Patterns of Osteoporosis Medications Selection After Drug Holiday or Continued Therapy: A Real-World Experience

ObjectivePublished literature on physicians’ preferences and sequential treatment patterns of osteoporosis therapy is scarce.MethodsA retrospective cohort study of patients who received bisphosphonates, denosumab, and/or raloxifene for at least 3 consecutive years or teriparatide for at least 18 months for osteoporosis. Data collection spanned 10 years, from October 2007 to September 2016, at a tertiary care center in the United States.ResultsIn total, 12 885 patients were identified on the basis of receiving at least 1 treatment at any point in time; 1814 patients were randomly reviewed, and 274 patients met the inclusion criteria. The mean age was 68.8 ± 10.7 years, and women represented 90.9% of all the cases. Primary care physicians and rheumatologists constituted 65.7% and 22.6% of the prescribers, respectively. Before instituting a drug holiday, alendronate was the most common initial treatment (percentage, mean duration ± standard deviation in years: 69%, 5.4 ± 2.4 years) followed by ibandronate (9.5%, 4.9 ± 2.1 years) and raloxifene (9.1%, 5.2 ± 1.6 years). Denosumab was the most common second course of treatment, accounting for 29.3% of 82 patients who were subsequently prescribed another therapy, followed by alendronate (24.4%) and zoledronate (20.7%). Among patients who were placed on a drug holiday and eventually restarted on osteoporosis therapy, denosumab was the most common treatment instituted (n = 21), accounting for 40% of the total patients, followed by alendronate (32%) and zoledronate (16%). There was a progressive decline in osteoporosis therapy over the duration of the study.ConclusionAlendronate was the most common initial therapy. Denosumab was the most common second course of treatment prescribed.     

Long-Term Drug Treatment of Obesity in a Private Practice Setting

ATKINSON, RICHARD L, ROY C BLANK, DONALD SCHUMACHER, NIKHIL V DHURANDHAR, DOUGLAS L RITCH. Long-term drug treatment of obesity in a private practice setting. This study evaluated the long-term efficacy and safety of the combination of phentermine and fenfluramine for the treatment of obesity in a private practice setting. A total of 1388 consecutive, qualified patients presenting to a private general internal medicine practice in Charlotte, NC, were enrolled with eligibility criteria including: age 18 years to 60 years, 20% over “desirable” bodyweight or body mass index <27, no serious medical or psychiatric disease, and no contraindications to drug therapy. Patients were instructed in diet, exercise, and behavior modification techniques and received phentermine (15 mg/day to 30 mg/day) and fenfluramine (20 mg/day to 60 mg/day) continuously for over 3 years. Average duration of treatment was 15. 9 months, and average weight loss at the last visit was 11. 6 kg, or 11. 7% of initial bodyweight. For patients completing 1 year of drug treatment, mean weight loss was 16. 5 kg, or 16% of initial weight. Weight loss persisted for 2 years, but partial regain was seen at 3 years. The dropout rates were 18% at 6 months, 39% at 1 year, 68% at 2 years, and 78% at 3 years. At 1 year, blood pressure of hypertensive patients fell from 151/95 mm Hg to 127/78 mm Hg, and serum cholesterol and triglycerides of hyperlipidemic patients fell by 0. 750 mmol/L (29 mg/dL) and 0. 937 mmol/L (83 mg/dL), respectively. Adverse events were modest. We conclude that, in a private practice setting, long-term treatment of obesity with the combination of phentermine, fenfluramine, and a weight maintenance program is generally safe and effective. More research is needed to determine efficacy and safety for longer than 3 years.     

