Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials

Well-founded pharmacokinetic information is one of the cornerstones of a New Drug Application (NDA) to the Food and Drug Administration (FDA) required to introduce a new drug or a generic equivalent (ANDA) to the marketplace. The service that laboratories engaged in therapeutic drug monitoring provide to support clinical activities is also needed by the pharmaceutical industry during the evaluation and introduction of drugs to the marketplace. In considering this alternative service activity, one must be aware of and compliant with rules established by the FDA for performance of such studies. As specified in CFR 21, Parts 58, 211, and 320, good clinical and laboratory practice indicates that the laboratory should employ a Lab Study Director, who is responsible for the validation of all procedures implemented to support a study protocol, ensures that the laboratory carries out the study following these defined procedures, and personally reviews the results of all testing. The laboratory must validate each procedure by demonstrating and documenting that the procedure does what it is designed to do while meeting the analytical performance specifications required by the study. Laboratory records of all activities must be maintained and available for inspection by the FDA on request. The FDA has authority over all activities related to NDA and ANDA submissions and can bring criminal charges if results of a study are changed because a laboratory deviates from standard procedure. Competent drug monitoring laboratories are fully capable of participating in clinical trials testing activities. Laboratory staff should be fully versed in the FDA rules governing these activities, validate all procedures, and establish systems to verify the procedures are carried out as specified.     

复方黄黛片治疗急性早幼粒细胞白血病的系统评价

目的 评价复方黄黛片( CRNTT)治疗急性早幼粒细胞白血病(APL)的疗效与安全性。方法计算机检索SinoMed、CNKI、VIP、万方、CBA、PubMed、MEDLINE、EMBASE、Cochrane图书馆临床对照试验资料库,并辅以手工检索,收集国内外公开发表的CRNIT治疗APL的随机对照试验(RCT)文献,检索年限截至201 1年3月。按纳入标准与排除标准筛选文献并评价纳入研究的质量,以完全缓解(CR)率、达CR所需时间、复发率、病死率、不良反应率等为评价指标,采用RevMan 5.1软件进行Meta分析。结果纳入6项RCT,包括391例APL患者,其中2项RCT研究目的为CRNIT与三氧化二砷(ATO)的比较,4项RCT研究目的为CRNIT与全反式维甲酸(ATRA)的比较,其中1项RCT增设CRNIT+ ATRA与ATRA的比较。达CR所需时间：CRNIT比ATRA、ATO长[加权均数差(WMD)=3.14,95％CI 0.99 ～5.29,P=0.004];头痛发生率：CRNTT低于ATRA（OR=0.10,95％CI 0.02～0.45,P=0.003）;5年无病生存率：CRNIT优于ATRA（OR= 7.22,95％CI 1.40～37.25,P=0.02）;CR率、复发率、病死率和4项不良反应指标（胃肠道症状、肝肾功能损害、皮肤损害、发热）的Meta分析结果差异无统计学意义。结论服用CRNIT达CR所需时间比ATRA、ATO长,CRNIT近期疗效与ATRA、ATO相近。服用CRNIT的5年无病生存率可能优于ATRA。     

Pathology of female infertility

This review focuses on infertility-related anatomical (ligneous cervicitis and postsurgical stenosis) and functional (abnormal mucus production, local cervical isoimmunity, and incompetence) disorders of the cervix, congenital anomalies, and underperfusion of the uterine corpus, myometrial lesions, endometrial failure, tubal obstruction, polycystic ovary syndrome, and endometriosis.     

Hysterosalpingography and hysteroscopy in female infertility

A total of 323 women of reproductive age (19-40 years) were submitted to a complete investigation of infertility routinely including hysterosalpingography and hysteroscopy. In 177 cases (54.7%) no pathological conditions were found by either of the applied methods, while in 65 cases (20.1%) similar abnormalities were observed by hysterosalpingography and hysteroscopy with a global correlation of 74.8%. Hysterosalpingography also presented false positive results in 11.7% and false negative ones in 13.3% of all the studied cases. In conclusion, the combined use of these techniques in infertility investigation gives complete and accurate information about the uterine cavity, despite the disadvantages of hysterosalpingography due to false positive and false negative results.     

