Quantitative Assessment of Acupuncture's Effectiveness in Osteoarthritis: A Model-Based Meta-Analysis

ObjectiveIn sham acupuncture-controlled acupuncture clinical trials, although sham acupuncture techniques are different from those of verum acupuncture, the same acupuncture points are often used for verum and sham acupuncture, raising the question of whether sham acupuncture is an appropriate placebo. We aimed to examine the effects of sham and verum acupuncture according to the points needled (same or different between verum and sham acupuncture) in knee osteoarthritis. MethodsTen databases were searched to find randomized controlled clinical trials (RCTs) assessing the effects of verum acupuncture with sham acupuncture or waiting lists on knee osteoarthritis. Sham acupuncture was classified as using the same acupuncture points as those in verum acupuncture (SATV) or using sham points (SATS). A frequentist network meta-analysis (NMA) was conducted, and the certainty of evidence was evaluated. ResultsA total of 10 RCTs involving 1628 participants were included. Verum acupuncture was significantly superior to SATS but not different from SATV in terms of pain reduction. Additionally, SATV was significantly superior to the waiting list. For physical function, no difference were found between verum acupuncture, SATV, and SATS. The certainty of evidence was low to moderate. ConclusionFor knee osteoarthritis, the pain reduction effect of acupuncture may differ according to the needling points of sham acupuncture, and the control group should be established according to the specific aim of the study design and treatment mechanism.

The aim of this study is to evaluate the relationship among radiological severity of osteoarthritis (OA), age, body mass index (BMI), gender and clinical findings in subjects with knee OA. One hundred and eighteen subjects consisting of 17 men and 101 women, mean aged 56.44±8.36, have phase I-II-III and IV knee OA according to Kellgren-Lawrence (K-L) radiological classification were included in this study. WOMAC index (Western Ontario and McMaster Universities Osteoarthritis Index) was used to evaluate pain, stiffness, physical function. According to results of regression analysis, significant variables were BMI (p=0.015) and radiological phase (p=0.001) on WOMAC pain score, gender (p=0.005) and radiological phase (p=0.010) on WOMAC stiffness score, gender (p=0.019) and BMI (0.004) on WOMAC function score, gender (p=0.014), BMI (p=0.004) and radiological phase (0.014) on WOMAC total score. According to results of correlation analysis there were no correlation between subjects’ ages and WOMAC pain (rho=-0.003, p=0.975), stiffness (rho=-0.012, p=0.898), function (rho=0.015, p=0.871) and total scores (rho=0.009, p=0.921). There were weak correlation between radiological phase and WOMAC pain (rho=0.327, p=0.001), stiffness (rho=0.278, p=0.05), function (rho=0.247, p=0.007) and total (rho=0.294, p=0.001) scores. There were weak correlations between BMI and WOMAC pain (rho=0.354, p=0.001), function (rho=0.356, p=0.001), total (rho=0.361, p=0.001) scores. This study reveals that there is a weak correlation between radiological classification and functional status. These results indicate that radiographic and clinical symptoms have to be discussed independently to determine the treatment of knee OA and evaluating clinical symptoms and functional status should gain importance in physiotherapy.

Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on μ-opioid receptors (MORs)

Objective: To evaluate the effectiveness of acupuncture for pain relief and function improvement in patients with knee osteoarthritis and to determine the feasibility of an eight-week acupuncture intervention. Design: Pilot randomized controlled trial. Setting: Three teaching hospitals in China. Subjects: Patients with knee osteoarthritis (Kellgren grade II or III). Interventions: Patients were randomly assigned to an eight-week (three sessions per week) intervention of either traditional Chinese acupuncture or sham acupuncture. Main measures: The primary outcome was response rate—the proportion of patients achieving score ⩾36% decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function at week 8 compared with baseline. Secondary outcomes included pain, function and quality of life. Results: Of 42 patients randomized, 36 (85.7%) completed the study. There was no significant difference in response rate between the traditional Chinese acupuncture and control groups: 61.9% (13 of 21) versus 42.9% (9 of 21) achieved score ⩾36% decrease in WOMAC pain and function at week 8 (P = 0.217). The sum of WOMAC pain and function scores at week 8 was 11.6 (9.1) in the traditional Chinese acupuncture group compared with 16.3 (10.9) in the control group (P = 0.183). There was no significant difference between groups. Three adverse events were recorded and were classified as mild. Conclusion: It showed that three sessions per week acupuncture intervention of knee osteoarthritis was feasible and safe. No difference was observed between groups due to small sample size. Larger (sample size ⩾ 296) randomized controlled trials of this intervention appear justified.