Long-Term Follow-up of Graves Orbitopathy After Treatment With Short- or Long-Term Methimazole or Radioactive Iodine

ObjectiveThe aim of this study was to compare long-term outcomes in terms of new onset or worsening of Graves orbitopathy (GO) in patients with Graves disease treated with different therapeutic modalities for hyperthyroidism.MethodsA total of 1163 patients with Graves disease were enrolled in this study; 263 patients were treated with radioiodine and 808 patients received methimazole (MMI) therapy for a median of 18 months, of whom 178 patients continued MMI for a total of 96 months (long-term methimazole [LT-MMI]). The thyroid hormonal status and GO were evaluated regularly for a median of 159 months since enrollment.ResultsThe rates of relapse, euthyroidism, and hypothyroidism at the end of follow-up were as follows: radioiodine treatment group: 16%, 22%, and 62%, respectively; short-term MMI group: 59%, 36%, and 5%, respectively; and LT-MMI group: 18%, 80%, and 2%, respectively. During the first 18 months of therapy, worsening of GO (11.5% vs 5.7%) and de novo development of GO (12.5% vs 9.8%) were significantly more frequent after radioiodine treatment (P <.004). Overall worsening and de novo development of GO from >18 to 234 months occurred in 26 (9.9%) patients in the radioiodine group and 8 (4.5%) patients in the LT-MMI group (P <.037). No case of worsening or new onset of GO was observed in patients treated with LT-MMI from >60 to 234 months of follow-up.ConclusionProgression and development of GO were associated more with radioiodine treatment than with MMI treatment; GO may appear de novo or worsen years after radioiodine treatment but not after LT-MMI therapy.     

A Retrospective Review of Patients with Atypical Femoral Fractures While on Long-Term Bisphosphonates: Including Pertinent Biochemical and Imaging Studies

ObjectiveTo elucidate the effects of prolonged bisphosphonate (BP) exposure on the development of atypical fragility fractures, and to define the associated risk factors.MethodsApproval was obtained from the institutional review board, and a retrospective chart analysis was performed on 51 patients who had been on BPs for at least 3 years and had complete subtrochanteric or diaphyseal femoral fracture(s) between January 2005 and April 2011. All relevant data were available for 25 patients (mean age, 67.52 years). All fractures included in the study were low- or no-energy. Relevant clinical and demographic data were collected regarding age, gender, ethnicity, height, weight, and comorbid medical conditions. Imaging and laboratory data collected on all patients included: calcium, alkaline phosphatase, 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone, serum c-telopeptide, and urine n-telopeptide levels, bone mineral density, radiography, and magnetic resonance imaging.ResultsMost of the patients in this study were Caucasian, were on alendronate, had bilateral findings, and almost half had prodromal symptoms. The 25-OHD level was suboptimal (<30 ng/mL) in 45.8% of the patients. Mean BP duration was 9.84 years, and mean bone density was in the osteopenic, not osteoporotic, range.ConclusionCharacteristics of patients with atypical BP-related fracture include relatively young age, long duration of BP use, suboptimal 25-OHD level, and bone density in the nonosteoporotic range. All of these may be significant risk factors for insufficiency fracture development. (Endocr Pract. 2013;19:456-461)     

Long-Term Follow-up of Patients with Hypertensive Disease Treated with Guanethidine

Sixty-three hypertensive patients treated with guanethidine, usually in conjunction with chlorthalidone, were followed up for periods as long as 2½ years. The guanethidine dosage was not found to be related to the size of the patient, duration of hypertension or its severity. Two patients developed intolerable syncope without satisfactory control of blood pressure. No aggravation of bronchitis or diabetes was observed. Faintness and diarrhea occasioned by the drug lessened with time. Symptomatic improvement was noted in the majority, as was improvement in the optic fundus, the electrocardiogram and the heart size. Four deaths were unrelated to therapy, but were the result of complications of underlying vascular disease.     

Circadian Time-Dependent Response of Childhood Lymphoblastic Leukemia to Chemotherapy: A Long-Term Follow-up Study of Survival

The evolution of 118 children treated for acute lymphoblastic leukemia between 1976 and 1984, and followed until 1991, was reviewed. Maintenance chemotherapy consisted of daily 6-mercaptopurine (6-MP), weekly methotrexate (MTX), and monthly vincristine and prednisone. Eighty-two children took 6-MP and MTX in the morning, and 36 took them in the evening. Disease-free survival, as determined by Kaplan-Meier analysis, was better for children on evening chemotherapy. Regression analysis (Cox proportional hazards model, with evening versus morning schedule as exposure variable, and age at diagnosis, leucocytosis at diagnosis, and sex as covariates) showed that for those surviving free of disease for longer than 78 weeks, the risk of relapse was 2.56 times greater for the morning schedule than for the evening one.     

