Comparison of a functional restoration program with active individual physical therapy for patients with chronic low back pain: a randomized controlled trial

OBJECTIVE: To compare the short-term outcomes of active individual therapy (AIT) with those of a functional restoration program (FRP). DESIGN: Prospective randomized controlled study. SETTING: Two rehabilitation centers and private ambulatory physiotherapy facilities. PARTICIPANTS: One hundred thirty-two adults with chronic low back pain. Fifty-one percent of patients on sick leave or out of work (mean duration, 180d in the 2y before treatment). INTERVENTIONS: For 5 weeks, FRP (at 25h/wk) or AIT (at 3h/wk). MAIN OUTCOME MEASURES: Trunk flexibility, back flexor, and extensor endurance (Ito and Sorensen tests), general endurance, pain intensity, Dallas Pain Questionnaire (DPQ) scores, daily activities, anxiety depression, social interest, and work and leisure activities, and self-reported improvement (work ability, resumption of sport and leisure activities). RESULTS: All outcome measures improved after treatment except endurance in AIT. There was no between-group difference for pain intensity or DPQ daily activities or work and leisure activities scores. Better results were observed in FRP for all other outcome measures. There was a significant effect of treatment and the initial value for the gain of the Sorensen score with a treatment or initial value interaction; a significant effect of treatment and initial value on the gains of Ito, endurance, and DPQ social interest and anxiety depression scores, with no treatment or initial value interaction; and a significant effect of initial value but not treatment for the gains of DPQ daily activities and work and leisure activities scores. CONCLUSIONS: Low-cost ambulatory AIT is effective. The main advantage of FRP is improved endurance. We speculate that this may be linked to better self-reported work ability and more frequent resumption of sports and leisure activities.     

Systematic review and network meta-analysis of treatment for moderate-to-severe ulcerative colitis

Background Biological drugs for moderate-to-severe ulcerative colitis have changed the therapeutic perspective, while small-molecule inhibitors and new promising drugs suggest new options. Aim Assess comparative efficacy and safety of biological and new small oral drugs: commercialized and under-investigation ones for patients naïve to biological drugs. Methods A systematic review was conducted to identify the randomized clinical trials phase 2 or 3, in adults with moderate-to-severe ulcerative colitis treated with biological drugs (infliximab, adalimumab, golimumab, vedolizumab and etrolizumab) or new oral small molecules (tofacitinib and ozanimod) as first line. A Bayesian network metaanalysis was performed to inform comparative efficacy and safety of different treatments. Efficacy outcomes were clinical remission, clinical response and mucosal healing for induction therapy and clinical remission, mucosal healing and sustained clinical remission for maintenance therapy. Safety was assessed with serious adverse events and rates of infections. Results 14 references were included for network meta-analysis. For induction therapy, infliximab was the best drug for induction of clinical response and remission, while ozanimod showed to be the best for induction of mucosal healing. Tofacitinib had the highest rate of maintaining clinical remission. All treatments were similar for serious adverse events, and vedolizumab and tofacitinib had the highest rates of infections. Conclusion This network meta-analysis suggests infliximab may be the best therapeutic option for moderate-to-severe ulcerative colitis. Vedolizumab seems to have better outcomes in maintenance than in induction therapy and it appears superior to golimumab and adalimumab. Tofacitinib, ozanimod and etrolizumab show encouraging results.     

Oncological patterns of care and outcomes for 265 elderly patients with newly diagnosed glioblastoma in France

The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS _n?=?95) or biopsy (B _n?=?170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT _n?=?76), chemotherapy (CT _n?=?52), and concomitant radiochemotherapy (CRC _n?=?39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B?+?RT and/or CT, RS?±?RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT _n?=?41, 199_[155–280]; B-CRC _n?=?21, 318_[166–480]; B-RT _n?=?37, 149_[130–214]; RS-CT _n?=?11, 245_[211–na]; RS-CRC _n?=?18, 372_[349–593]; RS-RT _n?=?39, 269_[218–343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible.     

