Comparison of outcome measures during treatment with the proprietary Harpagophytum extract doloteffin in patients with pain in the lower back, knee or hip.

Besides checking estimates of effectiveness and safety of using the proprietary Harpagophytum extract Doloteffin, this postmarketing surveillance compared various disease-specific* and generic** measures of effect. We enrolled 250 patients suffering from nonspecific low back pain (Back group: n = 104) or osteoarthritic pain in the knee (Knee group: n = 85) or hip (Hip group: n = 61). They took an 8-week course of Doloteffin at a dose providing 60 mg harpagoside per day. The measures of effect on pain and disability included the percentage changes from baseline of established instruments (Arhus low back pain index*, WOMAC index*, German version of the HAQ**) and unvalidated measures (total pain index*, three score index*, the patient's global assessment** of the effectiveness of treatment). Patients also received a diary for the daily recording of their pain and any additional treatments for it. The three groups differed in age, weight and characteristics of initial pain. 227 patients completed the study. Multivariate analysis confirmed that several dimensions of effect were recorded by the several outcome measures but, in all groups, both the generic and disease-specific outcome measures improved by week 4 and further by 8. In multivariable analysis, the improvement tended to be more when the initial pain and disability score was more: older patients tended to improve less than younger, the hip group tended to improve convincingly more than the back group, whereas the improvement in the knee group was less readily differentiated from that in the back group. The subgroup of Back patients who required NSAIDs during the 8 weeks used significantly more per patient than patients in the other two groups, but that requirement also declined more with time. About 10% of the patients suffered from minor adverse events that could possibly have been attributable to Doloteffin. Between 50% and 70% of the patients benefitted from Doloteffin with few adverse effects. Thus, Doloteffin is well worth considering for osteoarthritic knee and hip pain and nonspecific low back pain.     

Patient-perceived benefit during one year of treatment with Doloteffin

We recruited 114 patients (56 with chronic nonspecific low back pain, 37 with osteoarthritic knee and 21 with osteoarthritic hip pain) into a surveillance of the effects of taking Doloteffin at a dose providing 60 mg harpagoside per day for up to 54 weeks. Their symptoms and well-being were monitored at 4-6 week intervals by disease-specific and generic outcome measures, and the patients also kept a diary of their pain and requirement for rescue medication. The principal analyses were on the basis of Intention to Treat (ITT) with Last Value Carried Forward (LOCF). A Multivariate Analysis of Variance (MANOVA) indicated an appreciable overall improvement during the surveillance, similar in the Back, Knee and Hip groups. In separate ANOVAs, most of the individual outcome scores decreased significantly over time. Multiple regression analyses indicated that changes from baseline were independent of patients' characteristics. Additional analgesic requirements (which were very modest) declined during the year of surveillance. "Response during treatment", assessed according to criteria adapted from joint proposals of the Outcome Measures in Rheumatoid Arthritis Clinical Trials group and the Osteoarthritis Research Society International group, was achieved in 75% of patients, and was reflected in the percentages who rated the treatment as "good" or "very good". Adverse events were few and none were serious.     

A multicenter,double-blind,randomized, controlled phase III clinical trial of chicken type II collagen in rheumatoid arthritis

Introduction

Chicken type II collagen (CCII) is a protein extracted from the cartilage of chicken breast and exhibits intriguing possibilities for the treatment of autoimmune diseases by inducing oral tolerance. A 24-week, double-blind, double-dummy, randomized, methotrexate (MTX)-controlled study was conducted to evaluate the efficacy and safety of CCII in the treatment of rheumatoid arthritis (RA).

Methods

Five hundred three RA patients were included in the study. Patients received either 0.1 mg daily of CCII (n = 326) or 10 mg once a week of MTX (n = 177) for 24 weeks. Each patient was evaluated for pain, morning stiffness, tender joint count, swollen joint count, health assessment questionnaire (HAQ), assessments by investigator and patient, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) by using the standard tools at baseline (week 0) and at weeks 12 and 24. Additionally, rheumatoid factor (RF) was evaluated at weeks 0 and 24. Measurement of a battery of biochemical parameters in serum, hematological parameters, and urine analysis was performed to evaluate the safety of CCII.

