Comparison the effect of lateral wedge insole and acupuncture in medial compartment knee osteoarthritis: A randomized controlled trial

BackgroundThere is lack of well-designed trials evaluating structural benefits of non-pharmacologic therapies in knee osteoarthritis (OA). In this parallel-group randomized controlled trial, we aim to compare the possible advantages of lateral wedge insole and acupuncture in patients with medial knee OA.MethodPatients with grade two or three of medial knee OA were randomly allocated to group one who received an in shoe lateral wedge and group two who underwent acupuncture. We assessed patients' pain, function and knee joint cartilage thickness before and after intervention. Paired t-test and independent samples t-test were used for in group and between group analyses. (Level of evidence: 2.)ResultsTwenty patients in each group were recruited in the study. Pain significantly decreased after therapy in both groups one and two (paired t test, P < 0.001, 95% CI: 1.62–3.25 and 1.58–3.20 respectively). Function improved in each group (paired t test, P = 0.001, 95% CI of 0.94–2.38 in group one and 0.97–2.43 in group two). A non-clinically statistically significant difference regarding the femoral and tibial cartilage thickness was obtained in both groups one (P = 0.005, CI: − 0.43–0.82 and P = 0.037, CI: − 0.44–0.80 respectively) and two (P = 0.025, CI: − 0.45–0.79 and P = 0.035, CI: − 0.29–0.96 respectively). Between groups analysis showed no significant difference regarding abovementioned measures.ConclusionBoth lateral wedge insole and acupuncture can be effective in the treatment of medial knee osteoarthritis without any superiority of one over the other.Iranian Registry of Clinical Trials: IRCT201201108235N1.URL: http://irct.ir/searchen.php     

Going quasi: the premature disclosure effect in a randomized clinical trial

This paper describes a randomized clinical trial investigating a stress management program for women with breast cancer, which inadvertently turned quasi-experimental. Due to logistical considerations, group assignment was disclosed to participants (n = 63) prior to baseline assessment. Analyses of baseline measures unexpectedly revealed statistically significant differences between groups on psychological functioning. We suggest that what appears to be failed randomization may in fact point toward an important phenomenon which we have termed premature disclosure effect (PDE). A hierarchical regression model, developed to help explain the PDE, accounted for 47% of the variance. The findings indicate the importance of considering participant belief, preferences, and attributes when designing research protocols and interventions. Potential implications of PDE for clinical research in behavioral medicine are discussed and specific statistical methodologies suggested.     

Comparison between a GnRH antagonist and a GnRH agonist flare-up protocol in oocyte donors: a randomized clinical trial

BACKGROUND: Little information is available on the outcome of controlled ovarian hyperstimulation (COH) using GnRH antagonist in oocyte donation cycles especially in comparison with the short GnRH agonist protocol. This study was aimed at comparing the two stimulation protocols in oocyte donation (OD) cycles. METHODS: A total of 113 donors randomly received COH using either GnRH antagonist or GnRH agonist. The primary endpoint was the mean number of mature oocytes retrieved per started donor cycle. Secondary endpoints were the mean number of cumulus-oocyte-complexes (COCs) retrieved, the mean proportion of mature oocytes, pregnancy and implantation rates in recipients. RESULTS: Oocytes were distributed to 166 recipients. The mean number (+/- SD) of COC (11.6 +/- 5.8 versus 12.1 +/- 6.7), mature oocytes (8.4 +/- 4.4 versus 8.9 +/- 5.3) and the proportion of mature oocytes (70.8 versus 75.7%) retrieved per started donor cycle were similar in the antagonist and agonist groups, respectively. The implantation rate (26.1 versus 30.1%), clinical (40.2 versus 45.6%) and ongoing pregnancy rate per recipient cycle (32.2 versus 37.9%) were comparable in antagonist and agonist protocols, respectively. CONCLUSIONS: Similar mean number of mature oocytes and comparable pregnancy rates are achieved after OD in which donors received COH using GnRH antagonist or short GnRH agonist protocols.     

