Efficacy of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome : A Randomized Trial.

BACKGROUND: Acupuncture has promising effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but high-quality evidence is scarce. OBJECTIVE: To assess the long-term efficacy of acupuncture for CP/CPPS. DESIGN: Multicenter, randomized, sham-controlled trial. (ClinicalTrials.gov: NCT03213938). SETTING: Ten tertiary hospitals in China. PARTICIPANTS: Men with moderate to severe CP/CPPS, regardless of prior exposure to acupuncture. INTERVENTION: Twenty sessions of acupuncture or sham acupuncture over 8 weeks, with 24-week follow-up after treatment. MEASUREMENTS: The primary outcome was the proportion of responders, defined as participants who achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Ascertainment of sustained efficacy required the between-group difference to be statistically significant at both time points. RESULTS: A total of 440 men (220 in each group) were recruited. At week 8, the proportions of responders were 60.6% (95% CI, 53.7% to 67.1%) in the acupuncture group and 36.8% (CI, 30.4% to 43.7%) in the sham acupuncture group (adjusted difference, 21.6 percentage points [CI, 12.8 to 30.4 percentage points]; adjusted odds ratio, 2.6 [CI, 1.8 to 4.0]; P < 0.001). At week 32, the proportions were 61.5% (CI, 54.5% to 68.1%) in the acupuncture group and 38.3% (CI, 31.7% to 45.4%) in the sham acupuncture group (adjusted difference, 21.1 percentage points [CI, 12.2 to 30.1 percentage points]; adjusted odds ratio, 2.6 [CI, 1.7 to 3.9]; P < 0.001). Twenty (9.1%) and 14 (6.4%) adverse events were reported in the acupuncture and sham acupuncture groups, respectively. No serious adverse events were reported. LIMITATION: Sham acupuncture might have had certain physiologic effects. CONCLUSION: Compared with sham therapy, 20 sessions of acupuncture over 8 weeks resulted in greater improvement in symptoms of moderate to severe CP/CPPS, with durable effects 24 weeks after treatment. PRIMARY FUNDING SOURCE: China Academy of Chinese Medical Sciences and the National Administration of Traditional Chinese Medicine.

Acetic Acid Use in Chronic Wound Healing: A Multiple Case Series.

BACKGROUND: Acetic acid is bacteriostatic or bactericidal to many gram-negative and gram-positive microorganisms, especially Pseudomonas. Nevertheless, it has also been found to possess cytotoxic effects in concentrations as low as 0.25% inhibiting the epithelialization process during wound healing. CASES: In this multiple case series, we present 2 cases of chronic traumatic leg wounds treated with gauze moistened with acetic acid (0.25%), which were covered with a securing dressing and compression stockinet. Both patients were told to apply gauze moistened with acetic acid (0.25%) twice daily. In both cases, the wound progressed to blue-green drainage and wet yellow slough tissue to near-complete beefy granulation tissue. At this point, acetic acid was replaced with collagen or petrolatum dressing until complete wound closure was achieved. The treatment of these wounds illustrated successful use of acetic acid for chronic wound care. CONCLUSION: Our experience with these cases suggests that appearance of blue-green wound drainage and wet yellow slough tissue is a reasonable indication for the use of gauze moistened with acetic acid (0.25%). Further research is needed to test the efficacy of these principles in guiding acetic acid use in wound care.

Electroacupuncture vs Prucalopride for Severe Chronic Constipation: A Multicenter, Randomized, Controlled, Noninferiority Trial.

INTRODUCTION: This multicenter, randomized, noninferiority trial compared electroacupuncture with prucalopride for the treatment of severe chronic constipation (SCC). METHODS: Participants with SCC (≤ 2 mean weekly complete spontaneous bowel movements [CSBMs]) were randomly assigned to receive either 28-session electroacupuncture over 8 weeks with follow-up without treatment over 24 weeks or prucalopride (2 mg/d before breakfast) over 32 weeks. The primary outcome was the proportion of participants with ≥3 mean weekly CSBMs over weeks 3-8, based on the modified intention-to-treat population, with -10% as the noninferior margin. RESULTS: Five hundred sixty participants were randomized, 280 in each group. Electroacupuncture was noninferior to prucalopride for the primary outcome (36.2% vs 37.8%, with a difference of -1.6% [95% confidence interval, -8% to 4.7%], P < 0.001 for noninferiority); almost the same results were found in the per-protocol population. The proportions of overall CSBM responders through weeks 1-8 were similar in the electroacupuncture and prucalopride groups (24.91% vs 25.54%, with a difference of -0.63% [95% confidence interval, -7.86% to 6.60%, P = 0.864]). Except during the first 2-week treatment, no between-group differences were found in outcomes of excessive straining, stool consistency, and quality of life. Adverse events occurred in 49 (17.69%) participants in the electroacupuncture group and 123 (44.24%) in the prucalopride group. One non-treatment-related serious adverse event was recorded in the electroacupuncture group. DISCUSSION: Electroacupuncture was noninferior to prucalopride in relieving SCC with a good safety profile. The effects of 8-week electroacupuncture could sustain for 24 weeks after treatment. Electroacupuncture is a promising noninferior alternative for SCC (see Visual Abstract, http://links.lww.com/AJG/B776).

Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Randomized, Sham Acupuncture Controlled Trial.

PURPOSE: We investigated the effectiveness of acupuncture in patients with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: We performed this 32-week randomized, controlled trial with 8 weeks of treatment followed by 24 weeks of followup to compare acupuncture with sham acupuncture. Participants with chronic prostatitis/chronic pelvic pain syndrome were randomly assigned to acupuncture or noninvasive sham acupuncture. The primary outcome was the change in the NIH-CPSI (National Institutes of Health Chronic Prostatitis Symptom Index) total score from baseline to week 8. Secondary outcomes were the NIH-CPSI subscale scores, pain severity, the I-PSS (International Prostate Symptom Score), the global response rate and satisfaction assessment. RESULTS: A total of 68 participants 18 to 50 years old were enrolled and included in intent to treat analyses. Baseline characteristics were comparable in the 2 groups. The reduction in the NIH-CPSI total score differed significantly between the 2 groups at weeks 8, 20 and 32 with a difference of -5.7 (95% CI -7.8--3.7), -6.7 (95% CI -8.9--4.5) and -7.4 (95% CI -9.8--5.1), respectively (each p <0.001). All differences were greater than the 4-point minimal clinically important difference. No significant difference was found between the groups in NIH-CPSI pain and quality of life subscale scores or in I-PSS at week 4 (each p >0.05). For all other secondary outcomes the acupuncture group was statistically better than the sham acupuncture group. CONCLUSIONS: Acupuncture showed clinical and long-lasting benefits compared with sham acupuncture for chronic prostatitis/chronic pelvic pain syndrome. Randomized controlled trials with larger sample sizes are needed in the future.

Acupuncture for symptoms in menopause transition: a randomized controlled trial.

BACKGROUND: Acupuncture has been used for women during menopause transition, but evidence is limited. OBJECTIVE: We sought to evaluate the efficacy of electroacupuncture on relieving symptoms of women during menopause transition. STUDY DESIGN: We conducted a prospective, multicenter, randomized, participant-blinded trial in China mainland. Subjects were randomized to receive 24 treatment sessions of electroacupuncture at traditional acupoints or sham electroacupuncture at nonacupoints over 8 weeks with 24 weeks' follow-up. Primary outcome was the change from baseline in the total score of Menopause Rating Scale at week 8. Secondary outcomes included the changes from baseline in the average 24-hour hot flash score, the Menopause Rating Scale subscale scores, the total score of Menopause-Specific Quality of Life Questionnaire and its subscales, and serum female hormones. All analyses were performed with a 2-sided P value of < .05 considered significant based on the intention-to-treat principle. RESULTS: A total of 360 women (180 in each group) with menopause-related symptoms during menopause transition were enrolled from June 9, 2013, through Dec 28, 2015. At week 8, the reduction from baseline in the Menopause Rating Scale total score was 6.3 (95% confidence interval, 5.0-7.7) in the electroacupuncture group and 4.5 (95% confidence interval, 3.2-5.8) in the sham electroacupuncture group with a between-group difference of 1.8 (95% confidence interval, 0.9-2.8; P = .0002), less than the minimal clinically important difference of 5 points' reduction. For secondary outcomes, the between-group differences for the decrease in the mean 24-hour hot flash score were significant at weeks 8, 20, and 32, but all were less than the minimal clinically important difference in previous reports. Interestingly, the between-group differences for the Menopause-Specific Quality of Life Questionnaire total score reduction were 5.7 at week 8, 7.1 at week 20, and 8.4 at week 32, greater than the minimal clinically important difference of 4 points. Changes from baseline in follicle-stimulating hormone, luteinizing hormone, and estradiol levels at weeks 8 and 20 (P > .05 for all), with the exception of follicle-stimulating hormone/luteinizing hormone ratios (P = .0024 at week 8 and .0499 at week 20), did not differ between groups. CONCLUSION: Among women during menopause transition, 8 weeks' electroacupuncture treatment did not seem to relieve menopausal symptoms, even though it appeared to improve their quality of life. Generalizability of the trial results may be limited by mild baseline menopausal symptoms in the included participants.

