Limited Methodological Quality Research Articles

Charles Bonnet syndrome and cognitive impairment: a systematic review.

ABSTRACT Background: Charles Bonnet syndrome (CBS) is defined as complex persistent visual hallucinations in the absence of mental disorder. It is common in conditions causing significant visual impairment. Many authors advise reassurance, considering the condition benign. However, others have suggested that CBS may in some patients represent the early stages of dementia. This review seeks to systematically examine the evidence for any link between CBS and cognitive impairment. Methods: Literature search using OVID Medline, PsychINFO, and Embase. Results: Three studies where cognitive functioning was the primary focus of the research were found. All were small, did not properly apply diagnostic criteria, and reported conflicting results. Eight other studies commented on cognitive functioning, but none used tests sufficiently sensitive to detect changes seen in early dementia. One hundred and thirty four case reports were scrutinized, and reports found of 16 patients with CBS where dementia emerged. High rates of partial insight at diagnosis of CBS were seen in these patients. Conclusions: There have been no adequately powered studies, using accepted diagnostic criteria, where changes in cognitive functioning were the primary outcome. Existing studies are of limited methodological quality and allow no conclusion regarding a relationship between cognitive impairment and CBS to be reached. Numerous case reports of dementia developing in patients with CBS and partial insight raise the possibility of a link between these conditions. There is a clear need for properly constructed studies to investigate this.

Prenatal risk factors for Tourette Syndrome: a systematic review

BackgroundTourette Syndrome (TS) appears to be an inherited disorder, although genetic abnormalities have been identified in less than 1% of patients, and the mode of inheritance is uncertain. Many studies have investigated environmental factors that might contribute to the onset and severity of tics and associated comorbidities such as obsessive compulsive disorder (OCD) and attention deficit hyperactive disorder (ADHD). A systematic review and qualitative analysis were performed to provide a broad view of the association between pre- and perinatal factors and TS.MethodsThe Medline, Embase and PsycINFO databases were searched using terms specific to Tourette’s syndrome and keywords such as “pregnancy”, “prenatal”, “perinatal”, “birth” and “neonatal”. Studies were limited to studies on human subjects published in English or French through October 2012.Results22 studies were included. Studies were of limited methodological quality, with most samples derived from specialty clinics, and most exposures ascertained retrospectively. The majority of the results for demographic factors of parents, including age, education, socioeconomic status, and marital status, revealed no significant association with the onset of TS, or the presence of comorbidity. Many factors were reported to be significantly associated with the onset of TS, the presence of comorbidity and symptom severity, but the most consistently reported factors were maternal smoking and low birth weight.ConclusionsThere are few studies evaluating the relationship between pre and perinatal events and TS, and existing studies have major limitations, including the use of clinic rather than epidemiologically derived samples, retrospective data collection on pre and perinatal events and multiple hypothesis testing without appropriate statistical correction. The mechanism by which prenatal and perinatal adversities could lead to TS onset or symptom severity is unknown, but may be related to changes in the dopaminergic system as a result of early brain injury.

Analgesic Treatment in Laparoscopic Gastric Bypass Surgery: a Systematic Review of Randomized Trials

This review aimed to present an overview of the randomized controlled trials investigating analgesic regimens used in laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. Literature search was performed in PubMed and EMBASE databases in August 2013 in accordance to PRISMA guidelines. The literature search identified nine studies eligible for inclusion. The administration of nonsteroidal anti-inflammatory drugs, local anesthetics (intraperitoneally or subfascially/subcutaneously), transversus abdominis plane block, dexmedetomidine, and ketamine may improve analgesia compared to placebo/controls in LRYGB. None of the studies incorporated multimodal procedure-specific analgesic regimens. The Oxford quality scoring system scores indicated a generally limited methodological quality of the included studies. This review documents a need for high-quality, procedure-specific literature concerning analgesic treatment in LRYGB surgery.