Results

Four hundred fifty-four patients (94.43%) completed the 24-week follow-up. In both groups, there were decreases in pain, morning stiffness, tender joint count, swollen joint count, HAQ, and assessments by investigator and patient, and all differences were statistically significant. In the MTX group, ESR and CRP decreased. RF did not change in either group. At 24 weeks, 41.55% of patients in the CCII group and 57.86% in the MTX group met the American College of Rheumatology 20% improvement criteria (ACR-20) and 16.89% and 30.82%, respectively, met the ACR 50% improvement criteria (ACR-50). Both response rates for ACR-20 and ACR-50 in the CCII group were lower than those of the MTX group, and this difference was statistically significant (P < 0.05). The DAS28 (disease activity score using 28 joint counts) values of the two treatment groups were calculated, and there was a statistically significant difference between the two treatment groups (P < 0.05). Gastrointestinal complaints were common in both groups, but there were fewer and milder side effects in the CCII group than in the MTX group. The incidence of adverse events between the two groups was statistically significant (P < 0.05).

Conclusions

CCII is effective in the treatment of RA and is safe for human consumption. CCII exerts its beneficial effects by controlling inflammatory responses through inducing oral tolerance in RA patients.

Trials Registration

Clinical trial registration number: ChiCTR-TRC-00000093.     

Active immunization to tumor necrosis factor-α is effective in treating chronic established inflammatory disease: a long-term study in a transgenic model of arthritis

Introduction

Chicken type II collagen (CCII) is a protein extracted from the cartilage of chicken breast and exhibits intriguing possibilities for the treatment of autoimmune diseases by inducing oral tolerance. A 24-week, double-blind, double-dummy, randomized, methotrexate (MTX)-controlled study was conducted to evaluate the efficacy and safety of CCII in the treatment of rheumatoid arthritis (RA).

Methods

Five hundred three RA patients were included in the study. Patients received either 0.1 mg daily of CCII (n = 326) or 10 mg once a week of MTX (n = 177) for 24 weeks. Each patient was evaluated for pain, morning stiffness, tender joint count, swollen joint count, health assessment questionnaire (HAQ), assessments by investigator and patient, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) by using the standard tools at baseline (week 0) and at weeks 12 and 24. Additionally, rheumatoid factor (RF) was evaluated at weeks 0 and 24. Measurement of a battery of biochemical parameters in serum, hematological parameters, and urine analysis was performed to evaluate the safety of CCII.

Results

Four hundred fifty-four patients (94.43%) completed the 24-week follow-up. In both groups, there were decreases in pain, morning stiffness, tender joint count, swollen joint count, HAQ, and assessments by investigator and patient, and all differences were statistically significant. In the MTX group, ESR and CRP decreased. RF did not change in either group. At 24 weeks, 41.55% of patients in the CCII group and 57.86% in the MTX group met the American College of Rheumatology 20% improvement criteria (ACR-20) and 16.89% and 30.82%, respectively, met the ACR 50% improvement criteria (ACR-50). Both response rates for ACR-20 and ACR-50 in the CCII group were lower than those of the MTX group, and this difference was statistically significant (P < 0.05). The DAS28 (disease activity score using 28 joint counts) values of the two treatment groups were calculated, and there was a statistically significant difference between the two treatment groups (P < 0.05). Gastrointestinal complaints were common in both groups, but there were fewer and milder side effects in the CCII group than in the MTX group. The incidence of adverse events between the two groups was statistically significant (P < 0.05).

Conclusions

CCII is effective in the treatment of RA and is safe for human consumption. CCII exerts its beneficial effects by controlling inflammatory responses through inducing oral tolerance in RA patients.

Trials Registration

Clinical trial registration number: ChiCTR-TRC-00000093.     

Behavioral treatment of irritable bowel syndrome: a 1-year follow-up study

Sixteen clients afflicted with irritable bowel syndrome (IBS) were reassessed 1 year following completion of a multicomponent treatment package incorporating progressive muscle relaxation, thermal biofeedback, cognitive therapy, and IBS education. For the 14 patients who kept a 2-week symptom diary, significant reductions in ratings of abdominal pain and tenderness, diarrhea, and flatulence were obtained comparing pretreatment and follow-up symptom-diary ratings. Eleven of 14 clients were improved over pretreatment levels, 57% met the criteria for clinical improvement of at least a 50% reduction in major symptom scores, and all but 1 of 16 rated themselves as subjectively improved.     

Behavioral treatment of irritable bowel syndrome: A 1-year follow-up study

Sixteen clients afflicted with irritable bowel syndrome (IBS) were reassessed 1 year following completion of a multicomponent treatment package incorporating progressive muscle relaxation, thermal biofeedback, cognitive therapy, and IBS education. For the 14 patients who kept a 2-week symptom diary, significant reductions in ratings of abdominal pain and tenderness, diarrhea, and flatulence were obtained comparing pretreatment and follow-up symptom-diary ratings. Eleven of 14 clients were improved over pretreatment levels, 57% met the criteria for clinical improvement of at least a 50% reduction in major symptom scores, and all but 1 of 16 rated themselves as subjectively improved.     

