nils-herrmann/clean_scirepeval huggingface dataset:
High tibial osteotomy in knee instability: the rationale of treatment and early results

We treated 14 patients having knee instability and varus alignment with tibial osteotomy with or without ligament reconstruction. Five patients with varus angulated anterior cruciate deficiency (double varus) were treated with single-stage closed-wedge tibial osteotomy and anterior cruciate ligament reconstruction. The remaining nine patients had varying amount of posterior cruciate and postero-lateral corner ligament injuries with varus angulation (triple varus); six of these patients had a ligament reconstruction using the Ligament Advanced Reconstruction System ligament with tibial osteotomy (intra-articular–posterior cruciate ligament/extra-articular–postero-lateral corner reconstruction), while the remaining three had a tibial osteotomy without a ligament reconstruction. Four of the nine patients with triple varus had open-wedge tibial osteotomy, and the remaining five had closed-wedge tibial osteotomy. The mean time interval between injury and index surgery of an osteotomy and ligament surgery was 8.3 years (range 1–20 years). At a mean follow-up of 2.8 years after tibial osteotomy, 12 knees (86%) were stable and eliminated of giving way while the remaining 2 were unstable. In one of these patients the result was compromised with severe infection, while in another there was combined cruciate ligament deficiency with postero-lateral corner ligament deficiency. Thirteen (93%) of the patients were able to participate in light recreational activities. None of these patients could return to competitive sports. Five (35%) continued to have pain of varying degree. The mean Cincinnati Knee Score improved from a mean preoperative of 53 (range 40–58) to a mean postoperative of 74 (range 58–82). Accordingly, there were two poor, four fair and eight good results. In-patients with triple-varus, open-wedge tibial osteotomy had better scores than those with closed-wedge procedure. The results of this series are encouraging, and we recommend a high tibial osteotomy along with ligament reconstruction in these complex injuries with varus alignment.
The effect of niacinamide on osteoarthritis: A pilot study

To evaluate the effect of niacinamide, on selected parameters of osteoarthritis using a doubleblind, placebo controlled study design. Seventy two patients with osteoarthritis were randomized for treatment with niacinamide or an identical placebo for 12 weeks. Outcome measures included global arthritis impact and pain, joint range of motion and flexibility, erythrocyte sedimentation rate, complete blood count, liver function tests, cholesterol, uric acid, and fasting blood sugar. Compliance was monitored with a pill record sheet and interview. Global arthritis impact improved by 29% (95% confidence interval [CI] 6, 46) in subjects on niacinamide and worsened by 10% in placebo subjects (p=0.04). Pain levels did not change but those on niacinamide reduced their anti-inflammatory medications by 13% (95% CI 9, 94; p=0.01). Niacinamide reduced erythrocyte sedimentation rate by 22% (95% CI 6, 51; p<0.005) and increased joint mobility by 4.5 degrees over controls (8 degrees vs. 3.5 degrees; p=0.04). Side effects were mild but higher in the niacinamide group (40% vs 27%, p=0.003). This study indicates that niacinamide may have a role in the treatment of osteoarthritis. Niacinamide improved the global impact of osteoarthritis, improved joint flexibility, reduced inflammation, and allowed for reduction in standard anti-inflammatory medications when compared to placebo. More extensive evaluation of niacinamide in arthritis is warranted.
A double-blind randomized crossover study of oral thalidomide versus placebo for androgen dependent prostate cancer treated with intermittent androgen ablation.

We determined whether thalidomide can prolong progression-free survival in men with biochemically recurrent prostate cancer treated with limited androgen deprivation therapy.



A total of 159 patients were enrolled in a double-blind randomized trial to determine if thalidomide can improve the efficacy of a gonadotropin-releasing hormone agonist in hormone responsive patients with an increasing prostate specific antigen after primary definitive therapy for prostate cancer. Patients were randomized to 6 months of gonadotropin-releasing hormone agonist followed by 200 mg per day oral thalidomide or placebo (oral phase A). At the time of prostate specific antigen progression gonadotropin-releasing hormone agonist was restarted for 6 additional months. Patients were then crossed over to the opposite drug and were treated until prostate specific antigen progression (oral phase B). Testosterone and dihydroxytestosterone were likewise monitored throughout the study.