Should Blood Donors Be Routinely Screened for Glucose-6-Phosphate Dehydrogenase Deficiency? A Systematic Review of Clinical Studies Focusing on Patients Transfused With Glucose-6-Phosphate Dehydrogenase–Deficient Red Cells

The risk factors associated with the use of glucose-6-phosphate dehydrogenase (G6PD)-deficient blood in transfusion have not yet been well established. Therefore, the aim of this review was to evaluate whether whole blood from healthy G6PD-deficient donors is safe to use for transfusion. The study undertook a systematic review of English articles indexed in COCHRANE, MEDLINE, EMBASE, and CINHAL, with no date restriction up to March 2013, as well as those included in articles' reference lists and those included in Google Scholar. Inclusion criteria required that studies be randomized controlled trials, case controls, case reports, or prospective clinical series. Data were extracted following the Preferred Reporting Items for Systematic Reviews using a previously piloted form, which included fields for study design, population under study, sample size, study results, limitations, conclusions, and recommendations. The initial search identified 663 potentially relevant articles, of which only 13 studies met the inclusion criteria. The reported effects of G6PD-deficient transfused blood on neonates and children appear to be more deleterious than effects reported on adult patients. In most cases, the rise of total serum bilirubin was abnormal in infants transfused with G6PD-deficient blood from 6 hours up to 60 hours after transfusion. All studies on neonates and children, except one, recommended a routine screening for G6PD deficiency for this at-risk subpopulation because their immature hepatic function potentially makes them less able to handle any excess bilirubin load. It is difficult to make firm clinical conclusions and recommendations given the equivocal results, the lack of standardized evaluation methods to categorize red blood cell units as G6PD deficient (some of which are questionable), and the limited methodological quality and low quality of evidence. Notwithstanding these limitations, based on our review of the available literature, there is little to suggest that G6PD-deficient individuals should be excluded from donating red blood cells, although transfusions of such blood may potentially have negative impacts on premature neonates or patients who need repeated transfusions, and thus, for this group, screening for G6PD deficiency may be appropriate.

Cómo responder al paciente con cáncer avanzado que nos plantea el uso de cannabis como tratamiento sintomático

ObjectiveTo contribute ideas to answer advanced cancer patients asking about the use of medicinal cannabis as a symptomatic treatment. MethodBased on a real example, we present a summary of the pharmacology of natural and synthetic cannabinoids, the evidence on its effectiveness as a symptomatic treatment in advanced cancer, and the patient's attitude and expectations raised by the medicinal use of cannabis. ResultThere are more than 60 different cannabinoids (the most relevant: delta-9-tetrahydrocannabinol) and other substances in cannabis. In our setting, patients who ask about the use of cannabis as a symptomatic treatment do not look for synthetic cannabinoids approved in other countries, but rather prefer herbal cannabis or its derivatives. They usually consume smoked cannabis (favoring the earlier onset of plasma levels) or, rarely, in infusion. Use of medicinal cannabis causes a wide variation in plasma concentrations of delta-9-tetrahydrocannabinol. There is evidence supporting a certain effect of synthetic cannabinoids in pain relief (also as an adjuvant), and as antiemetic for chemotherapy-induced nausea and vomiting in cancer patients. This evidence is based primarily on results of studies with limited methodological quality. There is insufficient evidence to assert its effectiveness in the treatment of anorexia. Side effects of moderate doses of synthetic cannabinoids or medicinal cannabis are mostly mild, as well as their psycho-neurological profile. The attitude and expectations of the patient, and the way to consume of medical cannabis may favor that part of its benefit may be due to a placebo effect. ConclusionsMedicinal cannabis does not seem as active as patients expect, or as toxic as many professionals suspect. To respond to the advanced cancer patient asking about their use as symptomatic treatment is advisable to avoid prejudice, to respect and to act with caution seeking the patient's symptomatic benefit.

Hormonal versus non-hormonal contraceptives in women with diabetes mellitus type 1 and 2

