Systematic Literature Review In Medline Research Articles

The global epidemiology of chikungunya from 1999 to 2020: A systematic literature review to inform the development and introduction of vaccines.

Chikungunya fever is an acute febrile illness that is often associated with severe polyarthralgia in humans. The disease is caused by chikungunya virus (CHIKV), a mosquito-borne alphavirus. Since its reemergence in 2004, the virus has spread throughout the tropical world and several subtropical areas affecting millions of people to become a global public health issue. Given the significant disease burden, there is a need for medical countermeasures and several vaccine candidates are in clinical development. To characterize the global epidemiology of chikungunya and inform vaccine development, we undertook a systematic literature review in MEDLINE and additional public domain sources published up to June 13, 2020 and assessed epidemiological trends from 1999 to 2020. Observational studies addressing CHIKV epidemiology were included and studies not reporting primary data were excluded. Only descriptive analyses were conducted. Of 3,883 relevant sources identified, 371 were eligible for inclusion. 46% of the included studies were published after 2016. Ninety-seven outbreak reports from 45 countries and 50 seroprevalence studies from 31 countries were retrieved, including from Africa, Asia, Oceania, the Americas, and Europe. Several countries reported multiple outbreaks, but these were sporadic and unpredictable. Substantial gaps in epidemiological knowledge were identified, specifically granular data on disease incidence and age-specific infection rates. The retrieved studies revealed a diversity of methodologies and study designs, reflecting a lack of standardized procedures used to characterize this disease. Nevertheless, available epidemiological data emphasized the challenges to conduct vaccine efficacy trials due to disease unpredictability. A better understanding of chikungunya disease dynamics with appropriate granularity and better insights into the duration of long-term population immunity is critical to assist in the planning and success of vaccine development efforts pre and post licensure.

Importance of pesticides for lethal poisoning in India during 1999 to 2018: a systematic review

BackgroundPoisoning is a major problem in India. However, there is little systematic information on the key poisons responsible for most deaths by geographical area and over time. We aimed to review the literature to identify the poison classes causing the greatest number of deaths in India over the last 20 years.MethodsWe performed a systematic literature review in Medline, Embase and Google Scholar (1999–2018), and Indian online medical journals, to find papers that reported deaths from all forms of poisoning in India, with last search 20 April 2020. We included epidemiological studies, observational studies, randomised trials, interventional studies, and case series published from 1999 to 2018 that showed the number of deaths and autopsy studies indicating the specific poisons or poison classes. Studies providing the case fatality for specific poisons or classes, which enabled calculation of the number of deaths, were also included. We excluded deaths due to animal bites and stings, ethanol or methanol poisoning, and gas inhalation as well as papers reporting a single death (case study of single patient). We grouped the papers into 5-year intervals and identified the two most common poison classes in each paper. We used descriptive statistics to summarise the findings over time based on the causative poison and the location of the study.ResultsWe identified 186 papers reporting 16,659 poisoning deaths between 1999 and 2018. The number of publications per 5-year interval showed no clear trend over the period (48, 38, 67, and 36 for consecutive periods). Half of the deaths (n = 8338, 50.0%) were reported during the first 5 years of the study (1999–2003), the number of deaths declining thereafter (to n = 1714 in 2014–2018). Deaths due to pesticide poisoning (94.5%) were dominant across the study period compared to other classes of poison [hair dye paraphenylenediamine poisoning (2.6%), medicine overdose (1.4%) or plant poisoning (1.0%)]. Among the pesticides, aluminium phosphide was the most important lethal poison during the first 10 years before declining markedly; organophosphorus insecticides were important throughout the period, becoming dominant in the last decade as aluminium phosphide cases declined. Unfortunately, few papers identified the specific organophosphorus insecticide responsible for deaths.ConclusionUse of the published literature to better understand the epidemiology of lethal poisoning in India has clear limitations, including secular variation in publishing practices and interest in poisoning. Unfortunately, there are no long-term detailed, combination hospital and community studies from India to provide this information. In their absence, our review indicates that pesticides are the most important poison in India, with organophosphorus insecticides replacing aluminium phosphide as the key lethal poison after government regulatory changes in 2001 reduced the latter’s lethality. Plant and hair dye poisoning and medicines overdose caused few deaths. Aluminium phosphide deaths mostly occurred in northern Indian states, whereas deaths from organophosphorus insecticide poisoning occurred throughout India. Paraquat poisoning has become a clinical problem in the last 10 years. Lethal pesticide poisoning remains alarmingly common, emphasising the need for additional regulatory interventions to curtail the burden of pesticide poisoning deaths in India. More detailed reporting about the specific pesticide involved in lethal poisoning will be helpful to guide regulatory decisions.

