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Actas Urologicas Espanolas Oct 2016Clinical practice guidelines recommend measuring serum testosterone (ST) during androgenic suppression (AS) to assess its efficacy and define castration resistance (CR).... (Review)
Review
INTRODUCTION
Clinical practice guidelines recommend measuring serum testosterone (ST) during androgenic suppression (AS) to assess its efficacy and define castration resistance (CR). The objectives of this systematic review were to assess the level of scientific evidence that justify checking ST levels during AS, when to perform it and for what purpose.
MATERIAL AND METHODS
We performed a search in PubMed with the following mesh terms: androgen suppression, testosterone, and prostate cancer. The search was narrowed to original articles published in English.
RESULTS
We found 8 publications that analysed the clinical impact of ST concentrations during AS. In all of the series, ST was measured using chemiluminescent assays. However, only indirect methods based on liquid or gas chromatography for its extraction and subsequent quantification using mass spectrometry are recommended, especially for measuring low levels. The endpoints were specific survival and CR-free survival. Six studies were retrospective. The series were not uniform in terms of clinical stage, types of AS and ST assessment methods. In general, low ST levels (<20ng/dL or <32ng/dL) were related to longer CR-free survival. The measurements were performed every 3 or 6 months. Four studies confirmed the beneficial effect of adding bicalutamide when detecting microelevations above 50ng/dL.
CONCLUSIONS
The level of scientific evidence justifying the measurement of ST during AS is low, and the methods employed for quantifying ST levels are inadequate. However, we consider it useful to check ST levels during AS, and there appears to be an association between low ST levels and better disease outcomes. In the event of microelevations above 50ng/dL, we recommend the administration of bicalutamide.
Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Flutamide; Gonadotropin-Releasing Hormone; Humans; Male; Nitriles; Oligopeptides; Orchiectomy; Prostatic Neoplasms; Testosterone; Tosyl Compounds
PubMed: 26899928
DOI: 10.1016/j.acuro.2016.01.006 -
International Reviews of Immunology 2016Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most... (Review)
Review
Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most important abnormalities induced by senescent names immunosenescence. Emerging evidences suggest miR role in immunosenescence. We aimed to systemically review all relevant reports to clearly state miR effects on immunosenescence process. Sensitive electronic searches carried out. Quality assessment has been performed. Since majority of the included studies were laboratory works, and therefore heterogen, we discussed miR effects on immunological aging process nonstatically. Forty-six articles were found in the initial search. After exclusion of 34 articles, 12 studies enrolled to the final stage. We found that miRs have crucial roles in exact function of immune system. MiRs are involved in the regulation of the aging process in the immune system components and target certain genes, promoting or inhibiting immune system reaction to invasion. Also, miRs control life span of the immune system members by regulation of the genes involved in the apoptosis. Interestingly, we found that immunosenescence is controllable by proper manipulation of the various miRs expression. DNA methylation and histone acetylation have been discovered as novel strategies, altering NF-κB binding ability to the miR promoter sites. Effect of miRs on impairment of immune system function due to the aging is emerging. Although it has been accepted that miRs have determinant roles in the regulation of the immunosenescence; however, most of the reports are concluded from animal/laboratory works, suggesting the necessity of more investigations in human.
Topics: Animals; Apoptosis; B-Lymphocytes; Cell Differentiation; Cytokines; Gene Expression Regulation; Humans; Immune System; Immunosenescence; Lipopolysaccharides; Mice; MicroRNAs; NF-kappa B; Neutrophils; T-Lymphocytes
PubMed: 26327579
DOI: 10.3109/08830185.2015.1077828 -
American Journal of Kidney Diseases :... Dec 2015Early accurate detection of acute kidney injury (AKI) occurring after cardiac surgery may improve morbidity and mortality. Although several novel biomarkers have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Early accurate detection of acute kidney injury (AKI) occurring after cardiac surgery may improve morbidity and mortality. Although several novel biomarkers have been developed for the early detection of AKI, their clinical utility in the critical intraoperative and immediate postoperative period remains unclear.
STUDY DESIGN
Systematic review and meta-analysis.
SETTING & POPULATION
Adult patients having cardiac surgery.
SELECTION CRITERIA FOR STUDIES
EMBASE, CINAHL, Cochrane Library, Scopus, and PubMed from January 1990 until January 2015 were systematically searched for cohort studies reporting the utility of novel biomarkers for the early diagnosis of AKI after adult cardiac surgery. Reviewers extracted data for study design, population, timing of biomarker measurement and AKI occurrence, biomarker performance (area under the receiver operating characteristic curve [AUROC]), and risk of bias.