Adequate contraceptive advice is important in both women with diabetes mellitus type 1 and type 2 to reduce the risk of maternal and infant morbidity and mortality in unplanned pregnancies. A wide variety of contraceptives are available for these women. However, hormonal contraceptives might influence carbohydrate and lipid metabolism and increase micro- and macrovascular complications, so caution in selecting a contraceptive method is required. To investigate whether progestogen-only, combined estrogen and progestogen or non-hormonal contraceptives differ in terms of effectiveness in preventing pregnancy, in their side effects on carbohydrate and lipid metabolism, and in long-term complications such as micro- and macrovascular disease when used in women with diabetes mellitus. The search was performed in CENTRAL, MEDLINE, EMBASE, POPLINE, CINAHL, WorldCat, ECO, ArticleFirst, the Science Citation Index, the British Library Inside, and reference lists of relevant articles. The last search was performed in January 2013. In addition, experts in the field and pharmaceutical companies marketing contraceptives were contacted to identify published, unpublished or ongoing studies. Randomised and quasi-randomised controlled trials that studied women with diabetes mellitus comparing: 1. hormonal versus non-hormonal contraceptives; 2. progestogen-only versus estrogen and progestogen contraceptives; 3. contraceptives containing < 50 µg estrogen versus contraceptives containing ≥ 50 µg estrogen; and 4. contraceptives containing first-, second- and third-generation progestogens, drospirenone and cyproterone acetate. The principal outcomes were contraceptive effectiveness, diabetes control, lipid metabolism and micro- and macrovascular complications. Two investigators evaluated the titles and abstracts identified from the literature search. Quality assessment was performed independently with discrepancies resolved by discussion or consulting a third review author. Because the trials differed in studied contraceptives, participant characteristics and methodological quality, we could not combine the data in a meta-analysis. The trials were therefore examined on an individual basis and narrative summaries were provided. Four randomised controlled trials were included. No unintended pregnancies were reported during the study periods. Only one trial was of good methodological quality. It compared the influence of a levonorgestrel-releasing intrauterine device (IUD) versus a copper IUD on carbohydrate metabolism in women with type 1 diabetes mellitus. No significant difference was found between the two groups. The other three trials were of limited methodological quality. Two compared progestogen-only pills with different estrogen and progestogen combinations, and one also included the levonorgestrel-releasing IUD and copper IUD. The trials reported that blood glucose levels remained stable during treatment with most regimens. Only high-dose combined oral contraceptives and 30 µg ethinylestradiol + 75 µg gestodene were identified as slightly impairing glucose homeostasis. The three studies found conflicting results regarding lipid metabolism. Some combined oral contraceptives appeared to have a minor adverse effect while others appeared to slightly improve lipid metabolism. The copper IUD and progestogen-only oral contraceptives also slightly improved lipid metabolism and no influence was seen while using the levonorgestel-releasing IUD. Only one study reported on micro- and macrovascular complications. It observed no signs or symptoms of thromboembolic incidents or visual disturbances, however study duration was short. Only minor adverse effects were reported in two studies. The four included randomised controlled trials in this systematic review provided insufficient evidence to assess whether progestogen-only and combined contraceptives differ from non-hormonal contraceptives in diabetes control, lipid metabolism and complications. Three of the four studies were of limited methodological quality, sponsored by pharmaceutical companies and described surrogate outcomes. Ideally, an adequately reported, high-quality randomised controlled trial analysing both intermediate outcomes (that is glucose and lipid metabolism) and true clinical endpoints (micro- and macrovascular disease) in users of combined, progestogen-only and non-hormonal contraceptives should be conducted. However, due to the low incidence of micro- and macrovascular disease and accordingly the large sample size and long follow-up period needed to observe differences in risk, a randomised controlled trial might not be the ideal design.