Critical appraisal and issues regarding generalisability of comparative effectiveness studies of NOACs in atrial fibrillation and their relation to clinical trial data: a systematic review

ObjectiveTo critically appraise the published comparative effectiveness studies on non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF). Results were compared with expectations formulated on the basis of...

RE1 Financing and Reimbursement for Personalised Medicine - Are WE There YET?

The number of healthcare interventions that can facilitate personalised medicine (PM) is increasing, and several international and national initiatives have been launched to support the PM translation into clinical practice. Tumour agnostic drugs (Vitrakvi), gene therapies (Luxturna) and companion diagnostics (OncotypeDX) have made it into the clinic, however, translation remains variable, partly due to reimbursement challenges. Reimbursement delays discourage investment in PM research and development (R&D). Current landscape and promising examples in PM financing and reimbursement should be described to facilitate the engagement of stakeholders into providing models that would pave the way for the uptake of PM. Therefore, our objective was to review financing and reimbursement models for PM and summarise to what extent these models incentivise and facilitate uptake. We performed a systematic literature review in Medline, Embase, Web of Science, Econlit, Google Scholar, Google and subject-specific webpages to identify publications in English between 2009 and 2019 that described financing and reimbursement of PM. Data were synthesised narratively to report on the models, and on incentives and disincentives, facilitators and barriers for PM uptake. We included 114 papers. R&D of PM was financed through public and private sources. PM was reimbursed mainly through single fees, DRGs, and bundled payments. Risk-sharing outcome-based payments were applied primarily to gene, cell and targeted therapies (Luxturna, Kymriah, Strimvelis), and some companion diagnostics (OncotypeDX). The main barriers and disincentives to adoption of PM were the lack of demonstrable benefit in HTA, and existing reimbursement through billing and coding. Few examples of public-private risk-sharing outcome-based agreements showed potential to facilitate reimbursement and incentivise investment in R&D of PM. Public-private financing agreements and risk-sharing outcome-based reimbursement could overcome current limitations in the development and uptake of PM, and pave the way to realise the full benefits of PM on individual health and healthcare system sustainability.

Prehospital Tourniquets in Civilians: A Systematic Review.

Terrorist attacks and civilian mass-casualty events are frequent, and some countries have implemented tourniquet use for uncontrollable extremity bleeding in civilian settings. The aim of this study was to summarize current knowledge on the use of prehospital tourniquets to assess whether their use increases the survival rate in civilian patients with life-threatening hemorrhages from the extremities. Systematic literature review in Medline (Ovid), Embase (Ovid), Cochrane Library, and Epistemonikos was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. The search was performed in January 2019. All types of studies that examined use of tourniquets in a prehospital setting published after January 1, 2000 were included. The primary outcome was mortality with and without tourniquet, while adverse effects of tourniquet use were secondary outcomes. Among 3,460 screened records, 55 studies were identified as relevant. The studies were highly heterogeneous with low quality of evidence. Most studies reported increased survival in the tourniquet group, but few had relevant comparators, and the survival benefit was difficult to estimate. Most studies reported a reduced need for blood transfusion, with few and mainly transient adverse effects from tourniquet use. Despite relatively low evidence, the studies consistently suggested that the use of commercial tourniquets in a civilian setting to control life-threatening extremity hemorrhage seemed to be associated with improved survival, reduced need for blood transfusion, and few and transient adverse effects.