Clinical trials of acupuncture in chronic pain have largely failed to demonstrate efficacy of traditional over sham acupuncture. However, it should be noted that sham acupuncture is not inert. To determine if experimental-pressure pain assessment and chemical neuroimaging can identify differential responsiveness to sham as opposed to traditional acupuncture. Fifty patients with fibromyalgia were randomized to either 9 traditional (TA) or sham (SA) acupuncture treatments over a period of 4 weeks. Both participants and assessors were blinded. The main outcome measures were pressure-pain sensitivity at the thumbnail, insular glutamate+glutamine (Glx), and clinical pain. PATIENTS WITH LOW PAIN SENSITIVITY (LPS), BUT NOT WITH HIGH PAIN SENSITIVITY (HPS), HAD A SIGNIFICANTLY REDUCED CLINICAL PAIN RESPONSE TO SA (CHANGE IN MEAN [STANDARD DEVIATION (SD)]: HPS -8.65 [7.91]; LPS -2.14 [6.68]; p=0.03). This relationship was not the case for TA (HPS -6.90 [4.51]; LPS -6.41 [9.25]; p=0.88). SA-treated patients who were more sensitive also had greater baseline levels of insular Glx than patients who were less sensitive (Glx mean [SD]: HPS 11.3 [1.18]; LPS 10.2 [0.54]; p=0.04). Pressure-pain testing may identify patients who are less likely to respond to SA. This effect may relate to the levels of brain excitatory neurotransmitters.

This study aimed to evaluate the short-term and long-term efficacy of Mongolian medical warm acupuncture for sciatica caused by lumbar disc herniation (LDH). The patients diagnosed with sciatica caused by LDH were randomly divided into the warm acupuncture of the Mongolian medicine group (n = 42, warm acupuncture treatment), the sham acupuncture group (n = 38, sham acupuncture using blunt-tipped needles) and the conventional drug group (n = 40, ibuprofen sustained release capsule). All patients were treated for 4 weeks and followed up for 8 weeks. The visual analog scale for leg pain (VAS-LP), Mongolian medicine indicators (efficacy indicators), VAS for waist pain (VAS-WP) and the Mos 36-item short form health survey (SF-36) score were analyzed at baseline, after two-week treatment, after four-week treatment, at four-week follow-up and at eight-week follow-up. Warm acupuncture treatment significantly decreased the VAS-LP and VAS-WP scores of patients at treatment and follow-up (p < 0.05), and pain was improved compared to the conventional drug group and sham acupuncture group. The total effective rate was markedly higher in the warm acupuncture of the Mongolian medicine group compared with the conventional drug group at 8-week follow-up (p < 0.05), but sham acupuncture treatment resulted in no evident improvement in the Mongolian medicine indicators. Additionally, at treatment and follow-up, warm acupuncture of the Mongolian medicine group showed a significant increase in the physical function, physical role, body pain, and emotional and mental health role scores of the SF-36 survey compared with the sham acupuncture groups. Mongolian medical warm acupuncture effectively relieves leg and waist pain and improves the total therapeutic effect and the quality of daily life for patients with sciatica caused by LDH, with significant long-term efficacy. Our study provides a basis for warm acupuncture in the treatment of sciatica caused by LDH. Chinese Clinical Trial Registry ID: ChiCTR- INR-15007413.

BackgroundAcupuncture is commonly used to treat chronic sinusitis, though there is little documentation on the effect. This study presents the health-related quality of life (HRQoL) outcomes in a trial comparing traditional Chinese acupuncture, sham acupuncture, and conventional treatment for chronic sinusitis.FindingsIn a three-armed single blind randomized controlled study, we recruited 65 patients with symptoms of sinusitis >3 months and signs of sinusitis on computed tomography (CT). Patients were randomized to one of three study arms: (1) 2–4 weeks of medication with antibiotics, corticosteroids, 0.9% sodium chloride solution, and local decongestants (n = 21), (2) ten treatments with traditional Chinese acupuncture (n = 25), or (3) ten treatments with minimal acupuncture at non-acupoints (n = 19). Change in HRQoL was assessed over 12 weeks using the Chronic Sinusitis Survey (CSS) and Short form 36 (SF-36) questionnaires.In the study, we found only a non-significant difference on the CSS symptom scale between conventional medical therapy and traditional Chinese acupuncture. On the SF-36 scale role-physical the change was larger in the conventional group than in the sham group (p = 0.02), and on the mental health scale the change in the conventional therapy arm was larger than in the traditional Chinese acupuncture group (p = 0.03). There was no difference in effect on HRQoL on any scale between the sham and traditional Chinese acupuncture groups.ConclusionThere was no clear evidence of the superiority of one treatment over another on short-term HRQoL outcomes, although there was a statistically non-significant advantage of conventional therapy in a few dimensions.

Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials

Background:Neck pain is a common musculoskeletal symptom that has negative effects on quality of life and work productivity. Acupuncture has been widely used for neck pain, and a number of randomized controlled trials (RCTs) and systematic reviews (SRs) have evaluated its effectiveness. However, previous studies have obtained inconsistent results regarding the effects of acupuncture for neck pain, and there is no SR for the comparative efficacy and safety of various types of acupuncture. Therefore, we herein conducted a SR and network meta-analysis to compare and rank different types of acupuncture with respect to their effectiveness in treating neck pain.Methods:We searched 9 electronic databases for relevant RCTs published from their inception to July 1, 2021. Pairwise meta-analyses and network meta-analysis were performed with R software using the frequentist framework. Change of pain intensity was assessed as the primary outcome, and change of pain-related disability and efficacy rate were assessed as secondary outcomes. The Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument were used to evaluate the quality of the included RCTs and the certainty of the evidence.Results:A total of 65 RCTs involving 5266 participants and 9 interventions were included. Three network meta-analyses were constructed for the following: pain intensity (42 RCTs, 3158 participants), pain-related disability (21 RCTs, 1581 participants), and efficacy rate (40 RCTs, 3512 participants). The results indicated that fire acupuncture, electroacupuncture, and warm acupuncture were more effective than manual acupuncture in terms of pain intensity reduction and efficacy rate, and that electroacupuncture decreased pain-related disability more effectively than manual acupuncture. Fire acupuncture ranked first among the 9 interventions. The overall q of evidence was very low according to the GRADE assessment. The reported adverse events were not serious.Conclusion:Fire acupuncture, warm acupuncture, acupoint catgut embedding, and electroacupuncture ranked higher than other interventions (usual care, sham acupuncture, no treatment) in reducing the pain and disability index scores and the efficacy rate. However, the included trials were evaluated as being of low quality; thus, we recommend additional well-designed RCTs with larger sample sizes to confirm these findings.Systematic review registration:PROSPERO, CRD42021235274.

