Meta-analysis Of Case Reports Research Articles

Drug-Induced Thrombocytopenic Purpura: A Systematic Review and Meta-analysis of Case Reports

In the present systematic review and meta-analysis, the authors analysed case reports of drug-induced thrombocytopenia/drug-induced thrombocytopenic purpura (DITP) and its mechanisms. The search included electronic databases for case reports of DITP using specific keywords in MEDLINE via PubMed, PubMed Central, and Embase. All case reports were designated a score/criteria (definite, probable, or possible). The mechanism of DITP was also analysed in each case report. A total of 751 case reports were included in the meta-analysis. The incidences for all-score DITP by random and common effect models were 0.65% (95% confidence interval: 0.61–0.69) and, 0.65% (95% confidence interval: 0.62–0.68), respectively. The number of DITPs with scores of 1, 2, and 3 was found in 151, 300, and 300 patients, respectively. Amongst the drugs, the maximum number of DITPs were caused by antibiotics, antimalarials, monoclonal antibodies, antiplatelet drugs, disease-modifying antirheumatic drugs, anti-epileptics, anti-cancer chemotherapeutics, and non-steroidal anti-inflammatory drugs. Out of 751 cases, 478 patients were hospitalised, and 323 patients had external or internal bleeding, including 62 patients who had major bleeding intracranially or retroperitoneally and required transfusion of two or more units of red blood cells. Mortality occurred in 12 patients. Clinicians should be aware of the potential of drugs causing DITP as an important adverse event, as it may affect patient compliance and adherence to drugs. Unrecognised DITP may lead to severe thrombocytopenia and inappropriate patient management.

Rituximab in Subepidermal Blistering Diseases

Background: Although rituximab is known to be effective in the treatment of pemphigus, its role in subepidermal autoimmune blistering diseases is unclear and currently limited to off-label use. Summary: This is a meta-analysis of case reports, case series, and retrospective studies on the effectiveness and safety of rituximab in bullous pemphigoid, mucous membrane pemphigoid, ocular pemphigoid, and epidermolysis bullosa acquisita. We compared remission and relapse rates in patients who received rituximab with those who only received conventional medical therapy. Comparisons were also made among disease subgroups. Key Message: The present analysis suggests that patients with subepidermal autoimmune blistering diseases treated with rituximab achieve a higher rate of complete remission and encounter their first relapse after a longer time interval. However, time to remission and total relapse rates were similar between groups. Adverse events and mortality rates were no more common in patients who received rituximab. This analysis was limited by the absence of randomized controlled trials and the observation that rituximab was used as a late rescue therapy in most reports. In conclusion, rituximab may be effective in subepidermal blistering disease, but randomized controlled studies are required for the validation of current observational data.

A meta-analysis of case-reports and case-series of dacrystic epilepsy in children and adolescence

This meta-analysis aimed to advance our knowledge about dacrystic epilepsy in children in the present time. PubMed searches for peer-reviewed case reports and case series were conducted using the keywords “dacrystic epilepsy”, “dacrystic seizures”, “crying epilepsy”, “ictal crying”, “crying seizures”. The databases were developed in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The author collected relevant information to characterise the study population including clinical outcome. Eleven studies out of 353 citations between 1998 and 26 May 2021 met the inclusion criteria, including both single cases and series pertaining to dacrystic epilepsy. Eight case reports and three case series were eligible for this meta-analysis and included twenty one cases. The seizure patterns were dacrystic seizures alone in seven cases (33%), and a combination of dacrystic seizures and gelastic seizures in fourteen cases (67%). Neuroimaging revealed structural abnormality in 95% cases. Hypothalamic hamartoma was found in most of the cases (79%) with combined dacrystic seizures and gelastic seizures, whereas it was found in one case (16%) with dacrystic seizures alone. The other underlying lesions in children with dacrystic seizures alone were subependymal nodules and cortical hamartomas (17%), left mesial temporal sclerosis (33%), and cortical dysplasia (17%). Regarding outcome, antiepileptic drugs alone achieved seizure freedom in four cases (22%) only and others (78%) were difficult to treat cases excluding three cases where treatments were not mentioned. Six cases underwent surgical intervention and two cases received ablative radiotherapy. Lesional dacrystic epilepsy is predominant and pharmaco-resistant in children. However, antiepileptic drugs lead to achieving seizure remission in few cases.