Different Hydraulic Constructs to Optimize the Venous Drainage of DIEP Flaps in Breast Reconstruction: Decisional Algorithm and Review of the Literature.

Venous congestion is the most common perfusion-related complication of deep inferior epigastric artery perforator (DIEP) flap. Several hydraulic constructs can be created for venous superdrainage in case of flap venous engorgement or as a preventive measure. These can be classified based on the choice of the draining vein of the flap, either a second deep inferior epigastric vein (DIEV) or a superficial inferior epigastric vein (SIEV), and of the recipient vein, either a vein of the chest or the DIEV. We conducted a comprehensive systematic literature review in Medline, Scopus, EMBASE, Cochrane Library, and Google Scholar to find publications that reported on venous congestion in DIEP flap. The keywords used were DIEP Flap, breast reconstruction, venous congestion, supercharging, superdrainage, SIEV, and DIEV. Based on the studies found in the literature, we developed an algorithm to guide the surgeon's decision when choosing the veins for the superdrainage anastomosis. Several alternatives for venous anastomosis in superdrainage are available. We propose an algorithm to simplify the choice. The use of the ipsilateral SIEV to be connected to a vein of the chest appears to be advantageous. The anatomical position that allows the easiest anastomosis dictates which chest vein to favor.

Ethical and Social Implications of Using Predictive Modeling for Alzheimer's Disease Prevention: A Systematic Literature Review.

The therapeutic paradigm in Alzheimer's disease (AD) is shifting from symptoms management toward prevention goals. Secondary prevention requires the identification of individuals without clinical symptoms, yet "at-risk" of developing AD dementia in the future, and thus, the use of predictive modeling. The objective of this study was to review the ethical concerns and social implications generated by this new approach. We conducted a systematic literature review in Medline, Embase, PsycInfo, and Scopus, and complemented it with a gray literature search between March and July 2018. Then we analyzed data qualitatively using a thematic analysis technique. We identified thirty-one ethical issues and social concerns corresponding to eight ethical principles: (i) respect for autonomy, (ii) beneficence, (iii) non-maleficence, (iv) equality, justice, and diversity, (v) identity and stigma, (vi) privacy, (vii) accountability, transparency, and professionalism, and (viii) uncertainty avoidance. Much of the literature sees the discovery of disease-modifying treatment as a necessary and sufficient condition to justify AD risk assessment, overlooking future challenges in providing equitable access to it, establishing long-term treatment outcomes and social consequences of this approach, e.g., medicalization. The ethical/social issues associated specifically with predictive models, such as the adequate predictive power and reliability, infrastructural requirements, data privacy, potential for personalized medicine in AD, and limiting access to future AD treatment based on risk stratification, were covered scarcely. The ethical discussion needs to advance to reflect recent scientific developments and guide clinical practice now and in the future, so that necessary safeguards are implemented for large-scale AD secondary prevention.

Effectiveness, immunogenicity and safety of 23-valent pneumococcal polysaccharide vaccine revaccinations in the elderly: a systematic review.

