current economic hardship as well as exposure to increasing numbers of ACEs. Exposure to PI can be viewed as a marker of accumulative risk for intervention since youth impacted by PI are more likely to experience behavioral difficulties and associated adverse childhood experiences. Due to the associated adversity that impact youth exposed to PI, mental health providers need to be able to identify and screen for symptoms associated with trauma.