Risedronate may preserve bone microarchitecture in breast cancer survivors on aromatase inhibitors: A randomized, controlled clinical trial.

UNLABELLED: This study provides preliminary evidence that risedronate not only preserves BMD but may also attenuate the loss of bone microarchitecture over 2years during a time of accelerated bone loss in post-menopausal breast cancer survivors on aromatase inhibitors. INTRODUCTION: Accelerated bone loss and elevated fracture risk are associated with the use of aromatase inhibitors (AIs) in women with breast cancer. We previously reported that the oral bisphosphonate, risedronate, can maintain bone mineral density (BMD) in the hip and spine over 2-years in post-menopausal breast cancer survivors on AIs. In this study, we examined whether oral bisphosphonates can also preserve bone microarchitecture as measured by the trabecular bone score (TBS) in this population. METHODS: This 2-year randomized, double-blind, placebo-controlled trial included postmenopausal women over age 55 with breast cancer on an AI who had low bone mass. Participants provided informed consent and were randomized to risedronate 35mg once weekly or placebo. We examined 12- and 24-month changes in spine TBS, analyzed using linear mixed models. RESULTS: One-hundred and nine women with a mean age of 70.5years were included in the analysis. In the placebo group, BMD declined at the spine and hip over the 24-month period but was preserved in the active treatment group (data previously reported). TBS declined in the placebo group by -2.1% and -2.3% at 12- and 24-months, respectively (p<0.005). The TBS percent change in bisphosphonate-treated patients was -0.9% and -1.3% at 12 and 24-months but did not reach statistical significance (p=0.24 and 0.14). The 12- and 24-month between-group differences were 0.9 (p=0.38) and 0.8 (p=0.44) percentage points. TBS change correlated with spine BMD changes in the placebo group at 12- and 24-months (r=0.33 and 0.34, p<0.01) but not in the active treatment group. CONCLUSION: The oral bisphosphonate risedronate preserves BMD and may attenuate loss of bone microarchitecture over 2years during a time of accelerated bone loss in breast cancer survivors on AIs, but more definitive evidence is needed.

Effect of bariatric surgery on cardiometabolic risk in elderly patients: A population-based study.

AIM: Obesity is a major cardiovascular (CV) risk factor. Bariatric surgery (BSx) is an approved therapeutic alternative for class II-III obesity, but little evidence focuses on older adults. We assessed the effect of BSx on cardiometabolic variables and long-term CV risk in older adults. METHODS: We carried out a population-based, observational study from 1990-2009, of 40 consecutive elderly (age ≥60 years) residents of Olmsted County, MN, USA, with class II-III obesity treated with BSx at a University-based, academic health center. Data were obtained from the Rochester Epidemiology Project. Metabolic syndrome (MetS) was defined using American Heart Association/National Heart, Lung, Blood Institute (AHA/NHLBI) criteria (increased triglycerides, low high-density lipoprotein, increased blood pressure, increased glucose and body mass index as a modified measure of obesity instead of waist circumference). Change in CV risk factors, MetS prevalence, and impact on predicted CV risk using the Framingham risk score was ascertained at 1 year postoperatively and assessed statistically. RESULTS: Mean age and body mass index were 64.4 ± 3.7 and 45.0 ± 6.3 kg/m(2) , respectively, and 28 out of 40 (70%) were women. One participant died during the 11-month study period after BSx from respiratory complications related to BSx, and one participant died at 2 years. Percentage of excess weight loss decreased by 57.5% at 1 year. Prevalence 1 year after BSx decreased for diabetes (57.5% to 22.5%; P < 0.03), hypertension 87.5% to 73.7% (P = 0.003), dyslipidemia (80% to 42.5%; P < 0.001) and sleep apnea (62.5% to 23.7%; P < 0.001).MetS prevalence decreased from 80% to 45% (P < 0.002). Baseline risk was 14.1%, which changed at follow up at 8.2%. CONCLUSIONS: In older adults, BSx induces considerable weight loss, improves CV risk factors, decreases MetS prevalence and is an effective treatment in this population. Geriatr Gerontol Int 2016; 16: 618-624.

Risk perception of obesity and bariatric surgery in patients seeking treatment for obesity.

Bariatric surgery (BSx) produces clinically relevant weight loss that translates into improved quality of life, decreased mortality, and reduction in medical comorbidities, including cardiovascular (CV) risk. Little is known about patients' decision-making process to undergo BSx, but risk perception is known to influence medical decision-making. This study examined CV and BSx risk perception in obese subjects undergoing BSx (n = 268) versus those managed medically (MM) (n = 273). This retrospective population-based survey of subjects evaluated for BSx had 148 (55%) and 88 (32%) responders in the BSx and MM groups, respectively. Survey questions assessed risk perceptions and habits prior to weight loss intervention. CV risk was calculated using the Framingham Risk Score (FRS). At baseline, BSx subjects had a greater body mass index and greater prevalence of diabetes and depression. Follow-up mean weight loss was greater in the BSx group. BSx subjects perceived obesity as a greater risk to their overall health than the surgical risk. FRS declined in the BSx group (10 to 5%; p < 0.001) while there was no change in the MM group (8 to 8%; p = 0.54). Those without a measurable decrease in CV risk had a greater tendency to perceive the risk of BSx as greater than that of obesity. Obese subjects undergoing BSx are more likely than MM subjects to perceive obesity as a greater risk to their health than BSx. MM subjects generally underestimate their CV risk and overestimate the risk of BSx. Active discussion of CV risk using the FRS and the perception of risk associated with bariatric surgery can enhance patients' ability to make an informed decision regarding their management.