Acupuncture for Chronic Severe Functional Constipation: A Randomized Trial.

BACKGROUND: Acupuncture has been used for chronic constipation, but evidence for its effectiveness remains scarce. OBJECTIVE: To determine the efficacy of electroacupuncture (EA) for chronic severe functional constipation (CSFC). DESIGN: Randomized, parallel, sham-controlled trial. (ClinicalTrials.gov: NCT01726504). SETTING: 15 hospitals in China. PARTICIPANTS: Patients with CSFC and no serious underlying pathologic cause for constipation. INTERVENTION: 28 sessions of EA at traditional acupoints or sham EA (SA) at nonacupoints over 8 weeks. MEASUREMENTS: The primary outcome was the change from baseline in mean weekly complete spontaneous bowel movements (CSBMs) during weeks 1 to 8. Participants were followed until week 20. RESULTS: 1075 patients (536 and 539 in the EA and SA groups, respectively) were enrolled. The increase from baseline in mean weekly CSBMs during weeks 1 to 8 was 1.76 (95% CI, 1.61 to 1.89) in the EA group and 0.87 (CI, 0.73 to 0.97) in the SA group (between-group difference, 0.90 [CI, 0.74 to 1.10]; P < 0.001). The change from baseline in mean weekly CSBMs during weeks 9 to 20 was 1.96 (CI, 1.78 to 2.11) in the EA group and 0.89 (CI, 0.69 to 0.95) in the SA group (between-group difference, 1.09 [CI, 0.94 to 1.31]; P < 0.001). The proportion of patients having 3 or more mean weekly CSBMs in the EA group was 31.3% and 37.7% over the treatment and follow-up periods, respectively, compared with 12.1% and 14.1% in the SA group (P < 0.001). Acupuncture-related adverse events during treatment were infrequent in both groups, and all were mild or transient. LIMITATIONS: Longer-term follow-up was not assessed. Acupuncturists could not be blinded. CONCLUSION: Eight weeks of EA increases CSBMs and is safe for the treatment of CSFC. Additional study is warranted to evaluate a longer-term treatment and follow-up. PRIMARY FUNDING SOURCE: Ministry of Science and Technology of the People's Republic of China through the Twelfth Five-Year National Science and Technology Pillar Program.

Effect of Electroacupuncture on Urinary Leakage Among Women With Stress Urinary Incontinence: A Randomized Clinical Trial.

Importance: Electroacupuncture involving the lumbosacral region may be effective for women with stress urinary incontinence (SUI), but evidence is limited. Objective: To assess the effect of electroacupuncture vs sham electroacupuncture for women with SUI. Design, Setting, and Participants: Multicenter, randomized clinical trial conducted at 12 hospitals in China and enrolling 504 women with SUI between October 2013 and May 2015, with data collection completed in December 2015. Interventions: Participants were randomly assigned (1:1) to receive 18 sessions (over 6 weeks) of electroacupuncture involving the lumbosacral region (n = 252) or sham electroacupuncture (n = 252) with no skin penetration on sham acupoints. Main Outcomes and Measures: The primary outcome was change from baseline to week 6 in the amount of urine leakage, measured by the 1-hour pad test. Secondary outcomes included mean 72-hour urinary incontinence episodes measured by a 72-hour bladder diary (72-hour incontinence episodes). Results: Among the 504 randomized participants (mean [SD] age, 55.3 [8.4] years), 482 completed the study. Mean urine leakage at baseline was 18.4 g for the electroacupuncture group and 19.1 g for the sham electroacupuncture group. Mean 72-hour incontinence episodes were 7.9 for the electroacupuncture group and 7.7 for the sham electroacupuncture group. At week 6, the electroacupuncture group had greater decrease in mean urine leakage (-9.9 g) than the sham electroacupuncture group (-2.6 g) with a mean difference of 7.4 g (95% CI, 4.8 to 10.0; P < .001). During some time periods, the change in the mean 72-hour incontinence episodes from baseline was greater with electroacupuncture than sham electroacupuncture with between-group differences of 1.0 episode in weeks 1 to 6 (95% CI, 0.2-1.7; P = .01), 2.0 episodes in weeks 15 to 18 (95% CI, 1.3-2.7; P < .001), and 2.1 episodes in weeks 27 to 30 (95% CI, 1.3-2.8; P < .001). The incidence of treatment-related adverse events was 1.6% in the electroacupuncture group and 2.0% in the sham electroacupuncture group, and all events were classified as mild. Conclusions and Relevance: Among women with stress urinary incontinence, treatment with electroacupuncture involving the lumbosacral region, compared with sham electroacupuncture, resulted in less urine leakage after 6 weeks. Further research is needed to understand long-term efficacy and the mechanism of action of this intervention. Trial Registration: clinicaltrials.gov Identifier: NCT01784172.

