Adverse drug reactions associated with amitriptyline - protocol for a systematic multiple-indication review and meta-analysis

Background: Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-thecounter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals. Methods: A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including <100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using metaregression (for indication, outcome, and time points) and I2 statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment. Discussion: We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations

Intra-arterial treatment for acute ischemic stroke: a meta-analysis

Objective: To assess the potential benefit of treating patients with acute ischemic stroke using intra-arterial methods. Methods: A meta-analysis of published randomized controlled trials that compared standard therapy with intravenous tissue plasminogen activator (IVtPA) for thrombolysis to intra-arterial therapies in patients with acute stroke was performed. All studies reported were analyzed as one group and studies documenting patients with large vessel obstruction were analyzed as a second group. The standardized mean difference (SMD) and the odds ratio (OR) of the dichotomized outcomes of Modified Rankin Scale (mRS) of these trials was calculated. Results: Nine trials were identified with 2,711 patients treated. Meta-analysis of all studies, with and without large vessel obstruction documented, showed a significant benefit with intra-arterial therapy (SMD: 0.22 + 0.041; P=0.003). The dichotomized outcomes of mRS of these trials showed significant improvement (OR: 1.66 -2.43 in four of the five treatment arm groups examined). Meta-analysis of all publications with large vessel obstruction documented as an entry criteria showed a greater significant benefit with intra-arterial therapy (SMD: 0.35 + 0.05; P&lt;0.001). The dichotomized outcomes of mRS of these trials showed significant improvement (OR: 1.36 -2.38 in all five treatment arm groups examined). Some heterogeneity was observed between studies. Conclusion: Treatment of patients with acute ischemic stroke was associated with improved outcomes as measured by mRS. Patient selection, standard treatment, and study treatment factors contributed to the statistical evaluation of inter study heterogeneity and may have contributed to different study outcomes

Health-related preferences of older patients with multimorbidity: the protocol for an evidence map

Introduction: Interaction of conditions and treatments, complicated care needs and substantial treatment burden make patient–physician encounters involving multimorbid older patients highly complex. To optimally integrate patients’ preferences, define and prioritise realistic treatment goals and individualise care, a patient-centred approach is recommended. However, the preferences of older patients, who are especially vulnerable and frequently multimorbid, have not been systematically investigated with regard to their health status. The purpose of this evidence map is to explore current research addressing health-related preferences of older patients with multimorbidity, and to identify the knowledge clusters and research gaps. Methods and analysis: To identify relevant research, we will conduct searches in the electronic databases MEDLINE, EMBASE, PsycINFO, PSYNDEX, CINAHL, Social Science Citation Index, Social Science Citation Index Expanded and the Cochrane library from their inception. We will check reference lists of relevant articles and carry out cited reference research (forward citation tracking). Two independent reviewers will screen titles and abstracts, check full texts for eligibility and extract the data. Any disagreement will be resolved and consensus reached with the help of a third reviewer. We will include both qualitative and quantitative studies, and address preferences from the patients’ perspectives in a multimorbid population of 60 years or older. There will be no restrictions on the publication language. Data extraction tables will present study and patient characteristics, aim of study, methods used to identify preferences and outcomes (ie, type of preferences). We will summarise the data using tables and figures (ie, bubble plot) to present the research landscape and to describe clusters and gaps. Ethics and dissemination: Due to the nature of the proposed evidence map, ethics approval will not be required. Results from our research will be disseminated by means of specifically prepared materials for patients, at relevant (inter)national conferences and via publication in peer-reviewed journals

Implant-supported fixed and removable prostheses in the fibular mandible

Abstract Background To restore the health-related quality of life (HRQoL) of patients who underwent jaw resection and reconstruction surgery, dental rehabilitation is an essential procedure and also one of the most challenging for oral and maxillofacial surgeons. Even though recent studies have reported the possibility and reliability of dental implant rehabilitation with the fibula free flap (FFF), clinical reports of long-term follow-up cases are scarce. We herein reported seven cases of FFF reconstruction and implant rehabilitation. We also discussed implant planning strategy and surgical techniques. Methods From 2012 to 2019, seven patients were treated with FFF reconstructive jaw surgery combined with dental implant installation and fabrication of implant-supported prostheses at Seoul National University Dental Hospital, Seoul, Korea. Patient characteristics and FFF treatment results were collected. Records of dental implants were analyzed clinically and radiologically. Results Among the seven patients in this report, there were three males and four females, with an average age of 54.4 years. A total of 39 implants were placed in the fibular bone. The mean follow-up period after implant installation was 24 months. Five implants failed and were removed 3 months after installation. The implant success rate was 87.2%. Marginal bone loss at 12 months after loading was 0.23 ± 0.18 mm on the mesial side and 0.25 ± 0.26 mm on the distal side. Conclusion With the challenges present in FFF-reconstructed patients, an implant-supported prosthesis is a reliable option for stable and functional oral rehabilitation. The implant-supported prosthesis on the FFF has great results regarding restoration of function (mastication, swallowing, and speaking), appearance, and overall HRQoL. Collaboration between surgeons and prosthodontists is essential for a satisfying outcome

Non-coding RNAs versus protein biomarkers to diagnose and differentiate acute stroke:Systematic review and meta-analysis

