Use of cystatin C to inform metformin eligibility among adult veterans with diabetes.

AimsRecommendations for metformin use are dependent on eGFR category: eGFR >45 ml/min/1.73 m2 - "first-line agent"; eGFR 30-44 - "use with caution"; eGFR<30 - "do not use". Misclassification of metformin eligibility by creatinine-based MDRD GFR estimates (eGFRcr) may contribute to its misuse. We investigated the impact of cystatin c estimates of GFR (eGFRcys) on metformin eligibility.MethodsIn a consecutive cohort of 550 Veterans with diabetes, metformin use and eligibility were assessed by eGFR category, using eGFRcr and eGFRcys. Discrepancy in eligibility was defined as cases where eGFRcr and eGFRcys categories (<30, 30-44, 45-60, and >60 ml/min/1.73 m2) differed with an absolute difference in eGFR of >5 ml/min/1.73 m2. We modeled predictors of metformin use and eGFR category discrepancy with multivariable relative risk regression and multinomial logistic regression.ResultsSubjects were 95% male, median age 68, and racially diverse (45% White, 22% Black, 11% Asian, 22% unknown). Metformin use decreased with severity of eGFRcr category, from 63% in eGFRcr >60 to 3% in eGFRcr <30. eGFRcys reclassified 20% of Veterans into different eGFR categories. Factors associated with a more severe eGFRcys category compared to eGFRcr were older age (aOR = 2.21 per decade, 1.44-1.82), higher BMI (aOR = 1.04 per kg/m2, 1.01-1.08) and albuminuria >30 mg/g (aOR = 1.81, 1.20-2.73).ConclusionsMetformin use is low among Veterans with CKD. eGFRcys may serve as a confirmatory estimate of kidney function to allow safe use of metformin among patients with CKD, particularly among older individuals and those with albuminuria

Association of Tenofovir Use With Risk of Incident Heart Failure in HIV-Infected Patients.

BackgroundThe antiretroviral medication, tenofovir disoproxil fumarate (TDF), is used by most human immunodeficiency virus-infected persons in the United States despite higher risks of chronic kidney disease. Although chronic kidney disease is a strong risk factor for heart failure (HF), the association of TDF with incident HF is unclear.Methods and resultsWe identified 21 435 human immunodeficiency virus-infected patients in the United States Veterans Health Administration actively using antiretrovirals between 2002 and 2011. We excluded patients with a prior diagnosis of HF. TDF was analyzed categorically (current, past, or never use) and continuously (per year of use). Proportional hazards regression and fully adjusted marginal structural models were used to determine the association of TDF exposure with risk of incident HF after adjustment for demographic, human immunodeficiency virus-related, and cardiovascular risk factors. During follow-up, 438 incident HF events occurred. Unadjusted 5-year event rates for current, past, and never users of TDF were 0.9 (95%CI 0.7-1.1), 1.7 (1.4-2.2), and 4.5 (3.9-5.0), respectively. In fully adjusted analyses, HF risk was markedly lower in current TDF users (HR=0.68; 95%CI 0.53-0.86) compared with never users. Among current TDF users, each additional year of TDF exposure was associated with a 21% lower risk of incident HF (95%CI: 0.68-0.92). When limited to antiretroviral-naive patients, HF risk remained lower in current TDF users (HR=0.53; 95%CI 0.36-0.78) compared to never users.ConclusionsAmong a large national cohort of human immunodeficiency virus-infected patients, TDF use was strongly associated with lower risk of incident HF. These findings warrant confirmation in other populations, both with TDF and the recently approved tenofovir alafenamide fumarate

A randomised controlled trial of a brief cognitive behavioural intervention for men who have hot flushes following prostate cancer treatment (MANCAN)