Potential economic impact of using a proprietary willow bark extract in outpatient treatment of low back pain:An open non-randomized study

An open, non-randomised, study (postmarketing surveillance) was carried out on three groups of patients aged 18 to 80 presenting over an 18 month period with acute exacerbations of low back pain. The objective was to assess the possible economic impact of including a regular dose of proprietary willow bark extract (Assalix) in the treatment provided. A first group of 115 patients, presenting to 3 general practitioners in the first 3 months, was prescribed a daily dose of extract containing 120 mg of salicin (group W120). They also had access, if necessary, to the range of conventional treatments allowed for in the general practitioners' budgets. A second group of 112 patients presenting to the same general practitioners over the next 15 months, was prescribed extract equivalent to 240 mg salicin per day (group W240). A third "control" or "comparator" group of 224 patients, presenting to 3 orthopedists (specialists in physical medicine) over the whole 18 month period, received only the conventional therapeutic options allowed in the orthopedists' budgets (Group C). In the group C patients, the exacerbations had been shorter but the pain had been more intense as judged by Arhus Index and Total Pain Index. After 4 weeks of treatment, about 40% of group W240 patients were free of pain whether or not they had to resort to supplementary treatments. In group W120 as a whole, about 19% of patients were pain-free at 4 weeks, but only 8% of those who did not resort to supplementary treatment. In group C, 18% of patients were painfree. These findings were reflected reasonably well in the changes in the Arhus Index and Total Pain Index, and the findings in group W240 were consistent with those in a previous randomised controlled trial. Multivariable modelling to examine for possible confounding effects tended to identify membership of group W240 as an independent explanator of better pain relief than membership of group C. Though the measures of effect tended to be similar in group W120 as a whole and group C, the avoidance of more expensive conventional treatments in group W120 meant that the average cost per patient of treatment was reduced by about 35-50% (health service and private costings respectively). The better pain relief in group W240 was accompanied by an even smaller reliance on supplementary conventional treatments than in group W120 but the extra savings on these were outweighed by the extra cost of the additional Assalix so that the average cost per patient was reduced by 14-40% of the costs in group C. The possibility is discussed that, if orthopedists had relied more on regular full dosing with NSAIDs, they might have increased the effectiveness and reduced the cost of their treatment, though with the possibility of more side effects. Substituting established NSAIDs with COX-2 inhibitors might reduce the side effects, but at greater cost than with the Assalix.     

Short- and long-term effects of mud-bath treatment on hand osteoarthritis: a randomized clinical trial

The aim of this study was to evaluate both the short-term and the long-term effectiveness of spa therapy in patients with primary hand osteoarthritis (OA). This was a prospective randomized, single blind controlled trial. Sixty outpatients with primary bilateral hand OA were included in the study and randomized to one of two groups. One group (n?=?30) was treated with 12 daily local mud packs and generalized thermal baths with a sulfate-calcium-magnesium-fluorides mineral water added to usual treatment. The control group (n?=?30) continued regular outpatient care routine (exercise, NSAIDs and/or analgesics). Each patient was examined at baseline, after 2 weeks, and after 3, 6, 9 and 12 months. Primary outcome measures were global spontaneous hand pain on a visual analogue scale (VAS) and the functional index for hand osteoarthritis (FIHOA) score; secondary outcomes were health assessment questionnaire (HAQ), duration of morning stiffness, medical outcomes study 36-item short form (SF-36) and symptomatic drugs consumption. Our results demonstrated that the efficacy of spa therapy was significant in all the assessed parameters, both at the end of therapy and after 3 months; the values of FIHOA, HAQ and drugs consumption continued to be significantly better after 6 months in comparison with baseline. There were no significant modifications of the parameters throughout the follow-up in the control group. Differences between the two groups were significant for all parameters at the 15th day and at 3 months follow-up; regarding FIHOA, HAQ, and symptomatic drugs consumption, the difference between the two groups persisted and was significant at 6month follow-up. Tolerability of spa therapy seemed to be good. In conclusion, our results confirm that the beneficial effects of spa therapy in patients with hand OA last over time.     

Comparison of the Belgian Rheumatoid Arthritis Disability Assessment and Health Assessment Questionnaires as Tools to Predict the Need for Support Measures in Patients with Rheumatoid Arthritis

Objective

Scores on the Health Assessment Questionnaire (HAQ) predict the need for support measures in patients with rheumatoid arthritis (RA). In this study we compare the performance of the HAQ in this context with that of the more disease-specific Belgian Rheumatoid Arthritis Disability Assessment (BRADA) questionnaire.

