肾移植术后隐球菌性脑膜炎的临床分析

目的 分析肾移植术后隐球菌性脑膜炎的临床特点,以期提高临床医生的诊治水平.方法 回顾性分析肾移植术后隐球菌性脑膜炎的临床表现、实验室检查和治疗预后.结果 4例患者中,男2例,女2例,全部为首次同种异体肾移植.所有患者均有发热和头痛症状,多表现为轻度头痛和低热.3例患者隐球菌涂片和培养均为阳性.所有患者分别给予两性霉素B脂质体、伏立康唑、5-氟胞嘧啶等抗真菌治疗,其中1例合并两性霉素B鞘内注射.经2～4个月治疗后,4例隐球菌涂片转阴,临床症状消失,均在我院随访,至今未复发.结论 肾移植术后隐球菌性脑膜炎首发症状隐匿,临床表现不典型,极易误诊漏诊.早期明确诊断、多科室协作、规范足量治疗是提高此病救治成功的关键.     

Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials

Background

Significant pain from HIV-associated sensory neuropathy (HIV-SN) affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART). The prevalence of HIV-SN has increased despite the more widespread use of ART. With the global HIV prevalence estimated at 33 million, and with infected individuals gaining increased access to ART, painful HIV-SN represents a large and expanding world health problem. There is an urgent need to develop effective pain management strategies for this condition.

Method and Findings

Objective: To evaluate the clinical effectiveness of analgesics in treating painful HIV-SN. Design: Systematic review and meta-analysis. Data sources: Medline, Cochrane central register of controlled trials, www.clinicaltrials.gov, www.controlled-trials.com and the reference lists of retrieved articles. Selection criteria: Prospective, double-blinded, randomised controlled trials (RCTs) investigating the pharmacological treatment of painful HIV-SN with sufficient quality assessed using a modified Jadad scoring method. Review methods: Four authors assessed the eligibility of articles for inclusion. Agreement of inclusion was reached by consensus and arbitration. Two authors conducted data extraction and analysis. Dichotomous outcome measures (≥30% and ≥50% pain reduction) were sought from RCTs reporting interventions with statistically significant efficacies greater than placebo. These data were used to calculate RR and NNT values.

Results

Of 44 studies identified, 19 were RCTs. Of these, 14 fulfilled the inclusion criteria. Interventions demonstrating greater efficacy than placebo were smoked cannabis NNT 3.38 95%CI(1.38 to 4.10), topical capsaicin 8%, and recombinant human nerve growth factor (rhNGF). No superiority over placebo was reported in RCTs that examined amitriptyline (100mg/day), gabapentin (2.4g/day), pregabalin (1200mg/day), prosaptide (16mg/day), peptide-T (6mg/day), acetyl-L-carnitine (1g/day), mexilitine (600mg/day), lamotrigine (600mg/day) and topical capsaicin (0.075% q.d.s.).

Conclusions

Evidence of efficacy exists only for capsaicin 8%, smoked cannabis and rhNGF. However,rhNGF is clinically unavailable and smoked cannabis cannot be recommended as routine therapy. Evaluation of novel management strategies for painful HIV-SN is urgently needed.     

Current clinical trials with non-coding RNA-based therapeutics in malignant diseases: A systematic review

This systematic review aimed to shed light on the trend of current clinical trials of non-coding RNA (ncRNA)-based therapeutics for malignant diseases. We conducted a database search for published literature and ongoing clinical trials using PubMed, clinicaltrials.gov, and University Medical Information Network (UMIN) clinical trial registry. To ensure that our review was based on up-to-date clinical trials, we limited our search to literature published within the last five years (January 2017–September 2022). Furthermore, due to the “clinical” nature of our review, we focused only on studies involving human participants. Among ncRNAs, microRNAs have been extensively explored in observational studies of malignant diseases as potential diagnostic markers and prognostic predictors, as well as for their therapeutic monitoring and profiling capabilities. As therapeutic agents, microRNA or siRNA were estimated in interventional human clinical trials and showed promising outcomes; however, the number of trials was small. Evidence and ongoing clinical trials in which ncRNAs other than microRNA or siRNA have been evaluated for their potential as therapeutic agents are limited. Here, we summarized microRNA as a potential therapeutic agent in malignant diseases, but most of the current evidence suggests that it is useful as a potential biomarker. siRNA is also a promising ncRNA technique in cancer, however more data from clinical trials are warranted for clinical use.     