Smoking and attention: a review and reformulation of the stimulus-filter hypothesis

An accumulation of evidence suggests that smoking may be reinforcing, in part, due to nicotine's capacity to enhance attentional processing. Correspondingly, the stimulus-filter model of nicotine reinforcement asserts that nicotine facilitates cognitive performance by acting as a stimulus-barrier, thereby screening irrelevant and annoying stimuli from the smoker's awareness. A review of the available data suggests that while nicotine does appear to reliably enhance sustained, divided, and focused attention, the stimulus-filter model falls short of adequately explaining the findings. An alternative, attention, allocation model of nicotine reinforcement is reviewed, the tenets of which suggest that nicotine differentially augments attentional processing via its propensity to: (a) induce attentional narrowing, and (b) increase perceptual processing capacity. The motivational implications of the model, including smokers' use of nicotine to dampen stress, are discussed.     

The effect of pregnancy on survival in women infected with HIV: a systematic review of the literature and meta-analysis

OBJECTIVE: To investigate the effect of pregnancy on disease progression and survival in women infected with HIV by a systematic review of the literature and meta-analysis. METHODS: Appropriate publications were identified using electronic and hand searching of relevant journals from 1983 to 1996. Studies were included in the review if they were cohort studies, either prospective or retrospective, or case-control studies which investigated disease progression of pregnant women infected with HIV and included a control group of non-pregnant women infected with HIV for comparison. Methodological quality was assessed for each study. Data were extracted for predetermined outcome measures. Sensitivity analyses were performed to explore the association between pregnancy and disease progression for the following study characteristics: clinical setting (developed or developing countries), methodological quality (high or poor) and whether studies had controlled for potential confounding. RESULTS: Seven studies, all prospective cohorts, were eligible to be included in the review. The summary odds ratio for the risk of an adverse maternal outcome related to HIV infection and pregnancy were as follows: death 1.8 (85% CI 0.99-3.3); HIV disease progression 1.41 (95% CI 0.85-2.33); progression to an AIDS-defining illness 1.63 (95% CI 1.00-2.67) and fall of CD4 cell count to below 200 x 10(6)/L 0.73 (95% CI 0.17-3.06). Sensitivity analyses showed that HIV progression in pregnancy was significantly more common in a developing country setting (odds ratio 3.71, 95% CI 1.82-7.75) than in developed countries (odds ratio 0.55, 95% 0.27-1.11) and also significantly more common in high quality studies when compared to low quality ones, odds ratios 3.71 (95% CI 1.82-7.57) and 0.55 (95% CI 0.27-1.11), respectively. However, there appears to be less progression of HIV disease and progression to AIDS when studies attempted to control for confounding by matching or restriction techniques, although this was not statistically significant in either case. CONCLUSIONS: The findings of this review have implications for women infected with HIV who are pregnant or are considering a pregnancy. There does appear to be an association between adverse maternal outcomes and pregnancy in women infected with HIV, although this association is not strong. The relation may be due to the result of bias including residual confounding. Further large scale observational studies with long term follow up are required before this issue can be fully resolved.     

Vitamin C and cardiovascular disease: a systematic review

BACKGROUND: Laboratory studies suggest that antioxidants, such as Vitamin C, are important inhibitors of atherosclerotic lesions. Most epidemiological reviews have considered all antioxidants together. This review seeks to clarify the current state of knowledge specifically concerned with vitamin C. METHODS: All ecological studies, case-control studies, prospective studies and trials in humans that examined the association between vitamin C intake or blood levels of vitamin C and cardiovascular disease were included. Relevant references were located by MEDLINE search for articles published from 1966 to 1996, by an EMBASE search for articles published from 1980 to 1996, by searching personal bibliographies, books and reviews and from citations in located articles. RESULTS: For coronary heart disease four of seven ecological studies, one of four case-control studies and three of 12 cohort studies found a significant protective association with vitamin C intake or status. For strokes two of two ecological studies, none of one case-control study and two of seven cohort studies found a significant protective association. For total circulatory disease, two of three cohort studies reported a significant protective association. CONCLUSIONS: The evidence, albeit limited, is consistent with vitamin C having protective effect against stroke whereas the evidence that vitamin C is protective against coronary heart disease is less consistent. The lack of an association for coronary heart disease could be explained in terms of there being a true lack of effect, dietary measurement error, a threshold effect, and effect of seasonal variations in intake, an interaction with other dietary constituents or a relatively short duration of follow-up.     

