The efficacy and safety of burosumab in two patients with cutaneous skeletal hypophosphatemia syndrome.

Cutaneous skeletal hypophosphatemia syndrome (CSHS) is an ultra-rare mosaic disorder manifesting as skeletal dysplasia and FGF23-mediated hypophosphatemia, with some experiencing extra-osseous/extra-cutaneous manifestations, including both benign and malignant neoplasms. Like other disorders of FGF23-mediated hypophosphatemia including X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO), patients with CSHS have low serum phosphorus and active 1,25-dihydroxyvitamin D levels. Current treatment options for patients with CSHS include multiple daily doses of oral phosphorus and one or more daily doses of active vitamin D analog to correct the deficits. Recently, the fully human monoclonal antibody against FGF23 burosumab received US approval for the treatment of XLH and TIO, two rare diseases characterized by FGF23-mediated hypophosphatemia leading to rickets and osteomalacia. Given the similarities between the pathobiologies of these disorders and CSHS, we investigated the impact of burosumab on two patients, one pediatric and one adult, with CSHS who participated in separate, but similarly designed trials. In both the pediatric and adult patients, burosumab therapy was well-tolerated and contributed to clinically meaningful improvements in disease outcomes including normalization of phosphorus metabolism and markers of bone health, and improvements in skeletal abnormalities, fractures, and physical function. Reported adverse events were minimal, with only mild injection site reactions attributed to burosumab therapy. Together, these findings suggest that burosumab therapy is a promising therapeutic option for patients with CSHS.

Regression of calcinosis cutis after inkless tattoo in a patient with dermatomyositis: therapeutic potential of microneedling.

Calcinosis cutis is defined as abnormal deposition of calcium salts in the skin and subcutaneous tissues. Dystrophic calcification, the most common form of calcinosis cutis, is associated with autoimmune connective tissue diseases. This condition is associated with severe pain and can affect the patient's quality of life and lead to long-term disability. Treatment is often challenging, and there is a very limited evidence base for potential treatments of calcinosis cutis associated with systemic sclerosis and dermatomyositis. Inkless tattoo is very similar to microneedling, a minimally invasive procedure stimulating the wound-healing cascade contributing to elastin and collagen formation as well as neovascularization. This technique has not been reported as a potential therapeutic option for calcinosis cutis. Here, we present a patient with calcinosis cutis in the setting of dermatomyositis that responded dramatically to inkless tattoo application. Our results support the need for future studies of microneedling in patients with this disorder.

Comprehensive cost-effectiveness of diabetes management for the underserved in the United States: A systematic review.

BACKGROUND: Diabetes mellitus affects almost 10% of U.S. adults, leading to human and financial burden. Underserved populations experience a higher risk of diabetes and related complications resulting from a combination of limited disposable income, inadequate diet, and lack of insurance coverage. Without the requisite resources, underserved populations lack the ability to access healthcare and afford prescription drugs to manage their condition. The aim of this systematic review is to synthesize the findings from cost-effectiveness studies of diabetes management in underserved populations. METHODS: Original, English, peer-reviewed cost-effectiveness studies of diabetes management in U.S. underserved populations were obtained from 8 databases, and PRISMA 2009 reporting guidelines were followed. Evidence was categorized as strong or weak based on a combination of GRADE and American Diabetes Association guidelines. Internal validity was assessed by the Cochrane methodology. Studies were classified by incremental cost-effectiveness ratio as very cost-effective (ICER≤US$25,000), cost-effective (US$25,000US$100,000). Reporting and quality of economic evaluations was assessed using the CHEERS guidelines and Recommendations of Second Panel for Cost-Effectiveness in Health and Medicine, respectively. FINDINGS: Fourteen studies were included. All interventions were found to be cost-effective or very cost-effective. None of the studies reported all 24 points of the CHEERS guidelines. Given the considered cost categories vary significantly between studies, assessing cost-effectiveness across studies has many limitations. Program costs were consistently analyzed, and a third of the included studies (n = 5) only examined these costs, without considering other costs of diabetes care. INTERPRETATION: Cost-effectiveness studies are not based on a standardized methodology and present incomplete or limited analyses. More accurate assessment of all direct and indirect costs could widen the gap between intervention and usual care. This demonstrates the urgent need for a more standardized and comprehensive cost-effectiveness framework for future studies.

