Effects of Music Therapy on Quality of Life in Adults with Sickle Cell Disease (MUSIQOLS): A Mixed Methods Feasibility Study.

PURPOSE: To investigate the feasibility, acceptability, and preliminary efficacy of a 6-session music therapy protocol on self-efficacy, quality of life, and coping skills in adults with sickle cell disease (SCD). PATIENTS AND METHODS: Using a mixed-methods intervention design, adults with SCD (ages 21-57; mean age 32.33) were randomized (1:1) to either 1) a 6-session music therapy (MT) intervention (n = 12) or 2) waitlist control (WLC) (n = 12) using stratified randomization where factors were age in years (≤30 vs >30), and sex (male, female). All participants completed two weeks of daily electronic pain diary entries and self-efficacy, quality of life, and coping skills measures before and after their assigned study condition to explore preliminary efficacy. MT participants were taught music exercises accessed via smartphone and subsequently interviewed to determine feasibility and acceptability. RESULTS: The enrollment rate was 89%. All study measures were completed, with high rates of electronic pain diary completion at baseline (70%) and 2-week follow-up (66%). Interviews revealed two overall themes related to MT participants' experience: 1) participants learned new self-management skills and 2) MT improved participants' ability to cope with pain. MT participants demonstrated 100% attendance. In preliminary analyses, MT participants demonstrated significant improvements (means ± SD) in self-efficacy (5.42 ± 5.43, p = 0.008, d = 1.20), PROMIS sleep disturbance (-1.49 ± 6.68, p = 0.023, d = -0.99), PROMIS pain interference (-2.10 ± 4.68, p = 0.016, d = -1.06), and ASCQ-Me social functioning impact scores (2.97 ± 6.91, p = 0.018, d = 1.05) compared to WLC participants. CONCLUSION: Preliminary findings support the feasibility and acceptability of music therapy for home use in adults with SCD. While music therapy may assist adults with SCD in improving self-efficacy and quality of life, subsequent, fully-powered clinical research is needed to determine its efficacy.

Atopy patch tests may identify patients at risk for systemic contact dermatitis.

BACKGROUND: A subset of patients with positive patch tests demonstrates systemic contact dermatitis (SCD) upon ingestion or inhalation of the allergen. Concern has been raised about the use of patch tests for protein allergens (APTs) to detect SCD in atopic dermatitis (AD) patients. METHODS: We present atopy patch test (APT) data for 97 people. We reviewed APTs and tests for antigen-specific immunoglobulin E (IgE) to the same allergen in pediatric AD patients. We compared the frequency of APTs as a function of age in AD patients. To study the irritancy potential of APTs, we prospectively tested consenting non-AD dermatitis patients undergoing evaluation for allergic contact dermatitis and healthy controls to an APT panel. RESULTS: APT demonstrated fewer positive results than serum-specific IgE or skin prick tests to the same allergen. Positive APT to food was more common in children under 3 years, whereas positive APT to aeroallergens were more common in teens and adults. Only positive APTs to dust mite were significantly more common positive in subjects without AD. CONCLUSION: Our aggregate findings suggest that most APTs, but not dust mite, behave like conventional patch tests to low-potency allergens. They are more likely to be positive in patients with chronically inflamed skin and to identify allergens that cause SCD. The higher prevalence of APT positivity to foods in young children is consistent with food allergy as a trigger of AD (also known as SCD) being more common in children than adults. Positive APTs define patients who may have SCD; negative APTs may guide elimination diets.

Atopy and Sensitization to Allergens Known to Cause Systemic Contact Dermatitis.

BACKGROUND: Atopic dermatitis (AD) associated with respiratory atopy may represent a form of systemic contact dermatitis (SCD), whereby AD flares after ingestion or inhalation of allergens. OBJECTIVE: The aim of the study was to compare the prevalence of positive patch tests to allergens known to cause SCD in AD patients with and without respiratory atopy. METHODS: This is a retrospective study of patients with AD patch tested to 23 allergens known to cause SCD. Positive patch tests were compared between AD patients with and without respiratory atopy, stratified by age and wet or dry work occupation. CONCLUSIONS: Children and adolescents, but not adults, with AD and respiratory atopy were more likely than age-matched AD patients without respiratory atopy to have positive patch tests to these allergens (odds ratio, 2.33; 95% confidence interval, 1.13-4.79). Moreover, AD patients with respiratory atopy and engaging in wet work, but not dry work, occupations were more likely than AD patients without respiratory atopy to have positive patch tests to allergens known to cause SCD (odds ratio, 1.47; 95% confidence interval, 1.05-2.06). Thus, respiratory atopy and wet work are associated with sensitization to allergens known to cause SCD in patients with AD, and patch testing may be valuable in identifying systemic triggers of dermatitis in these patients.