Hemorrhage During Long-Term Anticoagulant Drug Therapy—Part II: Gastrointestinal Hemorrhage

Most of the gastrointestinal hemorrhages occurring during long-term anticoagulant drug therapy of 2,013 patients (reported in the literature) were caused by underlying lesions (44 to 77). Of the 44 lesions, only seven were diagnosed before treatment was started.Most of the episodes of hemorrhage occurred with the prothrombin activity at a so-called “safe” level. Closer investigation before the anticoagulant therapy was begun might have brought the underlying lesion to light.     

Hemorrhage During Long-Term Anticoagulant Drug Therapy—Part I: Intracranial Hemorrhage

Intracranial hemorrhage was the most serious hemorrhage as measured by death and disability, occurring during long-term anticoagulant drug therapy of 1,626 patients. Among 95 hemorrhagic episodes considered life-threatening or potentially crippling, 30 were intracranial and 56 were gastrointestinal. Over two-thirds of the patients with intracranial hemorrhage died, as against one-tenth of those with gastrointestinal hemorrhage.The incidence of intracranial hemorrhage is increased among hypertensive patients, but the results of a controlled study indicate that the incidence of intracranial hemorrhage is not affected by whether or not the hypertensive patient is receiving anticoagulant therapy. Hypertension is the important precipitating factor, not the prothrombin level. Even at excessively low prothrombin levels only one intracranial hemorrhage occurred in 337 instances.In this series, reducing coagulability to a desirable range did not increase the probability of intracranial hemorrhage. Once bleeding occurred, however, it increased the risk of death and disability.     

Good Quality of Life in Former Buruli Ulcer Patients with Small Lesions: Long-Term Follow-up of the BURULICO Trial

Background

Buruli Ulcer is a tropical skin disease caused by Mycobacterium ulcerans, which, due to scarring and contractures can lead to stigma and functional limitations. However, recent advances in treatment, combined with increased public health efforts have the potential to significantly improve disease outcome.

Objectives

To study the Quality of Life (QoL) of former Buruli Ulcer patients who, in the context of a randomized controlled trial, reported early with small lesions (cross-sectional diameter <10 cm), and received a full course of antibiotic treatment.

Methods

127 Participants of the BURULICO drug trial in Ghana were revisited. All former patients aged 16 or older completed the Dermatology Life Quality Index (DLQI) and the abbreviated World Health Organization Quality of Life scale (WHOQOL-BREF). The WHOQOL-BREF was also administered to 82 matched healthy controls. Those younger than 16 completed the Childrens'' Dermatology Life Quality Index (CDLQI) only.

Results

The median (Inter Quartile Range) score on the DLQI was 0 (0–4), indicating good QoL. 85% of former patients indicated no effect, or only a small effect of the disease on their current life. Former patients also indicated good QoL on the physical and psychological domains of the WHOQOL-BREF, and scored significantly higher than healthy controls on these domains. There was a weak correlation between the DLQI and scar size (ρ = 0.32; p<0.001).

Conclusions

BU patients who report early with small lesions and receive 8 weeks of antimicrobial therapy have a good QoL at long-term follow-up. These findings contrast with the debilitating sequelae often reported in BU, and highlight the importance of early case detection.     

Hemorrhage During Long-Term Anticoagulant Drug Therapy—Part IV: Selection and Management of Patients

Most serious hemorrhages that occur during long-term anticoagulant drug therapy are due either to poor patient selection or to poor management of the patient, or both.In each patient being considered for treatment, the risk of bleeding must be evaluated and classified as high, moderate or low.The clinician must especially assess the risk of intracranial hemorrhage in hypertensive patients, and must screen all patients for potential sources of gastrointestinal bleeding. There is ample time for such investigations, since initiating long-term anticoagulant therapy is not an emergency procedure.The desired level of prothrombin activity must be adjusted to the risks determined for each individual patient. There is no single “therapeutic range” applicable to all patients with their varying hemorrhagenic risks.Proper management includes sufficient laboratory testing to maintain the desired prothrombin level, and continued vigilance to detect signs of early bleeding.Preventable hemorrhage cannot be cited as evidence against the value of anticoagulant drug therapy.     