During oral phase A the median time to prostate specific antigen progression was 15 months for the thalidomide group compared to 9.6 months on placebo (p = 0.21). The median time to prostate specific antigen progression during oral phase B for the thalidomide group was 17.1 vs 6.6 months on placebo (p = 0.0002). No differences in time to serum testosterone normalization between the thalidomide and placebo arms were documented during oral phase A and oral phase B. Thalidomide was tolerable although dose reductions occurred in 47% (58 of 124) of patients.



Despite thalidomide having no effect on testosterone normalization, there was a clear effect on prostate specific antigen progression during oral phase B. This is the first study to our knowledge to demonstrate the effects of thalidomide using intermittent hormonal therapy.
Estimating treatment effects for individual patients based on the results of randomised clinical trials

To predict treatment effects for individual patients based on data from randomised trials, taking rosuvastatin treatment in the primary prevention of cardiovascular disease as an example, and to evaluate the net benefit of making treatment decisions for individual patients based on a predicted absolute treatment effect.



As an example, data were used from the Justification for the Use of Statins in Prevention (JUPITER) trial, a randomised controlled trial evaluating the effect of rosuvastatin 20 mg daily versus placebo on the occurrence of cardiovascular events (myocardial infarction, stroke, arterial revascularisation, admission to hospital for unstable angina, or death from cardiovascular causes). Population 17,802 healthy men and women who had low density lipoprotein cholesterol levels of less than 3.4 mmol/L and high sensitivity C reactive protein levels of 2.0 mg/L or more.



Data from the Justification for the Use of Statins in Prevention trial were used to predict rosuvastatin treatment effect for individual patients based on existing risk scores (Framingham and Reynolds) and on a newly developed prediction model. We compared the net benefit of prediction based rosuvastatin treatment (selective treatment of patients whose predicted treatment effect exceeds a decision threshold) with the net benefit of treating either everyone or no one.



The median predicted 10 year absolute risk reduction for cardiovascular events was 4.4% (interquartile range 2.6-7.0%) based on the Framingham risk score, 4.2% (2.5-7.1%) based on the Reynolds score, and 3.9% (2.5-6.1%) based on the newly developed model (optimal fit model). Prediction based treatment was associated with more net benefit than treating everyone or no one, provided that the decision threshold was between 2% and 7%, and thus that the number willing to treat (NWT) to prevent one cardiovascular event over 10 years was between 15 and 50.



Data from randomised trials can be used to predict treatment effect in terms of absolute risk reduction for individual patients, based on a newly developed model or, if available, existing risk scores. The value of such prediction of treatment effect for medical decision making is conditional on the NWT to prevent one outcome event.
The diagnostic value of small bowel wall vascularity after sulfur hexafluoride-filled microbubble injection in patients with Crohn's disease. Correlation with the therapeutic effectiveness of specific anti-inflammatory treatment.

To assess the value of small bowel wall vascularity after microbubble contrast agent injection in evaluating the therapeutic effectiveness of specific anti-inflammatory treatment in patients with Crohn's disease.



Fifteen patients (7 male and 8 female; mean age+/-SD, 40 years+/-6) with a biopsy-proven diagnosis of Crohn's disease--Crohn's disease activity index (CDAI)>150 (n=12 patients) or <150 (n=3)--involving the terminal loop of the small bowel (wall thickness>5 mm) were included. In each patient the terminal loop was scanned by contrast-enhanced ultrasound (CEUS) after sulfur hexafluoride-filled microbubble injection before and after 6-month anti-inflammatory treatment. The vascularity of the terminal loop was quantified in gray-scale levels (0-255) by a manually drawn ROI encompassing the thickened bowel wall and it was correlated with CDAI.