Pentoxifylline versus placebo in the treatment of infertility associated with minimal or mild endometriosis: a pilot randomized clinical trial

The present study is the first prospective randomized controlled trial of the effect of pentoxifylline on future fertility in infertile women with asymptomatic minimal or mild endometriosis. After completion of a basic infertility workup and laparoscopy, patients were entered into the study and randomly allocated to receive either a 12 month course of oral pentoxifylline (800 mg/day) (n = 30) or an oral placebo (n = 30). Those patients with other infertility factors were included in the study only if the factors were correctable and ultimately determined to be non-contributory. Life-table analysis was used to compare pregnancy rates between the two groups over a 12 month period that started immediately after laparoscopy. The 12 month actuarial overall pregnancy rates were 31 and 18.5% in the pentoxifylline and placebo groups respectively. However, this difference was not statistically significant by the chi(2)-test. Similarly, the Cox regression method showed no differences between the hazard of pregnancy in the two groups studied (odds ratio, 0.56; 95% confidence interval, 0.18-1.67). Therefore, there is no evidence from this study that immunomodulation with pentoxifylline aids fertility in those women with minimal or mild endometriosis. Further studies including more infertile patients with endometriosis are desirable in order to confirm our results.      

A randomized, single blind placebo controlled clinical trial on the effect of continuous ultrasound on low back pain

Low back pain (LBP) is a very common problem in primary care and a major cause of disability. There is no evidence for the efficacy of therapeutic modalities such as ultrasound in LBP In a randomized, single blind placebo controlled clinical trial, we aimed to evaluate the effect of continuous ultrasound (US) in patients with non specific LBP Of the fifty eight patients recruited, 10 patients (8 women and 2 men) randomly allocated to ultrasound (n=5) or placebo controlled (n=5) groups. The patients were treated by either US or sham-US for ten sessions, three days per week, every other day. The outcome measures were Functional Rating Index (FRI), Hmax/Mmax ratio and range of motion (ROM), which were measured at baseline, after 5 treatment sessions and at the end of treatment. To analyze the data, The Mann Whitney U test and Wilcoxon Signed Rank test were used. After treatment, both US and placebo groups showed statistically significant decrease in FRI scores indicating improvement in functional ability (p = 0.042 and p = 0.043, respectively). The mean changes of FRI during the second five treatment sessions and after the end of treatment was significantly better in the US group than in the placebo group (p = 0.016 and p = 0.032, respectively). Before and after treatment, the mean H reflex latency and Hmax/Mmax ratio, right and left side were similar in the groups (p > 0.05), and no significant changes were observed in the treatment groups (p > 0.05). After treatment, the extension and lateral flexion range of motion significantly increased in the US group (p = 0.04), but the back movements in the placebo group did not show significant changes (p > 0.05). The present study supports the significant effect of US on LBP, and suggests that US may improve the functional ability of patients with non specific low back pain.     

Discrepancies in endpoints between clinical trial protocols and clinical trial registration in randomized trials in oncology

Background

Clinical trials are an essential part of evidence-based medicine. Hence, to ensure transparency and accountability in these clinical trials, policies for registration have been framed with emphasis on mandatory submission of trial elements, specifically outcome measures. As these efforts evolve further, we sought to evaluate the current status of endpoint reporting in clinical trial registries.

Methods

We reviewed 71 oncology related randomized controlled trials published in three high impact journals. We compared primary (PEP) and non-primary endpoints (NPEP) between the clinical trial protocols of these trials and their corresponding registration in one of the 14 primary global clinical trial registries. A discrepancy was defined as the non-reporting or absence of an endpoint in either the protocol or registry. The primary endpoint was the rate of discrepancy between secondary endpoints in clinical trial protocols and clinical trial registries.

Results

Of the 71 clinical trials, a discrepancy in PEP was found in only 4 trials (6%). Secondary endpoint (SEP) differences were found in 45 (63%) trials. Among these 45 trials, 36 (80%) had SEPs that were planned in the protocol but not reported in the registry and 19 (42%) had SEPs with endpoints in the registry that were not found in the protocol. The total number of SEPs that were absent from the corresponding registry and protocol were 84 and 29, respectively. Of these endpoints, 48 (57%) and 9 (31%) were included in the published report of these trials.

Conclusion

Although recent regulations and enhanced procedures have improved the number and quality of clinical trial registrations, inconsistencies regarding endpoint reporting still exist. Though further guidelines for the registration of clinical trials will help, greater efforts to provide a correct, easily accessible, and complete representation of planned endpoints are needed.