Gender differences in ADHD: a meta-analysis and critical review

OBJECTIVE: To quantitatively review and critically evaluate literature examining gender differences in attention-deficit hyperactivity disorder (ADHD). METHOD: A meta-analysis of relevant research based on 18 studies meeting inclusion criteria was performed. Domains evaluated included primary symptomatology, intellectual and academic functioning, comorbid behavior problems, social behavior, and family variables. RESULTS: Gender differences were not found in impulsivity, academic performance, social functioning fine motor skills, parental education, or parental depression. However, compared with ADHD boys, ADHD girls displayed greater intellectual impairment, lower levels of hyperactivity, and lower rates of other externalizing behaviors; it was not possible to evaluate the extent to which referral bias affected these findings. Some gender differences were clearly mediated by the effects of referral source; among children with ADHD identified from nonreferred populations, girls with ADHD displayed lower levels of inattention, internalizing behavior, and peer aggression than boys with ADHD, while girls and boys with ADHD identified from clinic-referred samples displayed similar levels of impairment on these variables. CONCLUSIONS: The need for future research examining gender differences in ADHD is strongly indicated, with attention to methodological limitations of the current literature, including the potential confounding effects of referral bias, comorbidity, developmental patterns, diagnostic procedures, and rater source.     

The link between female infertility and cancer: epidemiology and possible aetiologies

Infertility has been suggested as a risk factor for various gynaecological cancers. Data analyses show that among infertile women, those with anovulation or polycystic ovarian syndrome (PCOS) have an increased risk of cancer. Clinical and laboratory data such as anthropometric measurements, endogenous hormones and growth factors may explain mechanisms which link tumorogenesis or tumour promotion to infertility. The possible association between ovulation induction and cancer is discussed both on theoretical grounds and based on epidemiological data. We conclude that according to epidemiological studies, laboratory data and on theoretical grounds, infertile patients have an increased lifetime risk of gynaecological cancer. The risk of cancer should be evaluated further for each subpopulation of infertile patients. Thus, more adequate means of monitoring these patients will become available. These data are necessary for a further evaluation of the possible cancer risks of infertility treatments.     

Educating young people about drugs: a systematic review

AIMS: To assess the effectiveness of interventions directed at the prevention or reduction of use of illicit substances by young people or those directed at reducing harm caused by continuing use. DESIGN: A systematic review was conducted. Reports were identified through electronic and hand searching and contact with known workers in the area. Studies were included if they reported evaluations of interventions targeting illicit drug use and provided sufficient detail of the intervention and design of the evaluation to allow judgements to be made of their methodological soundness. Meta-analyses were conducted combining the data of the methodologically sound studies. PARTICIPANTS AND SETTINGS TARGETED BY INTERVENTIONS: Evaluations of interventions were included if their targeted audience included young people aged between 8 and 25 years. Identified evaluations were delivered in a range of settings including: schools and colleges; community settings; the family; medical/therapeutic settings; mass media. MEASUREMENTS: Data extracted from each report included details of design, content and theoretical orientation of intervention, setting of the intervention, target audience, methods, population size, subject refusal rates, rates of attrition, outcome measures, length of follow-up and findings, including statistical power. FINDINGS: The majority of studies identified were evaluations of interventions introduced in schools and targeting alcohol, tobacco and marijuana simultaneously. These studies were methodologically stronger than interventions targeting other drugs and implemented outside schools. Meta-analyses showed that the impact of evaluated interventions was small with dissipation of programme gains over time. Interventions targeting hard to reach groups have not been evaluated adequately. CONCLUSIONS: Effort needs to be directed towards the development of improved evaluative solutions to the problems posed by these groups. There is still insufficient evidence to assess the effectiveness of the range of approaches to drugs education; more methodologically sound evaluations are required. There is also a need to target interventions to reflect the specific needs and experiences of recipients.     