Methods

In this multicenter observational study, patients with RA and disease duration of at least one year who consulted their rheumatologist for a routine follow-up visit filled out the HAQ, and BRADA questionnaires. The performance of HAQ and BRADA to predict the need for support measures available to patients with RA was evaluated using Receiver Operator Characteristic (ROC) curves, with the expert opinion of the rheumatologist as a reference.

Results

The study analyzed data of 301 patients with RA (70.8% females) with mean age 59.8±12.8, disease duration 11.4±9.3 years, and DAS28 values of 2.84±1.18. HAQ scores averaged 0.97±0.73 and BRADA scores were 3.92±3.49 over the last week and 3.89±3.50 over the last 3 months. The area under the ROC curves for the BRADA scores for the support measures investigated ranged from 0.702 to 0.862 and did not differ significantly from those of the HAQ (range 0.725–0.860).

Conclusion

The disease-specific BRADA questionnaire is equivalent to the HAQ in predicting the need for support measures in patients with stable RA.     

24 versus 48 Weeks of Peginterferon Plus Ribavirin in Hepatitis C Virus Genotype 6 Chronically Infected Patients with a Rapid Virological Response: A Non-Inferiority Randomized Controlled Trial

Objectives

The optimal treatment of hepatitis C virus (HCV) genotype 6 is unclear owing to its limited geographic distribution. Because of a high predictive value of rapid virological response (RVR) for sustained virological response (SVR), we conducted an open-label randomized controlled trial to compare 24- and 48-week peginterferon/ribavirin combination therapy for patients with HCV genotype 6 in Southern China who achieved an RVR.

Methods and Findings

Treatment-naive, non-cirrhotic patients with chronic hepatitis C genotype 6 were treated with pegylated interferon α-2a (180 μg/week) and ribavirin (800–1,200 mg, according to weight) for 4 weeks. Patients who achieved an RVR, which was defined as HCV RNA negativity at week 4 (<50 IU), were randomized to receive either an additional 20 or 44 weeks of treatment (24- and 48-week treatment groups, respectively). The primary outcome measure was SVR. From January 2011 to June 2014, 152(152/210, 72.4%) patients with HCV genotype 6a and RVR were randomized 1:1 to the 24- or 48-week treatment group. The SVR rates in the 24- and 48-week groups in the intention-to-treat analysis were 90.8% (69/76) and 88.2% (67/76), respectively; those in the per-protocol analysis were 95.7% (67/70) and 97.0% (64/66), respectively. More patients in the 48-week group had anemia (46.1% vs. 28.9%, P = 0.03), but other adverse events were comparable between the groups. The limitation of the present study was that only patients from Southern China were enrolled which may inhibit the extensive application of the findings.

Conclusion

Twenty-four weeks of peginterferon/ribavirin combination therapy was non-inferior to 48 weeks in patients with HCV genotype 6a in Southern China who achieved an RVR.

Trial Registration

ClinicalTrials.gov NCT01263860     

Changes in HIV Outcomes Following Depression Care in a Resource-Limited Setting: Results from a Pilot Study in Bamenda,Cameroon

Background

Little is known about how improved depression care affects HIV-related outcomes in Africa. In a sample of depressed HIV patients in a low income, sub-Saharan country, we explored how implementing measurement-based antidepressant care (MBC) affected HIV outcomes over 4 months of antidepressant treatment.

Methods

As part of a project adapting MBC for use in Cameroon, we enrolled 41 depressed HIV patients on antiretroviral therapy in a pilot study in which a depression care manager (DCM) provided an outpatient HIV clinician with evidence-based decision support for antidepressant treatment. Acute depression management was provided for the first 12 weeks, with DCM contact every 2 weeks and HIV clinician appointments every 4 weeks. We measured HIV clinical and psychiatric outcomes at 4 months.

Results

Participants were moderately depressed at baseline (mean Patient Health Questionnaire [PHQ] score = 14.4, range 13.1, 15.6). All HIV clinical outcomes improved by four month follow-up: mean (range) CD4 count improved from 436 (2, 860) to 452 (132, 876), mean (range) log-viral load decreased from 4.02 (3.86, 4.17) to 3.15 (2.81, 3.49), the proportion with virologic suppression improved from 0% to 18%, mean (range) HIV symptoms decreased from 6.4 (5.5, 7.3) to 3.1 (2.5, 3.7), the proportion reporting good or excellent health improved from 18% to 70%, and the proportion reporting any missed ARV doses in the past month decreased from 73% to 55%. Concurrently, psychiatric measures improved. The mean (range) PHQ score decreased from 14.4 (13.1, 15.6) to 1.6 (0.8, 2.4) and 90% achieved depression remission, while mean maladaptive coping style scores decreased and mean adaptive coping scores and self-efficacy scores improved.