Procalcitonin as a Biomarker for Predicting Amputation Level in Lower Extremity Infections.

Inflammatory markers are essential tools in the decision-making process for lower extremity infections. When coupled with objective findings, clinicians can more accurately diagnose and treat these entities. Typically, markers such as the white blood cell count, erythrocyte sedimentation rate, and C-reactive protein are used to initially assess these patients or monitor the progression of medical or surgical therapy. Procalcitonin is a newer inflammatory marker that is specific for an infectious process. Originally, procalcitonin was used to monitor antibiotic therapy and sepsis for patients in the intensive care setting, but it has now been expanded to other facets of medicine. The utility of procalcitonin has been described for diagnosing infection or osteomyelitis in diabetic foot ulcers. However, limited research has compared inflammatory marker levels and the level of amputation. A retrospective inpatient medical record review was performed of 156 consecutive patient occurrences during 25 months in which surgical intervention was required for a lower extremity infection and an initial procalcitonin level had been obtained. This initial procalcitonin value was then compared with the level of amputation at the final surgical intervention. A highly statistically significant difference was found when comparing those who underwent a below-the-knee or above-the-knee amputation (median procalcitonin 1.72 ng/mL) and those who did not (median procalcitonin 0.105 ng/mL; p < .001). Therefore, patients with higher initial procalcitonin values were more likely to undergo below-the-knee or above-the-knee amputation or require aggressive surgical intervention. Thus, the procalcitonin level can provide valuable initial information to the clinician.

Effect of Regulatory Requirement for Patient-Specific Prescriptions for Off-Label Medications on the Use of Intravitreal Bevacizumab.

IMPORTANCE: Requirements regulating pharmaceutical prescriptions can affect physicians' choice of therapy in a clinical setting. OBJECTIVE: To evaluate the change in bevacizumab use after the regulatory requirement for patient-specific prescriptions (PSPs) for off-label medications in Ohio. DESIGN, SETTING, AND PARTICIPANTS: This study retrospectively reviewed the aggregate data from the billing records of patients receiving 1.25-mg injections of bevacizumab, 0.3- or 0.5-mg injections of ranibizumab, or 2.0-mg injections of aflibercept for age-related macular degeneration or diabetic macular edema in a 9-member retinal specialty private practice. The review assessed 4488 intravitreal injections in the 3-month period before (May 1 to July 30, 2012) and 5253 injections in the 3-month period after (May 1 to July 30, 2013) the Ohio Board of Pharmacy's requirement of PSPs for bevacizumab. Relative proportions of the drugs used for intravitreal injections were calculated and frequencies were compared. A Likert scale survey was conducted among the 9 physicians to identify reasons for their change in prescription of bevacizumab. The survey inquired about (1) the burden of PSPs, (2) concern about differences in efficacy, and (3) concern about differences in safety. MAIN OUTCOMES AND MEASURES: Difference in drug use before and after the PSP requirement for bevacizumab and the physicians' reasons for change in their drug use. RESULTS: Bevacizumab use decreased from 2752 of 4488 pre-PSP injections (61.3%) to 1503 of 5253 post-PSP injections (28.6%), a change of -32.7% (95% CI, -34.6% to -30.8%; P < .001). Use of 0.5-mg ranibizumab injections increased from 1122 of 4488 pre-PSP injections (25.0%) to 1838 of 5253 post-PSP injections (35.0%), a change of 10.0% (95% CI, 8.2% to 11.8%; P < .001). Use of 0.3-mg ranibizumab injections increased from 0 of 4488 (before US Food and Drug Administration approval) to 429 of 5253 post-PSP injections (8.2%), a change of 8.2% (95% CI, 7.4% to 8.9%; P < .001). Use of aflibercept injections increased from 614 of 4488 pre-PSP injections (13.7%) to 1483 of 5253 post-PSP injections (28.2%), a change of 14.6% (95% CI, 13.0%-16.1%; P < .001). In the survey of the 9 physicians concerning their reasons for decreased use of bevacizumab, 7 (78%) strongly agreed and 1 (11%) agreed that the burden of PSPs changed their choice of drug used for injection. CONCLUSIONS AND RELEVANCE: Use of bevacizumab was reduced by 32.7% 1 year after the regulatory requirement for PSPs for compounded (repackaged) medications. This change seemed to have more association with the requirement for PSPs than with a known change in efficacy or safety concerns. Although this study was based on a single US practice, regulation of repackaged medication for safety concerns should also consider the evaluation of treatment burden, cost, and adherence.