The wound healing trajectory and predictors with combined electric stimulation and conventional care: one outpatient wound care clinic's experience.

BACKGROUND: Electric stimulation (E-stim) has been found to be an effective treatment in improving wound healing rates. However, the wound healing trajectory and its related predictors for complete wound closure (CWC) have not been reported with E-stim treatment. MATERIALS AND METHODS: This was a retrospective study. Data on 159 patients treated at an outpatient wound clinic utilizing combined intervention of E-stim and conventional care were included. The Kaplan-Meier healing curve together with linear regression models depicted the percentage of patients with CWC against time. RESULTS: With 100, 112 and 140 days of treatment, the percentages of patients with CWC were 59·12%, 61·01% and 65·41%, respectively. Linear regression models predicted that all patients would achieve CWC by 21·55, 22·26 and 24·80 weeks, respectively. The speed for the increase in the number and percentage of patients with CWC peaked between 50-75 days of treatment. To optimize timely healing, referral to other treatment facilities or change of treatment protocol is warranted around the peak time. With the combined intervention of E-stim and conventional care, positive predictors for CWC included a shorter wound duration at initial evaluation (P = 0·005, OR = 3·10), better compliance with appointments (P = 0·007, OR = 3·38) and the diagnosis of venous leg ulcer (P = 0·001, OR = 3·88). CONCLUSIONS: This study provided preliminary data on wound healing trajectory and predictors with combined E-stim and conventional care. E-stim seemed to expedite wound healing; however, further research studies are needed.

Depressive symptoms in patients with wounds: A cross-sectional study.

Depression slows wound healing in patients with chronic wounds. The prevalence of depressive symptoms differs in the literature and the current understandings of factors related to depression in patients with wounds have been limited. To investigate the prevalence of depressive symptoms and the associated factors in patients with wounds, we performed this retrospective study in which depressive symptoms were evaluated with the Patient Health Questionnaire 9-item (PHQ-9). Valid PHQ-9 scores were collected from 222 patients (112 males and 110 females; age: 64.1 ± 15.8) out of 260 consecutive patients evaluated at an outpatient physical therapy wound clinic during 2012-2015. The proportion of patients with minimal to severe depressive symptoms was 81.5% [80.8% in patients with venous leg ulcers (VLUs) and 82.0% in non-VLUs]; 22.1% patients with wounds had scored positive for depression (moderate to severe depressive symptoms). Specific proportions of positive depression screening were 26.6% in patients with VLUs and 18.8% in non-VLU patients, and 14.1 and 40.0% in patients with wounds <90 and ≥ 90 days as of initial examination, respectively. PHQ-9 scores were significantly decreased from 5.85 ± 6.01 at initial examination to 3.42 ± 4.35 at last visit (p < 0.001). The odds of a positive depression screening was 3.20 (95% CI = [1.49, 6.87]) in patients with wounds ≥ 90 days (vs. < 90 days) and 2.53 (95% CI = [1.26, 5.08]) in patients with pain related to the wounds (vs. without pain), after patients' age, gender, and race were controlled for. No difference was found in proportions of positive depression screening between VLUs and other wound diagnoses. Depressive symptoms were common in patients with wounds, especially in patients with wounds ≥90 days and with pain related to the wounds at initial examination. Therefore, clinicians should take into consideration patients' mental status upon management of wounds.

Acupuncture is Effective for Chronic Knee Pain: A Reanalysis of the Australian Acupuncture Trial.