Conclusion

In this pilot study of an evidence-based depression treatment intervention for HIV-infected patients in Cameroon, a number of HIV behavioral and non-behavioral health outcomes improved over 4 months of effective depression treatment. These data are consistent with the hypothesis that better depression care can lead to improved HIV outcomes.     

Physiotherapy Post Lumbar Discectomy: Prospective Feasibility and Pilot Randomised Controlled Trial

Objectives

To evaluate: acceptability and feasibility of trial procedures; distribution of scores on the Roland Morris Disability Questionnaire (RMDQ, planned primary outcome); and efficient working of trial components.

Design and Setting

A feasibility and external pilot randomised controlled trial (ISRCTN33808269, assigned 10/12/2012) was conducted across 2 UK secondary care outpatient physiotherapy departments associated with regional spinal surgery centres.

Participants

Consecutive consenting patients aged >18 years; post primary, single level, lumbar discectomy.

Interventions

Participants were randomised to either 1:1 physiotherapy outpatient management including patient leaflet, or patient leaflet alone.

Main Outcome Measures

Blinded assessments were made at 4 weeks post surgery (baseline) and 12 weeks post baseline (proposed primary end point). Secondary outcomes included: Global Perceived Effect, back/leg pain, straight leg raise, return to work/function, quality of life, fear avoidance, range of movement, medication, re-operation.

Results

At discharge, 110 (44%) eligible patients gave consent to be contacted. 59 (54%) patients were recruited. Loss to follow up was 39% at 12 weeks, with one site contributing 83% losses. Mean (SD) RMDQ was 10.07 (5.58) leaflet and 10.52 (5.94) physiotherapy/leaflet at baseline; and 5.37 (4.91) leaflet and 5.53 (4.49) physiotherapy/leaflet at 12 weeks. 5.1% zero scores at 12 weeks illustrated no floor effect. Sensitivity to change was assessed at 12 weeks with mean (SD) change -4.53 (6.41), 95%CI -7.61 to -1.44 for leaflet; and -6.18 (5.59), 95%CI -9.01 to -3.30 for physiotherapy/leaflet. RMDQ mean difference (95%CI) between change from baseline to twelve weeks was 1.65(-2.46 to 5.75). Mean difference (95%CI) between groups at 12 weeks was -0.16 (-3.36 to 3.04). Participant adherence with treatment was good. No adverse events were reported.

Conclusions

Both interventions were acceptable, and it is promising that they both demonstrated a trend in reducing disability in this population. A randomised controlled trial, using a different trial design, is needed to ascertain the effectiveness of combining the interventions into a stepped care intervention and comparing to a no intervention arm. Findings will guide design changes for an adequately powered randomised controlled trial, using RMDQ as the primary outcome.

Trial Registration

ISRCTN registry 33808269     

Capacity-Building and Clinical Competence in Infectious Disease in Uganda: A Mixed-Design Study with Pre/Post and Cluster-Randomized Trial Components

Trial Design

Best practices for training mid-level practitioners (MLPs) to improve global health-services are not well-characterized. Two hypotheses were: 1) Integrated Management of Infectious Disease (IMID) training would improve clinical competence as tested with a single arm, pre-post design, and 2) on-site support (OSS) would yield additional improvements as tested with a cluster-randomized trial.

Methods

Thirty-six Ugandan health facilities (randomized 1∶1 to parallel OSS and control arms) enrolled two MLPs each. All MLPs participated in IMID (3-week core course, two 1-week boost sessions, distance learning). After the 3-week course, OSS-arm trainees participated in monthly OSS. Twelve written case scenarios tested clinical competencies in HIV/AIDS, tuberculosis, malaria, and other infectious diseases. Each participant completed different randomly-assigned blocks of four scenarios before IMID (t0), after 3-week course (t1), and after second boost course (t2, 24 weeks after t1). Scoring guides were harmonized with IMID content and Ugandan national policy. Score analyses used a linear mixed-effects model. The primary outcome measure was longitudinal change in scenario scores.

