Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of symptoms in patients with multiple myeloma: a systematic review and meta‐analysis

Multiple myeloma (MM) is an incurable haematological disease. Due to novel agents, overall survival has improved in this group, yet there are no systematic reviews to understand the symptom profiles resulting from disease and treatment‐related toxicities. We aimed to synthesise data on the prevalence of symptoms in patients with MM.
A systematic review of health‐related quality of life in longitudinal studies of myeloma patients

Multiple myeloma (MM) patients report high symptom burden and reduced health‐related quality of life (HRQoL) compared to patients with other haematological malignancies. The aim of this review was to analyse published longitudinal studies including MM patients according to a change in HRQoL scores, which is perceived as beneficial to the patient according to two published guidelines.
Weight and Metabolic Outcomes 12 Years after Gastric Bypass

BACKGROUND Few long‐term or controlled studies of bariatric surgery have been conducted to date. We report the 12‐year follow‐up results of an observational, prospective study of Roux‐en‐Y gastric bypass that was conducted in the United States. METHODS A total of 1156 patients with severe obesity comprised three groups: 418 patients who sought and underwent Roux‐en‐Y gastric bypass (surgery group), 417 patients who sought but did not undergo surgery (primarily for insurance reasons) (nonsurgery group 1), and 321 patients who did not seek surgery (nonsurgery group 2). We performed clinical examinations at baseline and at 2 years, 6 years, and 12 years to ascertain the presence of type 2 diabetes, hypertension, and dyslipidemia. RESULTS The follow‐up rate exceeded 90% at 12 years. The adjusted mean change from baseline in body weight in the surgery group was ‐45.0 kg (95% confidence interval [CI], ‐47.2 to ‐42.9; mean percent change, ‐35.0) at 2 years, ‐36.3 kg (95% CI, ‐39.0 to ‐33.5; mean percent change, ‐28.0) at 6 years, and ‐35.0 kg (95% CI, ‐38.4 to ‐31.7; mean percent change, ‐26.9) at 12 years; the mean change at 12 years in nonsurgery group 1 was ‐2.9 kg (95% CI, ‐6.9 to 1.0; mean percent change, ‐2.0), and the mean change at 12 years in nonsurgery group 2 was 0 kg (95% CI, ‐3.5 to 3.5; mean percent change, ‐0.9). Among the patients in the surgery group who had type 2 diabetes at baseline, type 2 diabetes remitted in 66 of 88 patients (75%) at 2 years, in 54 of 87 patients (62%) at 6 years, and in 43 of 84 patients (51%) at 12 years. The odds ratio for the incidence of type 2 diabetes at 12 years was 0.08 (95% CI, 0.03 to 0.24) for the surgery group versus nonsurgery group 1 and 0.09 (95% CI, 0.03 to 0.29) for the surgery group versus nonsurgery group 2 (P<0.001 for both comparisons). The surgery group had higher remission rates and lower incidence rates of hypertension and dyslipidemia than did nonsurgery group 1 (P<0.05 for all comparisons). CONCLUSIONS This study showed long‐term durability of weight loss and effective remission and prevention of type 2 diabetes, hypertension, and dyslipidemia after Roux‐en‐Y gastric bypass. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)
Distinctive clinical characteristics and favorable outcomes in patients with large granular lymphocytosis after allo‐HCT: 12‐year follow‐up data

An increase in large granular lymphocytes (LGL) is frequently seen in patients following allogeneic hematopoietic cell transplantation (allo‐HCT) and it has been associated with better outcomes in some reports. We assessed 826 consecutive patients at our institution with over 12 years of follow‐up for the occurrence of LGL lymphocytosis after allo‐HCT. The 3‐year cumulative incidence of LGL lymphocytosis was 14.5% with a median duration of over 3.5 years. The development of LGL lymphocytosis was strongly correlated with CMV viremia and GVHD. The clinical course of patients with LGL lymphocytosis after allo‐HCT was indolent, with the majority of these patients not displaying any clinical signs or symptoms related to the LGL proliferation. LGL lymphocytosis was associated with better outcomes, including higher overall survival (OS 86.6% vs 44.7% at 3 years), lower non‐relapse mortality (NRM 5.5% vs 30.4% at 3 years), and lower risk of relapse (8.9% vs 22.9% at 3 years). A time‐dependent multivariable analysis confirmed the favorable impact of LGL lymphocytosis on OS and NRM, but not on the risk of relapse. In multivariable analysis, a longer duration of LGL lymphocytosis was associated with better OS and NRM. Improved immunomodulatory properties of these cells, regulating GVHD and infections, may explain the observed favorable outcomes of patients who developed LGL lymphocytosis following allo‐HCT.
Effectiveness of home blood pressure monitoring, Web communication, and pharmacist care on hypertension control: a randomized controlled trial.