Early follow-up of reverse total shoulder arthroplasty in patients sixty years of age or younger.

BACKGROUND: Reverse shoulder arthroplasty (RSA) is an accepted treatment that provides reproducible results in the treatment of shoulder arthritis and rotator cuff deficiency. Concerns over the longevity of the prosthesis have resulted in this procedure being reserved for the elderly. There are limited data in the literature with regard to outcomes in younger patients. We report on the early outcomes of RSA in a group of patients who were sixty years or younger and who were followed for a minimum of two years. METHODS: A retrospective multicenter review of sixty-six patients (sixty-seven RSAs) with a mean age of 52.2 years was performed. The indications included rotator cuff insufficiency (twenty-nine), massive rotator cuff disorder with osteoarthritis (eleven), failed primary shoulder arthroplasty (nine), rheumatoid arthritis (six), posttraumatic arthritis (four), and other diagnoses (eight). Forty-five shoulders (67%) had at least one prior surgical intervention, and thirty-one shoulders (46%) had multiple prior surgical procedures. RESULTS: At a mean follow-up time of 36.5 months, mean active forward elevation of the arm as measured at the shoulder improved from 54.6° to 134.0° and average active external rotation improved from 10.0° to 19.6°. A total of 81% of patients were either very satisfied or satisfied. The mean American Shoulder and Elbow Surgeons (ASES) score and visual analog scale (VAS) score for pain improved from 40.0 to 72.4 and 7.5 to 3.0, respectively. The ability to achieve postoperative forward arm elevation of at least 100° was the only significant predictor of overall patient satisfaction (p < 0.05) that was identified in this group. There was a 15% complication rate postoperatively, and twenty-nine shoulders (43%) had evidence of scapular notching at the time of the latest follow-up. CONCLUSIONS: RSA as a reconstructive procedure improved function at the time of short-term follow-up in our young patients with glenohumeral arthritis and rotator cuff deficiency. Objective outcomes in our patient cohort were similar to those in previously reported studies. However, overall satisfaction was much lower in this patient population (81%) compared with that in the older patient population as reported in the literature (90% to 96%).

Effectiveness of a comprehensive hand hygiene program for reduction of infection rates in a long-term care facility.

BACKGROUND: Alcohol-based hand rubs play a key role in reducing the transmission of pathogens in acute care settings, especially as part of a comprehensive hand hygiene program. However, their use in long-term care facilities (LTCFs) has been virtually unstudied. METHODS: Infection data, including those meeting McGeer et al and the Pennsylvania Patient Safety Authority's surveillance definitions, for lower respiratory tract infections (LRTIs) and skin and soft-tissue infections (SSTIs), as well as hospitalization data were collected in a 174-bed LTCF for 22 months (May 2009 to February 2011). In March 2010, a comprehensive hand hygiene program including increased product availability, education for health care personnel (HCP) and residents, and an observation tool to monitor compliance, was implemented. RESULTS: Infection rates for LRTIs were reduced from 0.97 to 0.53 infections per 1,000 resident-days (P = .01) following the intervention, a statistically significant decline. Infection rates for SSTIs were reduced from 0.30 to 0.25 infections per 1,000 resident-days (P = .65). A 54% compliance rate was observed among HCP. CONCLUSION: This study demonstrates that the use of alcohol-based hand rubs, as part of a comprehensive hand hygiene program for HCP and residents, can decrease infection rates in LTCFs.

A comparison of tau and 14-3-3 protein in the diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVE: To compare the respective efficiency of CSF tau (quantitative) and CSF 14-3-3 protein (qualitative) in the diagnosis of prion disease. METHODS: We made measurements on 420 live subjects, who subsequently underwent a postmortem neuropathology examination, including protein chemistry, immunohistochemistry, and histology. We performed tau by ELISA. We detected 14-3-3 protein by Western blot. Both assays were optimized for maximum efficiency (accuracy). RESULTS: We found tau and 14-3-3 proteins to be closely correlated, but tau had a significantly better ability to predict disease status than 14-3-3 protein. Also, tau distinguished disease status at least as well as when both assays' results are combined in a variety of ways. Importantly, the area under the receiver operating characteristic curve for tau (0.82) was significantly larger than that for 14-3-3 protein (0.68) (p < 0.001). Diagnostic test statistics are provided for the study subjects with 58.3% prevalence, and for a more typical, nonselected, 7.5% prevalence as received by our center. CONCLUSION: In this study, tau is superior to 14-3-3 protein as a marker in the diagnosis of Creutzfeldt-Jakob disease, and is as efficient singly compared to a variety of combinations with 14-3-3 protein. This is the first study of this magnitude to examine prion disease diagnostic tests in a carefully characterized patient population with detailed statistical evaluation.