     

A dietary supplement to improve the quality of sleep: a randomized placebo controlled trial

Background  

To evaluate the effect of a dietary supplement containing polyunsaturated fatty acids, in association with Humulus lupulus extract, on the quality of sleep using the Leeds sleep evaluation questionnaire (LSEQ) in subjects with moderate to severe sleep disorders.     

含幽门螺杆菌特异性抗体牛奶清除幽门螺杆菌效果的临床随机试验

目的:比较观察抗幽门螺杆菌抗体牛奶根除幽门螺杆菌的效果。方法:用4 株幽门螺杆菌(1 株为标准菌株,3 株为本地流行菌株)免疫奶牛,制备出抗幽门螺杆菌抗体牛奶。本次试验共筛选148 例患者,C-14 呼气试验阳性的患者为72 例,最后符合入选标准的为39 例,将符合标准的患者随机分为试验组和对照组,分别为21 例和18 例,试验组饮用含特异性幽门螺杆菌抗体的牛奶,对照组饮用普通牛奶,连续饮用2 个月后,观察结果。结果:试验组的21 名对象中,9 人C-14 呼气试验转为阴性,10 人降低。有效清除率达42.86%,而对照组未有清除,两组清除率有统计学意义(P =0.005,P<0.05)。结论:抗幽门螺杆菌抗体牛奶具有多克隆性和很高的效价,能够有效清除胃内幽门螺杆菌。     

The effect of hormone therapy on plasma homocysteine levels: a randomized clinical trial

OBJECTIVE: An elevated plasma homocysteine level is a risk factor for cardiovascular diseases. Hormone therapy (HT) may reduce fasting plasma homocysteine levels. We studied 80 postmenopausal women to determine the effect of medroxyprogesterone acetate (MPA) combined with conjugated equine estrogens (CEE) on fasting plasma homocysteine levels. DESIGN: In a randomized, double blind, prospective, placebo-controlled study, we randomly assigned 80 healthy postmenopausal women between CEE 0.625 mg/d combined with MPA 2.5 mg/d (n = 20), CEE 0.625 mg/d combined with MPA 5 mg/d (n = 20), unopposed CEE 0.625 mg/d (n = 20), and placebo (n = 20) all given for a duration of 6 months. Fasting plasma homocysteine levels were measured before and at the end of the treatment. RESULTS: Before treatment, plasma homocysteine concentrations were similar in all groups. After 6 months of unopposed CEE, the mean fasting plasma homocysteine levels decreased by 19.02% when compared with baseline levels (P < 0.05). The mean fasting plasma homocysteine concentrations decreased by 17.63% and 19.56% from baseline in both the CEE plus MPA 2.5 mg/d and CEE plus MPA 5 mg/d groups, respectively (P < 0.05 for each group). In contrast, plasma homocysteine levels increased by 11.66% in the placebo group. The homocysteine lowering effect did not differ significantly among the three groups of women receiving unopposed CEE alone and CEE plus MPA at two different doses. CONCLUSION: Six months of estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) significantly lower fasting plasma homocysteine levels in healthy postmenopausal women with equal efficacy.     

Comparison between micronucleated lymphocyte rates observed in healthy subjects and cancer patients

Micronucleated cell rates were assessed in cytokinesisblockedlymphocytes of 198 male and female healthy subjects (HS) notoccupationally exposed to genotoxic risks and of 70 male andfemale cancer patients (CP) prior to any anticancer treatment.In the HS group, spontaneous micronucleated cell rates (MN cellrates) were 9.7 ± 2.8 per 1000 binucleated lymphocytesand 9.8 ± 3.1 for males and females respectively. Inthe CP group, spontaneous MN cell rates were 21.1 ± 15.3per 1000 binucleated lymphocytes and 19.1 ± 11.2 formales and females respectively. Moreover, they were shown tohave a large inter–individual variability in the two groups.The study of inter-individual variation factors showed thatonly tobacco could affect MN cell rate in HS whereas age andsex apparently had no significant effect. In the CP group, onlyage significantly affected MN cell rate, whereas sex, tobacco,alcohol, imaging techniques and tumour stage had no significanteffect. There was no significant difference in the distributionof gender between HS and CP, whereas there was a significantdifference in the distribution of age and tobacco between thetwo groups. The comparison of MN cell rates in 54 HS and 54CP matched for age and sex showed a statistically significantdifference. Spontaneous MN cell rates of these two populationsreflect environmental exposure. Moreover, for CP it most probablyrefers to various cellular lesions and genetic damage. ⁵To whom correspondence should be addressed     