CONTEXT Treating hypertension decreases mortality and disability from cardiovascular disease, but most hypertension remains inadequately controlled. OBJECTIVE To determine if a new model of care that uses patient Web services, home blood pressure (BP) monitoring, and pharmacist-assisted care improves BP control. DESIGN, SETTING, AND PARTICIPANTS A 3-group randomized controlled trial, the Electronic Communications and Home Blood Pressure Monitoring study was based on the Chronic Care Model. The trial was conducted at an integrated group practice in Washington state, enrolling 778 participants aged 25 to 75 years with uncontrolled essential hypertension and Internet access. Care was delivered over a secure patient Web site from June 2005 to December 2007. INTERVENTIONS Participants were randomly assigned to usual care, home BP monitoring and secure patient Web site training only, or home BP monitoring and secure patient Web site training plus pharmacist care management delivered through Web communications. MAIN OUTCOME MEASURES Percentage of patients with controlled BP (<140/90 mm Hg) and changes in systolic and diastolic BP at 12 months. RESULTS Of 778 patients, 730 (94%) completed the 1-year follow-up visit. Patients assigned to the home BP monitoring and Web training only group had a nonsignificant increase in the percentage of patients with controlled BP (<140/90 mm Hg) compared with usual care (36% [95% confidence interval {CI}, 30%-42%] vs 31% [95% CI, 25%-37%]; P = .21). Adding Web-based pharmacist care to home BP monitoring and Web training significantly increased the percentage of patients with controlled BP (56%; 95% CI, 49%-62%) compared with usual care (P < .001) and home BP monitoring and Web training only (P < .001). Systolic BP was decreased stepwise from usual care to home BP monitoring and Web training only to home BP monitoring and Web training plus pharmacist care. Diastolic BP was decreased only in the pharmacist care group compared with both the usual care and home BP monitoring and Web training only groups. Compared with usual care, the patients who had baseline systolic BP of 160 mm Hg or higher and received home BP monitoring and Web training plus pharmacist care had a greater net reduction in systolic BP (-13.2 mm Hg [95% CI, -19.2 to -7.1]; P < .001) and diastolic BP (-4.6 mm Hg [95% CI, -8.0 to -1.2]; P < .001), and improved BP control (relative risk, 3.32 [95% CI, 1.86 to 5.94]; P<.001). CONCLUSION Pharmacist care management delivered through secure patient Web communications improved BP control in patients with hypertension. Trial Registration clinicaltrials.gov Identifier: NCT00158639.
Catheter Ablation for Atrial Fibrillation with Heart Failure

Background Mortality and morbidity are higher among patients with atrial fibrillation and heart failure than among those with heart failure alone. Catheter ablation for atrial fibrillation has been proposed as a means of improving outcomes among patients with heart failure who are otherwise receiving appropriate treatment. Methods We randomly assigned patients with symptomatic paroxysmal or persistent atrial fibrillation who did not have a response to antiarrhythmic drugs, had unacceptable side effects, or were unwilling to take these drugs to undergo either catheter ablation (179 patients) or medical therapy (rate or rhythm control) (184 patients) for atrial fibrillation in addition to guidelines‐based therapy for heart failure. All the patients had New York Heart Association class II, III, or IV heart failure, a left ventricular ejection fraction of 35% or less, and an implanted defibrillator. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure. Results After a median follow‐up of 37.8 months, the primary composite end point occurred in significantly fewer patients in the ablation group than in the medical‐therapy group (51 patients [28.5%] vs. 82 patients [44.6%]; hazard ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.87; P=0.007). Significantly fewer patients in the ablation group died from any cause (24 [13.4%] vs. 46 [25.0%]; hazard ratio, 0.53; 95% CI, 0.32 to 0.86; P=0.01), were hospitalized for worsening heart failure (37 [20.7%] vs. 66 [35.9%]; hazard ratio, 0.56; 95% CI, 0.37 to 0.83; P=0.004), or died from cardiovascular causes (20 [11.2%] vs. 41 [22.3%]; hazard ratio, 0.49; 95% CI, 0.29 to 0.84; P=0.009). Conclusions Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy. (Funded by Biotronik; CASTLE‐AF ClinicalTrials.gov number, NCT00643188.)
Differences in expression patterns of cathepsin C/dipeptidyl peptidase I in normal, pathological and aged mouse central nervous system