Effect of QRS morphology on clinical event reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled trials.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in reducing clinical events in systolic heart failure patients with a wide QRS. Previous retrospective studies suggest only patients with QRS prolongation due to a left bundle-branch block (LBBB) benefit from CRT. Our objective was to examine this by performing a meta-analysis of all randomized controlled trials of CRT. METHODS: Systematic searches of MEDLINE and the Food and Drug Administration official website were conducted for randomized controlled CRT trials. Trials reporting adverse clinical events (eg, all-cause mortality, heart failure hospitalizations) according to QRS morphology were included in the meta-analysis. RESULTS: Four randomized trials totaling 5,356 patients met the inclusion criteria. In patients with LBBB at baseline, there was a highly significant reduction in composite adverse clinical events with CRT (RR = 0.64 [95% CI (0.52-0.77)], P = .00001). However no such benefit was observed for patients with non-LBBB conduction abnormalities (RR = 0.97 [95% CI (0.82-1.15)], P = .75). When examined separately, there was no benefit in patients with right-bundle branch block (RR = 0.91 [95% CI (0.69-1.20)], P = .49) or non-specific intraventricular conduction delay (RR = 1.19 [95% CI (0.87-1.63)], P = .28). There was no heterogeneity among the clinical trials with regards to the lack of benefit in non-LBBB patients (I(2) = 0%). When directly compared, the difference in effect of CRT between LBBB versus non-LBBB patients was highly statistically significant (P = .0001 by heterogeneity analysis). CONCLUSIONS: While CRT was very effective in reducing clinical events in patients with LBBB, it did not reduce such events in patients with wide QRS due to other conduction abnormalities.

Impact of QRS duration on clinical event reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled trials.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in reducing clinical events in patients with heart failure and prolonged QRS interval. Studies using surrogate measures and subgroup analysis of large trials suggest that only patients with severely prolonged QRS benefit from CRT. Our objective was to determine whether the effect of CRT on adverse clinical events (eg, death, hospitalizations) is different in patients with moderately (ie, 120 to 149 milliseconds) [corrected] vs severely (ie, ≥150 milliseconds) prolonged QRS duration. METHODS: Searches of MEDLINE, SCOPUS, and Cochrane databases were conducted for randomized controlled CRT trials. Trials reporting clinical events according to different QRS ranges were identified. Five randomized trials fulfilling the inclusion criteria (total patients, n = 5813) were included in the meta-analysis. RESULTS: In patients with severely prolonged QRS, there was a reduction in composite clinical events with CRT (risk ratio, 0.60; 95% confidence interval [CI], 0.53-0.67) (P < .001). In contrast, there was no benefit of CRT in patients with moderately prolonged QRS (RR, 0.95; 95% CI, 0.82-1.10) (P = .49), resulting in a significantly different impact of CRT in the 2 QRS groups (P < .001). There was a significant relationship between baseline QRS duration and risk ratio (P < .001) with benefit of CRT appearing at a QRS of approximately 150 milliseconds and above. The differential response of the 2 QRS groups was evident for all New York Heart Association classes. CONCLUSIONS: Cardiac resynchronization therapy was effective in reducing adverse clinical events in patients with heart failure and a baseline QRS interval of 150 milliseconds or greater, but CRT did not reduce events in patients with a QRS of less than 150 milliseconds. These findings have implications for the selection of patients for CRT.

Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials.

BACKGROUND: Angiotensin-receptor blockers (ARBs) are a widely used drug class approved for treatment of hypertension, heart failure, diabetic nephropathy, and, recently, for cardiovascular risk reduction. Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta-analysis of randomised controlled trials of these drugs. METHODS: We searched Medline, Scopus (including Embase), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the US Food and Drug Administration website for studies published before November, 2009, that included any of the seven currently available ARBs. Randomised controlled trials with an ARB given in at least one group, with a follow-up of at least 1 year, and that enrolled at least 100 patients were included. New-cancer data were available for 61,590 patients from five trials. Data on common types of solid organ cancers were available for 68,402 patients from five trials, and data on cancer deaths were available for 93,515 patients from eight trials. FINDINGS: Telmisartan was the study drug in 30,014 (85.7%) patients who received ARBs as part of the trials with new cancer data. Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%, risk ratio [RR] 1.08, 95% CI 1.01-1.15; p=0.016). When analysis was limited to trials where cancer was a prespecified endpoint, the RR was 1.11 (95% CI 1.04-1.18, p=0.001). Among specific solid organ cancers examined, only new lung-cancer occurrence was significantly higher in patients randomly assigned to receive ARBs than in those assigned to receive control (0.9%vs 0.7%, RR 1.25, 1.05-1.49; p=0.01). No statistically significant difference in cancer deaths was observed (1.8%vs 1.6%, RR 1.07, 0.97-1.18; p=0.183). INTERPRETATION: This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis. Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug. These findings warrant further investigation.