BackgroundIn many industrialized countries routine vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV-23) is recommended to prevent pneumococcal disease in the elderly. However, vaccine-induced immunity wanes after a few years, and there are controversies around revaccination with PPSV-23. Here, we systematically assessed the effectiveness and safety of PPSV-23 revaccination.MethodWe conducted a systematic literature review in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from inception to June 2015. We included all study types that compared effectiveness, immunogenicity and/or safety of PPSV-23 as a primary vs. a revaccination dose in persons aged 50 years and older. With respect to immunogenicity, we calculated the ratio of geometric mean antibody concentrations and opsonophagocytic indexes at identical time-points after primary and revaccination. Additionally, we compared rates and severity of adverse events (AEs) after primary and revaccination.ResultsWe included 14 observational studies. 10 studies had a prospective design and analysed data on (i) the same individuals after a first and a second dose of PPSV-23 given 1 to 10 years later (n = 5) or (ii) two groups consisting of participants receiving PPSV-23 who were either vaccine-naïve or had received a first PPSV-23 dose 3 to 13 years earlier (n = 5). Three studies used electronic data bases to compare AEs after primary vs. revaccination doses of PPSV-23 after 1 to 10 years and one study had a cross-sectional design. Number of participants in the non-register-based and register-based studies ranged from 29 to 1414 and 360 to 316,000, respectively. 11 out of 14 included studies were at high risk of bias, three studies had an unclear risk of bias. None of the studies reported data on clinical effectiveness. Immunogenicity studies revealed that during the first two months antibody levels tended to be lower after revaccination as compared to primary vaccination. Thereafter, no obvious differences in antibody levels were observed. Compared to primary vaccination, revaccination was associated with an increased risk of local and systemic AEs, which, however, were usually mild and self-limiting. The risk and severity of AEs appeared to decrease with longer intervals between primary and revaccination.ConclusionData comparing the effectiveness of primary vs. revaccination with PPSV-23 are still lacking, because there are no studies with clinical endpoints. Data from observational studies indicates that revaccination with PPSV-23 is likely to induce long-term antibody levels that are comparable to those after primary vaccination. Given the high disease burden and the waning of vaccine-induced immunity, revaccination with PPSV-23 could be considered in the elderly. The increased risk of local and systemic AEs can likely be mitigated when giving revaccination at least five years after the primary dose. Adequately powered randomized controlled trials using clinical endpoints are urgently needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2040-y) contains supplementary material, which is available to authorized users.

Neurotoxocariasis: a systematic literature review.

Toxocariasis is a widespread zoonosis, which may result in central nervous system injury. We conducted a systematic literature review in MEDLINE, SciELO, ScienceDirect and Google Scholar up to April 2015 using a combination of the following search terms: "neurotoxocariasis" or "neurotoxocarosis", "toxocariasis" or "toxocarosis" and "cerebral" or "neurologic". One hundred cases of neurotoxocariasis were identified in literature. The majority of patients were male (58%), with a median age of 42years. The predominant clinical pictures were myelitis (60%), encephalitis (47%) and/or meningitis (29%). Fever was inconstant (23%). The suspected mode of transmission, mentioned in only 49% of cases, was mainly contact with dogs and/or cats (67%) and ingestion of contaminated food (31%). Diagnostic imaging examinations found hypodense lesions in cerebral scanner sequences and hyperintense lesions in cerebral MRI T2-weighted sequences in 65 and 57% of encephalitis cases respectively, and in 92% of myelitis cases in medullary MRI T2-weighted sequences. The detection of antibodies against Toxocara spp. was almost constant in blood and cerebrospinal fluid (CSF), 99 and 93%, respectively. The two most commonly used drugs were corticosteroids (72%) and/or albendazole (68%) for a period of at least 3weeks, which often needed to be repeated. Despite a low mortality rate (6%), complete remission was observed in only 40% of cases. Neurotoxocariasis, a completely preventable zoonosis, could lead to severe sequelae failing prompt diagnosis. A compatible clinical picture, presence of risk factors, blood eosinophilia and high titers of antibodies against Toxocara spp. in CSF should alert physicians.

How effective is postoperative packing in FESS patients? A critical analysis of published interventional studies.