Physiotherapy for patients with soft tissue shoulder disorders: a systematic review of randomised clinical trials.

OBJECTIVE: To assess the effectiveness of physiotherapy for patients with soft tissue shoulder disorders. DESIGN: A systematic computerised literature search of Medline and Embase, supplemented with citation tracking, for relevant trials with random allocation published before 1996. SUBJECTS: Patients treated with physiotherapy for disorders of soft tissue of the shoulder. MAIN OUTCOME MEASURES: Success rates, mobility, pain, functional status. RESULTS: Six of the 20 assessed trials satisfied at least five of eight validity criteria. Assessment of methods was often hampered by insufficient information on various validity criteria, and trials were often flawed by lack of blinding, high proportions of withdrawals from treatment, and high proportions of missing values. Trial sizes were small: only six trials included intervention groups of more than 25 patients. Ultrasound therapy, evaluated in six trials, was not shown to be effective. Four other trials favoured physiotherapy (laser therapy or manipulation), but the validity of their methods was unsatisfactory. CONCLUSIONS: There is evidence that ultrasound therapy is ineffective in the treatment of soft tissue shoulder disorders. Due to small trial sizes and unsatisfactory methods, evidence for the effectiveness of other methods of physiotherapy is inconclusive. For all methods of treatment, trials were too heterogeneous with respect to included patients, index and reference treatments, and follow up to merit valid statistical pooling. Future studies should show whether physiotherapy is superior to treatment with drugs, steroid injections, or a wait and see policy.     

A systematic review of randomised clinical trials of Tripterygium wilfordii for rheumatoid arthritis.

Tripterygium wilfordii is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis (RA). We have carried out a systematic review of randomised clinical trials (RCTs) which assess the effectiveness of T. wilfordii in this indication. We included only randomised and controlled studies which tested the effectiveness of T. wilfordii monopreparations in the treatment of RA. Studies in any language were included. A search of five electronic databases from inception to February 2005 identified 18 articles which could potentially meet our inclusion criteria. Only 16 of these could be retrieved from the scientific literature and after reading these in full, only two unique RCTs meeting our inclusion criteria were identified. Both indicated that T. wilfordii has beneficial effects on the symptoms of RA. However, the literature indicates that T. wilfordii is associated with serious adverse events which make the risk-benefit analysis for this herb unfavourable. Therefore, we cannot recommend its use.     

Efficacy and safety of telavancin in clinical trials: a systematic review and meta-analysis

Introduction

The epidemiology and antibiotic resistance of Staphylococcus aureus have evolved, underscoring the need for novel antibiotics, particularly against methicillin-resistant S. aureus (MRSA). Telavancin is a bactericidal lipoglycopeptide with potent activity against Gram-positive pathogens.

Objective

To systematically review and synthesize the available evidence from randomized controlled trials (RCTs) evaluating telavancin in the treatment of patients with infections due to Gram-positive organisms with the methodology of meta-analysis.

Results

Six RCTs comparing telavancin with vancomycin were included; 4 (2229 patients) referred to complicated skin and soft tissue infections (cSSTIs) and 2 (1503 patients) to hospital-acquired pneumonia (HAP). Regarding cSSTIs, telavancin and vancomycin showed comparable efficacy in clinically evaluable patients (odds ratio [OR] = 1.10 [95% confidence intervals: 0.82–1.48]). Among patients with MRSA infection, telavancin showed higher eradication rates (OR = 1.71 [1.08–2.70]) and a trend towards better clinical response (OR = 1.55 [0.93–2.58]). Regarding HAP, telavancin was non-inferior to vancomycin in terms of clinical response in two Phase III RCTs; mortality rates for the pooled trials were comparable with telavancin (20%) and vancomycin (18.6%). Pooled data from cSSTIs and HAP studies on telavancin 10 mg/kg indicated higher rates of serum creatinine increases (OR = 2.22 [1.38–3.57]), serious adverse events (OR = 1.53 [1.05–2.24]), and adverse event-related withdrawals (OR = 1.49 [1.14–1.95]) among telavancin recipients.

