Dupuytren's contracture: a retrospective database analysis to assess clinical management and costs in England

<p>Abstract</p> <p>Background</p> <p>Dupuytren's disease is a fibro-proliferative disorder affecting ~3-5% of the UK population. Current surgical treatments for Dupuytren's contracture (DC) include fasciectomy and fasciotomy. We assessed the clinical management of DC in England over a 5-year period; associated NHS costs were assessed for a 1-year period.</p> <p>Methods</p> <p>Hospital Episode Statistics were extracted from April 2003 to March 2008 for patients with Palmar Fascial Fibromatosis (ICD10 = M720) and DC-related procedures. Variables included demographics, OPCS, patient status and physician specialty. To estimate 2010-2011 costs, HRG4 codes and the National Schedule of Tariff 2010-11-NHS Trusts were applied to the 2007-2008 period.</p> <p>Results</p> <p>Over 5 years, 75,157 DC admissions were recorded; 64,506 were analyzed. Mean admissions per year were 12,901 and stable. Day cases increased from 42% (2003-2004) to 62% (2007-2008). The percent of patients having two or more admissions per year increased from 5.5% in 2003-2004 to 26.1% in 2007-2008. Between 2003 and 2007, 91% of procedures were Fasciectomy. Revision of Fasciectomy and Fasciotomy each accounted for ~4%; Amputation for 1%. In 2007, classification was extended to identify Digital Fasciectomy, its Revision and Dermofasciectomy. In 2007-2008, admissions were: 70% Palmar Fasciectomy, 16% Digital Fasciectomy, 1.3% Other Fasciectomy, 4.4% Revision of Palmar Fasciectomy, 1.3% Revision of Digital Fasciectomy, 3.8% Division of Palmar Fascia, 2.6% Dermofasciectomy and 1.1% Amputation. 79% of cases were overseen by trauma and orthopaedic surgeons, 19% by plastic surgeons. Mean (±SD) inpatient hospital length of stay was 1.5 (±1.4) days in 2003-2004 and 1.0 (±1.3) days in 2007-2008. Total estimated costs for 1 year (2010-2011) were £41,576,141. Per-patient costs were £2,885 (day case) and £3,534 (inpatient). Costs ranged from £2,736 (day-case Fasciectomy) to £9,210 (day-case Revision Digital).</p> <p>Conclusions</p> <p>Between 2003 and 2008, fasciectomy was the most common surgical procedure for DC in England. While procedure rates and physician specialties varied little, there was a reversal in surgical venue: inpatient operations decreased as day-case procedures increased. The change is likely due to economic trends and changes to the healthcare system. Estimated costs for 2010-2011 varied by procedure type and patient status. These findings can be used to understand clinical management of DC and guide healthcare policy.</p

Development and validation of the WEll-being and Satisfaction of CAREgivers of Children with Diabetes Questionnaire (WE-CARE)

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Tofacitinib versus Biologic Treatments in Moderate-to-Severe Rheumatoid Arthritis Patients Who Have Had an Inadequate Response to Nonbiologic DMARDs: Systematic Literature Review and Network Meta-Analysis

Objective. To compare the efficacy and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), as monotherapy and combined with disease-modifying antirheumatic drugs (DMARDs) versus biological DMARDs (bDMARDs) and other novel DMARDs for second-line moderate-to-severe rheumatoid arthritis (RA) patients by means of a systematic literature review (SLR) and network meta-analysis (NMA). Methods. MEDLINE®, EMBASE®, and Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials (RCTs) published between 1990 and March 2015. Efficacy data based on American College of Rheumatology (ACR) response criteria, improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI) at 6 months, and discontinuation rates due to adverse events were analyzed by means of Bayesian NMAs. Results. 45 RCTs were identified, the majority of which demonstrated a low risk of bias. Tofacitinib 5 mg twice daily (BID) and 10 mg BID monotherapy exhibited comparable efficacy and discontinuation rates due to adverse events versus other monotherapies. Tofacitinib 5 mg BID and 10 mg BID + DMARDs or methotrexate (MTX) were mostly comparable to other combination therapies in terms of efficacy and discontinuation due to adverse events. Conclusion. In most cases, tofacitinib had similar efficacy and discontinuation rates due to adverse events compared to biologic DMARDs