The present study aimed to assess the clinical effectiveness of absorbable packing alone, non-absorbable packing alone, and absorbable versus non-absorbable packing in the postoperative care of FESS patients, regarding bleeding control, adhesion formation, wound healing, and overall patient comfort. Systematic literature review in Medline and other database sources until July 2013, and critical analysis of pooled data were conducted. Blinded prospective randomized control trials, prospective, and retrospective comparative studies were included in study selection. The total number of analyzed studies was 19. Placing packs in the middle meatus after endoscopic procedures does not seem to be harmful for postoperative patient care. Regarding the postoperative bleeding rate, absorbable packing is not superior to no postoperative packing (strength of recommendation A). Comparing absorbable to non-absorbable packing, the former one seems slightly more effective than the latter in the aforementioned domain (strength of recommendation C). Absorbable packing was also found more effective than non-absorbable packing as a means of reducing the postoperative adhesion rate (strength of recommendation B), and more effective in comparison with not placing any packing material at all (strength of recommendation C). Non-absorbable packing also proves more effective than no postoperative packing in preventing the appearance of such adhesions (strength of recommendation A). Absorbable packing is also more comfortable compared to non-absorbable materials (strength of recommendation A), or no postoperative packing in FESS patients (strength of recommendation B). The comparative analysis between the different packing modalities performed in the present study may help surgeons design a more individualized postoperative patient care.

The Impact of Generic Substitution on Health and Economic Outcomes: A Systematic Review.

BackgroundGeneric drugs are considered therapeutically equivalent to their original counterparts and lower in acquisition costs. However, the overall impact of generic substitution (GS) on global clinical and economic outcomes has not been conclusively evaluated.ObjectiveTo test whether (1) generics and original products yield the same health outcomes, and (2) generic therapies save economic resources versus original therapies.MethodsWe performed a systematic literature review in Medline, Embase, and the Cochrane Database of Systematic Reviews to identify original studies that examine clinical or economic outcomes of GS. After standardized data extraction, reported outcomes were categorized as supporting or rejecting the hypotheses. Each reported outcome was assessed and accounted for supporting and opposing GS. One publication could provide multiple outcome comparisons.ResultsWe included 40 studies across ten therapeutic areas. Fourteen studies examined patients on de novo therapy; 24 studies investigated maintenance drug therapy, and two studies considered both settings. Overall, 119 outcome comparisons were examined. Of 97 clinical outcome comparisons, 67 % reported no significant difference between generic drugs and their off-patent counterparts. Of 22 economic comparisons, 64 % suggested that GS increased costs. Consequently, hypothesis (1) was supported but hypothesis (2) was not. We found no major differences among studies that investigated clinical outcomes with de novo or maintenance therapy.ConclusionThe review suggests that clinical effects are similar after GS. However, economic savings are not guaranteed. More systematic research comparing clinical and economic outcomes with or without GS is needed to inform policy on the use of generic substitution.

Relative Efficacy and Safety of Preservative-free Latanoprost (T2345) for the Treatment of Open-Angle Glaucoma and Ocular Hypertension

To assess the relative efficacy and tolerability of preservative-free latanoprost (T2345) compared with other prostaglandin analogues (PGA) for the treatment of open-angle glaucoma and ocular hypertension by adjusted indirect comparison meta-analysis. Randomized, controlled trials evaluating PGA for the treatment of open-angle glaucoma and ocular hypertension were identified by a systematic literature review in MEDLINE, EMBASE, and Cochrane Controlled Trials Register (up to December 2011) databases. The effect size for each treatment and heterogeneity were assessed by classical pairwise meta-analysis (direct comparisons). Adjusted indirect comparisons were performed by using Bucher method. The main endpoints were intraocular pressure (IOP) measured at 3 months and incidence of hyperemia. Twenty-one studies were included in the meta-analysis. No statistically significant differences in IOP at 3 months were seen between T2345 and travoprost [preserved with benzalkonium chloride (BAK), polyquaternium-1 or sofzia], and other BAK-preserved PGA: bimatoprost 0.03%, bimatoprost 0.01%, or latanoprost. T2345 was statistically significantly superior to BAK-tafluprost (mean difference: 0.47 mm Hg, 95% confidence interval, [-1.52;-0.28]). The risk of hyperemia was statistically significantly lower with T2345 than with all the other PGA. Indirect comparisons never found preservative-free latanoprost (T2345) to be statistically significantly inferior to the other PGA in terms of efficacy on IOP and showed statistically significant superiority over BAK-tafluprost. The risk of hyperemia was statistically significantly lower with T2345 than with all the other PGA.