Regional Scalp Block for Postcraniotomy Analgesia

Up to two-thirds of patients report moderate to severe surgical site pain after craniotomy procedures, and there is understandable reluctance to manage these symptoms with systemic opioids that may impair neurological assessment. Furthermore, there is a lack of consensus and evidence concerning alternative analgesia strategies for cranial neurosurgery. Regional scalp block (RSB) is an established technique that involves infiltration of local anesthetic (LA) at well-defined anatomical sites targeting the major sensory innervation of the scalp. However, the efficacy of RSB in reducing postoperative pain remains unclear. In this study, we sought to systematically identify and review randomized controlled trials (RCTs) of RSB and synthesize an overall estimate of efficacy in a quantitative meta-analysis. Medline, EMBASE, and the Cochrane Central Register of Controlled Trials databases were searched for all RCTs evaluating the effect of RSB on postoperative pain after craniotomy. Titles, abstracts, and papers were reviewed independently by 2 authors against predefined inclusion criteria. Two authors independently assessed the quality of included studies and extracted data on patient-reported pain scores, other analgesia requirements, and complications of RSB. Pain scores were scaled to a common 0 to 10 interval with higher scores indicating more severe pain. Meta-analysis of the pooled treatment effect was performed with a random-effects inverse-variance weighted model; heterogeneity was quantified with the I(2) statistic. The literature search identified 138 unique citations, from which 7 RCTs with a total recruitment of 320 patients met the inclusion criteria. All studies used standard LA drugs (lidocaine, bupivacaine, or ropivacaine); in 3 studies, LA was combined with epinephrine. In 3 studies, RSB was performed preoperatively; in the other 4 studies, it was administered postoperatively after wound closure. No complications attributable to RSB were reported. Meta-analysis found a pooled reduction in pain score at 1 hour postoperatively (N = 5 studies; mean difference, -1.61; 95% confidence interval, -2.06 to -1.15; P < 0.001; I(2) = 0%). Subgroup analysis of preoperative RSB showed significant reduction in pain scores at 2, 4, and 6 to 8 hours after surgery whereas postoperative RSB was associated with significant reduction in pain scores at 2, 4, 6 to 8 and 12 hours assessments. There was also an overall reduction in the opioid requirements over the first 24 hours postoperatively, although with significant heterogeneity among the studies (N = 6 studies; standardized mean difference, -0.79; 95% confidence interval, -1.55 to -0.03; P = 0.04; I(2) = 86%). Published RCTs of RSB are small and of limited methodological quality but meta-analysis shows a consistent finding of reduced postoperative pain. This evidence supports the use of RSB for patients undergoing craniotomy.

Medical and surgical treatment for ocular myasthenia.

Approximately 50% of people with myasthenia gravis present with purely ocular symptoms, so called ocular myasthenia. Of these between 50% to 60% develop generalized disease, most within two years. Their management is controversial. This is an update of a review first published in 2006 and previously updated in 2008 and 2010. To assess the effects of treatments for ocular myasthenia and to answer three specific questions. Are there any treatments that impact the progression from ocular to generalized disease? Are there any treatments that improve symptoms of diplopia or ptosis? What is the frequency of adverse effects associated with treatments used? In this updated review, we searched the Cochrane Neuromuscular Disease Group Specialized Register (3 August 2012), CENTRAL (2012, Issue 7), MEDLINE (January 1996 to July 2012) and EMBASE (January 1974 to July 2012) for randomized controlled trials (RCTs) as well as case-control and cohort studies. The titles and abstracts of all articles were read by both authors and the full texts of possibly relevant articles were reviewed. The references of all manuscripts included in the review were scanned to identify additional articles of relevance and experts in the field were contacted to identify additional published and unpublished data. Where necessary, we contacted authors for further information. Inclusion required meeting three criteria: (a) randomized (or quasi-randomized) controlled study design; (b) active treatment compared to placebo, no treatment or some other treatment; and (c) results reported separately for patients with ocular myasthenia (grade 1) as defined by the Myasthenia Gravis Foundation of America. We collected data regarding the risk of progression to generalized myasthenia gravis, improvement in ocular symptoms, and the frequency of treatment-related side effects. In the original review, we identified two RCTs relevant to the treatment of ocular myasthenia, only one of which reported results in terms of the pre-specified outcome measures used in this review. This study included only three participants and was of limited methodological quality. There were no new RCTs in searches conducted for this or previous updates. In the absence of data from RCTs, we present a review of the available observational data. The available randomized controlled literature does not permit any meaningful conclusions about the efficacy of any form of treatment for ocular myasthenia. Data from several reasonably good quality observational studies suggest that corticosteroids and azathioprine may be beneficial in reducing the risk of progression to generalized myasthenia gravis.

Impact of physical activity on activity of daily living in moderate to severe dementia: a critical review.

The objectives of this study were to describe the different modalities of physical activity programs designed for moderate to severe dementia and to identify their impact on functional independence in activities of daily living (ADL). A critical review of randomized controlled trials related to the impact of physical activity programs in moderately to severely demented persons on ADL performance and meta-analysis of the identified studies were performed. Among the 303 identified articles, five responded to the selection criteria. Four out of the five studies demonstrated limited methodological quality. In one high-quality study, physical activity programs significantly delayed deterioration of ADL performance. The program components and ADL assessment tools vary widely across studies. Although the proposed treatments have not proven their efficiency in improving the ADL status of the patients, they were able to limit the decline in ADL functioning. Future research is warranted in order to identify clinically relevant modalities for physical activity programs for people with moderate to severe dementia.