Diabetes affects around 20 million persons in the United States and is the fifth leading cause of death worldwide, consumes a large percentage of our health care resources, and remains a leading cause of cardiovascular (CV) and kidney disease. With the increasing rates of obesity in the United States, there are 41 million people with prediabetes, 50% of whom will develop frank type 2 diabetes mellitus over the next several years. Several clinical trials of subjects with hypertension or underlying CV disease have suggested that agents that block the renin-angiotensin system (RAS) prevent the development of new-onset diabetes (NOD). Pooled analyses of these trials have found, on average, a 25% reduction in NOD with angiotensin-converting enzyme (ACE) inhibitor–or angiotensin II receptor blocker (ARB)–based treatment regimens (usually with a diuretic). It remains unclear, however, whether this finding is attributable to the specific use of these agents or to the effects of the comparator agents studied, usually a β-blocker or thiazide-type diuretic. In addition, the progression to diabetes in these trials has always been a secondary outcome, which is, by definition, only hypothesis-generating. NOD has never been studied as a primary outcome. The Diabetes Reduction Assessment With Ramipril and Rosiglitazone Medication (DREAM) trial was conducted by the Canadian Institutes of Health Research, with additional financial support from industry. Subjects from 21 countries in 191 centers were enrolled to evaluate whether the ACE inhibitor, ramipril, reduces the risk of NOD in persons at high risk for its development. They had to be at least 30 years of age and have impaired fasting glucose (IFG) (fasting plasma glucose levels at least 110 mg/dL but <126 mg/dL) or impaired glucose tolerance (IGT) (fasting plasma glucose levels of at least 140 mg/dL but <200 mg/dL 2 hours after an oral glucose load) but no history of diabetes, CV disease, or intolerance to an ACE inhibitor. This double-blind placebo-controlled trial was performed using a 2 × 2 factorial design whereby both the ACE inhibitor ramipril and the thiazolidinedione rosiglitazone were compared with placebo. The 2 pharmacologic agents were reported separately; this review will deal only with the ACE inhibitor ramipril compared with placebo. Between July 2001 and August 2003, 24,592 participants were screened and 5808 entered a 17-day run-in period. The most common reasons for exclusion were ineligibility (94%) and refusal to participate (3%). After the run-in period, 2623 participants were randomly assigned to receive ramipril and 2646 participants received placebo. Ramipril was given as 5 mg daily for the first 2 months and then increased to 10 mg at the 2-month visit and to 15 mg after 1 year. Visits were scheduled at 2 months and 6 months after randomization and then at regular 6-month intervals until the final visit between February and April 2006. At each visit, adherence to study drug was assessed and reinforced, as was a healthy diet and lifestyle. Electrocardiography was performed at baseline, at 2 years, and at the end of the study. At the 2-year and final visits, a glucose tolerance test was performed if the fasting plasma glucose was 126 mg/dL or higher, if the fasting plasma glucose level exceeded 95 mg/dL and the glycosylated hemoglobin level exceeded 93% of the upper limit of normal, and to confirm or eliminate the diagnosis of diabetes in people in whom diabetes had not developed. Diabetes was diagnosed if 2 consecutive plasma glucose levels performed on separate days exceeded the diagnostic thresholds within a 3-month period (ie, a fasting plasma glucose of ≥126 mg/dL or a 2-hour plasma glucose ≥200 mg/dL) or if the outside physician following the patient prescribed an antidiabetic agent after a single abnormal glucose value. Glucose levels were available for 92.6% of individuals who had not reached a primary outcome by the end of the study. Participants were followed for a median of 3.0 years. The mean systolic BP at baseline was 136.1 mm Hg in the ramipril group and 136.0 mm Hg in the placebo group. At 2 months, mean systolic BP decreased by 8.2 mm Hg among those receiving ramipril and 3.9 mm Hg among those receiving placebo, a difference of 4.3 mm Hg, which persisted throughout the trial. Changes in diastolic BP were 4.3 mm Hg in the ramipril group and 1.6 mm Hg in the placebo group at 2 months (difference of 2.7 mm Hg) and also remained significant throughout the trial. Mean serum creatinine level did not change significantly in either group throughout the trial. The prespecified primary outcome was the development of NOD or death. Key secondary outcomes were fasting glucose levels, regression to normal glucose levels (fasting glucose level <110 mg/dL or 2-hour post-load glucose level <140 mg/dL) and a composite of cardiorenal events, defined as either CV events (clinical or silent myocardial infarction, stroke, death from CV events, revascularization procedures, heart failure, newly diagnosed angina with objective evidence of ischemia, or a ventricular arrhythmia requiring resuscitation) or renal events (on the basis of measurements in urine or blood at a central laboratory). Renal event data will be published at a future date. During the study, there was no difference in the occurrence of NOD or death (the primary end point) between individuals who received ramipril or placebo (18.1% of ramipril-treated patients compared with 19.5% of those who received placebo). There was also no difference in the development of NOD alone, which developed in 17.1% of the ramipril group and 18.5% of the placebo group. The rates of the primary outcomes were similar even after controlling for the use of other types of antihypertensive therapy, including thiazide-type diuretic (10% of participants), non-thiazide diuretic (6%), β-blocker (17%), calcium channel blocker (13%), or ARB (6%) therapy. The groups also did not differ in the incidence of CV events or hospitalization; however, significantly more ramipril than placebo recipients noted regression to normal glucose levels (43% vs 38%). There was no significant interaction with rosiglitazone; the hazard ratios for the primary outcome among those receiving ramipril were similar regardless of whether they received rosiglitazone. The authors conclude that the use of 15 mg of ramipril daily for 3 years in people with IFG or IGT and no evidence of established CV disease does not significantly prevent NOD or death.—Bosch J, Yusuf S, Gerstein HC, et al, for the DREAM Trial Investigators. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006;355:1551–1562. ACE inhibitors are among the most widely prescribed antihypertensive agents in the United States. They are currently recommended for the 6 compelling indications noted in the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). In addition to the benefits seen in patients with established CV disease, a number of widely publicized clinical trials have reported that the use of ACE inhibitors or ARBs decrease the incidence of NOD. These include the Heart Outcomes Prevention Evaluation (HOPE), where the use of the ACE inhibitor ramipril, given 10 mg daily (in addition to multiple other drugs), reduced the risk of NOD by 34% when compared with a group of patients on medications other than ramipril. This, however, was not a prespecified outcome, and the development of diabetes was ascertained only by self-report. By contrast, the use of ramipril was not associated with a reduction in NOD in the DREAM study. What explains the different results found in this recent trial? Unlike previous studies that evaluated the effect of antihypertensive drug therapy on the development of NOD, the DREAM investigation was specifically designed to evaluate the association of pharmacologic treatment and NOD as the primary end point. Previous studies, including HOPE, evaluated the development of diabetes either as a secondary outcome or in a post hoc analysis and, in many cases, the diagnosis of NOD was made primarily by self-report. Second, in contrast to other studies, patients in the DREAM study were only included in the trial if they had IFG or IGT and did not have established type 2 diabetes. Patients were screened at baseline with fasting glucose and an oral glucose tolerance test, and those who had overt diabetes or normal glucose levels were excluded. In previous studies, patients with undiagnosed diabetes may have been included, since baseline fasting plasma glucose and glucose tolerance were not routinely assessed. Finally, patients enrolled in the DREAM trial were younger (mean age, 55 years, compared with 65 years in other studies) and did not have evidence of CV disease on entry into the study. In previous studies, like HOPE, patients most often had known CV disease on entry. It is possible that ACE inhibitor therapy has a greater effect in individuals with established CV disease who may have increased activation of the renin-angiotensin-aldosterone system. It is also possible that the DREAM trial was too short in duration to detect a difference in incidence of NOD. In DREAM, the median follow-up was approximately 3 years compared with previous studies with ACE inhibitor and ARB therapy, which had a median follow-up of about 4.5 years. The Kaplan-Meier curves in DREAM suggest a trend toward benefit of ramipril in the prevention of NOD beginning at 3.5 years. Whether this is real or a chance phenomenon remains unclear, as does its clinical significance. Clinical trial evidence up to 6 years in duration continues to affirm the benefits and safety of thiazide-type diuretics despite their adverse effects on plasma glucose. For example, while there was a 3% increased risk of NOD noted with initial thiazide-type diuretic therapy compared with ACE inhibitor therapy in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), CV outcomes with initial thiazide-type diuretics were unsurpassed. This result and other data led to the recommendation in JNC 7 that thiazide-type diuretics should be used as initial antihypertensive therapy for most patients with hypertension. Whether possible metabolic effects moderate the clinical benefits of thiazide-type diuretics over a longer follow-up period continues to be debated. The most recent estimates predict that the prevalence of type 2 diabetes mellitus will more than double, from 5.6% in 2005 to 12.0% in 2050, and that 48.3 million people will have a diagnoses of diabetes in the United States by 2050. In addition, the tremendous increase in the rates of obesity and insulin resistance has led to an epidemic of individuals with IFG and/or IGT who are at high risk for progressing to type 2 diabetes. Whether small incremental changes in glucose over many years associated with some antihypertensive drug therapy carries the same risk as obesity-associated diabetes mellitus continues to be debated. For now, reduction of BP seems to be the most important target for improving clinical outcome in people both with and at risk for developing diabetes mellitus. Since most individuals require multiple antihypertensive agents to control their BP, combination regimens that target complementary pathophysiologic BP-lowering mechanisms are a rational approach to achieve BP control. While it is possible that a longer (ie, >3 years) and larger study would have shown a reduction in the development of NOD, the present 3-year trial with the use of the ACE inhibitor ramipril did not indicate that NOD was prevented among persons with IFG or IGT. The hypertension community awaits the outcomes of the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) study, evaluating initial fixed-dose combination therapy with an ACE/calcium channel blocker (benazepril/amlodipine) compared with an ACE/thiazide-type diuretic (benazepril/HCTZ) in individuals with and without diabetes. At present, continued use of thiazide-type diuretics with ACE inhibitors or ARBs as combination antihypertensive therapy is often required to control BP in most individuals with hypertension. With the publication of the DREAM results, enthusiasm for including RAS antagonists to decrease the risk of NOD has lessened. Traditional Chinese acupuncture (TCA) is advocated by some as an effective and well-tolerated treatment for essential hypertension. While a few case reports and several small clinical trials have suggested a benefit from acupuncture in patients with hypertension, the methodologic limitations of these trials have made it impossible to draw any definitive conclusions about the efficacy of TCA in lowering blood pressure (BP). The Stop Hypertension With Acupuncture Research Program (SHARP) pilot trial was designed to overcome the methodologic limitations of previous studies and evaluate the BP-lowering benefits of acupuncture. The SHARP trial was a prospective, double-blind, randomized, sham-controlled, parallel-group clinical pilot trial that was designed to test the safety and efficacy of 6 weeks of TCA in patients with moderate essential hypertension who were not receiving any antihypertensive medication. To be eligible, subjects had to be at least 18 years of age and have a systolic BP of 140–179 mm Hg or a diastolic BP of 90–109 mm Hg for 3 qualifying visits after cessation of all previous antihypertensive medications. In addition, they could not have had any TCA in the previous 6 months or have a medical contraindication to either TCA or the suspension of antihypertensive medications. Participants were randomly allocated into 1 of 3 treatment groups: (1) individualized TCA (IND); (2) standardized TCA (STD); or (3) sham acupuncture (CNTL). IND consisted of corporal acupuncture at 10–12 points selected and stimulated as prescribed for each individual by an experienced acupuncturist trained originally in China, plus auricular acupuncture at the 2 most active sites as identified by a point detector at the start of each session. STD consisted of corporal acupuncture with neutral stimulation at 5 bilateral points (10 total) plus auricular acupuncture at heart and jiang ya gou points as determined a priori by an expert panel convened for the purposes of this study. All diagnoses and treatment for IND and STD followed TCA principles previously established in the literature. CNTL consisted of sham acupuncture with no stimulation at 5 bilateral points (10 total) that do not correspond to any traditional Chinese meridians plus auricular acupuncture in Darwin's tubercle and the posterior ear lobe—all points considered inactive according to the tenets of TCA. Treatment consisted of no more than 12 twice-weekly 30-minute acupuncture sessions over 6 weeks. All participants received TCA from a team of licensed acupuncturists in a clinic established at the Massachusetts General Hospital. Treatment allocation was stratified by presence or absence of previous use of antihypertensive medications in the 6 months before study entry. All antihypertensive medications were tapered off according to a predetermined schedule before study initiation. After randomization, BP was measured at scheduled visits every 14 days until week 10 and subsequently at 4, 6, 9, and 12 months using a standardized technique by trained staff blinded to treatment allocation. In addition, blood chemistries, lipid profiles, complete blood cell counts, urinalysis, electrocardiography, and adverse events were analyzed at 10 weeks, 6 months, and 12 months. Quality-of-life data were obtained through use of the Medical Outcomes Study-Short Form self-administered questionnaires at baseline, 10 weeks, and 12 months. The predetermined primary end point was change in systolic BP from baseline to week 10, and the primary comparison was change in systolic BP for active (IND+STD) vs sham (CNTL) TCA. Between March 2001 and July 2002, 424 individuals underwent initial screening, of whom 192 met eligibility criteria and were randomized. Four subjects were lost to follow-up and 188 participants were available for the final evaluation. Patient characteristics in the 3 treatment groups were similar, with an average age of 55 years, 55% male, and an average baseline BP 149/93 mm Hg. Nearly all subjects (96%) received 12 treatments during an average of 42 days Mean systolic BP declined in all 3 groups between baseline and week 10 (the primary end point), with no statistically significant difference between those allocated to active (IND+STD, −3.56±1.92 mm Hg) compared with sham (CNTL, −3.84±1.93 mm Hg) acupuncture (P=.90). There was also no significant difference in diastolic BP decline between active (IND+STD) and sham (CNTL) acupuncture. In addition, there was no difference in systolic or diastolic BP between the 2 active treatment arms, IND and STD. When followed for 6 or 12 months, no significant treatment effect was noted on systolic or diastolic BP. Categorization of participants by age, race, sex, baseline BP, history of antihypertensive use, obesity, or primary TCA, diagnosis did not identify any subgroup that benefited from active TCA. Although BP increased modestly between measurements taken before and after an acupuncture session, no difference was seen between treatment groups. Ten-week change in physiologic and quality-of-life parameters did not differ between groups, except for fasting glucose, which was slightly lower in the CNTL group. Among the 141 participants who completed a masking assessment evaluation at 4 months, there was a nonsignificant trend toward subjects being able to determine their treatment assignment, but the number who guessed correctly was similar in all 3 groups (about 67%). Three study-related adverse events occurred—2 STD subjects experienced a hypertensive emergency and 1 CNTL subject experienced an episode of heart failure. In this well-designed prospective randomized clinical trial using an appropriate control group, 6 weeks of biweekly TCA has no demonstrable benefit on reducing BP in individuals with stage 1 hypertension who were not receiving antihypertensive drug therapy.—Macklin EA, Wayne PM, Kalish LA, et al. Stop Hypertension with the Acupuncture Research Program (SHARP): results of a randomized, controlled clinical trial. Hypertension. 2006;48:838–845. Previous evidence, mostly anecdotal observation, has suggested that TCA may have a role in the treatment of hypertension. The SHARP investigators appropriately considered these findings hypothesis-generating, leading them to design and execute a well-conceived prospective randomized clinical trial to test the hypothesis. Perhaps the most important design characteristics of this clinical trial were the use of appropriate blinding of acupuncturists and subjects, an appropriate control group (sham acupuncture in CNTL), and the use of 2 different previously validated types of TCA treatments (IND and STD). The study also benefited from careful measurement of an appropriate clinical outcome, the 10-week change in systolic BP. Like all randomized clinical trials, however, SHARP does have some shortcomings that may cause some to question the validity of the findings. As the investigators point out, the relatively wide confidence intervals in this small pilot study do not exclude the possibility of a small, but perhaps clinically significant, benefit (likely <4 mm Hg). The exclusion of subjects concomitantly treated with antihypertensive drug therapy does not rule out a possible beneficial effect when TCA is used in combination with BP-lowering medication, and the relatively short treatment period may not have allowed the full effects of TCA to be realized. Therefore, the results of this well-designed clinical trial make it unlikely that TCA provides substantial clinical benefit in patients with hypertension. Some of the perceived benefits of TCA, as pointed out by the SHARP investigators, may be the result of being treated by a clinician who “creates an expectation of medical improvement.” Practitioners of alternative medicine, including TCA, create confidence in the safety and efficacy of the treatments they offer, even though, in most cases and as in this study, they have not been shown to have a measurable clinical benefit. In contrast, much of the dialogue surrounding the use of drug therapy for the treatment of hypertension, both in the practitioner's office and in the media, focuses on the potential adverse effects associated with these agents. While it is important that clinicians not underestimate the potential tolerability issues of antihypertensive drug medications, it is also important to balance these issues with a clear explanation of the important clinical benefits and our confidence in these interventions. This should improve outcome and patient acceptance and adherence. As patients in the United States continue to use alternative medicines to treat hypertension, it is imperative that future clinical trials be designed and funded to determine the potential value of these treatments for improving the control of BP and other outcomes in hypertension.