Free Web-based Personal Health Records: An Analysis of Functionality

This paper analyzes and assesses the functionality of free Web-based PHRs as regards health information, user actions and connection with other tools. A systematic literature review in Medline, ACM Digital Library, IEEE Digital Library and ScienceDirect was used to select 19 free Web-based PHRs from the 47 PHRs identified. The results show that none of the PHRs selected met 100% of the 28 functions presented in this paper. Two free Web-based PHRs target a particular public. Around 90 % of the PHRs identified allow users throughout the world to create their own profiles without any geographical restrictions. Only half of the PHRs selected provide physicians with user actions. Few PHRs can connect with other tools. There was considerable variability in the types of data included in free Web-based PHRs. Functionality may have implications for PHR use and adoption, particularly as regards patients with chronic illnesses or disabilities. Support for standard medical document formats and protocols are required to enable data to be exchanged with other stakeholders in the health care domain. The results of our study may assist users in selecting the PHR that best fits their needs, since no significant connection exists between the number of functions of the PHRs identified and their popularity.

Functional Endoscopic Sinus Surgery Improves Sinus-Related Symptoms and Quality of Life in Children With Chronic Rhinosinusitis

To assess the current knowledge and evaluate the quality of evidence in the use of FESS for the treatment of chronic rhinosinusitis in children, regarding the respective changes in the quality-of-their-life (QoL) and the outcome that follows the operation. Systematic literature review in Medline and other database sources and meta-analysis of pooled data. 15 studies were systematically analyzed. Four represented Level II, five Level III, and six Level IV evidence. The total number of treated patients was 1301. Thirteen research groups reported that pediatric FESS is an effective treatment for chronic rhinosinusitis; the respective positive outcome ranged between 71 and 100% of operated children. Five studies concluded that this treatment modality is associated with significant improvement in the children's postoperative QoL. Systemic diseases and environmental factors may have unfavourable prognostic effects; cystic fibrosis is associated with at least 50% recurrence rate. The rate of major complications following pediatric FESS is 0.6%, and the respective rate of minor complications 2%. The surgical management in children with chronic rhinosinusitis, despite the reservations expressed by many clinicians, is effective when optimal medical treatment proves unsuccessful (grade B strength of recommendation), and is associated with improvement in the children's QoL (grade B strength of recommendation). FESS also improves the sinusitis-associated symptoms and QoL in children with cystic fibrosis (grade C strength of recommendation. Most complications of pediatric FESS reported in the literature are minor, and associated with difficulties in the postoperative assessment and care of pediatric patients.

Cochlear implantation for single-sided deafness: the outcomes. An evidence-based approach

The aim of the present paper is to critically review the current evidence on the efficacy of cochlear implantation as a treatment modality for single-sided deafness (SSD), and/or unilateral tinnitus. Systematic literature review in Medline and other database sources was conducted along with critical analysis of pooled data. The study selection includes prospective and retrospective comparative studies, case series and case reports. The total number of analyzed studies was 17. A total of 108 patients with SSD have been implanted; 66 patients due to problems associated with SSD, and 42 primarily because of debilitating tinnitus. Cochlear implantation in SSD leads to improved sound localization performance and speech perception in noise from the ipsilateral side with an angle of coverage up to (but not including) 90(°) to the front, when noise is present in the contralateral quartile (Strength of recommendation B). Speech and spatial hearing also subjectively improve following the insertion of a cochlear implant (Strength of recommendation B); this was not the case regarding the quality of hearing. Tinnitus improvement was also reported following implant placement (Strength of recommendation B); however, patients need to be advised that the suppression is mainly successful when the implant is activated. The overall quality of the available evidence supports a wider use of cochlear implantation in SSD following appropriate selection and counseling (overall strength of recommendation B). It remains to be seen if the long-term follow-up of large number of patients in well conducted high quality studies will confirm the above mentioned results.