Alzheimer's disease and smoking: bias in cohort studies.

The discrepancy between cohort and case-control studies regarding the association between smoking and Alzheimer's disease (AD) has been attributed to the competing risk of early mortality of smokers. A simulation study was conducted to show that the bias favoring smokers acts also on cohort studies. In the model, individuals {grow older} and have smoking habits according to published year-age-gender-specific patterns, with morbidity and mortality according to their demographic and smoking profiles. Those individuals dying of smoking-related causes ("phantoms") remain at risk of AD and of death from other causes. Three scenarios were considered: no association of AD and smoking, increased risk for smokers, and decreased risk for smokers. For each simulation of a cohort study, two incidence density ratios (IDR) were computed: one including the phantoms that developed AD (thus ignoring smoking-related deaths) and another excluding them (thus mimicking real-life studies). For all scenarios, the simulations show that smoking-related death creates a bias, resulting in smokers having an understated risk of AD compared to non-smokers. The speculation that the conflicting results of case-control and cohort studies are solely due to the increased mortality in smokers thus appears unjustified. Other factors must also be considered to explain the discrepancy in results.

Lifetime histories of trauma among pathological gamblers.

This study extends the work completed with pathological gamblers and substance abusers, looking at associations between a history of trauma and comorbid substance dependence, impulsivity, measures of problem severity, and personality variables. We studied 111 patients admitted to the gambling treatment program at the Brecksville VA Medical Center and found that 64% of gamblers reported a history of emotional trauma; 40.5%, physical trauma; and 24.3%, sexual trauma. Most of this trauma occurred in childhood. A history of trauma was associated with a greater relative frequency of suicide attempts and drug and alcohol dependence, more severe scores in measures of psychiatric distress, and limited effects on personality functioning.

Accuracy of endoscopic optical coherence tomography in the detection of dysplasia in Barrett's esophagus: a prospective, double-blinded study.

BACKGROUND: Endoscopic optical coherence tomography (EOCT) is a high-resolution, cross-sectional tissue-imaging technique that provides microscopic morphologic information. EOCT should detect dysplasia in Barrett's epithelium, but this has not been established in a prospective blinded study. This study evaluated the accuracy of EOCT for the diagnosis and the exclusion of dysplasia in patients with Barrett's esophagus. METHODS: A 2.4-mm diameter EOCT probe was modified for use with a cap-fitted, two-channel endoscope. Pairs of EOCT image streams and jumbo biopsy specimens were obtained. Endoscopy/EOCT procedures were performed by 4 endoscopists who separately reviewed the EOCT digital images for the absence or the presence of dysplasia (low grade, high grade, or cancer) for each biopsy specimen obtained. The endoscopists were blinded to the interpretation of the pathology. An experienced pathologist blinded to the endoscopic/EOCT findings evaluated each biopsy for the absence or the presence of dysplasia. The setting of the study was a major academic medical center. Adult patients with documented Barrett's esophagus greater than 2 cm were included in the study. The main outcome measurement was the accuracy of EOCT in the detection of dysplasia in patients with Barrett's esophagus. RESULTS: A total of 314 usable EOCT image stream/biopsy pairs were obtained in 33 patients. By using histology as the standard, the performance of EOCT was sensitivity, 68%; specificity, 82%; positive predictive value, 53%; negative predictive value, 89%; and diagnostic accuracy, 78%. Diagnostic accuracy for the 4 endoscopists ranged from 56% to 98%. Limitations of the study were the variability in endoscopists' accuracy rates, difficulty in real-time interpretation, and the need for refined criteria of dysplasia by EOCT imaging. CONCLUSIONS: The current EOCT system has an accuracy of 78% for the detection of dysplasia in patients with Barrett's esophagus. EOCT could be used to target biopsies to areas of Barrett's epithelium with a higher probability for the presence of dysplasia. However, further modifications, including increased resolution and identification of further potential OCT characteristics of dysplasia, are needed before EOCT can be used clinically.