Results

Scores were available for 856 scenarios. Mean correct scores at t0, t1, and t2 were 39.3%, 49.1%, and 49.6%, respectively. Mean score increases (95% CI, p-value) for t0–t1 (pre-post period) and t1–t2 (parallel-arm period) were 12.1 ((9.6, 14.6), p<0.001) and −0.6 ((−3.1, +1.9), p = 0.647) percent for OSS arm and 7.5 ((5.0, 10.0), p<0.001) and 1.6 ((−1.0, +4.1), p = 0.225) for control arm. The estimated mean difference in t1 to t2 score change, comparing arm A (participated in OSS) vs. arm B was −2.2 ((−5.8, +1.4), p = 0.237). From t0–t2, mean scores increased for all 12 scenarios.

Conclusions

Clinical competence increased significantly after a 3-week core course; improvement persisted for 24 weeks. No additional impact of OSS was observed. Data on clinical practice, facility-level performance and health outcomes will complete assessment of overall impact of IMID and OSS.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01190540","term_id":"NCT01190540"}}NCT01190540     

Dual vs. triple therapy for childhood Helicobacter pylori gastritis: a double-blind randomized multicentre trial

BACKGROUND: Data on the efficacy of eradication treatment for Helicobacter pylori gastritis in children are scarce. AIM: To evaluate the efficacy of triple therapy with lansoprazole plus amoxicillin and tinidazole vs. dual therapy with amoxicillin and tinidazole in a double-blind randomized multicentre trial, and the usefulness of eradication in terms of long-term symptom resolution. SUBJECTS: We enrolled 43 consecutive children undergoing endoscopy for upper gastrointestinal dyspepsia with H. pylori gastritis. They underwent a 13C-urea breath test, completed a 2-week symptom diary card, and were randomized. Treatment was given in a Redidose box (Redidose Company Ltd., Brighton, UK) containing either lansoprazole-amoxicillin-tinidazole (triple therapy) or placebo plus amoxicillin-tinidazole (dual therapy) for 1 week. The completion of a 2-week symptom diary card and the performance of a breath test were repeated 6 weeks and 6 months after the end of therapy. One to two years later, a structured telephone interview was conducted with 36 of the children. RESULTS: According to the breath test, 6 weeks after the end of therapy H. pylori was eradicated in 15 of 22 children on triple therapy [68.2%; 95% confidence interval (CI) = 45-88] and in 15 of 21 children on dual therapy (71%; 95% CI = 48-89; not significant), and 6 months after the end of therapy it was eradicated in 16 of 22 children on triple therapy (72.7%) and in 15 of 21 children on dual therapy. Six months after therapy, symptoms were analysed in 11 H. pylori-positive and 31 H. pylori-negative children, and it was found that dyspeptic symptoms had disappeared or improved in both groups, with no difference between them. One to two years later, 36 children were interviewed. Epigastric pain had recurred in three of 26 H. pylori-negative and in seven of 10 H. pylori-positive children (p = .001); in three of the latter, pain was severe and required additional treatment. CONCLUSION: One-week triple or dual therapy with two antibiotics achieved similar eradication rates. Soon after treatment, symptoms disappeared or improved in most children irrespective of eradication, but epigastric pain recurred in the majority of the still-infected children within 2 years.     

舒芬太尼复合吗啡硬膜外术后镇痛的最佳剂量配伍

目的：观察腹式子宫全切术后硬膜外镇痛应用舒芬太尼复合吗啡时两种药物不同剂量的镇痛效果和不良反应,以寻找其最佳剂量配伍。方法：选择90例美国麻醉医师协会（ASA）标准Ⅰ-Ⅱ级、年龄20-60岁拟行腹式子宫全切术的病人,均实施腰硬联合麻醉。随机分成3组,每组30例：Ⅰ组：舒芬太尼10μg＋吗啡2 mg＋氟哌利多1 mg＋1%罗哌卡因20 mg;Ⅱ组：舒芬太尼15μg＋吗啡1.5 mg＋氟哌利多1 mg＋1%罗哌卡因20 mg;Ⅲ组：舒芬太尼20μg＋吗啡1 mg＋氟哌利多1 mg＋1%罗哌卡因20mg。术中监测生命体征,记录术后24小时内的镇痛效果、不良反应及辅助镇痛药物的使用情况。镇痛效果评价采用视觉模拟评分（visual analogue scale,VAS）标准。结果：2组各个时间点VAS评分均明显低于1组（P〈0.05）,在术后6 h,8 h,12 h,18 h,24 h与3组有统计学差异（P〈0.05）,3组在2 h,4 h,6 h的VAS评分低于1组（P〈0.05）;2组恶心评分与3组相比明显较低（P〈0.05）,其他不良反应三组间没有统计学差异;各组患者在术后24h内辅助镇痛药物使用情况比较无统计学差异（P〉0.05）。结论：舒芬太尼15μg复合吗啡1.5 mg用于腹式子宫全切术后硬膜外镇痛效果优于其他常用剂量配伍,镇痛效果平稳确切且不良反应少,具有临床应用价值。     