Benign external hydrocephalus: a review, with emphasis on management

Benign external hydrocephalus in infants, characterized by macrocephaly and typical neuroimaging findings, is considered as a self-limiting condition and is therefore rarely treated. This review concerns all aspects of this condition: etiology, neuroimaging, symptoms and clinical findings, treatment, and outcome, with emphasis on management. The review is based on a systematic search in the Pubmed and Web of Science databases. The search covered various forms of hydrocephalus, extracerebral fluid, and macrocephaly. Studies reporting small children with idiopathic external hydrocephalus were included, mostly focusing on the studies reporting a long-term outcome. A total of 147 studies are included, the majority however with a limited methodological quality. Several theories regarding pathophysiology and various symptoms, signs, and clinical findings underscore the heterogeneity of the condition. Neuroimaging is important in the differentiation between external hydrocephalus and similar conditions. A transient delay of psychomotor development is commonly seen during childhood. A long-term outcome is scarcely reported, and the results are varying. Although most children with external hydrocephalus seem to do well both initially and in the long term, a substantial number of patients show temporary or permanent psychomotor delay. To verify that this truly is a benign condition, we suggest that future research on external hydrocephalus should focus on the long-term effects of surgical treatment as opposed to conservative management.

Präventive Maßnahmen zur Kontrakturprophylaxe in der geriatrischen Pflege. Eine systematische Übersichtsarbeit.

Contractures constitute a health problem in mobility-restricted geriatric patients. Contractures are clinically important due to their impact on functional outcome. Prophylactic interventions seem to be indispensable. We performed a systematic review studying the interventions used to prevent immobility-related contractures in the geriatric long-term care. The efficacy and safety of preventive methods was assessed. Electronic literature searches covered the databases PubMed, PEDro, CINAHL and the Cochrane Library (May 2010). Eligibility criteria for studies were: Investigation of an intervention aimed to prevent contractures, conducted in a geriatric and long-term care setting, inclusion of participants aged>65 years. The primary search focused on RCTs, systematic reviews und meta-analysis published between 1990 and May 2010 in English or German. The included studies were analysed and evaluated by one author while a second author checked the results. Methodological quality was critically evaluated using internationally accepted criteria. Eight studies met the inclusion criteria. Prophylactic interventions comprise mobility-encouraging and position-supportive interventions. Mobility-encouraging interventions aim to prevent contractures and immobility, for example offering range-of-motion exercises. Position-supportive interventions are transformations of motion and position, which are conducted with nurses' support. Due to limited methodological quality of these studies, the efficacy of certain measures remains unclear. Further studies on contracture prophylaxis investigating patient-relevant outcomes, interventions' adverse effects and costs are required.

Cost-Effectiveness of Interventions to Enhance Medication Adherence in Psychiatric Patients: A Systematic Review

It was conducted a systematic review of economic evaluations that assessed the cost-effectiveness of interventions to enhance the medication adherence in psychiatric patients. Several bibliographic databases were searched: MEDLINE, MEDLINE in process, PSYCINFO, EMBASE, Cochrane Controlled Trials Register, CINAHL, CRD, EconLit, Science Citation Index and Social Science Citation Index. Full economic evaluations which assessed interventions to enhance the adherence to drug therapy in adult patients with a mental illness were included. Data were extracted and the methodological quality of selected studies was assessed. The information was synthesized through narrative procedures. Four clinical trials and two ongoing studies fulfilled the selection criteria. Two studies did not find significant differences in adherence between the interventions (a compliance-enhancing program, a therapeutic drug monitoring and a pharmacy-based intervention) and the control groups; one study found that a compliance program was more effective than a non-specific counselling intervention over 18 months in psychotic patients; another study found better results in terms of adherence among high-severity depressed patients receiving a stepped collaborative care during 12 months in comparison to a control group; in moderate-severity patients the differences disappeared after the first 6 months. None of the four studies found significant differences in costs between groups because of the low statistical power. In summary, adherence enhancing programs could be cost-effective in psychiatric patients although this statement is based on few studies with limited methodological quality. It is necessary more and better research on the cost-effectiveness of interventions in the field of mental health.