Preoperative psychological distress has been reported to be an important risk factor for poor outcome following lower-extremity arthroplasty. We determined the independent impact of preoperative psychological distress on three, twelve, and twenty-four-month WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain and function scores and on change scores over those time periods. Data were obtained from an international group of 952 patients in thirteen centers participating in the Kinemax Outcomes Study. Patients completed the WOMAC and Short Form-36 (SF-36) questionnaires. The mental health (MH) scale of the SF-36 was used to quantify the impact of psychological distress on WOMAC pain and function scores. We also dichotomized patients into groups with and without psychological distress on the basis of evidence-based cut-points. Repeated-measures models were used to derive mean preoperative and three, twelve, and twenty-four-month WOMAC pain and function scores and general linear models were used to derive change scores for patients with and without psychological distress after adjustment for covariates. Psychological distress, when examined on a continuous scale, was found to predict pain and function at all time-points. WOMAC pain scores for psychologically distressed patients were 3 to 5 points lower, depending on the time-frame, than the scores for the non-distressed patients, after adjustment for covariates. WOMAC function scores did not differ significantly between the two groups following surgery. The changes in the WOMAC pain and function scores for the psychologically distressed patients were not significantly different from those for the non-distressed patients. Many patients with psychological distress demonstrate a substantial decrease in that distress following surgery. Patients who are distressed have slightly worse pain preoperatively and for up to two years following knee arthroplasty as compared with patients with no psychological distress. With the exception of preoperative scores, these differences are not likely to be measurable at the individual patient level. WOMAC pain and function change scores do not differ between patients with and without distress after adjustment for covariates. Prognostic Level I.