Complications of thoracic surgery: post-pneumonectomy bronchopleural fistula

: Bronchopleural fistula (BPF) describes an abnormal connection between a bronchus (main, lobar or segmental) and the pleural cavity. BPF is a recognized complication after pneumonectomy and is associated with significant morbidity and mortality. The risk of post-pneumonectomy BPF (PP-BPF) is greater in right sided operations, male patients, residual tumor, barotrauma, previous TB and active infection. If suspected, diagnosis of BPF should be made expeditiously with computed tomography scanning and bronchoscopy. The management depends on the timing of presentation, the size of the fistula and the clinical status of the patient. All patients require drainage of the infected pleural space and intravenous antibiotics. In early presentations, re-do thoracotomy followed by stump closure and reinforcement with a pedicled muscle flap is recommended. If the fistula is small (<5 mm) or the patient is not fit enough for major surgery, bronchoscopic repair using fibrin glue application, stents or closure devices can be attempted. Minimally invasive techniques can also be used as a temporizing measure while optimizing a patient for a major intervention. There are multiple case reports describing novel bronchoscopic techniques for management of BPF. The risk of BPF should be reduced in high-risk patient groups by implementing bronchial stump coverage (BSC) at the time of pneumonectomy. Overall, the literature is limited by the relative rarity of the problem. Much of the literature is based on retrospective studies and case series which leads to inherent biases preventing true comparative studies in operative techniques and outcomes. Meta-analysis of case reports and new randomized controlled trials may give more evidence to support the current findings. While some simple principles should be followed, management of BPF needs to be individualized to each patient’s clinical picture.

Common and rare carcinomas of the thymus.

Thymic carcinoma encompasses a diverse group of rare tumors that occur almost exclusively in the prevascular (anterior) mediastinum. Thymic carcinomas have a worse outcome than thymomas with a median time to death of under 3years. These tumors lack the typical lobulation of thymomas, exhibit commonly more cytologic atypia, are associated with a desmoplastic stromal reaction, and lack thymocytes, features that distinguish them from thymomas. The most common thymic carcinoma is squamous cell carcinoma; other subtypes include mucoepidermoid carcinoma, NUT carcinoma, and adenocarcinoma, among others. Largely due to multi-institutional and global efforts and meta-analysis of case reports and series, some of the thymic carcinoma subtypes have been studied in more detail and molecular studies have also been performed. Morphology and immunophenotype for the vast majority of thymic carcinoma subtypes are similar to their counterparts in other organs. Therefore, the distinction between thymic carcinoma and metastatic disease, which is relatively common in the prevascular mediastinum, can be challenging and in general requires clinical and radiologic correlation. Although surgical resection is the treatment of choice, only 46 to 68% of patients with thymic carcinoma can undergo resection as many other tumors present at high stage with infiltration into vital neighboring organs. These patients are usually treated with chemotherapy and/or radiation. The search for better biomarkers for prognosis and treatment of thymic carcinomas is important for improved management of these patients and possible targeted therapy.

Scapulothoracic Dissociation: a Systematic Review, Current Concepts, and Meta-analysis of Case Reports

Scapulothoracic dissociation is a rare entity which is frequently associated with arterial and brachial plexus injuries. It is frequently missed especially in the scenario of polytrauma. To examine the incidence, mode and mechanism of injury, associated injuries, diagnosis, treatment protocol, and existing current concepts in the literature. Ovid MEDLINE from January 1980 to August 2019. Published case reports/case series/observational studies. Patient characteristics were summarized descriptively. Appropriate statistical tests were applied. 54.3% of the patients between the age group of 20 and 40 with a male to female ratio of 6.2. In 51.9% of the cases, motorcycle accident was the mode of injury. 68.7% of the cases were associated with vascular injuries either at the level of subclavian or axillary. Brachial plexus involvement was seen in 86.1% of the cases. Isolated fracture of the clavicle was found in 53.9% of the cases. In 13.6% of the patients, scapulothoracic dissociation was associated with polytrauma. Zelle type 4 injuries were the commonest (51.9%). One-fourth of the patients were managed conservatively. Primary amputation was done in 15% of the cases. Mortality rate was about 10%. About 46% of the patients landed up in flail limb or amputation. The most significant predictors of the functional outcome were vascular injury, brachial plexus injury, and classification type. Polytrauma was the most significant predictor of mortality. The results from this systematic review have revealed the most common age group involved, mode of injury, and prognostic indicators and helped in the formulation of treatment protocol in the management of this rare but devastating injury which can be easily missed especially in the polytrauma scenarios.

Rituximab for treating inhibitors in people with inherited severe hemophilia.