Nutritional Supplements and Skeletal Health.

PURPOSE OF REVIEW: Nutrition influences skeletal health throughout the lifespan, from the impact of maternal intakes during development, through the development of peak bone mass, to the rate of bone loss during aging. However, there are limited data available on the effects of nutritional supplements on bone density, let alone fracture risk. This review will assess the current literature, focusing on human studies, and emphasizing nutrients where bone density or fracture data are available. RECENT FINDINGS: Calcium and vitamin D supplements, in combination, reduce fracture risk, particularly in populations with low intakes. Extensive recent analyses have supported the safety of these interventions at recommended intakes. There is growing evidence that specific isoflavones may improve bone density although fracture data are lacking. Multiple other nutrient supplements may benefit skeletal health, but data are limited. The effect size of nutrient interventions are relatively small, requiring large sample sizes for trials with bone outcomes, may be difficult to blind, and the impact of supplementation may depend on baseline intake. However, nutrition is the only intervention that can be implemented life long and on a population wide basis. Further investigation is needed into the potential benefits of nutritional supplements to determine in which settings supplements may add benefit in addition to dietary intakes.

New model of integrated care for uncontrolled type 2 diabetes in a retrospective, underserved adult population in the USA: a study protocol for an effectiveness and cost-effectiveness analysis.

INTRODUCTION: Type 2 diabetes prevalence is increasing in the USA, especially in underserved populations. Patient outcomes can be improved by providing access to specialty care within Federally Qualified Health Centers, possibly improving the cost-effectiveness of diabetes care. METHODS AND ANALYSIS: A new model of diabetes care based on multidisciplinary teams of clinical fellows, supported by an endocrinologist for underserved adult populations, is presented. The study uses a retrospective, non-randomised cohort of patients with diabetes who visited the community clinic between 1 January 2012 and 31 December 2018. A quasi-experimental method to analyse the causal evidence of the effect of the new model is presented. Discontinuity regression is used to compare two interventions, the intervention by a Clinical Fellow Endocrinology Programme and usual care by a primary care physician. Patients are referred to the Clinical Fellow Endocrinology Programme in case of uncontrolled diabetes (glycated haemoglobin (HbA1c)≥9%). The regression discontinuity design allows the construction of a treatment group for patients with an HbA1c equal or above the threshold in comparison with a control group for patients with an HbA1c below the threshold. The patient outcomes and cost-effectiveness of the new model are analysed. Regression models will be used to assess the differences between treatment and control groups. ETHICS AND DISSEMINATION: Quantitative patient data are received by the study team in a de-identified format for analysis via an institutional review board-approved protocol. The quantitative study has been approved by the Houston Methodist Research Institute Institutional Review Board, Houston, Texas, USA. Anticipated results will not only provide evidence about the impact of patient outcomes in underserved diabetic populations, but also give an idea of the cost-effectiveness of the new model and whether or not cost savings can be attained for patients, third-party payers and society. The results will help set up evidence-based policy guidelines in diabetes care. Results will be disseminated through papers, conferences and public health/policy fora.

A Randomized Controlled Trial of Exercise to Prevent Bone Loss in Premenopausal Women with Breast Cancer.