Context • In the October 2014 issue of the Journal of the American Medical Association (JAMA), Hinman et al published the results of an Australian clinical trial on acupuncture in a paper entitled "Acupuncture for Chronic Knee Pain: A Randomized Clinical Trial" (JAMA report), in which they concluded that neither acupuncture nor laser acupuncture had any greater effects than sham laser acupuncture for pain or function for patients aged 50 y and older with moderate-to-severe knee pain. That study has been criticized extensively by international scholars for its validity because serious methodological flaws existed throughout the study's design, implementation, and conclusions. Objective • The current study intended to re-examine the prior study's conclusions about the efficacy of acupuncture for chronic knee pain. Design • The current research team performed a reanalysis of relevant data from the JAMA report. Intervention • The original study included 4 groups: (1) an acupuncture group, which received needle acupuncture, inferred by the current authors to have been set up to be a positive control in the original study; (2) a laser acupuncture group, which received laser acupuncture; (3) a sham laser acupuncture group, which received sham laser acupuncture and acted as the negative controls for the laser acupuncture intervention; and (4) a control group, which received conventional care but no acupuncture or laser treatments. The study lasted 12 wk. Outcome Measures • The measures included evaluations in the following areas: (1) poststudy modifications-an evaluation of the consistency of the JAMA report with the study's intentions as identified for a grant that was originally approved and funded by the Australian National Health and Medical Research Council (NHMRC) in 2009, as indicated in the study's trial registration, and as compared with the published protocols and to the study's originally stated objectives; (2) high heterogeneity-an assessment of the heterogeneity among the 4 groups for the overall outcome related to pain; (3) ineffectiveness of laser acupuncture-an analysis of laser acupuncture's efficacy for chronic knee pain as stated in the JAMA report, using effect size (ES); (4) effectiveness of acupuncture-a reanalysis of acupuncture's efficacy for chronic knee pain in comparison with the original analysis in the JAMA report, using ES; and (5) acupuncture after data adjustment-a new analysis of acupuncture's efficacy for chronic knee pain using data from the original study that was discussed in the JAMA report, using ES, with an estimation after data adjustment and elimination of the dilution effect of the Zelen design. Results • Contrary to a general impression that acupuncture was the focus, laser acupuncture was the primary intervention tested in the actual study, "Laser Acupuncture in Patients With Chronic Knee Pain: A Randomized, Placebo Controlled Trial." The study discussed in the JAMA report was neither a truly randomized, controlled trial (RCT) for acupuncture nor was it an appropriately designed, randomized study in general. High heterogeneity was found among its groups in the evaluation of overall pain in patients. Both the ES of 0.60 that had been set by Hinman et al for the minimal clinically important difference (MCID) and the resulting interpretation of results in the JAMA report were not appropriate. Using the original study's criteria of efficacy, the reanalysis has confirmed that the laser acupuncture was not effective, whereas the acupuncture was found to be moderately effective for chronic knee pain (P < .05) for both overall pain and function at 12 wk, with an ES of 0.58, or after the adjustment of the data, with an ES of 0.67. Conclusions • The JAMA study was neither a conventional RCT nor an appropriately randomized trial, and its results are probably invalid. The ES of 0.60 for the MCID that was used in the JAMA study and the resulting explanation were not appropriate. Even with an ES of 0.60 for the MCID, acupuncture remained effective after data adjustment. Consequently, compared with conventional care, acupuncture treatment was found to be moderately effective for chronic knee pain in patients aged 50 y and older.

The reporting quality of randomized controlled trials in Chinese herbal medicine (CHM) formulas for diabetes based on the consort statement and its extension for CHM formulas.

Background: This study aimed to assess the overall reporting quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) formulas for patients with diabetes, and to identify factors associated with better reporting quality. Methods: Four databases including PubMed, Embase, Cochrane Library and Web of Science were systematically searched from their inception to December 2022. The reporting quality was assessed based on the Consolidated Standards of Reporting Trials (CONSORT) statement and its CHM formula extension. The overall CONSORT and its CHM formula extension scores were calculated and expressed as proportions separately. We also analyzed the pre-specified study characteristics and performed exploratory regressions to determine their associations with the reporting quality. Results: Seventy-two RCTs were included. Overall reporting quality (mean adherence) were 53.56% and 45.71% on the CONSORT statement and its CHM formula extension, respectively. The strongest associations with reporting quality based on the CONSORT statement were multiple centers and larger author numbers. Compliance with the CHM formula extension, particularly regarding the disclosure of the targeted traditional Chinese medicine (TCM) pattern (s), was generally insufficient. Conclusion: The reporting quality of RCTs in CHM formulas for diabetes remains unsatisfactory, and the adherence to the CHM formula extension is even poorer. In order to ensure transparent and standardized reporting of RCTs, it is essential to advocate for or even mandate adherence of the CONSORT statement and its CHM formula extension when reporting trials in CHM formulas for diabetes by both authors and editors.

Risk prediction models for mortality and readmission in patients with acute heart failure: A protocol for systematic review, critical appraisal, and meta-analysis.