INDEX TESTS
Novel urine, plasma, and serum AKI biomarkers, measured intraoperatively and in the early postoperative period (<24 hours).
REFERENCE TESTS
AKI was defined according to the RIFLE, AKIN, or 2012 KDIGO criteria.
RESULTS
We found 28 studies reporting intraoperative and/or early postoperative measurement of urine (n=23 studies) or plasma or serum (n=12 studies) biomarkers. Only 4 of these studies measured biomarkers intraoperatively. Overall, intraoperative discrimination by the urine biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury marker 1 (KIM-1) demonstrated AUROCs<0.70, whereas N-acetyl-β-d-glucosaminidase (NAG) and cystatin C had AUROCs<0.75. In the immediate 24-hour postoperative period, the urine biomarkers NGAL (16 studies), KIM-1 (6 studies), and liver-type fatty acid binding protein (6 studies) exhibited composite AUROCs of 0.69 to 0.72. The composite AUROCs for postoperative urine cystatin C, NAG, and interleukin 18 were ≤0.70. Similarly, the composite AUROCs for postoperative plasma NGAL (6 studies) and cystatin-C (5 studies) were <0.70.
LIMITATIONS
Heterogeneous AKI definitions.
CONCLUSIONS
In adults, known urinary, plasma, and serum biomarkers of AKI possess modest discrimination at best when measured within 24 hours of cardiac surgery.
Topics: Acetylglucosaminidase; Acute Kidney Injury; Biomarkers; Cardiac Surgical Procedures; Creatinine; Cystatin C; Fatty Acid-Binding Proteins; Humans; Postoperative Complications; Predictive Value of Tests
PubMed: 26253993
DOI: 10.1053/j.ajkd.2015.06.018 -
Urologia Internationalis 2014We performed a systematic review and meta-analysis to assess the efficacy and tolerability of degarelix for lower urinary tract symptom relief, prostate volume reduction... (Meta-Analysis)
Meta-Analysis Review
Degarelix versus goserelin plus bicalutamide therapy for lower urinary tract symptom relief, prostate volume reduction and quality of life improvement in men with prostate cancer: a systematic review and meta-analysis.
OBJECTIVE
We performed a systematic review and meta-analysis to assess the efficacy and tolerability of degarelix for lower urinary tract symptom relief, prostate volume reduction and quality of life improvement in men with prostate cancer (PCa).
MATERIALS AND METHODS
A literature review was performed to identify all of the published randomized controlled trials (RCTs) that used degarelix versus gonadotropin-releasing hormone agonists plus antiandrogens therapy for the treatment of PCa. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register.
RESULTS
Three publications involving a total of 466 patients were used in the analysis, including three RCTs that compared degarelix with goserelin plus bicalutamide therapy for PCa over 12 weeks. For the comparison of degarelix with goserelin plus bicalutamide therapy, International Prostate Symptom Score (IPSS) reduction (standardized mean difference [SMD] = -1.85, 95% confidence interval [CI] = -2.97 to -0.72, p = 0.001) and IPSS ≥13 (SMD = -2.68, 95% CI = -4.57 to -0.78, p = 0.006) indicated that decreases in IPSS were greater in degarelix-treated patients than in goserelin plus bicalutamide-treated patients.
CONCLUSIONS
Our meta-analysis indicates that, compared with goserelin plus bicalutamide, degarelix has significantly more pronounced effects on lower urinary tract symptoms.
Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Chi-Square Distribution; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lower Urinary Tract Symptoms; Male; Nitriles; Odds Ratio; Oligopeptides; Prostatic Neoplasms; Quality of Life; Time Factors; Tosyl Compounds; Treatment Outcome; Tumor Burden
PubMed: 24603064
DOI: 10.1159/000356272 -
PloS One 2013Pituitary adenomas (PAs) are commonly occurring neoplasms with diverse endocrine and neurological effects. Although somatic gene mutations are uncommon in sporadic PAs,... (Review)
Review
BACKGROUND
Pituitary adenomas (PAs) are commonly occurring neoplasms with diverse endocrine and neurological effects. Although somatic gene mutations are uncommon in sporadic PAs, recent studies lend support to epigenetic modification as a potential cause of tumorigenesis and tumor progression.