Before the beginning of the specific treatment all patients revealed diffuse transparietal contrast enhancement after microbubble injection, except for 3 patients who revealed contrast enhancement limited to the submucosa. In 13 patients the slope of the first ascending tract and the area under the enhancement curve were significantly lower after anti-inflammatory treatment (P<0.05; Wilcoxon test) with a significant correlation with the CDAI score (rho=0.85, P<0.05). In 2 patients no significant vascularity changes were found even though a mild reduction of CDAI score was identified (from 200 to 150 gray-scale levels).



CEUS is a useful method to assess the therapeutic effectiveness of specific medical anti-inflammatory treatment in patients with Crohn's disease.
Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition.

Contrary to expectation, most studies have demonstrated that initiation of an angiotensin-converting enzyme (ACE) inhibitor in conventional doses in patients with heart failure reduces the diuretic efficacy of furosemide. Recently, it has been suggested that single low doses (1 mg) but not high doses (25 mg) of captopril enhance furosemide-induced diuresis. It is not known whether the interaction between diuretics and ACE inhibitors are altered during long-term dosing.



Eight patients with heart failure treated with diuretics and ACE inhibitors for at least 3 months were studied. All patients were established on captopril 12.5 mg three times daily for 2 weeks before the study. Sodium intake was fixed before the study, and usual medication was withheld on study days. Intravenous furosemide was given on each of 2 study days to maintain a moderate, constant diuresis. Renal plasma flow and glomerular filtration rate (GFR) were determined using clearance techniques, and urine was collected hourly over 4 hours. Captopril 12.5 mg or placebo was given in a randomized, single-blind fashion at the end of the first hour. Compared with placebo, captopril reduced plasma concentrations of angiotensin II (23 +/- 18 versus 4 +/- 3 pg/ml 1 hour after dosing, P < .02) and systolic (131 +/- 31 versus 122 +/- 29 mm Hg, P < .01) and diastolic (74 +/- 15 versus 67 +/- 13 mm Hg, P < .05) blood pressures. GFR fell (55 +/- 24 versus 51 +/- 22 mL/min, P < .02) and effective renal plasma flow rose during the first (198 +/- 76 versus 231 +/- 49 mL/min) and second hours after dosing (185 +/- 69 versus 247 +/- 74 mL/min, P < .02). Similarly, urine volumes, in response to furosemide, increased after captopril (238 +/- 90 versus 283 +/- 111 mL, P < .05, and 245 +/- 78 versus 311 +/- 92 mL, P < .01, 1 and 2 hours after dosing). Urinary electrolyte concentrations fell, but total urinary sodium (22 +/- 7 versus 28 +/- 12 mmol/hr, P < .01) and chloride (20 +/- 6 versus 25 +/- 11 mmol/hr, P < .05) excretion increased in the 2 hours after dosing, as did fractional excretion of sodium (urinary sodium/urinary creatinine) (61 +/- 27 versus 75 +/- 36 mmol/mumol, P < .01).



Intense although transient ACE inhibition with captopril enhances the diuretic effects of furosemide during long-term ACE inhibition.
Cyclooxygenase products sensitize muscle mechanoreceptors in humans with heart failure.

Prior work in animals and humans suggests that muscle mechanoreceptor control of sympathetic activation [muscle sympathetic nerve activity (MSNA)] during exercise in heart failure (HF) patients is heightened compared with that of healthy humans and that muscle mechanoreceptors are sensitized by metabolic by-products. We sought to determine whether cyclooxygenase products and/or endogenous adenosine, two metabolites of ischemic exercise, sensitize muscle mechanoreceptors during rhythmic handgrip (RHG) exercise in HF patients. Indomethacin, which inhibits the production of prostaglandins, and saline control were infused in 12 HF patients. In a different protocol, aminophylline, which inhibits adenosine receptors, and saline control were infused in 12 different HF patients. MSNA was recorded (microneurography). During exercise following saline, MSNA increased in the first minute of exercise, consistent with baseline heightened mechanoreceptor sensitivity. MSNA continued to increase during 3 min of RHG, indicative that muscle mechanoreceptors are sensitized by ischemia metabolites. Indomethacin, but not aminophylline, markedly attenuated the increase in MSNA during the entire 3 min of low-level rhythmic exercise, consistent with the sensitization of muscle mechanoreceptors by cyclooxygenase products. Interestingly, even the early increase in MSNA was abolished by indomethacin infusion, indicative of the very early generation of cyclooxygenase products after the onset of exercise in HF patients. In conclusion, muscle mechanoreceptors mediate the increase in MSNA during low-level RHG exercise in HF. Cyclooxygenase products, but not endogenous adenosine, play a central role in muscle mechanoreceptor sensitization. Finally, muscle mechanoreceptors in patients with HF have heightened basal sensitivity to mechanical stimuli, which also appears to be mediated by the early generation of cyclooxygenase products, resulting in exaggerated early increases in MSNA.
Transfer of manualized CBT for social phobia into clinical practice (SOPHO-PRAX): a study protocol for a cluster-randomized controlled trial