Conclusion

Telavancin might be an alternative to vancomycin in cases of difficult-to-treat MRSA infections. The potent antistaphylococcal activity of telavancin should be weighted against the potential for nephrotoxicity.     

伊曲康唑治疗隐球菌性脑膜炎1例报告并文献复习

隐球菌性脑膜炎是一种严重危害人类健康的疾病,致死率和病残率均较高。伊曲康唑是三唑类广谱抗真菌药物,体外药敏试验显示其具有良好的抗隐球菌活性。但由于伊曲康唑难以通过血脑屏障,在脑脊液中的浓度较低,     

Garlic for hypertension: A systematic review and meta-analysis of randomized controlled trials

BackgroundIn the past decade, garlic has become one of the most popular complementary therapies for blood pressure (BP) control used by hypertensive patients. Numerous clinical studies have focused on the BP-lowering effect of garlic, but results have been inconsistent. Overall, there is a dearth of information available to guide the clinical community on the efficacy of garlic in hypertensive patients.AimTo systematically review the medical literature to investigate the current evidence of garlic for the treatment of hypertension.MethodsPubMed, the Cochrane Library and EMBASE were searched for appropriate articles from their respective inceptions until August 2014. Randomized, placebo-controlled trials comparing garlic vs. a placebo in patients with hypertension were considered. Papers were independently reviewed by two reviewers and were analyzed using Cochrane software Revman 5.2.ResultsA total of seven randomized, placebo-controlled trials were identified. Compared with the placebo, this meta-analysis revealed a significant lowering effect of garlic on both systolic BP (WMD: −6.71 mmHg; 95% CI: −12.44 to −0.99; P = 0.02) and diastolic BP (WMD: −4.79 mmHg; 95% CI: −6.60 to −2.99; P < 0.00001). No serious adverse events were reported in any of the trials.ConclusionThe present review suggests that garlic is an effective and safe approach for hypertension. However, more rigorously designed randomized controlled trials focusing on primary endpoints with long-term follow-up are still warranted before garlic can be recommended to treat hypertensive patients.     

艾滋病合并隐球菌性脑膜炎的治疗原则初探

随着艾滋病（AIDS）疫情的蔓延,患者人数日益增多,隐球菌性脑膜炎的发生率明显上升,尤其是在东南亚、南部和东部非洲。有研究显示,即使在发达国家AIDS合并隐球菌性脑膜炎的病死率也约为10％～25％,在资源有限地区该比例可高达43％。上海市（复旦大学附属）公共卫生临床中心2004～2006年收治住院的艾滋患者中,11．7％（10／85）患有隐球菌性脑膜炎;37．5％（3／8）死亡病例死于隐球菌性脑膜炎。     

腰椎置管治疗隐球菌性脑膜炎4例并文献复习

目的 观察早期腰椎置管引流加鞘内注射两性霉素B治疗伴有恶性高颅压隐球菌性脑膜炎的临床效果及探讨临床应用的可行性.方法 详细分析和归纳整理了我科应用腰椎置管法治疗的4例隐球菌性脑膜炎患者的临床资料.结果 4例患者经早期腰椎置管引流加鞘内注射两性霉素B治疗后临床症状迅速改善.经联合治疗后,痊愈3例,好转1例,4例患者随访至今均无复发.结论 早期腰椎置管引流加鞘内注射两性霉素B治疗隐球菌性脑膜炎能有效的降低隐球菌脑膜炎患者的高颅压,改善临床症状,提高疗效.     

Information giving in clinical trials: the views of medical researchers

It is both an ethical and a legal requirement that patients who participate in clinical trials must generally give their consent. As part of this process, patients must be provided with adequate information to enable them to decide whether or not to take part. In the UK, the pharmaceutical companies that sponsor such research, as well as Local Research Ethics Committees, specify in detail the information that must be given to trial participants. The researchers who conduct clinical trials inevitably form views on the amount of information they are required to provide, and about patients' comprehension of that information. The literature in this area suggests that some medical researchers may be unhappy with the amount of information that they must give patient participants. There have been, however, few systematic attempts to determine their views. This paper reports a study that explored researchers' views as to (i) the amount of information provided to trial participants, and (ii) participants' understanding of that information. Researchers generally felt that they were required to give trial participants an appropriate amount of information, and that most patients had at least a reasonable understanding of key aspects of the clinical trials' process. However, there were differing views as to the level of information that they felt patients themselves wanted. The researchers did not generally feel that the patients' inability to comprehend information rendered the process of obtaining 'informed consent' a waste of time. However, some did believe that they were required to burden patients with excessive information.     