Situations in 140 Characters: Assessing Real-World Situations on Twitter

Over 20 million Tweets were used to study the psychological characteristics of real-world situations over the course of two weeks. Models for automatically and accurately scoring individual Tweets on the DIAMONDS dimensions of situations were developed. Stable daily and weekly fluctuations in the situations that people experience were identified. Predicted temporal trends were found, providing validation for this new method of situation assessment. On weekdays, Duty peaks in the midmorning and declines steadily thereafter while Sociality peeks in the evening. Negativity is highest during the workweek and lowest on the weekends. pOsitivity shows the opposite pattern. Additionally, gender and locational differences in the situations shared on Twitter are explored. Females share both more emotionally charged (pOsitive and Negative) situations, while no differences were found in the amount of Duty experienced by males and females. Differences in the situations shared from Rural and Urban areas were not found. Future applications of assessing situations using social media are discussed.     

Long-Term Survival and Dialysis Dependency Following Acute Kidney Injury in Intensive Care: Extended Follow-up of a Randomized Controlled Trial

Background

The incidence of acute kidney injury (AKI) is increasing globally and it is much more common than end-stage kidney disease. AKI is associated with high mortality and cost of hospitalisation. Studies of treatments to reduce this high mortality have used differing renal replacement therapy (RRT) modalities and have not shown improvement in the short term. The reported long-term outcomes of AKI are variable and the effect of differing RRT modalities upon them is not clear. We used the prolonged follow-up of a large clinical trial to prospectively examine the long-term outcomes and effect of RRT dosing in patients with AKI.

Methods and Findings

We extended the follow-up of participants in the Randomised Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study from 90 days to 4 years after randomization. Primary and secondary outcomes were mortality and requirement for maintenance dialysis, respectively, assessed in 1,464 (97%) patients at a median of 43.9 months (interquartile range [IQR] 30.0–48.6 months) post randomization. A total of 468/743 (63%) and 444/721 (62%) patients died in the lower and higher intensity groups, respectively (risk ratio [RR] 1.04, 95% CI 0.96–1.12, p = 0.49). Amongst survivors to day 90, 21 of 411 (5.1%) and 23 of 399 (5.8%) in the respective groups were treated with maintenance dialysis (RR 1.12, 95% CI 0.63–2.00, p = 0.69). The prevalence of albuminuria among survivors was 40% and 44%, respectively (p = 0.48). Quality of life was not different between the two treatment groups. The generalizability of these findings to other populations with AKI requires further exploration.

Conclusions

Patients with AKI requiring RRT in intensive care have high long-term mortality but few require maintenance dialysis. Long-term survivors have a heavy burden of proteinuria. Increased intensity of RRT does not reduce mortality or subsequent treatment with dialysis.

Trial registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00221013","term_id":"NCT00221013"}}NCT00221013 Please see later in the article for the Editors'' Summary     

Bisphosphonates and risk of atrial fibrillation: a meta-analysis

Introduction  

Bisphosphonates are the most commonly used drugs for the prevention and treatment of osteoporosis. Although a recent FDA review of the results of clinical trials reported no clear link between bisphosphonates and serious or non-serious atrial fibrillation (AF), some epidemiologic studies have suggested an association between AF and bisphosphonates.     

Bisphosphonates and Risk of Cardiovascular Events: A Meta-Analysis

Background and Objectives

Some evidence suggests that bisphosphonates may reduce atherosclerosis, while concerns have been raised about atrial fibrillation. We conducted a meta-analysis to determine the effects of bisphosphonates on total adverse cardiovascular (CV) events, atrial fibrillation, myocardial infarction (MI), stroke, and CV death in adults with or at risk for low bone mass.