Background: Preoperative psychological distress has been reported to be an important risk factor for poor outcome following lower-extremity arthroplasty. We determined the independent impact of preoperative psychological distress on three, twelve, and twenty-four-month WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain and function scores and on change scores over those time periods. Methods: Data were obtained from an international group of 952 patients in thirteen centers participating in the Kinemax Outcomes Study. Patients completed the WOMAC and Short Form-36 (SF-36) questionnaires. The mental health (MH) scale of the SF-36 was used to quantify the impact of psychological distress on WOMAC pain and function scores. We also dichotomized patients into groups with and without psychological distress on the basis of evidence-based cut-points. Repeated-measures models were used to derive mean preoperative and three, twelve, and twenty-four-month WOMAC pain and function scores and general linear models were used to derive change scores for patients with and without psychological distress after adjustment for covariates. Results: Psychological distress, when examined on a continuous scale, was found to predict pain and function at all time-points. WOMAC pain scores for psychologically distressed patients were 3 to 5 points lower, depending on the time-frame, than the scores for the non-distressed patients, after adjustment for covariates. WOMAC function scores did not differ significantly between the two groups following surgery. The changes in the WOMAC pain and function scores for the psychologically distressed patients were not significantly different from those for the non-distressed patients. Conclusions: Many patients with psychological distress demonstrate a substantial decrease in that distress following surgery. Patients who are distressed have slightly worse pain preoperatively and for up to two years following knee arthroplasty as compared with patients with no psychological distress. With the exception of preoperative scores, these differences are not likely to be measurable at the individual patient level. WOMAC pain and function change scores do not differ between patients with and without distress after adjustment for covariates. Level of Evidence: Prognostic Level I. See Instructions to Authors for a complete description of levels of evidence.