INTRODUCTION: A considerable number of risk models, which predict outcomes in mortality and readmission rates, have been developed for patients with acute heart failure (AHF) to help stratify patients by risk level, improve decision making, and save medical resources. However, some models exist in a clinically useful manner such as risk scores or online calculators, while others are not, providing only limited information that prevents clinicians and patients from using them. The reported performance of some models varied greatly when predicting at multiple time points and being validated in different cohorts, which causes model users uncertainty about the predictive accuracy of these models. The foregoing leads to users facing difficulties in the selection of prediction models, and even sometimes being reluctant to utilize models. Therefore, a systematic review to assess the performance at multiple time points, applicability, and clinical impact of extant prediction models for mortality and readmission in AHF patients is essential. It may facilitate the selection of models for clinical implementation. METHOD AND ANALYSIS: Four databases will be searched from their inception onwards. Multivariable prognostic models for mortality and/or readmission in AHF patients will be eligible for review. Characteristics and the clinical impact of included models will be summarized qualitatively and quantitatively, and models with clinical utility will be compared with those without. Predictive performance measures of included models with an analogous clinical outcome appraised repeatedly, will be compared and synthesized by a meta-analysis. Meta-analysis of validation studies for a common prediction model at the same time point will also be performed. We will also provide an overview of critical appraisal of the risk of bias, applicability, and reporting transparency of included studies using the PROBAST tool and TRIPOD statement. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42021256416.

Effects of Electroacupuncture for Opioid-Induced Constipation in Patients With Cancer in China: A Randomized Clinical Trial.

Importance: Opioid-induced constipation (OIC) is prevalent among patients treated with opioids for cancer pain. Safe and effective therapies for OIC in patients with cancer remain an unmet need. Objective: To determine the efficacy of electroacupuncture (EA) for OIC in patients with cancer. Design, Setting, and Participants: This randomized clinical trial was conducted at 6 tertiary hospitals in China among 100 adult patients with cancer who were screened for OIC and enrolled between May 1, 2019, and December 11, 2021. Interventions: Patients were randomized to receive 24 sessions of EA or sham electroacupuncture (SA) over 8 weeks and then were followed up for 8 weeks after treatment. Main Outcomes and Measures: The primary outcome was the proportion of overall responders, defined as patients who had at least 3 spontaneous bowel movements (SBMs) per week and an increase of at least 1 SBM from baseline in the same week for at least 6 of the 8 weeks of the treatment period. All statistical analyses were based on the intention-to-treat principle. Results: A total of 100 patients (mean [SD] age, 64.4 [10.5] years; 56 men [56.0%]) underwent randomization; 50 were randomly assigned to each group. Among them, 44 of 50 patients (88.0%) in the EA group and 42 of 50 patients (84.0%) in the SA group received at least 20 (≥83.3%) sessions of treatment. The proportion of overall responders at week 8 was 40.1% (95% CI, 26.1%-54.1%) in the EA group and 9.0% (95% CI, 0.5%-17.4%) in the SA group (difference between groups, 31.1 percentage points [95% CI, 14.8-47.6 percentage points]; P < .001). Compared with SA, EA provided greater relief for most OIC symptoms and improved quality of life among patients with OIC. Electroacupuncture had no effects on cancer pain and its opioid treatment dosage. Electroacupuncture-related adverse events were rare, and, if any, all were mild and transient. Conclusions and Relevance: This randomized clinical trial found that 8-week EA treatment could increase weekly SBMs with a good safety profile and improve quality of life for the treatment of OIC. Electroacupuncture thus provided an alternative option for OIC in adult patients with cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03797586.

The Limbic-Prefrontal Network Modulated by Electroacupuncture at CV4 and CV12.

fMRI studies showed that acupuncture could induce hemodynamic changes in brain networks. Many of these studies focused on whether specific acupoints could activate specific brain regions and were often limited to manual acupuncture at acupoints on the limbs. In this fMRI study, we investigated acupuncture's modulation effects on brain functional networks by electroacupuncture (EA) at acupoints on the midline of abdomen. Acupoints Guanyuan (CV4) and Zhongwan (CV12) were stimulated in 21 healthy volunteers. The needling sensations, brain activation, and functional connectivity were studied. We found that the limbic-prefrontal functional network was deactivated by EA at CV4 and CV12. More importantly, the local functional connectivity was significantly changed during EA stimulation, and the change persisted during the period after the stimulation. Although minor differences existed, both acupoints similarly modulated the limbic-prefrontal functional network, which is overlapped with the functional circuits associated with emotional and cognitive regulation.