Risk factors for subarachnoid hemorrhage: a systematic review

BACKGROUND AND PURPOSE: Knowledge of modifiable risk factors for subarachnoid hemorrhage (SAH) is important in terms of prevention. We therefore conducted a systematic review of studies on risk factors for SAH, with emphasis on sufficiently precise criteria for the diagnosis of SAH. METHODS: To identify studies we performed a Medline search from 1966 to 1994 and searched the reference lists of all relevant publications. Studies were included only if they fulfilled predefined methodological criteria. Case-control studies were included if the diagnosis of SAH was proved by CT, angiography, or autopsy in at least 70% of patients. Longitudinal studies were included if the criteria for SAH were based on a review of the medical records. RESULTS: Nine longitudinal studies and 11 case-control studies were included. Significant risk factors were as follows: (1) smoking (relative risk [RR] for longitudinal studies, 1.9; 95% confidence interval [CI], 1.5 to 2.3; odds ratio [OR] for case-control studies, 3.5; 95% CI, 2.9 to 4.3); (2) hypertension (RR, 2.8; 95% CI, 2.1 to 3.6; OR, 2.9; 95% CI, 2.4 to 3.7) and (3) drinking 150 g or more of alcohol per week (RR, 4.7; 95% CI, 2.1 to 10.5; OR, 1.5; 95% CI, 1.1 to 1.9). Use of oral contraceptives, hormone replacement therapy, hypercholesterolemia, and physical activity were not significantly related to the risk of SAH. CONCLUSIONS: We conclude that smoking, hypertension, and alcohol abuse are important risk factors for SAH. Reduction of exposure to these risk factors might result in a decreased incidence of SAH.     

Feverfew as a preventive treatment for migraine: a systematic review

BACKGROUND: Feverfew is a popular herbal remedy advocated for the prevention of migraine. AIM: The aim of this systematic review was to look at the evidence for or against the clinical effectiveness of feverfew in migraine prevention. DATA SOURCES: Literature searches were performed using the following databases: Medline, Embase, Biosis, CISCOM, and the Cochrane Library (all from their inception to April 1998). STUDY SELECTION: Only randomized, placebo-controlled, double-blind trials were included. DATA EXTRACTION: All articles were read by two independent reviewers. Data were extracted in a predefined, standardized fashion. The methodological quality of all trials was evaluated using the Jadad score. MAIN RESULTS: Five trials met the inclusion/exclusion criteria. The majority favor feverfew over placebo. Yet important caveats exist. CONCLUSION: The clinical effectiveness of feverfew in the prevention of migraine has not been established beyond reasonable doubt.     

Dynamic exercise therapy in rheumatoid arthritis: a systematic review

The aim of this systematic review was to determine the effectiveness of dynamic exercise therapy in improving joint mobility, muscle strength, aerobic capacity and daily functioning in patients with rheumatoid arthritis (RA). In addition, possible unwanted effects such as an increase in pain, disease activity and radiological progression were studied. A computer-aided search of the MEDLINE, Embase and SCISEARCH databases was performed to identify controlled trials on the effect of exercise therapy. Randomized trials were selected on the effect of dynamic exercise therapy in RA patients with an exercise programme fulfilling the following criteria: (a) intensity level such that heart rates exceeded 60% of maximal heart rate during at least 20 min; (b) exercise frequency > or = 2 a week; and (c) duration of intervention > or = 6 weeks. Two blinded reviewers independently selected eligible studies, rated the methodological quality and extracted data. Six out of 30 identified controlled trials met the inclusion criteria. Four of the six included studies fulfilled > or = 7/10 methodological criteria. Because of heterogeneity in outcome measures, data could not be pooled. The results suggest that dynamic exercise therapy is effective in increasing aerobic capacity and muscle strength. No detrimental effects on disease activity and pain were observed. The effects of dynamic exercise therapy on functional ability and radiological progression are unclear. It is concluded that dynamic exercise therapy has a positive effect on physical capacity. Research on the long-term effect of dynamic exercise therapy on radiological progression and functional ability is needed.     