Cathepsin C (CC) (EC 3.4.14.1, dipeptidyl peptidase I) is a lysosomal cysteine protease that is required for the activation of several granule‐associated serine proteases in vivo. CC has been shown to be constitutively expressed in various tissues, but the enzyme is hardly detectable in central nervous system (CNS) tissues. In the present study, we investigated the regional and cellular distribution of CC in normal, aging and pathological mouse brains. Immunoblotting failed to detect CC protein in whole brain tissues of normal mice, as previously described. However, low proteolytic activity of CC was detected in a brain region‐dependent manner, and granular immunohistochemical signals were found in neuronal perikarya of particular brain regions, including the accessory olfactory bulb, the septum, CA2 of the hippocampus, a part of the cerebral cortex, the medial geniculate, and the inferior colliculus. In aged mice, the number of CC‐positive neurons increased to some extent. The protein level of CC and its proteolytic activity showed significant increases in particular brain regions of mouse models with pathological conditions – the thalamus in cathepsin D‐deficient mice, the hippocampus of ipsilateral brain hemispheres after hypoxic–ischemic brain injury, and peri‐damaged portions of brains after penetrating injury. In such pathological conditions, the majority of the cells that were strongly immunopositive for CC were activated microglia. These lines of evidence suggest that CC is involved in normal neuronal function in certain brain regions, and also participates in inflammatory processes accompanying pathogenesis in the CNS.
Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease

BACKGROUND Patients with chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype may benefit from treatment with mepolizumab, a monoclonal antibody directed against interleukin‐5. METHODS We performed two phase 3, randomized, placebo‐controlled, double‐blind, parallel‐group trials comparing mepolizumab (100 mg in METREX, 100 or 300 mg in METREO) with placebo, given as a subcutaneous injection every 4 weeks for 52 weeks in patients with COPD who had a history of moderate or severe exacerbations while taking inhaled glucocorticoid‐based triple maintenance therapy. In METREX, unselected patients in the modified intention‐to‐treat population with an eosinophilic phenotype were stratified according to blood eosinophil count (≥150 per cubic millimeter at screening or ≥300 per cubic millimeter during the previous year). In METREO, all patients had a blood eosinophil count of at least 150 per cubic millimeter at screening or at least 300 per cubic millimeter during the previous year. The primary end point was the annual rate of moderate or severe exacerbations. Safety was also assessed. RESULTS In METREX, the mean annual rate of moderate or severe exacerbations in the modified intention‐to‐treat population with an eosinophilic phenotype (462 patients) was 1.40 per year in the mepolizumab group versus 1.71 per year in the placebo group (rate ratio, 0.82; 95% confidence interval [CI], 0.68 to 0.98; adjusted P=0.04); no significant between‐group differences were found in the overall modified intention‐to‐treat population (836 patients) (rate ratio, 0.98; 95% CI, 0.85 to 1.12; adjusted P>0.99). In METREO, the mean annual rate of moderate or severe exacerbations was 1.19 per year in the 100‐mg mepolizumab group, 1.27 per year in the 300‐mg mepolizumab group, and 1.49 per year in the placebo group. The rate ratios for exacerbations in the 100‐mg and 300‐mg mepolizumab groups versus the placebo group were 0.80 (95% CI, 0.65 to 0.98; adjusted P=0.07) and 0.86 (95% CI, 0.70 to 1.05; adjusted P=0.14), respectively. A greater effect of mepolizumab, as compared with placebo, on the annual rate of moderate or severe exacerbations was found among patients with higher blood eosinophil counts at screening. The safety profile of mepolizumab was similar to that of placebo. CONCLUSIONS Mepolizumab at a dose of 100 mg was associated with a lower annual rate of moderate or severe exacerbations than placebo among patients with COPD and an eosinophilic phenotype. This finding suggests that eosinophilic airway inflammation contributes to COPD exacerbations. (Funded by GlaxoSmithKline; METREX and METREO ClinicalTrials.gov numbers, NCT02105948 and NCT02105961.)
Cost-Offsets of New Medications for Treatment of Schizophrenia