Disclosure of Funding Sources and Conflicts of Interest in Phase III Surgical Trials: Survey of Ten General Surgery Journals

Background

Discussions regarding disclosure of funding sources and conflicts of interest (COI) in published peer-reviewed journal articles are becoming increasingly more common and intense. The aim of the present study was to examine whether randomized controlled trials (RCTs) published in leading surgery journals report funding sources and COI.

Methods

All articles reporting randomized controlled phase III trials published January 2005 through December 2010 were chosen for review from ten international journals. We evaluated the number of disclosed funding sources and COI, and the factors associated with such disclosures.

Results

From a review of 657 RCT from the ten journals, we discovered that presence or absence of a funding source and COI was disclosed by 47 % (309) and 25.1 % (165), respectively. Most articles in “International Committee of Medical Journal Editors (ICMJE)-affiliated journals” did not disclose COI. Disclosure of funding was associated with a journal impact factor >3 (51.7 vs 41.6 %; p < 0.01), statistician/epidemiologist involvement (64.2 vs 43.7 %; p < 0.001), publication after 2008 (52.9 vs 41.1 %; p < 0.01), and the journal being ICMJE-affiliated (49.3 vs 40 %; p < 0.05). Conflict of interest disclosure was associated with publication after 2008 (38.7 vs 11.3 %; p < 0.001), and with the journal not being affiliated with ICMJE (36.9 vs 21.3 %; p < 0.001).

Conclusions

Of the published studies we investigated, over half did not disclose funding sources (i.e., whether or not there was a funding source), and almost three quarters did not disclose whether COI existed. Our findings suggest the need to adopt best current practices regarding disclosure of competing interests to fulfill responsibilities to readers and, ultimately, to patients.     

Detection of specific chromosomal aberrations in urine using BCA-1 (oligo-CGH-array) enhances diagnostic sensitivity and predicts the aggressiveness of non-muscle-invasive bladder transitional cell carcinoma

Introduction

Bladder carcinoma (B-TCC) is the fifth most prevalent carcinoma in the United States (US) or Europe. In addition, B-TCC is the most expensive carcinoma per patient between diagnosis and death, because of its 50–80 % recurrence rate. B-TCC is an optimal carcinoma for which to detect DNA alterations in urine, which is easily obtainable. Chromosomal aberrations in tumors have been closely related to the carcinogenesis process.

Material and Methods

We developed a highly specific and sensitive oligo-CGH-array for the diagnosis and follow-up of B-TCC, based on the detection of chromosomal aberrations in urine samples. One hundred and sixty-four urine samples were analyzed. The qualitative results, including chromosomal aberrations, were obtained. Quantitative results are expressed as a percentage of chromosomal alterations on the autosomes.

Results

From the urine samples, we were able to differentiate B-TCC from non-malignant conditions with an accuracy of 100 % for patients without history of B-TCC. For follow-up of B-TCC in clinical practice, at least a deletion (8p; 9p; 9q) or a cut-off of >2 % of chromosomal imbalance was considered as a positive test. According to our criteria, 100 % of high-grade tumors were diagnosed, and the sensitivity to predict positive cystoscopy was 95 % (specificity 73 %). A cut-off >9 % was a strong signature of high-grade TCC (odds ratio 53 CI 95 % 7–417; p = 0.0002).

Conclusion

We developed a sensitive clinical tool for the detection of B-TCC using DNA extracted from patient urine. This tool is also able to identify low-grade B-TCC and identify high-risk patients harboring a high-grade disease.     

