Surgical treatment of humeral head avascular necrosis in patients with sickle cell disease: a systematic review.

BACKGROUND: Sickle cell disease is the leading etiology for atraumatic humeral head avascular necrosis worldwide. Treatment of this condition is not standardized, with only few studies evaluating clinical outcomes after surgical interventions. The aim of this study was to review the available evidence on the results of surgical intervention for humeral head avascular necrosis in the sickle cell disease population. METHODS: A systematic electronic search was conducted using PubMed (MEDLINE), EMBASE, and Cochrane Library databases. Relevant studies that reported the outcomes of surgical intervention for humeral head avascular necrosis for patients with sickle cell disease were reviewed. Outcome parameters were pain, range of motion, specific shoulder outcome scores, and complications. RESULTS: Six studies, three retrospective cohorts (2 level III and 1 level IV) and three case series (level IV), were included in this review. A total of forty-three patients with sickle cell disease, comprising forty-nine shoulders, underwent different surgical procedures. Surgical procedures were core decompression, arthroscopic intervention, humeral head resurfacing, shoulder hemiarthroplasty, and total shoulder arthroplasty. CONCLUSION: Surgical intervention for humeral head avascular necrosis in patients with sickle cell disease is selected based on the osteonecrosis stage. In the precollapse stage, core decompression is regarded as the first surgical option. However, in the light of current evidence, it has not been confirmed to prevent or delay natural progression of the disease. Shoulder arthroplasty is reserved for late stages, which despite the fairly good outcomes, data for long-term implant survival and complications are not well documented.

EEG of asymptomatic first-degree relatives of patients with juvenile myoclonic, childhood absence and rolandic epilepsy: a systematic review and meta-analysis.

Rolandic (RE), childhood absence (CAE) and juvenile myoclonic (JME) epilepsy encompass centrotemporal sharp waves, 3-Hz spike waves and >3-Hz spike or polyspike waves, respectively. Evidence abounds for genetic roles in all three syndromes, yet involved genes for the vast majority of patients remain unknown. It has long been proposed that while each disease is genetically complex, its specific EEG trait may represent a genetically simpler endophenotype. This meta-analysis of the literature focuses on the frequency of EEG traits in clinically unaffected first-degree relatives towards determining inheritance patterns of the EEG endophenotypes. We used the Preferred Reporting Items for Systematic Review and Meta-Analysis for protocols (PRISMA-P) and searched Medline, EMBASE, CINHAL and the Cochrane Central Register of Controlled Trials. Following extensive screening, 15 studies were included with a total of 3,858 asymptomatic relatives. The prevalence of 'abnormal' EEG waves was 21%, 42% and 33% for JME, CAE and RE, respectively, close to what would be expected based on Mendelian inheritance. However, breaking down the reported EEG abnormalities, most consisted not of the respective EEG signature traits -prevalences of which were as low as 5%- but of non-specific EEG 'abnormalities'/variants. Prevalence of non-specific EEG 'abnormalities'/variants in the general population ranges from 0.1 to 10%. Underlying this 100-fold-wide range is a spectrum of what is considered 'abnormal' or variant. The prevalences of 'abnormalities'/variants in asymptomatic siblings in RE, CAE and JME significantly exceed even the highest value in the general population and fall within Mendelian expectations. These results suggest that EEG 'abnormalities'/variants shared with the general population are enriched in the three syndromes and are endophenotypes inherited in a genetically simple near-Mendelian fashion. Future work with modern EEG variant definitions should uncover genetic variants contributing to neuronal hypersynchrony in epilepsy.

Self-reported barriers and facilitators to preventive human papillomavirus vaccination among adolescent girls and young women: a systematic review.

OBJECTIVE: Widespread uptake of preventive human papillomavirus vaccination among target groups is an important public health goal. To evaluate barriers and facilitators to human papillomavirus vaccination, we conducted a systematic review of self-reported views of adolescent girls and young women. METHODS: Twenty-two studies including 8079 females aged 9-26 years in North America, published between 2008 and 2011 (representing studies conducted post-vaccine availability), were included. Two reviewers performed all levels of screening and data abstraction in duplicate. We collated findings pertaining to vaccination barriers and facilitators, study characteristics, and study quality. RESULTS: Participants were mainly unvaccinated (70%) and sexually active. Twenty-one barriers to vaccination were identified. Cost was the most frequently reported barrier, followed by feelings that vaccination was unnecessary, and concerns regarding vaccine safety and side effects. Facilitators included perceived benefit of vaccination, health care provider recommendations, and social norms. Few studies specifically sought to isolate the views of adolescents, though not being sexually active was the most commonly reported barrier among this group. CONCLUSION: Understanding factors which arbitrate in vaccination decisions among key target groups can improve the success of health promotion interventions. Additional studies of superior methodological quality are needed to produce reliable data to inform health promotion strategies.

Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis.

BACKGROUND: Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains. METHODS: We identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk × 100%). RESULTS: We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I2 <50%) across all meta-analyses, except for the LAIV meta-analyses among children (I2 = 79%). CONCLUSIONS: The TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs.

A systematic review of recent clinical practice guidelines on the diagnosis, assessment and management of hypertension.

BACKGROUND: Despite the availability of clinical practice guidelines (CPGs), optimal hypertension control is not achieved in many parts of the world; one of the challenges is the volume of guidelines on this topic and their variable quality. To systematically review the quality, methodology, and consistency of recommendations of recently-developed national CPGs on the diagnosis, assessment and the management of hypertension. METHODOLOGY/PRINCIPAL FINDINGS: MEDLINE, EMBASE, guidelines' websites and Google were searched for CPGs written in English on the general management of hypertension in any clinical setting published between January 2006 and September 2011. Four raters independently appraised each CPG using the AGREE-II instrument and 2 reviewers independently extracted the data. Conflicts were resolved by discussion or the involvement of an additional reviewer. Eleven CPGs were identified. The overall quality ranged from 2.5 to 6 out of 7 on the AGREE-II tool. The highest scores were for "clarity of presentation" (44.4%-88.9%) and the lowest were for "rigour of development" (8.3%-30% for 9 CGPs). None of them clearly reported being newly developed or adapted. Only one reported having a patient representative in its development team. Systematic reviews were not consistently used and only 2 up-to-date Cochrane reviews were cited. Two CPGs graded some recommendations and related that to levels (but not quality) of evidence. The CPGs' recommendations on assessment and non-pharmacological management were fairly consistent. Guidelines varied in the selection of first-line treatment, adjustment of therapy and drug combinations. Important specific aspects of care (e.g. resistant hypertension) were ignored by 6/11 CPGs. The CPGs varied in methodological quality, suggesting that their implementation might not result in less variation of care or in better health-related outcomes. CONCLUSIONS/SIGNIFICANCE: More efforts are needed to promote the realistic approach of localization or local adaptation of existing high-quality CPGs to the national context.

Determinants of hand hygiene noncompliance in intensive care units.

BACKGROUND: Hand hygiene (HH) is single most effective preventive measure for health care-associated infection, but compliance rates remain low. This study estimated HH compliance among health care workers (HCWs) and examined factors associated with noncompliance. METHODS: An observational study design was carried out in 5 intensive care units (ICUs) at the University Hospital in Riyadh, Saudi Arabia. Among 242 HCWs, a total of 3,940 HH opportunities were observed by 6 trained medical interns and students. The World Health Organization's "Five Moments for Hand Hygiene" procedure was used as a basis for the observations. RESULTS: The overall observed noncompliance rate was 58%. The factors associated with noncompliance were HCW job title (physicians, odds ratio [OR], 2.8; 95% confidence interval [CI], 1.8-4.2; allied health professionals, OR, 2.9, 95% CI, 1.9-4.6); working the a.m. shift (OR, 1.5; 95% CI, 1.3-1.8), working in a pediatric ICU (OR, 1.8; 95% CI, 1.5-2.2), and performance of HH before patient contact (OR, 4.5; 95% CI, 2.6-7.8). CONCLUSIONS: Overall HH noncompliance was high in ICUs of this hospital. The demanding ICU work setting was an important factor associated with noncompliance. HH compliance was highest among therapists and technicians because of fewer patient interactions and thus fewer HH noncompliance opportunities per person. Further studies on the relationship between work environment demands and HH compliance rates are needed.

Sodium oxybate for narcolepsy with cataplexy: systematic review and meta-analysis.