METHODS
A systematic literature review of the PubMed and Google Scholar databases was conducted to identify abstracts (n=1,082) pertaining to key targets and mechanisms implicated in epigenetic dysregulation of PAs published between 1993-2013. Data regarding histopathological subtype, target genes, mode of epigenetic modification, and clinical correlation were recorded and analyzed.
RESULTS
Of the 47 that studies met inclusion criteria and focused on epigenomic assessment of PAs, only 2 were genome-scale analyses. Current evidence supports epigenetic alteration in at least 24 PA genes, which were categorized into four groups based on function and epigenetic alteration: 1) Sixteen tumor suppressor genes silenced via DNA methylation; 2) Two oncogenes overexpressed via histone acetylation and hypomethylation; 3) Three imprinted genes with selective allelic silencing; and 4) One epigenome writer inducing abnormal genome-scale activity and 5) Two transcription regulators indirectly modifying the genome. Of these, 5 genes (CDKN2A, GADD45y, FGFR2, caspase-8, and PTAG) showed particular susceptibility to epigenetic modification, with abnormal DNA methylation in >50% of PA samples. Several genes displayed correlations between epigenetic modification and clinically relevant parameters, including invasiveness (CDKN2A; DAPK; Rb1), sex (MAGE-A3), tumor size (GNAS1), and histopathological subtype (CDKN2A; MEG3; p27; RASSF1A; Rb1).
CONCLUSIONS
Epigenetic modification of selected PA genes may play a key role in tumorigenesis and progression, which may translate into important diagnostic and therapeutic applications.
Topics: Apoptosis Regulatory Proteins; Caspase 8; Cyclin-Dependent Kinase Inhibitor p16; DNA Methylation; Epigenesis, Genetic; Humans; Pituitary Neoplasms; Receptor, Fibroblast Growth Factor, Type 2
PubMed: 24367530
DOI: 10.1371/journal.pone.0082619 -
Journal of Ethnopharmacology Jul 2013Polygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum), also known as Reynoutria japonica Houtt and Huzhang in China, is a traditional and popular Chinese medicinal... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Polygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum), also known as Reynoutria japonica Houtt and Huzhang in China, is a traditional and popular Chinese medicinal herb. Polygonum cuspidatum with a wide spectrum of pharmacological effects has been used for treatment of inflammation, favus, jaundice, scald, and hyperlipemia, etc.
AIM OF THE REVIEW
The present paper reviews the traditional applications as well as advances in botany, phytochemistry, pharmacodynamics, pharmacokinetics and toxicology of this plant. Finally, the tendency and perspective for future investigation of this plant are discussed, too.
MATERIALS AND METHODS
A systematic review of literature about Polygonum cuspidatum is carried out using resources including classic books about Chinese herbal medicine, and scientific databases including Pubmed, SciFinder, Scopus, the Web of Science and others.
RESULTS
Polygonum cuspidatum is widely distributed in the world and has been used as a traditional medicine for a long history in China. Over 67 compounds including quinones, stilbenes, flavonoids, counmarins and ligans have been isolated and identified from this plant. The root of this plant is used as the effective agent in pre-clinical and clinical practice for regulating lipids, anti-endotoxic shock, anti-infection and anti-inflammation, anti-cancer and other diseases in China and Japan.
CONCLUSION
As an important traditional Chinese medicine, Polygonum cuspidatum has been used for treatment of hyperlipemia, inflammation, infection and cancer, etc. Because there is no enough systemic data about the chemical constituents and their pharmacological effects or toxicities, it is important to investigate the pharmacological effects and molecular mechanisms of this plant based on modern realization of diseases' pathophysiology. Drug target-guided and bioactivity-guided isolation and purification of the chemical constituents from this plant and subsequent evaluation of their pharmacologic effects will promote the development of new drug and make sure which chemical constituent or multiple ingredients contributes its pharmacological effects. Additionally, chemicals and their pharmacological effects of the other parts such as the aerial part of this plant should be exploited in order to avoid resource waste and find new chemical constituents.