Broad claims are frequently made that new medications will offset all or part of their costs by reducing other areas of Medicaid spending. In this paper we examine the net impact on spending for new drugs used to treat schizophrenia. We extend research in this area by taking a new approach to identification of spending impacts of new drugs. We specify and estimate models of spending on treatment of schizophrenia using 7 years of Florida Medicaid data. The estimates indicate that use of the new drugs result in net spending increases. This may be due to increased adherence to treatment.
Hemophilia B Gene Therapy with a High‐Specific‐Activity Factor IX Variant

Background The prevention of bleeding with adequately sustained levels of clotting factor, after a single therapeutic intervention and without the need for further medical intervention, represents an important goal in the treatment of hemophilia. Methods We infused a single‐stranded adeno‐associated viral (AAV) vector consisting of a bioengineered capsid, liver‐specific promoter and factor IX Padua (factor IX–R338L) transgene at a dose of 5×1011 vector genomes per kilogram of body weight in 10 men with hemophilia B who had factor IX coagulant activity of 2% or less of the normal value. Laboratory values, bleeding frequency, and consumption of factor IX concentrate were prospectively evaluated after vector infusion and were compared with baseline values. Results No serious adverse events occurred during or after vector infusion. Vector‐derived factor IX coagulant activity was sustained in all the participants, with a mean (±SD) steady‐state factor IX coagulant activity of 33.7±18.5% (range, 14 to 81). On cumulative follow‐up of 492 weeks among all the participants (range of follow‐up in individual participants, 28 to 78 weeks), the annualized bleeding rate was significantly reduced (mean rate, 11.1 events per year [range, 0 to 48] before vector administration vs. 0.4 events per year [range, 0 to 4] after administration; P=0.02), as was factor use (mean dose, 2908 IU per kilogram [range, 0 to 8090] before vector administration vs. 49.3 IU per kilogram [range, 0 to 376] after administration; P=0.004). A total of 8 of 10 participants did not use factor, and 9 of 10 did not have bleeds after vector administration. An asymptomatic increase in liver‐enzyme levels developed in 2 participants and resolved with short‐term prednisone treatment. One participant, who had substantial, advanced arthropathy at baseline, administered factor for bleeding but overall used 91% less factor than before vector infusion. Conclusions We found sustained therapeutic expression of factor IX coagulant activity after gene transfer in 10 participants with hemophilia who received the same vector dose. Transgene‐derived factor IX coagulant activity enabled the termination of baseline prophylaxis and the near elimination of bleeding and factor use. (Funded by Spark Therapeutics and Pfizer; ClinicalTrials.gov number, NCT02484092.)
Low levels of awareness of pharmaceutical cost-assistance programs among inner-city seniors.

be better informed if they conduct their own independent search for information about off-label indications than if they rely on industry’s promotional efforts. We also agree that the current drug regulatory system does not guarantee the availability of sufficient information to support rational use of therapeutic interventions and that new approaches are needed to ensure such data are available, for both label and off-label indications. We outlined 1 possible reform for off-label use in our Commentary. If sponsors want to promote off-label uses, or if off-label uses reach a certain threshold, then a full FDA evaluation of supplemental new drug applications would generally help provide patients and physicians with the information required to use the drugs wisely and well for these new indications.
Transmission of Nipah Virus — 14 Years of Investigations in Bangladesh