Limited Evidence that Cantilevers Are Associated With Slightly Lower Survival Rates of Implant-Supported Fixed Partial Dentures

Systematic review conclusion. Implant-supported fixed partial dentures (FPDs) with cantilevers have a higher incidence of technical complications and lower five-year survival rates compared with those for FPDs without cantilevers.Critical summary assessment. The authors included only three studies (totaling 175 patients) of limited methodological quality, which weakened their conclusions.Evidence quality rating. Limited. Systematic review conclusion. Implant-supported fixed partial dentures (FPDs) with cantilevers have a higher incidence of technical complications and lower five-year survival rates compared with those for FPDs without cantilevers. Critical summary assessment. The authors included only three studies (totaling 175 patients) of limited methodological quality, which weakened their conclusions. Evidence quality rating. Limited. In partially dentate patients who require implant-supported fixed partial dentures (FPDs), do FPDs with cantilevers exhibit different survival rates, associated complications or both compared with FPDs without cantilevers? The authors searched one electronic database for systematic reviews and clinical studies that compared the survival rates and associated complications (technical and biological) of implant-supported FPDs with and without cantilevers. Search criteria specified English-language studies published up to November 2008 that involved a follow-up period of at least five years. The authors did not contact the authors of some of the excluded studies to obtain missing information. The authors identified a total of 103 articles from their initial search. Two independent reviewers chose 11 of these articles for full-text review. They identified an additional article from a hand search of the literature. After conducting a full-text review of the 12 articles, the reviewers selected a total of three studies composed of 175 patients (a total of 216 FPDs). The five-year weighted mean survival rate of the implant-supported FPDs with cantilevers was 91.9 percent, whereas the weighted mean survival rate of the FPDs without cantilevers was 95.8 percent. Implant fracture was the main cause of failure for the FPDs with cantilevers. The weighted mean rate of technical complications was 20.3 percent for the FPDs with cantilevers and 9.7 percent for the FPDs without cantilevers. Porcelain fractures and bridge-screw loosening were the most common complications. The authors did not report any statistically significant differences between the two groups with regard to peri-implant bone-level change. Both prosthetic designs demonstrated high five-year survival rates, but FPDs with cantilevers experienced a higher incidence of minor technical complications. Regarding bone level around the implants (a potential biological complication), the cantilever design did not demonstrate any statistically significant differences from the non-cantilever design.

Zotepine versus other atypical antipsychotics for schizophrenia

In many parts of the world, particularly in industrialised countries, second generation (atypical) antipsychotic drugs have become first line treatment for people suffering from schizophrenia. The question as to whether the effects of various second generation antipsychotic drugs differ is a matter of debate. To evaluate the effects of zotepine compared with other second generation antipsychotic drugs for people suffering from schizophrenia and schizophrenia-like psychoses. We searched the Cochrane Schizophrenia Group Trials Register (November 2009), inspected references of all identified studies for further trials and contacted authors of trials for additional information. We included only randomised clinical controlled trials that compared zotepine with any forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole or ziprasidone in people suffering from only schizophrenia or schizophrenia-like psychoses. SS and KK extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. We included three studies (total n=289; 2 RCTs zotepine vs clozapine; 1 RCT zotepine vs clozapine vs risperidone (at 4 mg, 8 mg doses) vs remoxipride. All studies were of limited methodological quality. When zotepine was compared with clozapine, it was clozapine that was found to be more effective in terms of global state (n=59, 1 RCT, RR No clinically significant response 8.23 CI 1.14 to 59.17). Mental state scores also favoured clozapine (n=59, 1 RCT, MD average score (BPRS total, high = poor) 6.00 CI 2.17 to 9.83) and there was less use of antiparkinson medication in the clozapine group (n=116, 2 RCTs, RR 20.96 CI 2.89 to 151.90). In the comparison of zotepine and risperidone, mental state scoring found no significant difference between the groups (vs 4 mg: n=40, 1 RCT, MD average endpoint score (BPRS total, high=poor) 1.40 CI -9.82 to 12.62; vs 8 mg: n=40, 1 RCT, MD -1.30 CI -12.95 to 10.35) and use of antiparkinson medication was equivocal (vs 4 mg: n=40, 1 RCT, MD 1.80 CI -0.64 to 4.24; vs 8 mg: n=40, 1 RCT, MD 2.50 CI -0.05 to 5.05). Finally, when zotepine was compared with remoxipride, again no effect was found for mental state (n=58, 1 RCT, MD average endpoint score (BPRS total, high=poor) 5.70 CI -4.13 to 15.53) and there was no significant difference between the two groups in terms of use of antiparkinson medication (n=49, 1 RCT, RR 0.97 CI 0.41 to 2.29).Data on important other outcomes such as other adverse events, service use or satisfaction with care, quality of life were not available. The evidence base around zotepine is insufficient to provide firm conclusions on its absolute or relative effects. This is despite it being in use in Austria, France, Germany, Japan and the UK.