A novel mutation in the succinate dehydrogenase subunit D gene in siblings with the hereditary paraganglioma-pheochromocytoma syndrome.

Germline mutations in the succinate dehydrogenase complex subunit D gene are now known to be associated with hereditary paraganglioma-pheochromocytoma syndromes. Since the initial succinate dehydrogenase complex subunit D gene mutation was identified about a decade ago, more than 131 unique variants have been reported. We report the case of two siblings presenting with multiple paragangliomas and pheochromocytomas; they were both found to carry a mutation in the succinate dehydrogenase complex subunit D gene involving a substitution of thymine to guanine at nucleotide 236 in exon 3. This particular mutation of the succinate dehydrogenase complex subunit D gene has only been reported in one previous patient in Japan; this is, therefore, the first report of this pathogenic mutation in siblings and the first report of this mutation in North America. With continued screening of more individuals, we will be able to create a robust mutation database that can help us understand disease patterns associated with particular variants and may be a starting point in the development of new therapies for familial paraganglioma syndromes.

Treatment of hyperprolactinemia: a systematic review and meta-analysis.

BACKGROUND: Hyperprolactinemia is a common endocrine disorder that can be associated with significant morbidity. We conducted a systematic review and meta-analyses of outcomes of hyperprolactinemic patients, including microadenomas and macroadenomas, to provide evidence-based recommendations for practitioners. Through this review, we aimed to compare efficacy and adverse effects of medications, surgery and radiotherapy in the treatment of hyperprolactinemia. METHODS: We searched electronic databases, reviewed bibliographies of included articles, and contacted experts in the field. Eligible studies provided longitudinal follow-up of patients with hyperprolactinemia and evaluated outcomes of interest. We collected descriptive, quality and outcome data (tumor growth, visual field defects, infertility, sexual dysfunction, amenorrhea/oligomenorrhea and prolactin levels). RESULTS: After review, 8 randomized and 178 nonrandomized studies (over 3,000 patients) met inclusion criteria. Compared to no treatment, dopamine agonists significantly reduced prolactin level (weighted mean difference, -45; 95% confidence interval, -77 to -11) and the likelihood of persistent hyperprolactinemia (relative risk, 0.90; 95% confidence interval, 0.81 to 0.99). Cabergoline was more effective than bromocriptine in reducing persistent hyperprolactinemia, amenorrhea/oligomenorrhea, and galactorrhea. A large body of noncomparative literature showed dopamine agonists improved other patient-important outcomes. Low-to-moderate quality evidence supports improved outcomes with surgery and radiotherapy compared to no treatment in patients who were resistant to or intolerant of dopamine agonists. CONCLUSION: Our results provide evidence to support the use of dopamine agonists in reducing prolactin levels and persistent hyperprolactinemia, with cabergoline proving more efficacious than bromocriptine. Radiotherapy and surgery are useful in patients with resistance or intolerance to dopamine agonists.

Clinical review. Risk factors for low bone mass-related fractures in men: a systematic review and meta-analysis.

CONTEXT: Testing men at increased risk for osteoporotic fractures has been recommended. OBJECTIVE: The aim of this study was to estimate the magnitude of association and quality of supporting evidence linking multiple risk factors with low bone mass-related fractures in men. DATA SOURCES: We searched MEDLINE, EMBASE, Web of Science, SCOPUS and Cochrane CENTRAL through February 2010. We identified further studies by reviewing reference lists from selected studies and reviews. STUDY SELECTION: Eligible studies had to enroll men and quantitatively evaluate the association of risk factors with low bone density-related fractures. DATA EXTRACTION: Reviewers working independently and in duplicate determined study eligibility and extracted study description, quality, and outcome data. DATA SYNTHESIS: Fifty-five studies provided data sufficient for meta-analysis. The quality of these observational studies was moderate with fair levels of multivariable adjustment and adequate exposure and outcome ascertainment. Statistically significant associations were established for age, low body mass index, current smoking, excessive alcohol use, chronic corticosteroid use, history of prior fractures, history of falls, history of hypogonadism, history of stroke, and history of diabetes. Statistical heterogeneity of the meta-analytic estimates of all associations was significant except for chronic corticosteroid use. None of these associations were of large magnitude (i.e. adjusted odds ratios were generally <2). No evidence supporting a particular effective testing or screening strategy was identified. CONCLUSIONS: Multiple risk factors for fractures in men were identified, but their usefulness for stratifying and selecting men for bone density testing remains uncertain.