Hemophilia A and B are inherited coagulation disorders characterized by a reduced or absent level of factor VIII or factor IX respectively. The severe form is characterized by a factor level less than 0.01 international units (IU) per milliliter. The development of inhibitors in hemophilia is the main complication of treatment, because the presence of these antibodies, reduces or even nullifies the efficacy of replacement therapy, making it very difficult to control the bleeding. People with inhibitors continue to have significantly higher risks of morbidity and mortality, with considerable treatment costs. Given the wide 'off-label' use of rituximab for treating people with hemophilia and inhibitors, its efficacy and safety need to be evaluated. This is an update of a previously published Cochrane Review. To assess the efficacy and safety of rituximab for treating inhibitors in people with inherited severe hemophilia A or B. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, complied from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews and also searched for ongoing or unpublished studies. We also undertook further searches of other bibliographic databases and trial registries. Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 19 March 2020. Randomized controlled trials and controlled clinical trials investigating the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. No randomized controlled trials matching the selection criteria were eligible for inclusion. No randomized controlled trials on rituximab for treating inhibitors in people with hemophilia were identified. We were unable to identify any relevant trials on the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. The research evidence available is from case reports and case series. Randomized controlled trials are needed to evaluate the efficacy and safety of rituximab for this condition. However, prior to the publication of any possible future randomized controlled trials, meta-analysis of case reports and case series may provide some evidence.

Atypical polypoid adenomyoma follow-up and management: Systematic review of case reports and series and meta-analysis.

Atypical polypoid adenomyoma (APA) is a rare uterine tumor typically found in fertile age and associated with infertility. Among young nullipara women, conservative treatment is proposed despite the high recurrence rate and the association with endometrial cancer.Our aim was to assess the risk of recurrence with different conservative treatments in fertile ages and the prevalence of malignant or pre-malignant associated lesions to better address an adequate patient counselling when treatment modalities are discussed. This study is a systematic review and meta-analysis of case reports and case series about APA management and follow-up. A literature search was carried from Medline and Scopus for studies published from January 1, 1980 to December 31, 2018. We included 46 observational studies and 296 cases in fertile women. The prevalence of APA relapse was 44% (CI.95 33-57%) and was lower in cases treated with operative hysteroscopy (22%; CI.95 11-39%) than in cases treated with blind curettage and polypectomy (38%; CI.95 15-67%). The prevalence of the concomitant or during the follow-up diagnosis of endometrial carcinoma was 16% (CI.95 9-29%). The risk of cancer development during follow-up was significantly less in cases treated with histeroscopy (10.56% new cumulative diagnosis at 5 years follow up; CI.95 0-23.7%) than blind curettage and polypectomy (35.5% new cumulative diagnosis at 5 years; CI.95 11.65-52.92%; P < .05). Medical treatment with medroxyprogesterone acetate after surgery does not reduce APA recurrence. Pregnancy was observed in 79% cases in which the desire was expressed. This review suggests that conservative treatment performed by operative hysteroscopy is the optimal choice because it lowers the risk of recurrence, improves the accuracy of concomitant carcinoma or hyperplasia diagnosis, and leaves the possibility of future pregnancies.

Agreement between results of meta-analyses from case reports and clinical studies, regarding efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II (MPS-II). A new tool for evidence-based medicine in rare diseases

BackgroundA preliminary exploratory study shows solid agreement between the results of case reports and clinical study meta-analyses in mucopolysaccharidosis Type I (MPS-I) adult patients. The aim of the present study is to confirm previous results in another patient population, suffering from mucopolysaccharidosis Type II (MPS-II).MethodsA systematic review and meta-analysis of case reports published by April 2018 was conducted for MPS-II patients treated with enzyme replacement therapy (ERT). The study is reported in accordance with PRISMA and MOOSE guidelines (PROSPERO database code CRD42018093408). The assessed population and outcomes were the same as previously analyzed in a meta-analysis of MPS-II clinical studies. The primary endpoint was the percent of clinical cases showing improvement in efficacy outcome, or no harm in safety outcome after ERT initiation. A restrictive procedure to aggregate case reports, by selecting standardized and well-defined outcomes, was proposed. Different sensitivity analyses were able to evaluate the robustness of results.ResultsEvery outcome classified as “acceptable evidence group” in our case report meta-analysis had been graded as “moderate strength of evidence” in the aforementioned meta-analysis of clinical studies. Sensitivity, specificity, and positive-negative predictive values for results of both meta-analyses reached 100%, and were deemed equivalent.ConclusionsAggregating case reports quantitatively, rather than analyzing them qualitatively, may improve conclusions in rare diseases and personalized medicine. Additionally, we propose some methods to evaluate publication bias and heterogeneity of the included studies in a meta-analysis of case reports.