Surgical Compared with Conservative Treatment for Acute Nondisplaced or Minimally Displaced Scaphoid Fractures

There is a current trend in orthopaedic practice to treat nondisplaced or minimally displaced fractures with early open reduction and internal fixation instead of cast immobilization. This trend is not evidence-based. In this systematic review and meta-analysis, we pool data from trials comparing surgical and conservative treatment for acute nondisplaced and minimally displaced scaphoid fractures, thus aiming to summarize the best available evidence. A systematic literature search of the medical literature from 1966 to 2009 was performed. We selected eight randomized controlled trials comparing surgical with conservative treatment for acute nondisplaced or minimally displaced scaphoid fractures in adults. Data from included studies were pooled with use of fixed-effects and random-effects models with standard mean differences and risk ratios for continuous and dichotomous variables, respectively. Heterogeneity across studies was assessed with calculation of the I(2) statistic. Four hundred and nineteen patients from eight trials were included. Two hundred and seven patients were treated surgically, and 212 were treated conservatively. Most trials lacked scientific rigor. Our primary outcome parameter, standardized functional outcome, which was assessed for 247 patients enrolled in four trials, significantly favored surgical treatment (p < 0.01). With regard to our secondary parameters, we found heterogeneous results that favored surgical treatment in terms of satisfaction (assessed in one study), grip strength (six studies), time to union (three studies), and time off work (five studies). In contrast, we found no significant differences between surgical and conservative treatment with regard to pain (two studies), range of motion (six studies), the rates of nonunion (six studies) and malunion (seven studies), and total treatment costs (two studies). The rate of complications was higher in the surgical treatment group (23.7%) than in the conservative group (9.1%), although this difference was not significant (p = 0.13). There was a nearly significantly higher rate of scaphotrapezial osteoarthritis in the surgical treatment group (p = 0.05). Based on primary studies with limited methodological quality, this study suggests that surgical treatment is favorable for acute nondisplaced and minimally displaced scaphoid fractures with regard to functional outcome and time off work; however, surgical treatment engenders more complications. Thus, the long-term risks and short-term benefits of surgery should be carefully weighed in clinical decision-making.

Effectiveness of Particle Repositioning Maneuvers in the Treatment of Benign Paroxysmal Positional Vertigo: A Systematic Review

Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo. The purpose of this systematic review was to determine whether patients diagnosed with posterior canal (PC) BPPV, based on positional testing, and treated with a particle repositioning maneuver will show the resolution of benign paroxysmal positional nystagmus (BPPN) on the Dix-Hallpike Test performed 24 hours or more after treatment. Data were obtained from an electronic search of the MEDLINE, EMBASE, and CINAHL databases from 1966 through September 2009. The study topics were randomized controlled trials (RCTs), quasi-RCTs, the diagnosis of PC BPPV, treatment with the particle repositioning maneuver, and outcome measured with a positional test 24 hours or more after treatment. Data extracted were study descriptors and the information used to code for effect size. In 2 double-blind RCTs, the odds in favor of the resolution of BPPN were 22 times (95% confidence interval=3.41-141.73) and 37 times (95% confidence interval=8.75-159.22) higher in people receiving the canalith repositioning procedure (CRP) than in people receiving a sham treatment. This finding was supported by the results reported in 8 nonmasked quasi-RCTs. Studies with limited methodological quality suggested that a liberatory maneuver (LM) was more effective than a control intervention; there was no significant difference in the effectiveness of the LM and the effectiveness of the CRP; the self-administered CRP was more effective than the self-administered LM; and the CRP administered together with the self-administered CRP was more effective than the CRP administered alone. The Brandt-Daroff exercises were the least effective self-administered treatments. The limitations included the methodological quality of the studies, the lack of quality-of-life measures, and confounding factors in reporting vertigo. Randomized controlled trials provided strong evidence that the CRP resolves PC BPPN, and quasi-RCTs suggested that the CRP or the LM performed by a clinician or with proper instruction at home by the patient resolves PC BPPN. There were no data on the effects of the maneuvers on outcomes relevant to patients.