Background/Introduction/Objective: Premenopausal women treated for breast cancer are at high risk for bone loss. This trial examined the effects of a 1-year combined aerobic and resistance exercise program on bone mineral density (BMD) in women treated for premenopausal breast cancer. MATERIALS AND METHODS: Premenopausal women (n = 206) age ≤ 55 years at cancer diagnosis who were within two years of receiving adjuvant chemotherapy were randomized to a 12-month exercise program or a control group. BMD was measured by dual-energy X-ray absorptiometry at baseline and after 1 year; blood was drawn for skeletal markers. Change from baseline to end of study was compared within and between treatment groups using paired and unpaired t-tests. RESULTS: Lumbar spine BMD declined in both treatment groups with no significant difference between treatment groups (-0.008 ± 0.003 g/cm2 exercise vs. -0.014 ± 0.003 g/cm2 control, p = 0.24). However, among the women who did not lose lean mass during the study (n = 100, 54 control, 46 exercise), the exercise intervention prevented lumbar spine bone loss (0.001 ± 0.005 g/cm2 treatment group vs. -0.014 ± 0.005 g/cm2 control group, p = 0.03). Bone turnover markers decreased significantly in both groups with no differences between groups. CONCLUSIONS: Among women who maintained lean mass, our exercise intervention prevented bone loss; however, our intervention did not prevent bone loss among women who lost muscle mass. Additional investigation into exercise regimens that can prevent both bone and muscle loss may help prevent long-term consequences of premenopausal breast cancer treatment.

Stage-Based Management of Type 2 Diabetes Mellitus with Heart Failure.

Type 2 diabetes negatively impacts heart failure outcomes. Insulin resistance, central adiposity, dyslipidemia, and altered cellular substrate metabolism each have a mechanistic role. Management strategies focused solely on glycemic control have had limited success. However, three new classes of drugs, each with several options, offer the promise of improved diabetes management in heart failure. Unlike earlier classes, these medications have had favorable cardiovascular outcomes. In this review, we present a therapeutic guide for metabolic treatment based on the stages of heart failure.

The Parathyroid Gland and Heart Disease.

The parathyroid glands are critical to maintaining calcium homeostasis through actions of parathyroid hormone (PTH). Recent clinical and molecular research has shown that direct and indirect actions of PTH also affect the heart and vasculature through downstream actions of G protein-coupled receptors in the myocardium and endothelial cells. Patients with disorders of the parathyroid gland have higher incidences of hypertension, arrhythmias, left ventricular hypertrophy, heart failure, and calcific disease which translate into increased cardiac morbidity and mortality. Importantly, clinical research also suggests that early treatment of parathyroid disorders through medical or surgical management may reverse cardiovascular remodeling and mitigate cardiac risk factors.

Hypothyroidism and the Heart.

Hypothyroidism is a commonly encountered clinical condition with variable prevalence. It has profound effects on cardiac function that can impact cardiac contractility, vascular resistance, blood pressure, and heart rhythm. With this review, we aim to describe the effects of hypothyroidism and subclinical hypothyroidism on the heart. Additionally, we attempt to briefly describe how hypothyroid treatment affects cardiovascular parameters.

FRACTURE LIAISON SERVICES: MULTIDISCIPLINARY APPROACHES TO SECONDARY FRACTURE PREVENTION.

OBJECTIVE: A well-recognized gap exists between evidence-based recommendations for post-fracture care and actual clinical practice, demonstrated by the high percentage of fragility fracture patients who are neither diagnosed nor treated for osteoporosis. Our purpose is to review fracture liaison service (FLS) models and to evaluate national and international experiences in secondary fracture prevention. METHODS: We performed a systematic search of publication databases (MEDLINE, SCOPUS) and included randomized controlled trials, meta-analyses, and review articles using the following keywords: Fracture liaison services, Secondary prevention of fracture, Post-fracture healthcare gap, and fragility fractures. References were included from 2001-2015. We subsequently performed reference searches of retrieved articles and available literature was reviewed. RESULTS: The efficacy of secondary fracture prevention programs correlates strongly with their intensity. Type A FLS Models are most successful in initiating diagnostic and treatment plans for fragility fracture patients. Adoption of FLS programs improves care by lowering mortality and refracture rates while also lowering healthcare costs. The quality of evidence supporting associations between FLS programs and improved outcomes was moderately strong due to the availability of longitudinal data from nationalized health systems. CONCLUSION: As our population ages and challenges to the healthcare system loom ever larger, it is imperative that we fund and champion fracture liaison services. The fracture liaison service has recently emerged as a novel clinical approach that uses coordinated, multidisciplinary care to improve post-fracture outcomes and reduce recurrent fractures. These programs are simple, targeted, high-yield and have the potential to protect our most vulnerable patients. ABBREVIATIONS: DXA = dual-energy x-ray absorptiometry FLS = fracture liaison service NCQA = National Committee of Quality Assurance NHS = National Health Service PCP = primary care physician PQRS = Physician Quality Reporting System QCDR = Qualified Clinical Data Registry.