STUDY OBJECTIVES: To assess the efficacy and safety of sodium oxybate (SXB) in narcolepsy-cataplexy patients. DESIGN: Systematic review and meta-analysis. PATIENTS: Adults with narcolepsy-cataplexy. INTERVENTIONS: SXB. MEASUREMENTS AND RESULTS: Electronic databases (e.g., MEDLINE) and references of included studies were searched to identify randomized controlled trials (RCTs) assessing the efficacy and safety of SXB for patients with narcolepsy-cataplexy. Risk of bias was appraised using the Cochrane risk of bias tool. Meta-analysis was conducted in Review Manager Version 5. Six RCTs and 5 companion reports were included after screening 14 full-text articles and 483 citations. All were private-industry funded. SXB (usually 9 g/night) was superior to placebo for reducing mean weekly cataplexy attacks (n = 2 RCTs, mean difference [MD]: -8.5, 95% CI: -15.3, -1.6), increasing maintenance wakefulness test (MWT) (n = 2, MD: 5.18, 95% CI: 2.59-7.78), reducing sleep attacks (n = 2, MD: -9.65, 95% CI: -17.72, -1.59), and increasing Clinical Global Impression scores (n = 3, relative risk, RR: 2.42, 95% CI: 1.77-3.32). SXB did not significantly increase REM sleep versus placebo (n = 2, MD: -0.49, 95% CI: -3.90, 2.92). Patients receiving SXB had statistically more adverse events versus placebo, including nausea (n = 3, relative risk [RR]: 7.74, 95% CI: 3.2, 19.2), vomiting (n = 2, RR: 11.8, 95% CI: 1.6, 89.4), and dizziness (n = 3, RR: 4.3, 95% CI: 1.1, 16.4). Enuresis was not significantly different from placebo (n = 2, RR: 2.6, 95% CI: 0.8, 9.8). All meta-analyses had minimal statistical heterogeneity (p-value > 0.1). CONCLUSION: Narcolepsy patients on SXB have significant reductions in cataplexy and daytime sleepiness. SXB is well tolerated in patients with narcolepsy, and most adverse events were mild to moderate in severity.

Effect of influenza vaccines against mismatched strains: a systematic review protocol.

BACKGROUND: Influenza vaccines are most effective when the antigens in the vaccine match those of circulating influenza strains. The extent to which the vaccine is protective when circulating strains differ from vaccine antigens, or are mismatched, is uncertain. We propose to systematically review the cross-protection offered by influenza vaccines against circulating influenza A or B viruses that are not antigenically well-matched to vaccine strains. METHODS/DESIGN: This is a protocol for a systematic review and meta-analysis. Placebo-controlled randomized clinical trials (RCTs) reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of influenza strains that differed from those circulating will be included. The primary outcome is the incidence of laboratory-confirmed influenza (polymerase chain reaction (PCR) or viral culture). The secondary outcome is the incidence of laboratory-confirmed influenza through antibody assay (a less sensitive test than PCR or viral culture) alone or combined with PCR, and/ or viral culture. The review will be limited to RCTs written in English.We will search MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, previous influenza reviews, and the reference lists of included studies to identify potentially relevant RCTs. Two independent reviewers will conduct all levels of screening, data abstraction, and quality appraisal (using the Cochrane risk of bias tool).If appropriate, random effects meta-analysis of vaccine efficacy will be conducted in SAS (version 9.2) by calculating the relative risk. Vaccine efficacy will be calculated using the following formula: (1 - relative risk × 100). The results will be analyzed by type of vaccine (live attenuated, trivalent inactivated, or other). Subgroup analysis will include the effects of age (children, adults, older participants), and influenza A versus influenza B on the results. For influenza B we will also consider variable degrees of antigenic mismatch (lineage and drift mismatch). DISCUSSION: Our results can be used by researchers and policy-makers to help predict the efficacy of influenza vaccines during mismatched influenza seasons. Furthermore, the review will be of interest to patients and clinicians to determine whether to get immunized or support immunization for a particular influenza season.

Histamine H2 receptor antagonists for decreasing gastrointestinal harms in adults using acetylsalicylic acid: systematic review and meta-analysis.