Relaxation techniques for acute pain management: a systematic review

A papain-type cysteine endopeptidase with a molecular mass of 35 kDa for the mature enzyme, was purified from germinating castor bean (Ricinus communis L.) endosperm by virtue of its capacity to process the glyoxysomal malate dehydrogenase precursor protein to the mature subunit in vitro (C. Gietl et al., 1997, Plant Physiol 113: 863-871). The cDNA clones from endosperm of germinating seedlings and from developing seeds were isolated and sequence analysis revealed that a very similar or identical peptidase is synthesised in both tissues. Sequencing established a presequence for co-translational targeting into the endoplasmic reticulum, an N-terminal propeptide and a C-terminal KDEL motif for the castor bean cysteine endopeptidase precursor. The 45-kDa pro-enzyme stably present in isolated organelles was enzymatically active. Immunocytochemistry with antibodies raised against the purified cysteine endopeptidase revealed highly specific labelling of ricinosomes, organelles which co-purify with glyoxysomes from germinating Ricinus endosperm. The cysteine endopeptidase from castor bean endosperm, which represents a senescing tissue, is homologous to cysteine endopeptidases from other senescing tissues such as the cotyledons of germinating mung bean (Vigna mungo) and vetch (Vicia sativa), the seed pods of maturing French bean (Phaseolus vulgaris) and the flowers of daylily (Hemerocallis sp.).     

Prevalence and risk of rupture of intracranial aneurysms: a systematic review

BACKGROUND AND PURPOSE: The estimates on the prevalence and the risk of rupture of intracranial saccular aneurysms vary widely between studies. We conducted a systematic review on prevalence and risk of rupture of intracranial aneurysms and classified the data according to study design, study population, and aneurysm characteristics. METHODS: We searched for studies published between 1955 and 1996 by means of a MEDLINE search and a cumulative review of the reference lists of all relevant publications. Two authors independently assessed eligibility of all studies and extracted data on study design and on numbers and characteristics of patients and aneurysms. RESULTS: For data on prevalence we found 23 studies, totalling 56,304 patients; 6685 (12%) of these patients were from 15 angiography studies. Prevalence was 0.4% (95% confidence interval, 0.4% to 0.5%) in retrospective autopsy studies, 3.6% (3.1 to 4.1) for prospective autopsy studies, 3.7% (3.0 to 4.4) in retrospective angiography studies, and 6.0% (5.3 to 6.8) in prospective angiography studies. For adults without specific risk factors, the prevalence was 2.3% (1.7 to 3.1); it tended to increase with age. The prevalence was higher in patients with autosomal dominant polycystic kidney disease (relative risk [RR], 4.4 [2.7 to 7.2]), a familial predisposition (RR, 4.0 [2.7 to 6.0]), or atherosclerosis (RR, 2.3 [1.7 to 3.1]). Only 8% (5 to 11) of the aneurysms were >10 mm. For the risk of rupture, we found nine studies, totalling 3907 patient-years. The overall risk per year was 1.9% (1.5 to 2.4); for aneurysms = 10 mm, the annual risk was 0.7% (0.5 to 1.0). The risk was higher in women (RR, 2.1[1.1 to 3.9]) and for aneurysms that were symptomatic (RR, 8.3 [4.0 to 17]), >10 mm (RR, 5.5 [3.3 to 9.4]), or in the posterior circulation (RR, 4.1 [1.5 to 11]). CONCLUSIONS: Data on prevalence and risk of rupture vary considerably according to study design, study population, and aneurysm characteristics. If all available evidence with inherent overestimation and underestimation is taken together, for adults without risk factors for subarachnoid hemorrhage, aneurysms are found in approximately 2%. The vast majority of these aneurysms are small (=10 mm) and have an annual risk of rupture of approximately 0.7%.     

Smoking cessation in peri- and postmenopausal women: A review.