A systematic review of lower extremity arterial revascularization economic analyses.

OBJECTIVE: Economic evaluation remains an understudied aspect of lower extremity vascular reconstructions. This study reviewed the economic-based literature with respect to open and endovascular treatment of peripheral arterial disease. METHODS: This systematic review included economic analyses of open and endovascular treatment of lower extremity peripheral arterial disease, including claudication and critical limb ischemia. Studies were categorized as model-based, cost-consequences, or econometric cost-analyses. Clinical, financial, and time-based outcomes were examined. RESULTS: From a candidate list of 1351 studies, 19 were appropriate for the review, comprising 3 model-based, 12 cost-consequence, and 4 cost-analyses. Because of the small numbers, claudication and critical limb ischemia studies were analyzed together. There was a trend favoring initial cost-savings with endovascular therapy. Whether this benefit is sustained over time is unknown. We were prevented from drawing cost-efficacy inferences because of a noted lack of standardized patient-centric outcomes, longitudinal data, and reintervention data. CONCLUSIONS: The existing lower extremity arterial revascularization economic literature is inadequate for drawing cost-efficacy conclusions and cannot inform guidelines for open vs endovascular treatment. Overcoming this limitation will require the inclusion of cost (initial and reintervention) and patient-centric outcomes in future studies evaluating lower extremity revascularization technologies. All journals, particularly vascular journals, should enforce standard reporting guidelines of effectiveness and economic studies to enable appropriate comparative and cost-effectiveness analyses.

Effect of evaporative coolers on skin test reactivity to dust mites and molds in a desert environment.

Dust mites and molds are usually not found in arid environments and have a lower prevalence in desert areas. Evaporative (swamp) coolers increase indoor humidity significantly. The purpose of this study is to determine whether evaporative coolers affect the skin test rate to dust mites and molds in patients. Patients with asthma or allergic rhinitis who were undergoing skin testing for molds, indoor allergens, grasses, weeds, and trees were asked about presence of central, window, and evaporative cooler air conditioning in their home. All were tested using the prick technique with controls. One hundred ninety patients between 1 and 42 years (mean, 5.4 years) were evaluated. Fifty-nine (31%) had an evaporative cooler in their home. Twenty-five (42%) of those with evaporative coolers had a positive skin test to at least one mold compared with 26 (19%) without coolers (chi-square, 10.5; p = 0.001). Twenty (34%) of those with evaporative coolers had a positive skin test to dust mites compared with 23 (17.5%) without coolers (chi-square, 6.2; p = 0.013). Children < or = 6 years of age had the greatest skin test prevalence (chi-square, 4.3; p = 0.03). In the desert, children in homes using evaporative coolers are significantly more likely to have positive skin tests to molds or mites. This appears to be because of humidity caused by these devices. Patients with asthma in homes with evaporative coolers should be counseled about the risk for mold and dust-mite allergy. Humidity monitoring, cooler maintenance, and filter changes should be discussed.

Functional role of CLC-2 chloride inward rectifier channels in cardiac sinoatrial nodal pacemaker cells.

A novel Cl(-) inward rectifier channel (Cl,ir) encoded by ClC-2, a member of the ClC voltage-gated Cl(-) channel gene superfamily, has been recently discovered in cardiac myocytes of several species. However, the physiological role of Cl,ir channels in the heart remains unknown. In this study we tested the hypothesis that Cl,ir channels may play an important role in cardiac pacemaker activity. In isolated guinea-pig sinoatrial node (SAN) cells, Cl,ir current was activated by hyperpolarization and hypotonic cell swelling. RT-PCR and immunohistological analyses confirmed the molecular expression of ClC-2 in guinea-pig SAN cells. Hypotonic stress increased the diastolic depolarization slope and decreased the maximum diastolic potential, action potential amplitude, APD(50), APD(90), and the cycle-length of the SAN cells. These effects were largely reversed by intracellular dialysis of anti-ClC-2 antibody, which significantly inhibited Cl,ir current but not other pacemaker currents, including the hyperpolarization-activated non-selective cationic "funny" current (I(f)), the L-type Ca(2+) currents (I(Ca,L)), the slowly-activating delayed rectifier I(Ks) and the volume-regulated outwardly-rectifying Cl(-) current (I(Cl,vol)). Telemetry electrocardiograph studies in conscious ClC-2 knockout (Clcn2(-/-)) mice revealed a decreased chronotropic response to acute exercise stress when compared to their age-matched Clcn2(+/+) and Clcn2(+/-) littermates. Targeted inactivation of ClC-2 does not alter intrinsic heart rate but prevented the positive chronotropic effect of acute exercise stress through a sympathetic regulation of ClC-2 channels. These results provide compelling evidence that ClC-2-encoded endogenous Cl,ir channels may play an important role in the regulation of cardiac pacemaker activity, which may become more prominent under stressed or pathological conditions.