Topics: Animals; Fallopia japonica; Humans; Medicine, Chinese Traditional; Plant Preparations
PubMed: 23707210
DOI: 10.1016/j.jep.2013.05.007 -
Maturitas Jun 2013Dietary supplements are popular among patients with prostate cancer (PC). The objective of this systematic review was to critically examine double-blind,... (Review)
Review
Dietary supplements are popular among patients with prostate cancer (PC). The objective of this systematic review was to critically examine double-blind, placebo-controlled randomised clinical trials (RCTs) of non-herbal dietary supplements and vitamins (NHDS) for evidence that prostate specific antigen (PSA) levels were reduced in PC patients. Five databases were searched from their inception through December 2012 to identify studies that met our inclusion criteria. Methodological quality was independently assessed by two reviewers using the Cochrane tool. Eight RCTs met the eligibility criteria and were of high methodological quality. The following supplements were tested: isoflavones (genistein, daidzein, and glycitein), minerals (Se) or vitamins (vitamin D) or a combination of antioxidants, bioflavonoids, carotenoids, lycopenes, minerals (Se, Zn, Cu, and Mg), phytoestrogens, phytosterols, vitamins (B2, B6, B9, B12, C, and E), and other substances (CoQ10 and n-acetyl-l cysteine). Five RCTs reported no significant effects compared with placebo. Two RCTs reported that a combination of antioxidants, isoflavones, lycopenes, minerals, plant oestrogens and vitamins significantly decreased PSA levels compared with placebo. One RCT did not report differences in PSA levels between the groups. In conclusion, the hypothesis that dietary supplements are effective treatments for PC patients is not supported by sound clinical evidence. There are promising data for only two specific remedies, which contained a mixture of ingredients, but even for these supplements, additional high quality evidence is necessary before firm recommendations would be justified.
Topics: Acetylcysteine; Antioxidants; Dietary Supplements; Humans; Male; Minerals; Plant Extracts; Prostate-Specific Antigen; Prostatic Neoplasms; Trace Elements; Vitamins
PubMed: 23567264
DOI: 10.1016/j.maturitas.2013.03.006 -
The Cochrane Database of Systematic... Apr 2012Spinal muscular atrophy (SMA) is caused by degeneration of anterior horn cells, which leads to progressive muscle weakness. Children with SMA type II do not develop the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Spinal muscular atrophy (SMA) is caused by degeneration of anterior horn cells, which leads to progressive muscle weakness. Children with SMA type II do not develop the ability to walk without support and have a shortened life expectancy, whereas children with SMA type III develop the ability to walk and have a normal life expectancy. There are no known efficacious drug treatments that influence the disease course of SMA. This is an update of a review first published in 2009.
OBJECTIVES
To evaluate whether drug treatment is able to slow or arrest the disease progression of SMA types II and III and to assess if such therapy can be given safely. Drug treatment for SMA type I is the topic of a separate updated Cochrane review.
SEARCH METHODS
We searched the Cochrane Neuromuscular Disease Group Specialized Register (8 March 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE (January 1991 to February 2011), EMBASE (January 1991 to February 2011) and ISI Web of Knowledge (January 1991 to March 8 2011). We also searched clinicaltrials.gov to identify as yet unpublished trials (8 March 2011).
SELECTION CRITERIA
We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA types II and III. Participants had to fulfil the clinical criteria and have a deletion or mutation of the survival motor neuron 1 (SMN1) gene (5q11.2-13.2) that was confirmed by genetic analysis.The primary outcome measure was to be change in disability score within one year after the onset of treatment. Secondary outcome measures within one year after the onset of treatment were to be change in muscle strength, ability to stand or walk, change in quality of life, time from the start of treatment until death or full time ventilation and adverse events attributable to treatment during the trial period.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed and extracted data from all potentially relevant trials. Pooled relative risks and pooled standardised mean differences were to be calculated to assess treatment efficacy. Risk of bias was systematically analysed.
MAIN RESULTS
Six randomised placebo-controlled trials on treatment for SMA types II and III were found and included in the review: the four in the original review and two trials added in this update. The treatments were creatine (55 participants), phenylbutyrate (107 participants), gabapentin (84 participants), thyrotropin releasing hormone (9 participants), hydroxyurea (57 participants), and combination therapy with valproate and acetyl-L-carnitine (61 participants). None of these studies were completely free of bias. All studies had adequate blinding, sequence generation and reports of primary outcomes.None of the included trials showed any statistically significant effects on the outcome measures in participants with SMA types II and III. One participant died due to suffocation in the hydroxyurea trial and one participant died in the creatine trial. No participants in any of the other four trials died or reached the state of full time ventilation. Serious side effects were infrequent.
AUTHORS' CONCLUSIONS
There is no proven efficacious drug treatment for SMA types II and III.