FSH Levels Predict Bone Loss in Premenopausal Women Treated for Breast Cancer More Than One Year After Treatment.

CONTEXT: Biomarkers to predict bone loss in premenopausal women after breast cancer treatment have not been examined. OBJECTIVE: To determine whether baseline FSH predicts subsequent bone loss. DESIGN: Secondary data analysis of the Exercise for Bone Health: Young Breast Cancer Survivors study, in which women were randomized to a 12-month exercise program or monthly health newsletter. SETTING: Community dwelling women. PARTICIPANTS: A total of 206 women age less than or equal to 55 years at breast cancer diagnosis who had received adjuvant chemotherapy and were at least 1 year after diagnosis. INTERVENTION: Serum collected at baseline (an average of 302 ± 148 d after completing chemotherapy) was analyzed for FSH. MAIN OUTCOME MEASURE: Change in bone mineral density. RESULTS: In linear regression models, baseline FSH levels predicted bone loss over the ensuing 12 months at the lumbar spine and femoral neck including after adjustment for age, ethnicity, treatment group (exercise vs control), baseline bone density, and high-sensitivity C-reactive protein (P < .001). In multiply adjusted models, the 12-month rate of change in bone density was +0.007% in the lowest tertile of FSH (FSH = 9 ± 7 IU/L, mean ± SD), -0.96% in the middle tertile (mean FSH = 41 ± 11 IU/L), and -2.2% in the highest tertile (mean FSH = 86 ± 19 IU/L), P for trend <.001. CONCLUSIONS: Among premenopausal women with breast cancer treated with chemotherapy, baseline FSH levels are strongly associated with subsequent bone loss. Further studies are needed to establish the optimal timing of FSH measurement in relation to breast cancer treatment and to investigate potential strategies to prevent bone loss.

Carotid endarterectomy in the elderly: does gender effect outcome?

OBJECTIVES: Carotid endarterectomy (CEA) has a positive effect on stroke free survival in patients with either symptomatic or asymptomatic severe carotid bifurcation stenosis. However, most trials have excluded octogenarians. In addition, concerns have arisen regarding the benefits of CEA in the elderly population, especially in women. In this study, we performed an outcome analysis in patients undergoing CEA comparing those eighty and older to their younger counterparts. Additionally, we evaluated the elderly group based on gender. METHODS: Over the past 10 years, all patients undergoing CEA for asymptomatic and symptomatic carotid disease have been entered into our vascular surgery registry. Demographics, indications for operative intervention, outcomes and survival of patients who had undergone CEA were reviewed. Procedures were preferentially performed under regional anesthesia with selective shunting. Chi square analysis was used to assess significance and assumed for P<0.05. RESULTS: Over the last 10 years, 125 carotid endarterectomies were performed in 125 patients eighty years of age or older. Fifty-six were male and 69 were female. Mean age was 83 (range: 80-97). Asymptomatic disease was identified in 28 of the male patients (50%) and 44 of the female patients (64%). There were no deaths and a permanent neurological deficit occurred in one female patient. There was no difference in thirty-day morbidity or mortality in female patients compared to males. CONCLUSIONS: These observations suggest that CEA can be safely performed in selected elderly patients with asymptomatic or symptomatic carotid artery stenosis. Furthermore, women over 80 may expect equally optimistic results as their male counterparts.