Return to activity following fasciotomy for chronic exertional compartment syndrome

Diagnosis of chronic exertional compartment syndrome (CECS) is relatively rare but has been well documented in athletes. There are, however, few reports regarding return to athletic activity after surgery among elite-level athletes. We hypothesized that a majority of elite-level athletes would successfully return to their previous level of competition following fasciotomy for CECS. A retrospective chart review was performed to identify elite-level athletes (collegiate or professional sport participation) who underwent fasciotomy for CECS over a 3-year period. Data collected included sport or activity, treatment and surgical details, time away from sport/activity after surgery, and ability to return to prior level of activity. Six males and seven females were included in the analysis. Patient age ranged from 17 to 24 years with a mean of 19.7 years. Six patients underwent unilateral lower extremity compartment release, and seven underwent bilateral lower extremity compartment release. The anterior and lateral compartments alone were released in 11 patients (84.6 %). Two patients (15.4 %) underwent four-compartment releases. Eleven patients (84.6 %) were able to return to their previous elite level of sport participation at a mean of 10.6 weeks following surgical fasciotomy. Patients who had four-compartment release had a more than 3.5 week average longer return to full sporting activities (p = 0.011). Fasciotomy is effective in allowing elite athletes with CECS to return to sport.     

Drug interactions and protease inhibitors used in the treatment of hepatitis C: How to manage?

Purpose

The first-generation protease inhibitors (PI) boceprevir and telaprevir combined with pegylated interferon have revolutionized the treatment of type-1 hepatitis C by increasing the rates of sustained virologic response. However, they induce drug interactions, and their clinical relevance is difficult to predict. This review compiles available data on drug–drug interactions (DDI) based on their pharmacokinetic and pharmacodynamic properties with the aim of assisting clinicians in managing DDI

Methods

PubMed, drug interaction databases and hepatology and infectious disease conference abstracts were systematically searched using the key search terms “interaction”, “hepatitis C”, “telaprevir” and “boceprevir”. All known interactions were compiled and reclassified according to their pharmacokinetic and pharmacodynamic mechanisms. The state of knowledge of interaction mechanisms are reported and a therapeutic approach is proposed.

Results

Boceprevir and telaprevir are both substrates and potent inhibitors of cytochrome P450 3A4 and the drug transporter P-glycoprotein. They induce overdosage but can sometimes decrease the effect of other drugs by inducing other cytochromes. Overdosage or low dosage mainly affects drugs with a narrow therapeutic range, such as immunosuppressants or antiretrovirals. The distribution and elimination of PI are unaffected by interactions. In terms of pharmacodynamic interactions, PI can trigger drug-induced QT interval prolongation, which means that clinicians should manage such risk factors as potassium/magnesium levels or avoid other QT-prolonging drugs.

Conclusions

Management of hepatitis C therapy is complex. The key to interpreting DDI data is a solid understanding of the pharmacokinetic and pharmacodynamic profiles of the drugs involved. Their ability to inhibit cytochrome P450 3A4 and prolong the QT interval can have significant clinical consequences. This review provides a practical guide to the safe and effective management of therapy with boceprevir and telaprevir.     

Homocysteine and nitrite levels are modulated by MTHFR 677C>T polymorphism in obese women treated with simvastatin

Higher homocysteine (Hcy) levels are associated with cardiovascular risk. The aim of the present study was to evaluate the effect of simvastatin treatment on circulating Hcy levels in obese women without hypertension, diabetes or dyslipidaemia; and to determine whether the 677C>T polymorphism located in methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) gene modulates the effects of this treatment on Hcy and nitrite (as a biomarker of nitric oxide (NO) bioavailability). Twenty‐five obese women (body mass index ≥ 30 kg/m²) who had received 20 mg/day simvastatin for 6 weeks were enrolled in the study. Venous blood samples were collected to measure plasma biomarkers and gene polymorphisms. Simvastatin treatment significantly reduced total cholesterol, low‐density lipoprotein–cholesterol, thiobarbituric acid‐reactive substances, high‐sensitivity C‐reactive protein and Hcy, whereas nitrite levels were increased. The reduction in Hcy levels in carriers of the T allele was ?20.3% compared with –9.4% in patients with the CC genotype. Importantly, before treatment, nitrite levels were significantly higher in patients with the CC genotype compared with T allele carriers, whereas after treatment these levels were similar between groups. Our findings demonstrate that obese women without comorbidities and carrying the T variant of the 677C>T polymorphism of MTHFR exhibit benefits with simvastatin treatment, mainly in terms of increased NO levels.