Background Nipah virus is a highly virulent zoonotic pathogen that can be transmitted between humans. Understanding the dynamics of person‐to‐person transmission is key to designing effective interventions. Methods We used data from all Nipah virus cases identified during outbreak investigations in Bangladesh from April 2001 through April 2014 to investigate case‐patient characteristics associated with onward transmission and factors associated with the risk of infection among patient contacts. Results Of 248 Nipah virus cases identified, 82 were caused by person‐to‐person transmission, corresponding to a reproduction number (i.e., the average number of secondary cases per case patient) of 0.33 (95% confidence interval [CI], 0.19 to 0.59). The predicted reproduction number increased with the case patient's age and was highest among patients 45 years of age or older who had difficulty breathing (1.1; 95% CI, 0.4 to 3.2). Case patients who did not have difficulty breathing infected 0.05 times as many contacts (95% CI, 0.01 to 0.3) as other case patients did. Serologic testing of 1863 asymptomatic contacts revealed no infections. Spouses of case patients were more often infected (8 of 56 [14%]) than other close family members (7 of 547 [1.3%]) or other contacts (18 of 1996 [0.9%]). The risk of infection increased with increased duration of exposure of the contacts (adjusted odds ratio for exposure of >48 hours vs. ≤1 hour, 13; 95% CI, 2.6 to 62) and with exposure to body fluids (adjusted odds ratio, 4.3; 95% CI, 1.6 to 11). Conclusions Increasing age and respiratory symptoms were indicators of infectivity of Nipah virus. Interventions to control person‐to‐person transmission should aim to reduce exposure to body fluids. (Funded by the National Institutes of Health and others.)
Alpelisib for PIK3CA‐Mutated, Hormone Receptor–Positive Advanced Breast Cancer

Background PIK3CA mutations occur in approximately 40% of patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer. The PI3Kα‐specific inhibitor alpelisib has shown antitumor activity in early studies. Methods In a randomized, phase 3 trial, we compared alpelisib (at a dose of 300 mg per day) plus fulvestrant (at a dose of 500 mg every 28 days and once on day 15) with placebo plus fulvestrant in patients with HR‐positive, HER2‐negative advanced breast cancer who had received endocrine therapy previously. Patients were enrolled into two cohorts on the basis of tumor‐tissue PIK3CA mutation status. The primary end point was progression‐free survival, as assessed by the investigator, in the cohort with PIK3CA‐mutated cancer; progression‐free survival was also analyzed in the cohort without PIK3CA‐mutated cancer. Secondary end points included overall response and safety. Results A total of 572 patients underwent randomization, including 341 patients with confirmed tumor‐tissue PIK3CA mutations. In the cohort of patients with PIK3CA‐mutated cancer, progression‐free survival at a median follow‐up of 20 months was 11.0 months (95% confidence interval [CI], 7.5 to 14.5) in the alpelisib–fulvestrant group, as compared with 5.7 months (95% CI, 3.7 to 7.4) in the placebo–fulvestrant group (hazard ratio for progression or death, 0.65; 95% CI, 0.50 to 0.85; P<0.001); in the cohort without PIK3CA‐mutated cancer, the hazard ratio was 0.85 (95% CI, 0.58 to 1.25; posterior probability of hazard ratio <1.00, 79.4%). Overall response among all the patients in the cohort without PIK3CA‐mutated cancer was greater with alpelisib–fulvestrant than with placebo–fulvestrant (26.6% vs. 12.8%); among patients with measurable disease in this cohort, the percentages were 35.7% and 16.2%, respectively. In the overall population, the most frequent adverse events of grade 3 or 4 were hyperglycemia (36.6% in the alpelisib–fulvestrant group vs. 0.7% in the placebo–fulvestrant group) and rash (9.9% vs. 0.3%). Diarrhea of grade 3 occurred in 6.7% of patients in the alpelisib–fulvestrant group, as compared with 0.3% of those in the placebo–fulvestrant group; no diarrhea of grade 4 was reported. The percentages of patients who discontinued alpelisib and placebo owing to adverse events were 25.0% and 4.2%, respectively. Conclusions Treatment with alpelisib–fulvestrant prolonged progression‐free survival among patients with PIK3CA‐mutated, HR‐positive, HER2‐negative advanced breast cancer who had received endocrine therapy previously. (Funded by Novartis Pharmaceuticals; SOLAR‐1 ClinicalTrials.gov number, NCT02437318.)