Comprehensive rehabilitation programmes in the chronic phase after severe brain injury: A systematic review

The aim of this study was to perform a systematic review of the effectiveness of comprehensive rehabilitation programmes for adults in the chronic phase after severe acquired brain injury. PubMed, PsychINFO and PsychLit were searched for articles published between 1990 and 2008 and a quality assessment was performed. The comprehensive programmes were subdivided into neurobehavioral interventions, residential community reintegration and day-treatment programmes. The extracted data included study characteristics, patient characteristics and intervention characteristics. Thirteen studies met pre-established criteria. Two studies were randomized controlled trials, 5 were controlled comparative studies and 6 were uncontrolled longitudinal cohort studies. Overall, their methodological quality was limited. The investigated programmes led to substantial improvement in daily life functioning and community integration of severe chronic brain injury patients, with lasting effects at follow-up. Day-treatment programmes had the highest level of evidence. Comprehensive rehabilitation programmes appear to be effective in terms of a reduction in psychosocial problems, a higher level of community integration and an increase in employment. Although this is the first review to differentiate between specific programmes, clear-cut clinical recommendations cannot yet be set out due to limited methodological quality and poor description of patient and intervention characteristics. Specific recommendations for future studies are given.

Chemonukleolyse und intradiskale Elektrotherapie: was ist die gegenwärtige Evidenz?

We evaluated the efficacy and safety of chemonucleolysis and intradiscal electrothermal therapy (IDET) on the basis of the data presented in recently published papers with respect to pain relief, function, and complication rates. Detailed searches for English and German articles published between 2003 and 2008 were performed in a number of electronic databases. Further publications were identified by manual search. For summarizing the evidence, we considered only systematic reviews and controlled studies. The internal validity of reviews and studies was judged by two authors independently. Data extraction was performed by one author, and the extracted data was checked for completeness and correctness by a second author. The evidence of the efficacy of chemonucleolysis using chymopapain or collagenase is summarized in two recent, high-quality systematic reviews. We found 5 controlled studies evaluating nucleolysis using an oxygen-ozone mixture (O (2)O (3)-nucleolysis). Some of those studies were of limited methodological quality, but all showed the efficacy of O (2)O (3)-nucleolysis in comparison to microdiscectomy or the use of alternative substances. There is hardly any data regarding O (2)O (3)-nucleolysis complications. Regarding IDET, the authors of the 6 identified systematic reviews come to different conclusions about the efficacy of the procedure. The results of the 3 included controlled IDET studies, of which 2 are of high methodological quality, are also conflicting. The complication rates range from 0 to 15 %. In summary, the evidence of efficacy is presently more compelling for chemonucleolysis than for IDET. This may also be because indications for chemonucleolysis are more firmly established. However, safety aspects should be better evaluated and presented in the literature.

The devil is in the details…or not? A primer on individual patient data meta-analysis

A systematic review is the process by which primary studies are identified, critically appraised, and interpreted according to a predefined plan to answer clinically important questions with minimal bias and...

The devil is in the details…or not? A primer on individual patient data meta-analysis

A systematic review is the process by which primary studies are identified, critically appraised, and interpreted according to a predefined plan to answer clinically important questions with minimal bias and random error. When the results are quantitatively combined, the review is referred to as a “meta-analysis.” Meta-analysis provides more precise estimates of treatment benefits and harms, may reveal treatment effects that would otherwise go undetected in individual trials, and provides a succinct “bottom line” for a clinical question based on the best available evidence.1 A variation of this method is individual patient data (IPD) meta-analysis where analyses are done using original data and outcomes for each person enrolled in relevant studies; patient databases from each study are combined into a single large database, and analysed using methods that account for variation both within studies and between studies. What is the difference between conventional and IPD meta-analysis? In conventional meta-analysis, aggregated data are extracted from published and unpublished reports according to a predetermined protocol. Analysis is performed by calculating a weighted average for effect (eg, relative risk) across randomised trials.2 Limitations of this approach include risk of publication bias,3 heterogeneity in trial results,4 inability to perform intention-to-treat analyses when relevant patient data are excluded or missing,5 and limited methodological quality of source studies.6 Because each randomised trial in a …