Efficacy of Direct Acting Oral Anticoagulants in Treatment of Left Ventricular Thrombus

Direct acting oral anticoagulants (DOACs) are increasingly used as off-label alternatives to vitamin K antagonists for the treatment of left ventricular (LV) thrombus. However, efficacy data is limited to small case series and one meta-analysis of case reports. We aimed to determine the efficacy and safety of DOACs in treatment of LV thrombus utilizing transthoracic echocardiography (TTE) and clinical outcomes. We identified 52 patients (mean age = 64 years, 71% men) treated with a DOAC for LV thrombus (n = 26 apixaban, n = 24 rivaroxaban, and n = 2 dabigatran). Thirty-five of the 52 patients had a follow-up TTE after DOAC initiation. The primary end point was defined as resolution of LV thrombus (in patients with a subsequent TTE), or death, major bleeding requiring transfusion, intracranial hemorrhage, ischemic stroke, or peripheral embolization. An experienced echocardiographer (M.L.M.) reviewed all TTEs for presence or absence of LV thrombus without knowledge of time point or clinical data. Twenty-nine of the 35 (83%) patients who underwent follow-up TTE had resolution of LV thrombus, with a mean duration of 264 days. Of the total study population, there was 1 cardioembolic event (transient ischemic attack) 52 days after initiating DOAC, 3 gastrointestinal bleeds requiring transfusion, and 1 patient with epistaxis requiring transfusion. All patients with a hemorrhagic complication were receiving concomitant antiplatelet therapy. DOAC therapy appears promising for the treatment of LV thrombus. A larger, prospective study is warranted to confirm these results.

Contemporary management and clinical outcomes of mucormycosis: A systematic review and meta-analysis of case reports

With the advent of newer antifungals, optimum treatment of mucormycosis remains to be fully elucidated. This study systematically evaluated the contemporary management and outcomes of mucormycosis. Mucormycosis cases in patients aged ≥18 years published between January 2000 and January 2017 were identified through Ovid MEDLINE and Embase. Of the 3619 articles identified, 600 (851 individual patient cases) were included in the review. Of the 851 patient cases, antifungal treatment details were available for 785. Intravenous (i.v.) amphotericin B formulations remained the most commonly prescribed first-line antifungals (760/785; 96.8%): 88.2% (670/760) were initiated as monotherapy and 11.8% (90/760) as combination antifungal therapy. Posaconazole oral suspension monotherapy was prescribed as an initial antifungal in 11 cases. It was also administered as maintenance or salvage therapy in 39 and 25 cases, respectively. Itraconazole capsule monotherapy (n = 10) was prescribed primarily for cutaneous disease in patients not receiving any immunosuppressive therapy. All-cause 90-day mortality was 41.0% (349/851). Initial treatment with combination antifungals did not reduce 90-day mortality compared with i.v. conventional amphotericin B or i.v. liposomal amphotericin B monotherapy [35/90 (38.9%) vs. 146/369 (39.6%) vs. 91/258 (35.3%), respectively; P = 0.541]. Concomitant surgical and antifungal therapy was associated with significantly lower 90-day mortality compared with treatment with antifungals alone (OR = 0.23, 95% CI 0.13-0.41; P < 0.001). The findings suggest that first-line antifungals with good efficacy remain an urgent unmet need. Whilst surgery is fundamental to improving survival, the clinical utility of combination antifungal therapy or posaconazole monotherapy requires further investigation.

Single-site neural tube closure in human embryos revisited.

Since the multi-site closure theory was first proposed in 1991 as explanation for the preferential localizations of neural tube defects, the closure of the neural tube has been debated. Although the multi-site closure theory is much cited in clinical literature, single-site closure is most apparent in literature concerning embryology. Inspired by Victor Hamburgers (1900-2001) statement that "our real teacher has been and still is the embryo, who is, incidentally, the only teacher who is always right", we decided to critically review both theories of neural tube closure. To verify the theories of closure, we studied serial histological sections of 10 mouse embryos between 8.5 and 9.5 days of gestation and 18 human embryos of the Carnegie collection between Carnegie stage 9 (19-21 days) and 13 (28-32 days). Neural tube closure was histologically defined by the neuroepithelial remodeling of the two adjoining neural fold tips in the midline. We did not observe multiple fusion sites in neither mouse nor human embryos. A meta-analysis of case reports on neural tube defects showed that defects can occur at any level of the neural axis. Our data indicate that the human neural tube fuses at a single site and, therefore, we propose to reinstate the single-site closure theory for neural tube closure. We showed that neural tube defects are not restricted to a specific location, thereby refuting the reasoning underlying the multi-site closure theory. Clin. Anat. 30:988-999, 2017. © 2017 Wiley Periodicals, Inc.