Cognitive-behavioral therapy (CBT) is generally known to be efficacious in the treatment of social phobia when applied in RCTs, namely when the treatment manual is based on the Clark-Wells approach. However, little is known about the efficacy of manualized treatments in routine clinical practice (Phase IV of psychotherapy research). The present study (SOPHO-PRAX) is a continuation of a large multicenter randomized clinical trial (SOPHO-NET) and analyzes the extent to which additional training practitioners in manualized procedures enhances treatment effect.



Thirty-six private practitioners will be included in three treatment centers and randomly designated to either training in manualized CBT or no specific training. The treatment effects of the therapies conducted by both groups of therapists will be compared. A total of 162 patients (n=116 completers; n=58 per condition) will be enrolled. Liebowitz Social Anxiety Scale (LSAS) will serve as primary outcome measure. Remission from social phobia is defined as LSAS total ≤ 30 points. Data will be collected at treatment begin, after 8, 15, and 25 sessions (50 min each), at treatment completion, as well at 6 and 12 months post-treatment.



The present CBT trial combines elements of randomized controlled trials and naturalistic studies in an innovative way. It will directly inform about the incremental effects of procedures established in a controlled trial into clinical practice. Study results are relevant to healthcare decisions and policy. They may serve to improve quality of treatment, and shorten the time frame between the development and widespread dissemination of effective methods, thereby reducing health cost expenditure.The results of this study will not only inform about the degree to which the new methods lead to an improvement of treatment course and outcome, but also about whether the effects of routine psychotherapeutic treatment are comparable to those of the controlled, strictly manualized treatments of the SOPHO-NET study.


 This study was funded by the German Federal Ministry of Education and Research (SOPHO-NET: BMBF 01GV0607; SOPHO-PRAX: BMBF 01GV1001).
Efficacy and safety of pamidronate in Modic type 1 changes: study protocol for a prospective randomized controlled clinical trial

Erosive degenerative disc disease, also known as Modic type 1 changes, is usually characterized by low back pain with an inflammatory pain pattern, as seen in spondyloarthropathies. Intravenous pamidronate has proven to be effective in patients with ankylosing spondylitis who are refractory to nonsteroidal antiinflammatory drugs, and in painful bone diseases in general, such as Paget's disease, fibrous dysplasia or vertebral fractures. We therefore hypothesize that pamidronate would be effective in treating low back pain associated with Modic type 1 changes.



This study, called PEPTIDE (short for the French title "Etude Prospective sur l'Efficacité et la tolérance du PamidronaTe dans les dIscopathies Degeneratives Erosives"), will be a double-blind, randomized, placebo-controlled, parallel group, phase two clinical trial. A total of 48 patients will be recruited. These patients will be randomly assigned to one of the two groups, with 24 patients in each group: one group will be given pamidronate and the other a placebo. Pamidronate will be administered at a dose of 90 mg per day for two days consecutively, and every patient, irrespective of treatment group, will be given paracetamol to maintain blinding by preventing drug-induced fever. The primary outcome measure is a between-group difference of 30 points on a 100 mm Visual Analogue Scale (VAS) at three months. Secondary outcome measures are improvement in functional status and the drug's safety. Primary and secondary outcome measures will be assessed at each visit (inclusion, at six weeks, three months, and six months). If the primary goal is not attained, the patient will be offered a rigid or semi-rigid back brace, irrespective of the treatment group.