The placebo is powerful: estimating placebo effects in medicine and psychotherapy from randomized clinical trials

The logic of the randomized double‐blind placebo control group design is presented, and problems with using the design in psychotherapy are discussed. Placebo effects are estimated by examining clinical trials in medicine and psychotherapy. In medicine, a recent meta‐analysis of clinical trials with treatment, placebo, and no treatment arms was conducted (Hróbjartsson & Gøtzsche, 2001), and it was concluded that placebos have small or no effects. A re‐analysis of those studies, presented here, shows that when disorders are amenable to placebos and the design is adequate to detect the effects, the placebo effect is robust and approaches the treatment effect. For psychological disorders, particularly depression, it has been shown that pill placebos are nearly as effective as active medications whereas psychotherapies are more effective than psychological placebos. However, it is shown that when properly designed, psychological placebos are as effective as accepted psychotherapies. © 2005 Wiley Periodicals, Inc. J Clin Psychol 61: 835–854, 2005.     

Immunology: Immunotherapy and recurrent abortion: a randomized clinical trial

We conducted a randomized trial comparing expectant managementversus immunotherapy with paternal leukocytes to improve obstetricoutcome in women with unexplained recurrent abortion. Eligiblefor the study were women with unexplained recurrent abortion(three or more miscarriages and no live birth), negative findingsof immunological screening and no inhibition of the mixed lymphocyteculture. These women were seen for the first time between October1988 and March 1991 in a network of obstetric departments inNorthern Italy. Subjects positive for HLA DR3 or with a partnerpositive for hepatitis virus B antigen were not eligible. Atotal of 44 women entered the study. Patients were randomlyallocated to immunotherapy (22 women) or expectant management(22 women). Women allocated to immunotherapy were given 200x10⁶purified paternal lymphocytes before pregnancy. Median follow-upwas 24 months (range 10–39) in the immunotherapy groupand 25 months (range 11–38) in the expectant managementgroup. Out of the 22 women randomized to immunotherapy, 16 becamepregnant and the corresponding value was 14 in the expectantmanagement group. Spontaneous abortion occurred in six out ofthe 16 pregnancies observed in the treated women. Among the14 pregnancies observed in the expectant management group, twoaborted and one late fetal death occurred. The cumulative proportionsof women who became pregnant over 4 years were 37 and 45% inthe immunotherapy and expectant management groups respectively;this difference was not significant. No adverse effect was observedin treated women.     

Estrogen replacement therapy and cognitive functions in healthy postmenopausal women: a randomized trial

This study aimed to evaluate the effect of estrogen replacement therapy on verbal cognitive performance of middle-aged postmenopausal women. Middle-aged (40 to 59 years) hysterectomized, oligosymptomatic women receiving 0.625 mg/day of conjugated equine estrogens (N = 27) or placebo (N = 32) in a double-blind parallel group design were compared according to their performance on a verbal memory battery before and after six 28-day cycles of treatment. Both groups had similar age and educational level. The estrogen group performed better on digit span-forward and on the recall of the easy stimuli on the verbal-paired associates test regardless of age, education, physical symptoms, number of years of menopause, or blood estradiol levels. However, the small magnitude of difference in the effect on attentional span suggests that the estrogen-related improvement is unlikely to be of clinical relevance. Estrogen replacement therapy did not improve verbal memory in middle-aged, hysterectomized, postmenopausal, asymptomatic women.     