OBJECTIVES:This study sought to verify the effects of acupuncture as an adjuvant treatment for the control of asthma.METHODS:This was a randomized, controlled, crossover trial conducted at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A total of 74 patients with mild/moderate, persistent asthma were randomized into two therapeutic groups: Group A – 31 patients underwent 10 real weekly acupuncture sessions, followed by a 3-week washout period and 10 sham weekly acupuncture sessions; and Group B - 43 patients underwent 10 sham weekly acupuncture sessions, followed by a 3-week washout period and 10 real weekly acupuncture sessions. Patients used short- and long-acting β-2 agonists and inhaled corticosteroids when necessary. Prior to treatment and after each period of 10 treatment sessions, the patients were evaluated for spirometry, induced sputum cell count, exhaled nitric oxide (NO) and with the Short Form 36 (SF-36) and Questionnaire on Quality of Life-Asthma (QQLA) questionnaires. Daily peak flow and symptom diaries were registered. The level of significance adopted was 5% (α=0.05).RESULTS:In Group B, after real acupuncture, there was a decrease in eosinophils (p=0.035) and neutrophils (p=0.047), an increase in macrophages (p=0.001) and an improvement in peak flow (p=0.01). After sham acupuncture treatment, patients experienced less coughing (p=0.037), wheezing (p=0.013) and dyspnea (p=0.014); similarly, after real acupuncture, patients reported less coughing (p=0.040), wheezing (p=0.012), dyspnea (p<0.001) and nocturnal awakening episodes (p=0.009). In Group A, there was less use of rescue medication (p=0.043). After the sham procedure, patients in Group A experienced less coughing (p=0.007), wheezing (p=0.037), dyspnea (p<0.001) and use of rescue medication (p<0.001) and after real acupuncture, these patients showed improvements in functional capacity (p=0.004), physical aspects (p=0.002), general health status (p<0.001) and vitality (p=0.019). Sham acupuncture also led to significant differences in symptoms, but these were not different from those seen with real acupuncture. Spirometry and exhaled NO levels did not show a difference between sham and real acupuncture treatment. In addition, no significant difference was demonstrated between treatments regarding the quality of life evaluation.CONCLUSION:Real and sham acupuncture have different effects and outcomes on asthma control. The crossover approach was not effective in this study because both interventions led to improvement of asthma symptoms, quality of life and inflammatory cell counts. Thus, sham acupuncture cannot serve as a placebo in trials with acupuncture as the main intervention for asthma.