Device for lengthening of a musculotendinous unit by direct continuous traction in the sheep

Background Retraction, atrophy and fatty infiltration are signs subsequent to chronic rotator cuff tendon tears. They are associated with an increased pennation angle and a shortening of the muscle fibers in series. These deleterious changes of the muscular architecture are not reversible with current repair techniques and are the main factors for failed rotator cuff tendon repair. Whereas fast stretching of the retracted musculotendinous unit results in proliferation of non-contractile fibrous tissue, slow stretching may lead to muscle regeneration in terms of sarcomerogenesis. To slowly stretch the retracted musculotendinous unit in a sheep model, two here described tensioning devices have been developed and mounted on the scapular spine of the sheep using an expandable threaded rod, which has been interposed between the retracted tendon end and the original insertion site at the humeral head. Traction is transmitted in line with the musculotendinous unit by sutures knotted on the expandable threaded rod. The threaded rod of the tensioner is driven within the body through a rotating axis, which enters the body on the opposite side. The tendon end, which was previously released (16 weeks prior) from its insertion site with a bone chip, was elongated with a velocity of 1 mm/day. Results After several steps of technical improvements, the tensioner proved to be capable of actively stretching the retracted and degenerated muscle back to the original length and to withstand the external forces acting on it. Conclusion This technical report describes the experimental technique for continuous elongation of the musculotendinous unit and reversion of the length of chronically shortened muscle

Towards the creation of decellularized organ constructs using irreversible electroporation and active mechanical perfusion

<p>Abstract</p> <p>Background</p> <p>Despite advances in transplant surgery and general medicine, the number of patients awaiting transplant organs continues to grow, while the supply of organs does not. This work outlines a method of organ decellularization using non-thermal irreversible electroporation (N-TIRE) which, in combination with reseeding, may help supplement the supply of organs for transplant.</p> <p>Methods</p> <p>In our study, brief but intense electric pulses were applied to porcine livers while under active low temperature cardio-emulation perfusion. Histological analysis and lesion measurements were used to determine the effects of the pulses in decellularizing the livers as a first step towards the development of extracellular scaffolds that may be used with stem cell reseeding. A dynamic conductivity numerical model was developed to simulate the treatment parameters used and determine an irreversible electroporation threshold.</p> <p>Results</p> <p>Ninety-nine individual 1000 V/cm 100-μs square pulses with repetition rates between 0.25 and 4 Hz were found to produce a lesion within 24 hours post-treatment. The livers maintained intact bile ducts and vascular structures while demonstrating hepatocytic cord disruption and cell delamination from cord basal laminae after 24 hours of perfusion. A numerical model found an electric field threshold of 423 V/cm under specific experimental conditions, which may be used in the future to plan treatments for the decellularization of entire organs. Analysis of the pulse repetition rate shows that the largest treated area and the lowest interstitial density score was achieved for a pulse frequency of 1 Hz. After 24 hours of perfusion, a maximum density score reduction of 58.5 percent had been achieved.</p> <p>Conclusions</p> <p>This method is the first effort towards creating decellularized tissue scaffolds that could be used for organ transplantation using N-TIRE. In addition, it provides a versatile platform to study the effects of pulse parameters such as pulse length, repetition rate, and field strength on whole organ structures.</p

Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis

INTRODUCTION: No published studies exist comparing the effectiveness of tofacitinib with other advanced therapies for the treatment of rheumatoid arthritis (RA) in real-world clinical practice. Here, we report differences in effectiveness of tofacitinib compared with standard of care, tumor necrosis factor inhibitors (TNFi), with or without concomitant methotrexate (MTX), using US Corrona registry data. METHODS: This observational cohort study included RA patients receiving tofacitinib (from 6 November 2012; N = 558) or TNFi (from 1 November 2001; N = 8014) with or without MTX until 31 July 2016. Efficacy outcomes at 6 months included modified American College of Rheumatology 20% responses, Clinical Disease Activity Index (CDAI) and Pain. Outcomes were compared between patients receiving TNFi and tofacitinib with or without MTX and by line of therapy. Outcomes within therapy lines were compared using propensity-score matching; between-group differences were estimated using mixed-effects regression models. RESULTS: Patients receiving tofacitinib had longer RA duration and a greater proportion had previously received biologics than those receiving TNFi; other baseline characteristics were comparable. In patients receiving second- and third-line TNFi therapy, CDAI low disease activity/remission response rates were significantly better with concomitant MTX. Too few patients received tofacitinib as second line for meaningful assessment. No significant differences were observed in outcomes between tofacitinib as monotherapy and tofacitinib with concomitant MTX. CONCLUSIONS: In clinical practice, TNFi efficacy is improved with concomitant MTX in the second and third line. In the third/fourth line, patients are likely to achieve similar efficacy with tofacitinib monotherapy, or TNFi or tofacitinib in combination with MTX. FUNDING: Pfizer Inc

Acinetobacter baumannii isolates from pets and horses in Switzerland: molecular characterization and clinical data

Objectives We investigated whether Acinetobacter baumannii isolates of veterinary origin shared common molecular characteristics with those described in humans. Methods Nineteen A. baumannii isolates collected in pets and horses were analysed. Clonality was studied using repetitive extragenic palindromic PCR (rep-PCR) and multilocus sequence typing (MLST). PCR and DNA sequencing for various β-lactamase, aminoglycoside-modifying enzyme, gyrA and parC, ISAba1 and IS1133, adeR and adeS of the AdeABC efflux pump, carO porin and class 1/2/3 integron genes were performed. Results Two main clones [A (n = 8) and B (n = 9)] were observed by rep-PCR. MLST indicated that clone A contained isolates of sequence type (ST) ST12 (international clone II) and clone B contained isolates of ST15 (international clone I). Two isolates of ST10 and ST20 were also noted. Seventeen isolates were resistant to gentamicin, 12 to ciprofloxacin and 3 to carbapenems. Isolates of ST12 carried blaOXA-66, blaADC-25, blaTEM-1, aacC2 and IS1133. Strains of ST15 possessed blaOXA-69, blaADC-11, blaTEM-1 and a class 1 integron carrying aacC1 and aadA1. ISAba1 was found upstream of blaADC (one ST10 and one ST12) and/or blaOXA-66 (seven ST12). Twelve isolates of different STs contained the substitutions Ser83Leu in GyrA and Ser80Leu or Glu84Lys in ParC. Significant disruptions of CarO porin and overexpressed efflux pumps were not observed. The majority of infections were hospital acquired and in animals with predisposing conditions for infection. Conclusions STs and the molecular background of resistance observed in our collection have been frequently described in A. baumannii detected in human patients. Animals should be considered as a potential reservoir of multidrug-resistant A. baumanni

Stress Granules and RNA Processing Bodies are Novel Autoantibody Targets in Systemic Sclerosis

Autoantibody profiles represent important patient stratification markers in systemic sclerosis (SSc). Here, we performed serum-immunoprecipitations with patient antibodies followed by mass spectrometry (LC-MS/MS) to obtain an unbiased view of all possible autoantibody targets and their associated molecular complexes recognized by SSc

Severe Acute Pharyngitis Caused by Group C Streptococcus

INTRODUCTION: Adult group C beta-hemolytic streptococcal pharyngitis has a prevalence of approximately 5%. It can present with a broad spectrum of severity. CASE REPORT: We report a 30-year-old woman who presented with severe Group C streptococcal pharyngitis. DISCUSSION: She presented with a 9-day history of progressive symptoms, including fever, sore throat, neck swelling, and recent onset of hoarseness. In the 9 days before the emergency room (ER) presentation, the patient had visited the ER twice complaining of a sore throat. At both visits, the physicians performed rapid antigen strep testing. Each time her test was negative and the physicians recommended symptomatic therapy. Her symptoms continued to worsen leading to her repeat presentation. At this time she had severe pharyngitis with markedly enlarged tonsils. Neck CT excluded peritonsillar abscess. Rapid strep testing was again negative, but her throat culture grew group C beta-hemolytic streptococcus. CONCLUSION: This presentation illustrates the importance of a systematic approach to evaluating patients with negative rapid strep tests and worsening pharyngitis

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780