To date, only local treatments, for example intradiscal corticosteroid therapy, lumbar arthrodesis or back braces have been studied in randomized, controlled trials, with controversial results. This trial is currently ongoing and, if conclusive, should provide physicians with an acceptable alternative to those treatments. The results should be publicly available in spring 2015.
Double-Blind, randomized comparative study of the antihypertensive effect of nicardipine slow-release and nifedipine slow-release in hypertensive patients with coronary heart disease

The main aim of this study was to investigate whether a new slow-release formulation of nicardipine can control hypertension and whether its antihypertensive effect is manifest throughout the dose intervals. In a randomized, double-blind placebo-controlled study, the antihypertensive effect of two calcium antagonists (Type II) was investigated in two independent groups of hypertensive patients with coronary artery disease. One group of patients received 40 mg nicardipine slow-release b.i.d. and the other 20 mg nifedipine slow-release b.i.d. The effect of the active drugs on blood pressure (BP), heart rate, and hemodynamics was compared with placebo within each group. In addition, a group comparison was made to establish whether nicardipine had any advantage over nifedipine. Twenty-eight patients [27 female, 1 male; 55 (41–72) years old], 18 with previous myocardial infarction (MI) entered the study (nicardipine, 15 patients; nifedipine, 13 patients). A placebo period of 3 days was followed by a 13-day drug treatment period. From the first to last trial day, BP and heart rate were measured three times daily. At the end of the placebo and the active drug periods, the following measurements were caried out: ambulatory BP monitoring by half-hourly recording for 12.5 hours with the Remler system, ergometric tests with ECG, and right heart catheterization. Both drugs lowered the BP at rest, during exercise, and during usual daily activities. The antihypertensive effect of nicardipine was significant for the daytime mean arterial BP (MAP) and for systolic BP and diastolic BP at various stages of the exercise tests. The difference between the effect of nicardipine and nifedipine was not significant. The BP profiles were, in general, at a lower level with both active drugs in comparison to placebo. The exception was the diastolic BP, especially of the nicardipine patients, in the afternoon about 10 hours after the morning medication. Heart rate increased slightly in both groups under ambulatory conditions, but was more pronounced with exercise load. The BP variability, with mean values of about 46 mmHg for systolic BP and 28 mmHg for diastolic BP, was identical within the groups with placebo and with active drugs. There was no influence on the double product, effort tolerance, ST-segment depression, and the hemodynamic parameters. Adverse effects observed during the study were mild and transient. Although this slow-release formulation of nicardipine was proven to have an overall antihypertensive effect, the study results call for improving the formulation to ensure a sustained antihypertensive effect between dose intervals. Neither of the two tested slow-release formulations show any advantage.
Detraining outcomes with expiratory muscle strength training in Parkinson disease.

Expiratory muscle strength training (EMST) is efficacious for improving maximum expiratory pressure (MEP), cough function, and swallowing safety in Parkinson disease (PD). However, there are no published reports describing detraining effects following EMST in persons with PD. Moreover, there are no published reports describing detraining effects following any behavioral swallowing intervention. Ten participants with PD underwent 3 mo of detraining following EMST. Measures of MEP and swallowing safety were made prior to beginning EMST (baseline), posttreatment (predetraining), and 3 mo postdetraining. Participants demonstrated, on average, a 19% improvement in MEP from pre- to post-EMST. Following the 3 mo detraining period, MEP declined by 2% yet remained 17% above the baseline value. No statistically significant changes were found in swallowing safety from post-EMST to postdetraining period. Following the 3 mo detraining period, seven participants demonstrated no change in swallowing safety, one worsened, and two had improvements. This preliminary study highlights the need for the design of maintenance programs to sustain function following intensive periods of training.