A substantial portion of smokers are peri- or postmenopausal women. Cigarette smoking and menopause have overlapping negative health consequences and may act synergistically to contribute to worse health outcomes in this population. Little is known about issues specific to peri- and postmenopausal women attempting to quit smoking; however, it can be hypothesized that they face unique challenges in quitting smoking. Particularly, negative affect and vasomotor menopausal symptoms may make smoking cessation particularly challenging in this group of women. Peri- and postmenopausal women are also more prone to weight gain following smoking cessation, and concerns about postcessation weight gain may contribute to reduced motivation to quit smoking or to relapse to smoking. Recent evidence suggests that estrogen level may be positively associated with nicotine reward, which may aid in the smoking cessation efforts of postmenopausal women while possibly contributing to worse outcomes in perimenopausal women. Unfortunately, no known studies have compared premenopausal women with peri- or postmenopausal women on smoking cessation outcome variables. Studies in postmenopausal women indicate that hormone therapy (HT) use does not affect nicotine withdrawal, smoking cessation outcomes, or weight gain following smoking cessation; however, a lack of randomized trials limits the strength of these conclusions. Evidence of the effects of HT on mood following smoking cessation is conflicting. Further research is needed to identify the unique factors influencing smoking cessation in peri- and postmenopausal women and to develop and test interventions that target these variables in a way that improves cessation rates among this population. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Group polarization: A critical review and meta-analysis.

Reviews recent (1974–1982) group polarization studies that address either 1 of the 2 primary explanatory mechanisms thought to underly group polarization: social comparison and persuasive argumentation processes (SCP and PAP). A summary of the effect sizes of 21 published articles (33 independent effects) suggests that SCP and PAP occur in combination to produce polarization, although the persuasive argumentation effects tend to be larger. Four questions that suggest how to integrate PAP and SCP into a more conceptually coherent position—a position that served to integrate group polarization with other social psychological phenomena—are presented. (68 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Toxic shock syndrome: case report of a postpartum female and a literature review

1. 1alpha,25-dihydroxyvitamin3 (VD) is a nuclear hormone that has important cell regulatory functions but also a strong calcemic effect. EB1089 is a potent antiproliferative VD analogue, which has a modified side chain resulting in increased metabolic stability and a selective functional profile. Since EB1089 is considered for potential systemic application, it will be investigated to what extent its recently identified metabolites (hydroxylated at positions C26 and C26a) contribute to biological profile of the VD analogue. 2. Limited protease digestion analysis demonstrated that EB1089 is able to stabilize the high affinity ligand binding conformation of the VDR, starting at concentrations of 0.1 nM and affecting up to 80% of all receptor molecules. The metabolites EB1445 and EB1470 showed to be 100 fold less potent than EB1089, whereas the remaining three metabolites (EB1435, EB1436 and EB1446) showed a clearly reduced ability to stabilize the high affinity ligand binding conformation. Interestingly, at pharmacological concentrations all EB1089 metabolites stabilized a second, apparently lower affinity conformation to a much higher extent than EB1089. 3. In reporter gene assays all metabolites showed lower potency than EB1089. Moreover, the preference of EB1089 for activation of VDR binding to sites formed by inverted palindromic arrangements spaced by nine nucleotide (IP9-type VD response elements) appeared to be reduced (with EB1445 and EB1470) or completely lost (with EB1435, EB1436 and EB1446). The ranking of EB1089 and its metabolites that was obtained by limited protease digestion and reporter gene assays was confirmed by an analysis of their antiproliferative effect in breast cancer cells. . The potency and selectivity of the EB1089 metabolites in mediating gene regulatory effects was found to be drastically reduced in comparison to the parent compound suggesting that the contribution of the metabolites to the biological effect of EB1089 is minor. However, the compounds showed to be interesting tools for understanding the selective biological profile of EB1089.     

Agoraphobia outcome measurement: A review and meta-analysis.

A review of outcome measures used in 106 studies, along with a meta-analysis of instruments used in 42 studies investigating the effectiveness of treatments for agoraphobia during the 1980s, is presented. Articles reporting case studies, preliminary reports, and duplicate results are excluded. Content areas covered, source of instrument ratings, and methods of data collection for each instrument are considered. Nine distinct instruments or categories of instruments are meta-analyzed. The size of treatment effects and judgments of improvement are highly dependent on which outcome measures are used in a given study. Intercorrelations of effect sizes suggest commonalities and specific contributions of instruments. Promising instruments are named. Applications for agoraphobia research and outcome measurement in general are presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)