Community-based efforts to promote physical activity: A systematic review of interventions considering mode of delivery, study quality and population subgroups

Despite the known benefits of physical activity, the majority of adults in developed countries lead sedentary lifestyles. The community setting is a promising venue for physical activity-promoting interventions. Our objectives were to investigate the effectiveness of community-based physical activity interventions by mode of delivery, study quality and to analyse intervention effectiveness in different subgroups in the population. We conducted a systematic literature review in Medline and other databases to identify controlled, community-based physical activity interventions published between 2001 and 2012. We performed several post hoc subgroup comparisons for mode of delivery, study quality and selected population characteristics, using net per cent change in physical activity outcomes between baseline and follow-up as an effect measure. We identified 55 studies on exercise/walking sessions, face-to-face counselling, public campaigns and interventions by mail, the Internet and telephone presenting data on 20,532 participants. Overall, half of the studies reported positive physical activity outcomes (total net per cent change: 16.4%; p=0.159; net per cent change for high-quality studies, i.e. studies meeting more than 5 out of 7 quality criteria: 16.2%; p=0.010). Interventions using face-to-face counselling or group sessions were most effective (net per cent change: 35.0%; p=0.014). Net per cent change was also higher in studies exclusively tailored to women (27.7%; p=0.005) or specific ethnic groups (38.9%; p=0.034). This systematic review supports the effectiveness of community-based physical activity interventions in high-quality studies. Our results suggest that interventions using personal contact as well as tailored interventions are most promising.

Is cartilage better than temporalis muscle fascia in type I tympanoplasty? Implications for current surgical practice

The aim of this study was to compare the hearing results and graft integration rates in patients undergoing myringoplasty for the reconstruction of the tympanic membrane, with the use of either cartilage or temporalis muscle fascia (TMF). A systematic literature review in Medline and other database sources up to February 2012 was carried out, and the pooled data were meta-analyzed. Twelve studies were systematically analyzed. One represented level I, one level II and ten level III evidence. The total number of treated patients was 1,286. Cartilage reconstruction was used in 536, TMF in 750 cases. Two level III studies showed a significant difference between the pre- and postoperative air-bone gap closure, in favor of cartilage grafting. The mean graft integration rate was 92.4% in the cartilage group and 84.3% in the TMF group (p<0.05). The rates of re-perforations were 7.6 and 15.5%, respectively (p<0.05). Among the other complications of type I tympanoplasty, retraction pockets, otitis media with effusion, anterior blunting, and graft lateralization were usually surgically managed, whereas most of the rest were minor and could be dealt with conservatively. The graft integration rate in myringoplasty is higher after using cartilage, in comparison with fascia reconstructions (grade C strength of recommendation), and the rate of re-perforation is significantly lower. Although cartilage is primarily used as grafting material in cases of Eustachian tube dysfunction, adhesive otitis media, and subtotal perforation in everyday surgical practice, a wider utilization for the reconstruction of the tympanic membrane in myringoplasties can be recommended.

Homoparentalidade masculina: revisando a produção científica

Este estudo teve por objetivo compreender de que modo a parentalidade homossexual masculina vem sendo investigada na literatura cientifica nacional e internacional. Por meio de uma revisao sistematica nas bases MedLine, SciELO, PsycINFO e CINAHL, de 2000 a 2011, foram recuperados 12 artigos. No contexto internacional, os estudos se concentram em delineamentos empiricos focalizando casais homossexuais e seus filhos. No Brasil, predominam estudos teoricos sobre a familia homoparental. A Psicanalise emerge como principal referencial teorico. Sao necessarias pesquisas empiricas no contexto brasileiro, haja vista a aprovacao da uniao estavel entre pessoas do mesmo sexo e abertura de jurisprudencia para adocao por esses casais. Outras abordagens teoricas sao requeridas para que se possa compreender o contexto desenvolvimental das familias e casais de mesmo sexo com criancas em um cenario social em permanente transformacao.