BACKGROUND: It is unclear if histamine H2 receptor antagonists (H2 blockers) prevent a variety of gastrointestinal harms among patients taking acetylsalicylic acid (ASA) over long periods. METHODS: Electronic databases (e.g., MEDLINE, Embase and Cochrane Central Register of Controlled Trials; from inception to November 2010) and reference lists of retrieved articles were searched. Randomized placebo-controlled trials (RCTs) assessing the efficacy of H2 blockers in reducing gastrointestinal harms (bleeding, ulcers) among adults taking ASA for 2 weeks or longer were included. Two reviewers independently abstracted study and patient characteristics and appraised study quality using the Cochrane risk-of-bias tool. Peto odds ratio (OR) meta-analysis was performed, 95% confidence intervals (CIs) were calculated, and statistical heterogeneity was assessed using the I (2) and χ(2) statistics. RESULTS: Six RCTs (4 major publications and 2 companion reports) with a total of 498 participants (healthy volunteers or patients with arthritis, cardiovascular or cerebrovascular disease, or diabetes mellitus) were included. One trial adequately reported allocation concealment and sequence generation, with the other 3 trials being judged as unclear for both aspects. In one RCT, no statistically significant differences for gastrointestinal hemorrhage requiring admission to hospital (p = 0.14) or blood transfusion (p = 0.29) were observed between the group receiving concomitant famotidine and ASA and the group receiving concomitant placebo and ASA. After a median of 8 weeks' follow-up, H2 blockers were more effective than placebo in reducing gastrointestinal hemorrhage (2 RCTs, total of 447 patients, OR 0.07, 95% CI 0.02-0.23) and peptic ulcers (3 RCTs, total of 465 patients, OR 0.21, 95% CI 0.12-0.36) among patients taking ASA for 2 weeks or longer. Despite substantial clinical heterogeneity across the studies, including types of H2 blockers, dosing of ASA and underlying conditions, no statistical heterogeneity was observed. INTERPRETATION: H2 blockers reduced gastrointestinal harm among patients taking ASA for 2 weeks or longer. These results should be interpreted with caution, because of the small number of studies identified for inclusion.

Enteral versus parenteral nutrition for acute pancreatitis.

BACKGROUND: Acute pancreatitis creates a catabolic stress state promoting a systemic inflammatory response and nutritional deterioration. Adequate supply of nutrients plays an important role in recovery. Total parenteral nutrition (TPN) has been standard practice for providing exogenous nutrients to patients with severe acute pancreatitis. However, recent data suggest that enteral nutrition (EN) is not only feasible, but safer and more effective.Therefore, we sought to update our systematic review to re-evaluate the level of evidence. OBJECTIVES: To compare the effect of TPN versus EN on mortality, morbidity and length of hospital stay in patients with acute pancreatitis. SEARCH STRATEGY: Trials were identified by computerized searches of The Cochrane Controlled Trials Register, MEDLINE, and EMBASE. Additional studies were identified by searching Scisearch, bibliographies of review articles and identified trials. The search was undertaken in August 2000 and updated in September 2002, October 2003, November 2004 and November 2008. No language restrictions were applied. SELECTION CRITERIA: Randomized clinical trials comparing TPN to EN in patients with acute pancreatitis. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data and assessed trial quality. A standardized form was used to extract relevant data. MAIN RESULTS: Eight trials with a total of 348 participants were included. Comparing EN to TPN for acute pancreatitis, the relative risk (RR) for death was 0.50 (95% CI 0.28 to 0.91), for multiple organ failure (MOF) was 0.55 (95% CI 0.37 to 0.81), for systemic infection was 0.39 (95% CI 0.23 to 0.65), for operative interventions was 0.44 (95% CI 0.29 to 0.67), for local septic complications was 0.74 (95% CI 0.40 to 1.35), and for other local complications was 0.70 (95% CI 0.43 to 1.13). Mean length of hospital stay was reduced by 2.37 days in EN vs TPN groups (95% CI -7.18 to 2.44). Furthermore, a subgroup analysis for EN vs TPN in patients with severe acute pancreatitis showed a RR for death of 0.18 (95% CI 0.06 to 0.58) and a RR for MOF of 0.46 (95% CI 0.16 to 1.29). AUTHORS' CONCLUSIONS: In patients with acute pancreatitis, enteral nutrition significantly reduced mortality, multiple organ failure, systemic infections, and the need for operative interventions compared to those who received TPN. In addition, there was a trend towards a reduction in length of hospital stay. These data suggest that EN should be considered the standard of care for patients with acute pancreatitis requiring nutritional support.