Physical function continues to improve when clinical remission is sustained in rheumatoid arthritis patients

IntroductionTo investigate the course of functional status assessed by health assessment questionnaire (HAQ) in rheumatoid arthritis (RA) patients with sustained clinical remission (REM).MethodsIn recent RA clinical trials, we identified patients with subsequent visits of ≥24 weeks in clinical REM according to the disease activity score using 28-joint counts including C-reactive protein (DAS28) (≤2.6), or simplified disease activity index (SDAI) (≤3.3). Area under the curve (AUC) and mean HAQ scores throughout the time in sustained REM were compared using t test, analyses of variance (ANOVA) and adjusted general linear modeling (GLM) with repeated measures. In Cox regression analyses, the time to regain full physical function was modeled. Sensitivity analyses were performed in patients of sustained SDAI low disease activity (LDA; SDAI ≤11).ResultsA total of 610 out of 4364 patients achieved sustained DAS28 REM (14 %) and 252 SDAI REM (5.8 %). ANOVA testing for linear trend showed significant decrease of mean HAQ from week 0 (start of REM) to week 24, regardless of REM criteria used. AUC of HAQ throughout 24 weeks of REM was higher in DAS28 compared to SDAI REM (p ≤0.01). GLM adjusting for covariates showed significant decrease of monthly HAQ scores from week 0 to 24 (DAS28: 0.276, 0.243, 0.229, 0.222, 0.219, 0.209 to 0.199; p = 0.0001; SDAI: 0.147, 0.142, 0.149, 0.129, 0.123, 0.117 to 0.114; p = 0.029). Similarly, a decrease of HAQ over time was found in patients of sustained SDAI LDA. In DAS28 REM, the chance of regaining full physical function was higher for female (hazard ratio HR [95 % confidence interval]: 1.41 [1.13–1.76]) and early RA patients (disease duration ≤2 years: HR 1.29 [1.01–1.65]); in SDAI REM no significant differences were found.ConclusionsPhysical function continues to improve if the target of REM or LDA is sustained. The stringency of the remission criteria determines achievement of the best possible functional improvement.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0719-x) contains supplementary material, which is available to authorized users.     

重组人表皮生长因子凝胶联合赛肤润对慢性伤口患者疼痛评分及不良反应的影响

摘要 目的：探讨重组人表皮生长因子(Recombinant human epidermal growth factor,rhEGF)凝胶联合赛肤润对慢性伤口患者疗效及对疼痛评分与不良反应的影响。方法：2017年3月-2019年9月选择在本院进行诊治的胃肠外科术后慢性伤口患者108例,根据治疗方法分为联合组与对照组各54例。对照组给予赛肤润治疗,联合组在对照组治疗的基础上给予rhEGF凝胶治疗,两组都持续给药观察14 d,记录患者疼痛与不良反应情况。结果：联合组治疗第3 d、第7 d、第14 d的疼痛VAS评分都低于对照组(P<0.05)。联合组治疗期间的皮肤坏死、伤口感染、发热等不良反应发生率为3.7 %,低于对照18.5 %(P<0.05)。联合组治疗后第3 d伤口愈合率为83.3 %,高于对照组的59.3 %(P<0.05),治疗后第7 d、第14 d的联合组伤口愈合率稍高于对照组,对比无统计学意义（P>0.05）。两组治疗后的血清血管内皮生长因子(vascular endothelial growth factor,VEGF)含量高于治疗前(P<0.05),联合组高于对照组(P<0.05)。结论：rhEGF凝胶联合赛肤润在慢性伤口患者的应用能促进缓解疼痛评分,减少不良反应的发生,促进VEGF的表达,从而加快伤口愈合。     

Effect of one year of a gluten-free diet on the clinical evolution of irritable bowel syndrome plus fibromyalgia in patients with associated lymphocytic enteritis: a case-control study

Introduction

Irritable bowel syndrome (IBS), lymphocytic enteritis (LE) and fibromyalgia syndrome (FMS) are three common disorders. Since a gluten-free diet (GFD) has been shown to be helpful in LE, we aimed to assess its effect in a series of LE patients also diagnosed with IBS and FMS.