Laryngeal Involvement in Connective Tissue Disorders. Is it Important for Patient Management?

Connective tissue disorders (CTDs) involve multiple organ systems and may have a significant impact on the overall health and quality of life of the affected individuals. The present paper aims to review the current knowledge on the laryngeal manifestations of CDTs, and describe the available diagnostic and treatment options. Systematic literature review in Medline and other database sources. Information from related books was also included. Prospective controlled, double-blind prospective, prospective, and transversal cohort studies, case series, case reports, systematic reviews, and consensus papers. Laryngeal involvement mostly occurs in rheumatoid arthritis (13-75% of patients). It is not uncommon in active and progressive clinical course, though can also occur in silent or inactive CDTs. The crico-arytenoid joint is the most commonly affected site. Common symptoms include throat pain, dyphonia and hoarseness. Careful clinical assessment of the larynx by flexible naso-endoscopy, video-stroboscopy, or direct laryngoscopy, and appropriate imaging are required for pertinent patient management. Stridor is a sign of a life-threatening condition, and may require prompt surgical intervention. However, mild symptomatology may mislead clinicians, and the related diagnosis may be significantly delayed. The current evidence as identified in the present study suggest that laryngeal manifestations of CDTs are often underdiagnosed, due to a range of non- specific symptoms. A multidisciplinary team approach with ENT input is necessary to improve the overall patient management.

Lower gastrointestinal perforation in rheumatoid arthritis patients treated with conventional DMARDs or tocilizumab: a systematic literature review

Tocilizumab, a monoclonal antibody targeting the IL-6 receptor, has recently been added to the therapeutic armamentarium against rheumatoid arthritis (RA). Despite its overall safety, concerns have been raised regarding diverticular perforation in patients receiving the drug. The aim of our research was to document the incidence of diverticular disease in RA patients treated in the pre-disease-modifying anti-rheumatic drug (DMARD) era, following treatment with conventional DMARDs, and subsequent to tocilizumab therapy. We performed a systematic literature review in MEDLINE, EMBASE, Conference Proceedings Citation Index-Science, Cochrane Central Register of Controlled Trials and Current Controlled Trials up to Nov. 2010. The publication titles and abstracts were independently assessed by two reviewers for relevance and quality, and the review was conducted following guidelines from the Centre for Reviews and Dissemination. In the pre-DMARD period of RA management, where patients were largely treated with NSAIDs and corticosteroids, gastrointestinal (GI) complications were a substantial cause of mortality with diverticulitis and colonic ulcers accounting for almost a third of GI-related deaths. In contrast, our search did not reveal any evidence of diverticular perforation in patients treated with conventional DMARDs. Eighteen cases of lower GI perforation (16 of whom had diverticulitis) have been documented in recent conference proceedings following tocilizumab treatment in clinical trials, with a lower GI perforation rate of 1.9 per 1,000 patient years (PY). This lies between the reported rate of GI perforations for corticosteroids and anti-TNF-α agents in the United Health Care database, with rates of 3.9 per 1,000PY (95% CI 3.1-4.8) and 1.3 per 1,000PY (95% CI 0.8-1.9), respectively. The majority of these patients were concurrently prescribed NSAIDs and/or long-term corticosteroids. Traditional DMARD therapy for RA appears not only to have modified the risk of lower GI perforation but prevented it. The risk of diverticular perforation may be slightly higher in patients treated with tocilizumab compared with conventional DMARDs or anti-TNF agents, but lower than that for corticosteroids. The mechanism of action of IL-6 antagonism in the pathophysiology of diverticular perforation has yet to be elucidated.