Efficacy and safety of lumbrokinase plus aspirin versus aspirin alone for acute ischemic stroke (LUCENT): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Lumbrokinase has been widely used for patients with acute ischemic stroke (AIS) in China; however, because rigorously designed studies are lacking, safety and efficacy of lumbrokinase in the treatment of acute ischemic stroke remains largely unknown. In this multicenter, randomized, and controlled trial, we aim to compare lumbrokinase plus aspirin versus aspirin alone in patients with acute ischemic stroke. METHODS: A total of 220 eligible participants will be randomized to either the intervention or control group with a 1:1 ratio. These participants must be diagnosed with acute ischemic stroke for the first time, whose symptoms appear within 72 h. Their NIHSS score must be greater than 5 and less than 15, and their age must be between 35 and 85 years old. They must have not received intravenous thrombolysis, arterial thrombolysis, or intravascular intervention. Participants in the intervention group will be treated with lumbrokinase plus aspirin for the first 90 days. Participants in the control group will use placebo plus aspirin for the first 90 days. Then, all participants will be treated with aspirin only and followed up for another 90 days (180-day follow-up). The primary outcome is the modified Rankin Scale (mRS) score. The secondary outcomes are National Institutes of Health Stroke Scale (NIHSS) score, Activity of Daily Living (ADL) Scale score, coagulation function, and serum hypersensitive C-reactive protein. The exploratory outcomes are fasting lipid panel, recurrence rate, the occurrence of cardiovascular and cerebrovascular events, and the mortality rate. Safety evaluations include liver function and kidney function, serum fibrinogen, adverse events, serious adverse events, and bleeding events. Adherence of participants will also be assessed. DISCUSSION: This trial will investigate the efficacy and safety of lumbrokinase plus aspirin as compared to aspirin alone in the treatment of acute ischemic stroke. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000032952 . Registered on May 16, 2020.

[A genetic and clinical study in a family with familial hypercholesterolemia].

OBJECTIVE: To investigate the low density lipoprotein receptor (LDLR) gene and apolipoprotein (Apo) B gene mutation in a Chinese family with familial hypercholesterolemia (FH) and give the kindreds clinical check-ups. METHODS: After physical examination, the kindreds underwent ECG and ultrasound checks. Blood samples were tested for lipid profiles. The promoter and all eighteen exons of LDLR gene were investigated by using PCR and agarose gel electrophoresis in combination with DNA sequence analysis. The results were compared with the normal sequences in GenBank and FH database (www.ucl.ac.uk/fh) to find mutations. In addition, the apolipoprotein B100 gene for known mutations (R3500Q, R3531C, R3501W and R3480W) that cause familial defective ApoB100 (FDB) was also tested using the same method. RESULTS: A novel homozygous G > A mutation at the 1581 bp of exon 10 was detected in the proband and his siblings. It caused a substitution of amino acid Glu to Gly at codon 496. A novel heterozygous G > A mutation at the 1581 bp of exon 10 was detected in his parents. No mutations of R3500Q, R3531C, R3501W and R3480W of ApoB100 were observed. ECGs were normal. Atherosclerosis were found in all family members by ultrasound checks. CONCLUSIONS: The homozygous G > A mutation at the 1581 bp of exon 10 was first determined in our country. The change of amino acid Glu to Gly is responsible for FH of the family. The type of the gene mutation was not found in the FH database (www. ucl.ac.uk/fh). It's a new type of LDLR mutation.

Dyspnea Measurement in Acute Heart Failure: A Systematic Review and Evidence Map of Randomized Controlled Trials.

Background: Dyspnea is the most common presenting symptom among patients hospitalized for acute heart failure (AHF). Dyspnea relief constitutes a clinically relevant therapeutic target and endpoint for clinical trials and regulatory approval. However, there have been no widely accepted dyspnea measurement standards in AHF. By systematic review and mapping the current evidence of the applied scales, timing, and results of measurement, we hope to provide some new insights and recommendations for dyspnea measurement. Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception until August 27, 2020. Randomized controlled trials (RCTs) with dyspnea severity measured as the endpoint in patients with AHF were included. Results: Out of a total of 63 studies, 28 had dyspnea as the primary endpoint. The Likert scale (34, 54%) and visual analog scale (VAS) (22, 35%) were most widely used for dyspnea assessment. Among the 43 studies with detailed results, dyspnea was assessed most frequently on days 1, 2, 3, and 6 h after randomization or drug administration. Compared with control groups, better dyspnea relief was observed in the experimental groups in 21 studies. Only four studies that assessed tolvaptan compared with control on the proportion of dyspnea improvement met the criteria for meta-analyses, which did not indicate beneficial effect of dyspnea improvement on day 1 (RR: 1.16; 95% CI: 0.99-1.37; p = 0.07; I 2 = 61%). Conclusion: The applied scales, analytical approaches, and timing of measurement are in diversity, which has impeded the comprehensive evaluation of clinical efficacy of potential therapies managing dyspnea in patients with AHF. Developing a more general measurement tool established on the unified unidimensional scales, standardized operation protocol to record the continuation, and clinically significant difference of dyspnea variation may be a promising approach. In addition, to evaluate the effect of experimental therapies on dyspnea more precisely, the screening time and blinded assessment are factors that need to be considered.