BACKGROUND: Stroke diagnosis is dependent on lengthy clinical and neuroimaging assessments, while rapid treatment initiation improves clinical outcome. Currently, more sensitive biomarker assays of both non-coding RNA- and protein biomarkers have improved their detectability, which could accelerate stroke diagnosis. This systematic review and meta-analysis compares non-coding RNA- with protein biomarkers for their potential to diagnose and differentiate acute stroke (subtypes) in (pre-)hospital settings.METHODS: We performed a systematic review and meta-analysis of studies evaluating diagnostic performance of non-coding RNA- and protein biomarkers to differentiate acute ischemic and hemorrhagic stroke, stroke mimics, and (healthy) controls. Quality appraisal of individual studies was assessed using the QUADAS-2 tool while the meta-analysis was performed with the sROC approach and by assessing pooled sensitivity and specificity, diagnostic odds ratios, positive- and negative likelihood ratios, and the Youden Index.SUMMARY OF REVIEW: 112 studies were included in the systematic review and 42 studies in the meta-analysis containing 11627 patients with ischemic strokes, 2110 patients with hemorrhagic strokes, 1393 patients with a stroke mimic, and 5548 healthy controls. Proteins (IL-6 and S100 calcium-binding protein B (S100B)) and microRNAs (miR-30a) have similar performance in ischemic stroke diagnosis. To differentiate between ischemic- or hemorrhagic strokes, glial fibrillary acidic protein (GFAP) levels and autoantibodies to the NR2 peptide (NR2aAb, a cleavage product of NMDA neuroreceptors) were best performing whereas no investigated protein or non-coding RNA biomarkers differentiated stroke from stroke mimics with high diagnostic potential.CONCLUSIONS: Despite sampling time differences, circulating microRNAs (&lt; 24 h) and proteins (&lt; 4,5 h) perform equally well in ischemic stroke diagnosis. GFAP differentiates stroke subtypes, while a biomarker panel of GFAP and UCH-L1 improved the sensitivity and specificity of UCH-L1 alone to differentiate stroke.</p

Clinical feasibility and benefits of a tapered, sand-blasted, and acid-etched surfaced tissue-level dental implant

Abstract Background It has been 50 years since Brånemark first introduced the concept of osseointegration. Since then, numerous ongoing research, developments, and optimization of implant properties have been conducted. Despite the high survival and success rates of dental implants, failures still occur in a small number of patients that are being rehabilitated by implants. The purpose of this study was to evaluate the survival and success rate of the Stella® implants that incorporate sand-blasted and acid-etched (S&E) surface treatment and tapered body design to confirm their clinical feasibility and benefits after placement. Methods We reviewed 61 partially and fully edentulous patients who underwent a tapered, S&E surfaced tissue-level implant placement between May 2013 and February 2016 in the Department of Oral and Maxillofacial Surgery in the Seoul National University Dental Hospital. Patient characteristics and treatment results were collected, and records of dental implants were analyzed clinically and radiologically. Results A total of 105 implant fixtures were placed in these patients. The mean age at the time of the surgery was 63.7 years with a range of 31 to 88 years. In total, 4.0-mm and 4.5-mm diameter implants were the most frequently used dental implants (40%, 49%) in this study. Implants 8.5 mm in length were predominantly used (60%). Seventy dental implants were placed in the mandible (70%), and only one dental implant was placed in the maxillary anterior region. At the end of the 5-year observation period, the success rate of the Stella® implants was 98.1%. Among the 105 implants placed, 2 were considered to be failures. Summarizing the clinical and radiographic results, the remaining 103 implants were considered successfully integrated. Conclusion The overall success rate was 98.1%. The tapered, S&E surfaced tissue-level implant system exhibited great performance in a variety of clinical situations including failed implant sites that enabled predictable and successful treatment outcomes. The effectives of a tapered design of tissue level, not a parallel design, are shown in this clinical report

Establishing and validating noninvasive prenatal testing procedure for fetal aneuploidies in Vietnam

Noninvasive prenatal testing (NIPT) for fetal aneuploidies has been widely adopted in developed countries. Despite the sharp decrease in the cost of massively parallel sequencing, the technical know-how and skilled personnel are still one of the major limiting factors for applying this technology to NIPT in low-income settings. Here, we present the establishment and validation of our NIPT procedure called triSure for detection of fetal aneuploidies.We established the triSure algorithm based on the difference in proportion of fetal and maternal fragments from the target chromosome to all chromosomes. Our algorithm was validated using a published data set and an in-house data set obtained from high-risk pregnant women in Vietnam who have undergone amniotic testing. Several other aneuploidy calling methods were also applied to the same data set to benchmark triSure performance.The triSure algorithm showed similar accuracy to size-based method when comparing them using published data set. Using our in-house data set from 130 consecutive samples, we showed that triSure correctly identified the most samples (overall sensitivity and specificity of 0.983 and 0.986, respectively) compared to other methods tested including count-based, sized-based, RAPIDR and NIPTeR.We have demonstrated that our triSure NIPT procedure can be applied to pregnant women in low-income settings such as Vietnam, providing low-risk screening option to reduce the need for invasive diagnostic tests

Early Pandemic Influenza (2009 H1N1) in Ho Chi Minh City, Vietnam: A Clinical Virological and Epidemiological Analysis

Rogier van Doorn and colleagues analyze the initial outbreak, attempts at containment, and establishment of community transmission of pandemic H1N1 influenza in Ho Chi Minh City, Vietnam

Liax Is a Surrogate Marker For Cell Envelope Stress and Daptomycin Non-Susceptibility in Enterococcus Faecium

Daptomycin (DAP) is often used as a first-line therapy to treat vancomycin-resistan