OBJECTIVE: Hot flushes and night sweats (HFNS) are experienced by up to 80% of prostate cancer patients undergoing androgen deprivation therapy (ADT). This study evaluates the effects of a guided self-help cognitive behavioural therapy (CBT) intervention on HFNS problem-rating (primary outcome), HFNS frequency, mood and health-related quality of life (secondary outcomes) in patients undergoing ADT. METHODS: Patients reporting treatment-induced HFNS were randomly assigned to CBT (n = 33) or treatment as usual (TAU) (n = 35), stratified for cancer type. The CBT intervention included a booklet, CD plus telephone contact during a 4-week period. Validated self-report questionnaires were completed at baseline, 6 weeks and 32 weeks after randomisation. The primary outcome was HFNS problem rating (perceived burden of HFNS) at 6 weeks after randomisation. Potential moderators and mediators were examined. Data analysis was conducted on a modified intention-to-treat basis. RESULTS: Compared with TAU, CBT significantly reduced HFNS problem rating (adjusted mean difference: -1.33, 95% CI -2.07 to -0.58; p = 0.001) and HFNS frequency (-12.12, 95% CI -22.39 to -1.84; p = 0.02) at 6 weeks. Improvements were maintained at 32 weeks, but group differences did not reach significance. There were significant reductions in negative HFNS Beliefs and Behaviours following CBT, but not in mood or quality of life. CONCLUSIONS: Guided self-help CBT appears to be a safe and effective brief treatment for men who have problematic HFNS following prostate cancer treatments. Further research might test the efficacy of the intervention in a multicentre trial

Can self-report questionnaires create illness cognitions in middle-aged men?

Objective: To examine the effect of questionnaire context on self-reported illness cognition. Design: A single-item measure of the perceived impact of lower urinary tract symptoms (LUTS) was embedded twice in a questionnaire battery completed by community-dwelling middle-aged males (N = 1,790). The impact measure was placed in two distinct questionnaire contexts; at the end of a general somatic symptoms questionnaire, and following an illness-specific symptoms questionnaire. The order of the two questionnaire contexts was counter-balanced in a random sub-sample. Main Outcome Measures: An established single-item measure of the perceived impact of LUTS. Results: Concordance between the two single-item measures was moderate. Scores on a single-item measure of impact were significantly lower when assessed immediately following the completion of a LUTS-specific questionnaire than when assessed following the completion of a general symptoms questionnaire. There was no evidence of order effects. The observed effect was moderated by the severity of LUTS such that the difference in perceived impact scores between contexts (where general symptoms context > illness-specific context) increased as urinary symptoms increased. Conclusion: Questionnaire context systematically influenced responses on self-report measures of illness impact. The magnitude of the context effect was largest in the highest quintile of LUTS severity, a difference of >0.5 on a scale with a range of 3. These findings may have implications for situations where patient reported outcome measures are used to evaluate healthcare interventions or inform treatment decisions

First-order phase transition from hypernuclear matter to deconfined quark matter obeying new constraints from compact star observations

We reconsider the problem of the hyperon puzzle and its suggested solution by quark deconfinement within the two-phase approach to hybrid compact stars with recently obtained hadronic and quark matter equations of state. For the hadronic phase we employ the hypernuclear equation of state from the lowest order constrained variational method and the quark matter phase is described by a sufficiently stiff equation of state based on a color superconducting nonlocal Nambu-Jona-Lasinio model with constant (model nlNJLA) and with density-dependent (model nlNJLB) parameters. We study the model dependence of the phase transition obtained by a Maxwell construction. Our study confirms that also with the present set of equations of state quark deconfinement presents a viable solution of the hyperon puzzle even for the new constraint on the lower limit of the maximum mass from PSR J0740+6620. In this work we provide with model nlNJLB for the first time a hybrid star EoS with an intermediate hypernuclear matter phase between the nuclear and color superconducting quark matter phases, for which the maximum mass of the compact star reaches $2.2~M_\odot$, in accordance with most recent constraints. In model nlNJLA such a phase cannot be realised because the phase transition onset is at low densities, before the hyperon threshold density is passed. We discuss possible consequences of the hybrid equation of state for the deconfinement phase transition in symmetric matter as it will be probed in future heavy-ion collisions at FAIR, NICA and corresponding energy scan programs at the CERN and RHIC facilities.Comment: 37 pages, 13 figures, 1 table, references added, text and figures revised, version accepted for publication in Phys. Rev.