BRAF/MEK Pathway is Associated With Breast Cancer in ER-dependent Mode and Improves ER Status-based Cancer Recurrence Prediction.

BACKGROUND: Aberrant BRAF/MEK signaling was found in nearly 50% of human malignancies and proved to play a critical role in the tumorigenesis of multiple cancers. However, this pathway was relatively seldom studied in breast cancer, and the role of this pathway in the pathogenesis of breast cancer is still controversial. MATERIALS AND METHODS: Breast cancer gene expression data from The Cancer Genome Atlas (TCGA) and 43 Affymetrix microarray datasets were analyzed. The BRAF/MEK pathway activity was presented with phosphorylated ERK level (for the TCGA dataset) or computed by a gene signature-based algorithm (for Affymetrix datasets). Aberrant activation of BRAF/MEK pathway in breast cancer was assessed in matched normal/tumor tissues. The associations of the BRAF/MEK pathway with clinical outcome in patients with breast cancer were analyzed by logistic regression, Cox regression, and Kaplan-Meier methods. RESULTS: Down-regulation of the BRAF/MEK pathway was observed in atypical ductal hyperplasia, ductal carcinoma in situ, and invasive breast cancers, with the exception of human epidermal growth factor receptor 2-positive and triple-negative breast cancers. Higher BRAF/MEK pathway activities were associated with better survival in estrogen receptor (ER)-positive (overall hazard ratio [HR], 0.85; P = 5.47E-5; n = 3128) or progesterone receptor-positive (overall HR, 0.85; P = 4.19E-3; n = 1537) breast cancers, but with worse survival in ER-negative (overall HR, 1.13; P = .01; n = 1107) or progesterone receptor-negative (overall HR, 1.13; P = .01; n = 1219) breast cancers. Combination with BRAF/MEK pathway activities could improve ER status-based recurrence prediction for breast cancer. CONCLUSION: BRAF/MEK pathway was associated with the recurrence risk of breast cancer in an ER status-dependent mode. Combination with BRAF/MEK pathway activities could improve the ER status-based recurrence prediction in breast cancer.

Outcomes and Characteristics of Wound Healing in an Outpatient Physical Therapy Clinic.

INTRODUCTION: Detailed understandings regarding the outcomes and characteristics of healing in wounds of different etiologies are lacking. OBJECTIVE: In the present study, data on 265 patients treated at an outpatient physical therapy wound care clinic were extracted. METHODS: Using Kaplan-Meier analyses, wound healing outcomes for different wound etiologies were evaluated and compared. RESULTS: The results revealed venous leg ulcers (VLUs) healed faster than non-VLUs, pressure ulcers (PUs), diabetic foot ulcers (DFUs), and arterial wounds but not faster than surgical and traumatic wounds (STWs). The estimated medians (mean for arterial wounds) of total treatment durations for complete wound closure were 87, 152, 100, 170, 525.44, 773 days in VLUs, non-VLUs, STWs, DFUs, arterial wounds, and PUs, respectively. Compared with patients with VLUs, patients with non-VLUs were younger (69.72 vs. 61.35, respectively), had a higher proportion of men (odds ratio [OR] = 2.26), were less likely to have more than 1 wound (OR = 0.25), reached complete wound closure upon discharge (OR = 0.41), or had a body mass index value greater than or equal to 25 (OR = 0.39). CONCLUSIONS: Venous leg ulcers and other wound etiologies (ie, STWs, PUs, DFUs, and arterial wounds) appear to differ in wound healing outcomes and certain characteristics. These results may be of interest to clinicians, patients, health care policy makers, and insurers. Future research is warranted to compare wound healing outcomes and patient characteristics among different settings.

SARS-CoV-2 and Anti-Cardiolipin Antibodies.

The current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to distinct diagnostic and management challenges for front-line healthcare workers. The risk of excessive coagulation activation leading to a cascade of thrombotic events in critically ill patients with SARS-CoV-2 is now well reported. We discuss a recent case of COVID-19 with concurrent acute pulmonary embolism and a positive cardiolipin antibody (IgM). The presence of antiphospholipid antibodies is key to diagnosing antiphospholipid syndrome (APS). However, their presence can be transient or persistent after viral infections. Serial inflammatory markers in conjunction with anti-phospholipid antibody testing is critical for the diagnosis of APS in this emerging patient population. Our case report reviews details suggestive of APS in the setting of SARS-CoV-2 and aims to provide clinical diagnostic clues that could help warrant further workup and assist with management strategies.