To compare the clinical outcomes of osteoarthritis indices (WOMAC and Lequesne scores) and adverse events in the treatment of osteoarthritis (OA) of the knee with platelet-rich plasma (PRP) versus hyaluronic acid (HA) or placebo. A systematic review and meta-regression were performed to compare outcomes between PRP injections versus HA or placebo. Relevant randomized control trials were identified from Medline and Scopus from date of inception to 13 August 2015. Nine of 551 studies were eligible; 6, 5, 5, 5, 2, 2, 2 and 7 studies were included in pooling of WOMAC total, pain, stiffness and function scores, Lequesne score, IKDC score, EQ-VAS score and adverse events in OA knee patients, respectively. The PRP injections had -15.4 (95% CI -28.6, -2.3, p=0.021), lower mean WOMAC total scores, and 8.83 (95% CI 5.88, 11.78, p<0.001), 7.37 (95% CI 4.33, 10.05, p=0.021) higher mean IKDC and EQ-VAS scores when compared to HA injections. However, PRP injections had no significant differences in WOMAC pain, stiffness and function scores, as well as Lequesne score and adverse events when compared to HA or placebo. In short-term outcomes (≤1year), PRP injection has improved functional outcomes (WOMAC total scores, IKDC score and EQ-VAS) when compared to HA and placebo, but has no statistically significant difference in adverse events when compared to HA and placebo. This study suggests that PRP injection is more efficacious than HA injection and placebo in reducing symptoms and improving function and quality of life. It has the potential to be the treatment of choice in patients with mild-to-moderate OA of the knee who have not responded to conventional treatment. I.

This study aimed to compare the efficacy of acupuncture to that of sham acupuncture, placebo pills, and nonhormonal drugs to provide the necessary quantitative information for establishing medication guidelines for menopausal hot flashes. A comprehensive literature search was performed using public databases. Randomized clinical studies on acupuncture therapy for the treatment of hot flashes in menopausal women were identified. A time-course model was established to describe the efficacy characteristics of acupuncture and sham acupuncture, which were compared with the efficacy of nonhormonal drugs and placebo pills reported in the literature. A total of 17 studies involving 1,123 participants were included. The quality of all the studies included in the analysis is medium to high, and there was no obvious risk of bias. It was found that the baseline number of hot flashes was an important factor affecting the efficacy of acupuncture and sham acupuncture. After correcting the baseline to eight hot flashes per day, the frequency of hot flashes decreased from baseline for traditional acupuncture (TA), electro-acupuncture (EA), TA&EA (merger analysis of TA and electro-acupuncture), and sham acupuncture were 3.1 (95% confidence interval [CI]: 2.8-3.4), 3.6 (95% CI: 3.2-4.0), 3.2 (95% CI: 2.9-3.5), and 2.6 (95% CI: 2.2-3.0) times/d at week 8, respectively. Compared with findings reported in the literature, we found the efficacy of electro-acupuncture was comparable to that of selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and neuroleptic agents such as gabapentin and escitalopram. Furthermore, the efficacy of TA&EA (merged) was significantly higher than that of placebo pills (2.3, 95% CI: 1.8-2.9). The efficacy of TA&EA (merged) was higher than that of sham acupuncture and significantly higher than that of placebo pills. The efficacy of electro-acupuncture was higher than that of traditional acupuncture, significantly higher than that of sham acupuncture, and comparable to that of selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and neuroleptic agents.