Topics: Acetylcarnitine; Adolescent; Amines; Child; Child, Preschool; Creatine; Cyclohexanecarboxylic Acids; Disease Progression; Gabapentin; Humans; Hydroxyurea; Neuroprotective Agents; Phenylbutyrates; Randomized Controlled Trials as Topic; Spinal Muscular Atrophies of Childhood; Thyrotropin-Releasing Hormone; Valproic Acid; gamma-Aminobutyric Acid
PubMed: 22513940
DOI: 10.1002/14651858.CD006282.pub4 -
The Cochrane Database of Systematic... Dec 2011Spinal muscular atrophy (SMA) is caused by degeneration of anterior horn cells, which leads to progressive muscle weakness. Children with SMA type II do not develop the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Spinal muscular atrophy (SMA) is caused by degeneration of anterior horn cells, which leads to progressive muscle weakness. Children with SMA type II do not develop the ability to walk without support and have a shortened life expectancy, whereas children with SMA type III develop the ability to walk and have a normal life expectancy. There are no known efficacious drug treatments that influence the disease course of SMA. This is an update of a review first published in 2009.
OBJECTIVES
To evaluate whether drug treatment is able to slow or arrest the disease progression of SMA types II and III and to assess if such therapy can be given safely. Drug treatment for SMA type I is the topic of a separate updated Cochrane review.
SEARCH METHODS
We searched the Cochrane Neuromuscular Disease Group Specialized Register (8 March 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE (January 1991 to February 2011), EMBASE (January 1991 to February 2011) and ISI Web of Knowledge (January 1991 to March 8 2011). We also searched clinicaltrials.gov to identify as yet unpublished trials (8 March 2011).
SELECTION CRITERIA
We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA types II and III. Participants had to fulfil the clinical criteria and have a deletion or mutation of the survival motor neuron 1 (SMN1) gene (5q11.2-13.2) that was confirmed by genetic analysis.The primary outcome measure was to be change in disability score within one year after the onset of treatment. Secondary outcome measures within one year after the onset of treatment were to be change in muscle strength, ability to stand or walk, change in quality of life, time from the start of treatment until death or full time ventilation and adverse events attributable to treatment during the trial period.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed and extracted data from all potentially relevant trials. Pooled relative risks and pooled standardised mean differences were to be calculated to assess treatment efficacy. Risk of bias was systematically analysed.
MAIN RESULTS
Six randomised placebo-controlled trials on treatment for SMA types II and III were found and included in the review: the four in the original review and two trials added in this update. The treatments were creatine (55 participants), phenylbutyrate (107 participants), gabapentin (84 participants), thyrotropin releasing hormone (9 participants), hydroxyurea (57 participants), and combination therapy with valproate and acetyl-L-carnitine (61 participants). None of these studies were completely free of bias. All studies had adequate blinding, sequence generation and reports of primary outcomes.None of the included trials showed any statistically significant effects on the outcome measures in participants with SMA types II and III. One participant died due to suffocation in the hydroxyurea trial and one participant died in the creatine trial. No participants in any of the other four trials died or reached the state of full time ventilation. Serious side effects were infrequent.
AUTHORS' CONCLUSIONS
There is no proven efficacious drug treatment for SMA types II and III.
Topics: Acetylcarnitine; Adolescent; Amines; Child; Child, Preschool; Creatine; Cyclohexanecarboxylic Acids; Gabapentin; Humans; Hydroxyurea; Neuroprotective Agents; Phenylbutyrates; Randomized Controlled Trials as Topic; Spinal Muscular Atrophies of Childhood; Thyrotropin-Releasing Hormone; Valproic Acid; gamma-Aminobutyric Acid
PubMed: 22161400
DOI: 10.1002/14651858.CD006282.pub3 -
PloS One Dec 2010Significant pain from HIV-associated sensory neuropathy (HIV-SN) affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART). The prevalence of... (Meta-Analysis)
Meta-Analysis Review
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.
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 (2.4 g/day), pregabalin (1200 mg/day), prosaptide (16 mg/day), peptide-T (6 mg/day), acetyl-L-carnitine (1g/day), mexilitine (600 mg/day), lamotrigine (600 mg/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.
Topics: Analgesics; Anti-Retroviral Agents; Cannabis; Capsaicin; HIV Infections; Humans; Nerve Growth Factor; Peripheral Nervous System Diseases; Placebos; Plant Extracts; Randomized Controlled Trials as Topic; Research Design; Risk; Treatment Outcome
PubMed: 21203440
DOI: 10.1371/journal.pone.0014433