Methods

A systematic search of MEDLINE and EMBASE through July 2014 identified 58 randomized controlled trials with longer than 6 months in duration that reported CV events. Absolute risks and the Mantel-Haenszel fixed-effects odds ratios (ORs) and 95% confidence intervals (CIs) of total CV events, atrial fibrillation, MI, stroke, and CV death were estimated. Subgroup analyses by follow-up duration, population characteristics, bisphosphonate types, and route were performed.

Results

Absolute risks over 25–36 months in bisphosphonate-treated versus control patients were 6.5% versus 6.2% for total CV events; 1.4% versus 1.5% for atrial fibrillation; 1.0% versus 1.2% for MI; 1.6% versus 1.9% for stroke; and 1.5% versus 1.4% for CV death. Bisphosphonate treatment up to 36 months did not have any significant effects on total CV events (14 trials; ORs [95% CI]: 0.98 [0.84–1.14]; I² = 0.0%), atrial fibrillation (41 trials; 1.08 [0.92–1.25]; I² = 0.0%), MI (10 trials; 0.96 [0.69–1.34]; I² = 0.0%), stroke (10 trials; 0.99 [0.82–1.19]; I² = 5.8%), and CV death (14 trials; 0.88 [0.72–1.07]; I² = 0.0%) with little between-study heterogeneity. The risk of atrial fibrillation appears to be modestly elevated for zoledronic acid (6 trials; 1.24 [0.96–1.61]; I² = 0.0%), not for oral bisphosphonates (26 trials; 1.02 [0.83–1.24]; I² = 0.0%). The CV effects did not vary by subgroups or study quality.

Conclusions

Bisphosphonates do not have beneficial or harmful effects on atherosclerotic CV events, but zoledronic acid may modestly increase the risk of atrial fibrillation. Given the large reduction in fractures with bisphosphonates, changes in osteoporosis treatment decision due to CV risk are not justified.     

Follow-up computed tomography in patients operated on for liver malignancies

The aim of the investigation was to study a role of computed tomography (CT) in choosing treatment policy for patients after hepatectomy. In 186 patients with liver malignancies, 558 follow-up studies were performed 3 months to 8 years after surgery and adjuvant treatment. RESULTS: the permanent change of the liver, which is detectable at postoperative CT, is its outline deformity. Inverted (87%), irregular (56%), and, less frequently, convex (13%) outlines were identified. Among 41 patients who had postoperatively undergone adjuvant chemoembolization, 7 (17%) patients were seen to have a local compact lipidiol concentration adjacent to the resection plane. CT carried out in 19 patients with suspected postoperative complications could recognize the cause of complications (liver abscesses, abdominal fluid, bilomas) in 15 (78.9%) cases. In 20 patients, compact lipidiol accumulation in the vicinity of the resection plane was the most common, but not pathognomonic sign of tumor resection in the resection plane. Thus, CT plays an important role in the follow-up of patients after liver resections for malignancies in both the early and late postoperative periods.     

Bisphosphonates and bone resorption: effects on collagenase and lysosomal enzyme excretion

When added to cultures of parathyroid hormone (PTH)- bones, dichloromethylenebisphosphonate (C12MBP) and 3-amino-1-hydroxypropydilene-1,1-bisphosphonate (AHPrBP) inhibit completely and in a parallel manner the development of resorption lacunae, the loss of calcium by the explants and their PTH-induced excretion of lysosomal hydrolases (β-glucuronidase and N-acetyl-β-glucosaminidase). The loss of collagen (hydroxyproline) by the bones is usually less inhibited than their loss of calcium and their heparin-induced excretion of collagenase is unaffected. To interpret these data, it is proposed that these bisphosphonates act more on the activity of osteoclasts, suppressing simultaneously their excretion of lysosomal enzymes and their erosion of mineralized bone matrix, than on that of other cell types (osteoblasts ?) responsible for collagenase production and the removal of uncalcified collagen.