Methods

The study sample comprised 97 IBS plus FMS adult females, of whom 58 had LE (Marsh stage 1), and 39 had a normal duodenal biopsy (Marsh stage 0). All patients fulfilled the Rome III and American College of Rheumatology 1990 criteria. All participants followed a GFD, the effectiveness of which was assessed by changes in the results of several tests, including those of the Fibromyalgia Impact Questionnaire (FIQ), the Health Assessment Questionnaire (HAQ), tender points (TPs), the Short Form Health Survey (SF-36), and the Visual Analogue Scales (VAS) for gastrointestinal complaints, pain and fatigue.

Results

At baseline, all patients had a poor quality of life (QoL) and high VAS scores. After one year on a GFD, all outcome measures were somewhat better in the Marsh stage 1 group, with a mean decrease of 26 to 29% in the TPs, FIQ, HAQ and VAS scales, accompanied by an increase of 27% in the SF-36 physical and mental component scores. However, in the IBS plus FMS/Marsh stage 0 group, the GFD had almost no effect.

Conclusions

This pilot study shows that a GFD in the LE-related IBS/FMS subgroup of patients can produce a slight but significant improvement in all symptoms. Our findings suggest that further studies of this subject are warranted.     

Supplementation with alkaline minerals reduces symptoms in patients with chronic low back pain

The cause of low back pain is heterogeneous, it has been hypothesised that a latent chronic acidosis might contribute to these symptoms. It was tested whether a supplementation with alkaline minerals would influence symptoms in patients with low back pain symptoms. In an open prospective study 82 patients with chronic low back pain received daily 30 g of a lactose based alkaline multimineral supplement (Basica) over a period of 4 weeks in addition to their usual medication. Pain symptoms were quantified with the "Arhus low back pain rating scale" (ARS). Mean ARS dropped highly significant by 49% from 41 to 21 points after 4 weeks supplemention. In 76 out of 82 patients a reduction in ARS was achieved by the supplementation. Total blood buffering capacity was significantly increased from 77.69 +/- 6.79 to 80.16 +/- 5.24 mmol/L (mean +/- SEM, n = 82, p < 0.001) and also blood pH rose from 7.456 +/- 0.007 to 7.470 +/- 0.007 (mean +/- SEM, n = 75, p < 0.05). Only intracellular magnesium increased by 11% while other intracellular minerals were not significantly changed in sublingual tissue as measured with the EXA-test. Plasma concentrations of potassium, calcium, iron, copper, and zinc were within the normal range and not significantly influenced by the supplementation. Plasma magnesium was slightly reduced after the supplemenation (-3%, p < 0.05). The results show that a disturbed acid-base balance may contribute to the symptoms of low back pain. The simple and safe addition of an alkaline multimineral preparate was able to reduce the pain symptoms in these patients with chronic low back pain.     

Changes in Disability,Physical/Mental Health States and Quality of Life during an 8-Week Multimodal Physiotherapy Programme in Patients with Chronic Non-Specific Neck Pain: A Prospective Cohort Study

AimThe aim of this study was to analyse the effect of an 8-week multimodal physiotherapy programme (MPP), integrating physical land-based therapeutic exercise (TE), adapted swimming and health education, as a treatment for patients with chronic non-specific neck pain (CNSNP), on disability, general health/mental states and quality of life.Methods175 CNSNP patients from a community-based centre were recruited to participate in this prospective study. Intervention: 60-minute session (30 minutes of land-based exercise dedicated to improving mobility, motor control, resistance and strengthening of the neck muscles, and 30 minutes of adapted swimming with aerobic exercise keeping a neutral neck position using a snorkel). Health education was provided using a decalogue on CNSNP and constant repetition of brief advice by the physiotherapist during the supervision of the exercises in each session. Study outcomes: primary: disability (Neck Disability Index); secondary: physical and mental health states and quality of life of patients (SF-12 and EuroQoL-5D respectively). Differences between baseline data and that at the 8-week follow-up were calculated for all outcome variables.ResultsDisability showed a significant improvement of 24.6% from a mean (SD) of 28.2 (13.08) at baseline to 16.88 (11.62) at the end of the 8-week intervention. All secondary outcome variables were observed to show significant, clinically relevant improvements with increase ranges between 13.0% and 16.3% from a mean of 0.70 (0.2) at baseline to 0.83 (0.2), for EuroQoL-5D, and from a mean of 40.6 (12.7) at baseline to 56.9 (9.5), for mental health state, at the end of the 8-week intervention.ConclusionAfter 8 weeks of a MPP that integrated land-based physical TE, health education and adapted swimming, clinically-relevant and statistically-significant improvements were observed for disability, physical and mental health states and quality of life in patients who suffer CNSNP. The clinical efficacy requires verification using a randomised controlled study design.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02046876","term_id":"NCT02046876"}}NCT02046876