Sublingual immunotherapy in youngsters: adherence in a randomized clinical trial

Background Adherence is essential for effective treatment. Although several trials on the efficacy of sublingual immunotherapy (SLIT) in youngsters have been published, few contain data on medication intake. Objective We aimed to quantify adherence both to study protocol and medication intake as well as to identify factors that may influence adherence to SLIT in youngsters with rhinoconjunctivitis. Methods Two hundred and four youngsters (6–18 years) with hayfever participated in a randomized controlled trial and used grass pollen extract or placebo for 2 years. The primary outcome of the trial was the mean daily total rhinoconjunctivitis symptom score in the second grass pollen season. Participants having completed the follow‐up were considered adherent to the study protocol. Adherence to medication intake was assessed by weighing the study medication. Participants who completed the follow‐up and used 80% of the prescribed medication were considered adherent to medication intake. Patient‐, disease‐ and treatment‐related factors were analysed. Results One hundred and fifty‐four youngsters completed the study. The main reason for discontinuation was the inability to take medication according to schedule. Drop‐outs were older, had more difficulty following the medication instructions and their overall evaluation of the treatment effect was lower. The number and reasons for drop‐out did not differ between treatment groups. In total, 77% of the participants was adherent to medication intake. Self‐reported adherence was 99%. Non‐adherent participants experienced more severe symptoms before the trial. Symptom scores did not differ between adherent and non‐adherent participants. In adherent as well as non‐adherent participants, no difference was found between verum and placebo group with respect to symptom scores. Conclusion Adherence to both study protocol and medication intake was good. Drop‐out was affected by age, evaluation of the treatment effect and medication instructions. Non‐adherence to medication intake was influenced by the severity of the disease before the trial. The ineffectiveness of SLIT could not be explained by non‐adherence.     

A controlled trial of real and simulated acupuncture in the management of chronic asthma

In 25 patients with moderate to severe asthma, we compared the therapeutic effectiveness of classic Chinese acupuncture with that of "placebo" acupuncture administered in a randomly ordered, subject- and evaluator-blind, crossover fashion twice weekly for 4 weeks. Real and placebo acupuncture periods were each preceded and followed by 3- to 4-week periods during which no acupuncture was administered. Outcome variables consisted of the following: daily symptoms and medication use self-scored on patient diaries, spirometry and whole body plethysmography performed once weekly during the entire course of the study and repeated serially during 3 hours after real and placebo acupuncture treatment, patients' self-assessment of acute efficacy of acupuncture therapy, and physician's physical findings before and after acupuncture treatment. Two-way analysis of variance failed to reveal a significant effect of either form of acupuncture on symptoms, medication use, or lung function measurements. Similarly, no significant acute effect of acupuncture on lung function, self-ratings of efficacy, or physician's physical findings was found by covariance analysis or the Wilcoxon signed-rank test. When data during the entire course of the study were examined on an individual basis by analysis of variance with repeated measures, only two subjects demonstrated significantly favorable responses to real versus placebo acupuncture, but one subject demonstrated the reverse, suggesting that these responses were not specifically related to acupuncture therapy. Thus, our findings failed to demonstrate any short- or long-term benefit of acupuncture therapy in the management of moderate to severe asthma.     

Effects of acupuncture on skin and muscle blood flow in healthy subjects

In 14 healthy female subjects, the effects of needle stimulation (acupuncture) on skin and muscle blood flow were investigated using a non-invasive custom-designed probe and photoplethysmography (PPG). In randomised order, 2–7 days apart, three modes of needle stimulation were performed on the anterior aspect of the tibia: superficial insertion (SF), insertion into the anterior tibial muscle (Mu), and insertion into the muscle including manipulation of the needle in order to elicit a distinct sensation of distension, heaviness or numbness (DeQi). Before intervention, the subjects rested for 30 min. After the intervention, the needle was left in situ for 20 min. Blood flow recordings were performed intermittently from 10 min prior to the intervention to the end of the trial. In a fourth session, serving as control, corresponding measurements were performed without any needle stimulation. Area under curve was calculated for 5-min periods prior to and after stimulation, respectively, and for the remaining 15-min period after stimulation. Compared to the control situation, muscle blood flow increased following both Mu and DeQi for 20 min, with the latter being more pronounced for the initial 5 min. Skin blood flow increased for 5 min following DeQi. However, no increase was found following SF. The DeQi stimulation was preceded by higher visual analogue scale ratings of anxiety prior to stimulation, which might have influenced skin blood flow to some extent. The results indicate that the intensity of the needling is of importance, the DeQi stimulation resulting in the most pronounced increase in both skin and muscle blood flow.