15 Capgras delusion: a meta-analysis of case reports in the english language

15 Capgras delusion: a meta-analysis of case reports in the english language

Rituximab for treating inhibitors in people with inherited severe hemophilia.

Hemophilia A and B are inherited coagulation disorders characterized by a reduced or absent level of factor VIII or factor IX respectively. The severe form is characterized by a factor level less than 0.01 international units (IU) per milliliter. The development of inhibitors in hemophilia is the main complication of treatment, because the presence of these antibodies, reduces or even nullifies the efficacy of replacement therapy, making it very difficult to control the bleeding. People with inhibitors continue to have significantly higher risks of morbidity and mortality, with considerable treatment costs. Given the wide 'off-label' use of rituximab for treating people with hemophilia and inhibitors, its efficacy and safety need to be evaluated. This is an update of a previously published Cochrane Review. To assess the efficacy and safety of rituximab for treating inhibitors in people with inherited severe hemophilia A or B. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, complied from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews and also searched for ongoing or unpublished studies. We also undertook further searches of other bibliographic databases and trial registries.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 16 February 2017. Randomized controlled trials and controlled clinical trials investigating the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. No randomized controlled trials matching the selection criteria were eligible for inclusion. No randomized controlled trials on rituximab for treating inhibitors in people with hemophilia were identified. We were unable to identify any relevant trials on the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. The research evidence available is from case reports and case series. Randomized controlled trials are needed to evaluate the efficacy and safety of rituximab for this condition. However, prior to the publication of any possible future randomized controlled trials, meta-analysis of case reports and case series may provide some evidence.

Quality, coherence and co-operation: a framework for studying the mediation of qualities in food networks and collective marketing strategies.

The aim of this article is to present an analytical framework to examine how qualities are mediated between producers and consumers, and how this is linked to the way the food chain is constructed, who is involved, and the way the market is developed. The framework is a reorientation to see food networks as consisting of triadic value relations that transform and mediate qualities through the chain, using an analytical typology of quality dimensions. From this perspec- tive, a meta-analysis of case reports from collective farmers' marketing initiatives in Europe has been performed. The cases differ greatly in the number of quality dimensions involved, and they represent very different strategies to mediate the qualities from field to table. We find that the performance of the marketing strat - egy is related to coherence in terms of whether the individual value relations are able to carry the involved quality dimensions throughout the whole network. In conclusion, this framework is a promising tool to radicalize our understanding of how qualities are mediated through food networks.

Predictors of adverse events after endovascular abdominal aortic aneurysm repair: A meta-analysis of case reports

IntroductionEndovascular abdominal aortic aneurysm repair is a life-saving intervention. Nevertheless, complications have a major impact. We review the evidence from case reports for risk factors of complications after endovascular abdominal aortic aneurysm repair.Case presentationWe selected case reports from PubMed reporting original data on adverse events after endovascular abdominal aortic aneurysm repair. Extracted risk factors were: age, sex, aneurysm diameter, comorbidities, re-interventions, at least one follow-up visit being missed or refusal of a re-intervention by the patient. Extracted outcomes were: death, rupture and (non-)device-related complications.In total 113 relevant articles were selected. These reported on 173 patients. A fatal outcome was reported in 15% (N = 26) of which 50% came after an aneurysm rupture (N = 13). Non-fatal aneurysm rupture occurred in 15% (N = 25). Endoleaks were reported in 52% of the patients (N = 90). In half of the patients with a rupture no prior endoleak was discovered during follow-up. In 83% of the patients one or more re-interventions were performed (N = 143). Mortality was higher among women (risk ratio 2.9; 95% confidence interval 1.4 to 6.0), while the presence of comorbidities was strongly associated with both ruptures (risk ratio 1.6; 95% confidence interval 0.9 to 2.9) and mortality (risk ratio 2.1; 95% confidence interval 1.0 to 4.7). Missing one or more follow-up visits (≥1) or refusal of a re-intervention by the patient was strongly related to both ruptures (risk ratio 4.7; 95% confidence interval 3.1 to 7.0) and mortality (risk ratio 3.8; 95% confidence interval 1.7 to 8.3).ConclusionFemale gender, the presence of comorbidities and at least one follow-up visit being missed or refusal of a re-intervention by the patient appear to increase the risk for mortality after endovascular abdominal aortic aneurysm repair. Larger aneurysm diameter, higher age and multimorbidity at the time of surgery appear to increase the risk for rupture and other complications after endovascular abdominal aortic aneurysm repair. These risk factors deserve further attention in future studies.

Withdrawn.

Ahead of print article withdrawn by publisher.