Acupuncture for functional recovery after stroke: a systematic review of sham-controlled randomized clinical trials

Background

Acupuncture is frequently advocated as an adjunct treatment during stroke rehabilitation. The aim of this review was to assess its effectiveness in this setting.

Methods

We searched 25 databases and 12 major Korean traditional medicine journals from their inception to October 2009. We included randomized controlled trials, with no language restrictions, that compared the effects of acupuncture (with or without electrical stimulation) with sham acupuncture. We assessed the methodologic quality of the trials using the Cochrane risk-of-bias criteria and the PEDro (Physiotherapy Evidence Database) scale.

Results

Ten of 664 potentially relevant studies met our inclusion criteria. For acute and subacute stages after stroke, we included seven trials. A meta-analysis of the five studies that assessed functionality did not show a significant difference in favour of acupuncture, with high heterogeneity. A post-hoc sensitivity analysis of three trials with low risk of bias did not show beneficial effects of acupuncture on activities of daily living at the end of the intervention period (n = 244; standard mean difference 0.07, 95% confidence interval [CI] −0.18 to 0.32; I² = 0%) or after follow-up (n = 244; standard mean difference 0.10, 95% CI −0.15 to 0.35; I² = 0%). For the chronic stage after stroke, three trials tested effects of acupuncture on function according to the Modified Ashworth Scale; all failed to show favourable effects.

Interpretation

Our meta-analyses of data from rigorous randomized sham-controlled trials did not show a positive effect of acupuncture as a treatment for functional recovery after stroke.Acupuncture is often used as an adjunct to mainstream rehabilitation after stroke. It involves the insertion of an acupuncture needle into the skin at certain points of the body. Acupuncture is claimed to be effective for a wide range of conditions, such as pain, musculoskeletal disorders and several neurologic diseases.¹ Possible mechanisms of its effects on neurologic conditions include stimulation of neuronal cell proliferation,² facilitation of neural plasticity,³ reduction of the post-ischemic inflammatory reaction⁴ and prevention of neuronal apoptosis.⁵Before acupuncture can be recommended for routine use, we require evidence from rigorous randomized clinical trials. In acupuncture trials, it is difficult to allow blinding of the treatment allocation.⁶ A placebo must be indistinguishable from the real treatment and inert.⁶ “Sham” is used to describe any control procedure that is used to blind treatment allocation in clinical trials of acupuncture.⁶ Several sham procedures are now available, such as the use of penetrating acupuncture on nonacupuncture points, superficial puncture of the skin on acupuncture points and nonpenetration on acupuncture points with sham needle devices.⁶Several reviews assessing the effects of acupuncture for stroke have been published. However, some did not include all of the relevant articles published in Asian countries; others included interventions other than acupuncture; and several were not systematic. We conducted a systematic review to critically evaluate all of the currently available randomized sham-controlled trials of acupuncture as an adjunct to mainstream stroke rehabilitation.     

Herbal remedies for anxiety - a systematic review of controlled clinical trials.

Anxiety is a prominent indication for herbal medicine. This systematic review was therefore aimed at summarising the evidence for or against the anxiolytic efficacy of such treatments. Six databases were searched for all randomised clinical trials testing herbal monopreparations in the alleviation of anxiety. Seven such studies and one systematic review were located. Eight different herbals were studied. The herbal medicines, which, according to these data are associated with anxiolytic activity in humans, are Piper methysticum and Bacopa monniera. Only for kava were independent replications available. It was concluded that there is a lack of rigorous studies in this area and that only kava has been shown beyond reasonable doubt to have anxiolytic effects in humans.     

Effect of statin therapy on paraoxonase-1 status: A systematic review and meta-analysis of 25 clinical trials

BackgroundDecreased activity of the enzyme paraoxonase-1 (PON1) has been demonstrated in cardiovascular diseases. Statins, the forefront of pharmacotherapy for dyslipidemia, have been shown to enhance PON1 activity but clinical findings have not been conclusive.ObjectiveTo systematically review the clinical findings on the impact of statin therapy on PON1 status (protein concentrations and activities of paraoxonase and arylesterase) and calculate an effect size for the mentioned effects through meta-analysis of available data.MethodsScopus and Medline databases were searched to identify clinical trials. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential confounders on the estimated effect sizes.ResultsMeta-analysis suggested that statin therapy is associated with a significant elevation of PON1 paraoxonase and arylesterase activities, but not PON1 protein concentration. The PON1-enhancing effects of statins were robust in the sensitivity analyses and were independent of statin dose, treatment duration and changes in plasma low-density lipoprotein cholesterol concentration.ConclusionThe increase of paraoxonase and arylesterase activities with statins is a pleiotropic lipid-independent clinical benefit that may partly explain the putative effects of statins in preventing cardiovascular outcomes.     

Human albumin administration in critically ill patients: systematic review of randomised controlled trials

Objective: To quantify effect on mortality of administering human albumin or plasma protein fraction during management of critically ill patients. Design: Systematic review of randomised controlled trials comparing administration of albumin or plasma protein fraction with no administration or with administration of crystalloid solution in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia. Subjects: 30 randomised controlled trials including 1419 randomised patients. Main outcome measure: Mortality from all causes at end of follow up for each trial. Results: For each patient category the risk of death in the albumin treated group was higher than in the comparison group. For hypovolaemia the relative risk of death after albumin administration was 1.46 (95% confidence interval 0.97 to 2.22), for burns the relative risk was 2.40 (1.11 to 5.19), and for hypoalbuminaemia it was 1.69 (1.07 to 2.67). Pooled relative risk of death with albumin administration was 1.68 (1.26 to 2.23). Pooled difference in the risk of death with albumin was 6% (95% confidence interval 3% to 9%) with a fixed effects model. These data suggest that for every 17 critically ill patients treated with albumin there is one additional death. Conclusions: There is no evidence that albumin administration reduces mortality in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia and a strong suggestion that it may increase mortality. These data suggest that use of human albumin in critically ill patients should be urgently reviewed and that it should not be used outside the context of rigorously conducted, randomised controlled trials.

Key messages

• Human albumin solution has been used in the treatment of critically ill patients for over 50 years
• Currently, the licensed indications for use of albumin are emergency treatment of shock, acute management of burns, and clinical situations associated with hypoproteinaemia
• Our systematic review of randomised controlled trials showed that, for each of these patient categories, the risk of death in the albumin treated group was higher than in the comparison group
• The pooled relative risk of death with albumin was 1.68 (95% confidence interval 1.26 to 2.23) and the pooled difference in the risk of death was 6% (3% to 9%) or six additional deaths for every 100 patients treated
• We consider that use of human albumin solution in critically ill patients should be urgently reviewed

     

The effectiveness and efficacy of Rhodiola rosea L.: A systematic review of randomized clinical trials

Objective

To critically assess the current evidence from randomized clinical trials (RCTs) for or against the effectiveness or efficacy of Rhodiola rosea.

Data sources

Systematic literature searches were performed in six electronic databases: AMED (1985-July 2009), CINAHL (1982-July 2009), The Cochrane Library (search in July 2009), EMBASE (1974-July 2009), MEDLINE (1950-July 2009) and Web of Science (searched in July 2009). No language restrictions were imposed. Reference lists of all retrieved articles were searched, and experts and manufacturers were contacted for unpublished RCT.

Review methods

RCTs testing the efficacy or effectiveness of mono-preparations of R. rosea as sole treatment administered orally against a control intervention in any human individual suffering from any condition or healthy human volunteers were included. Studies were selected, data extracted, and quality assessed by two independent reviewers.

Results

Eleven RCTs met the inclusion criteria; all were placebo-controlled. Six trials investigated the effects of R. rosea on physical performance, four on mental performance, and two in patients diagnosed with mental health condition. The methodological quality of most trials was moderate or good. Only few mild adverse events were reported.

Conclusion

R. rosea may have beneficial effects on physical performance, mental performance, and certain mental health conditions. There is, however, a lack of independent replications of the single different studies. Five of the 10 RCTs reached more than three points on the Jadad score (i.e., good quality). More research seems warranted.