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The Cochrane Database of Systematic... Dec 2016Various central nervous system-penetrant antibiotics are bactericidal in vitro and in vivo against the causative agent of Lyme neuroborreliosis (LNB), Borrelia... (Review)
Review
BACKGROUND
Various central nervous system-penetrant antibiotics are bactericidal in vitro and in vivo against the causative agent of Lyme neuroborreliosis (LNB), Borrelia burgdorferi. These antibiotics are routinely used clinically to treat LNB, but their relative efficacy is not clear.
OBJECTIVES
To assess the effects of antibiotics for the treatment of LNB.
SEARCH METHODS
On 25 October 2016 we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched clinical trial registers on 26 October 2016. We reviewed the bibliographies of the randomized trials identified and contacted the authors and known experts in the field to identify additional published or unpublished data. There were no language restrictions when searching for studies.
SELECTION CRITERIA
Randomized clinical trials of antibiotic treatment of LNB in adults and children that compared any antibiotic treatment, including combinations of treatments, versus any other treatment, placebo, or no treatment. We excluded studies of entities considered as post-Lyme syndrome.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified seven randomized studies involving 450 European participants with LNB for inclusion in this systematic review. We found no trials conducted in the United States. Marked heterogeneity among these studies prevented meta-analysis. None of the studies included a placebo control on the initial antibiotic treatment, and only one was blinded. None were delayed-start studies. All were active comparator studies, and most were not adequately powered for non-inferiority comparison. The trials investigated four antibiotics: penicillin G and ceftriaxone in four studies, doxycycline in three studies, and cefotaxime in two studies. One study tested a three-month course of oral amoxicillin versus placebo following initial treatment with intravenous ceftriaxone. One study was limited to children. The trials measured efficacy using heterogeneous physician- or patient-reported outcomes, or both. In some cases cerebrospinal fluid analysis was included as an indirect biomarker of disease and outcome. None of the studies reported on our proposed primary outcome, 'Improvement in a measure of overall disability in the long term (three or more months).' None of the trials revealed any between-group differences in symptom resolution in response to active treatment. In general, treatment was tolerated well. The quality of adverse event reporting, however, was low.
AUTHORS' CONCLUSIONS
There is mostly low- to very low-quality clinical evidence from a limited number of mostly small, heterogeneous trials with diverse outcome measures, comparing the relative efficacy of central nervous system-penetrant antibiotics for the treatment of LNB. The few existing randomized studies have limited power and lack consistent and well-defined entry criteria and efficacy endpoints. It is not possible to draw firm conclusions on the relative efficacy of accepted antibiotic drug regimens for the treatment of LNB. The majority of people are reported to have good outcomes, and symptoms resolve by 12 months regardless of the antibiotic used. A minority of participants did not improve sufficiently, and some were retreated. These randomized studies provide some evidence that doxycycline, penicillin G, ceftriaxone, and cefotaxime are efficacious in the treatment of European LNB. No evidence of additional efficacy was observed when, in one study, an initial antibiotic treatment with intravenous ceftriaxone was followed by additional longer treatment with oral amoxicillin. There is a lack of evidence identified through our high-quality search strategy on the efficacy of antibiotics for treatment of LNB in the United States.
Topics: Amoxicillin; Anti-Bacterial Agents; Borrelia burgdorferi; Cefotaxime; Ceftriaxone; Doxycycline; Humans; Lyme Disease; Lyme Neuroborreliosis; Penicillin G; Randomized Controlled Trials as Topic
PubMed: 27931077
DOI: 10.1002/14651858.CD006978.pub2 -
Clinical Genetics Feb 2013This systematic review investigated the inheritance of the classical chronic myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential... (Review)
Review
This systematic review investigated the inheritance of the classical chronic myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and chronic myelogenous leukemia (CML). Sixty-one articles were included and provided 135 families with a total of 341 participants distributed to various subtypes of MPN: 50% PV, 23% ET, 14% PMF, 10% CML and 3% non-MPN hematological disorder. Women developed the disease earlier than men (43.1 years vs 47.3 years; p = 0.074), while the general average age of onset was 46 years, notably younger than sporadic cases. The clinical phenotype of the families showed a homogenous (67%) and a heterogeneous (33%) pattern, with the majority being PV-PV pairs (36%) and PV-PMF pairs (17%), respectively. This observation suggests that the susceptibility gene (or genes) is not restricted to one subtype supporting the hypothesis of a mutation in an early multipotent stem cell. Furthermore, a major subgroup of families provided evidence of an autosomal dominant (AD) inheritance with reduced penetrance. This study suggests that the origin of MPNs may occur in at least three different settings: (i) a sporadic, (ii) genetic heterogeneity with polygenetic and environmental impact and (iii) a familial phenotype following an AD inheritance.
Topics: Chronic Disease; Female; Genetic Predisposition to Disease; Humans; Inheritance Patterns; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential
PubMed: 23094849
DOI: 10.1111/cge.12044 -
Molecular Genetics and Metabolism Jul 2023Sengers syndrome (OMIM# 212350) is a rare autosomal recessive mitochondrial disease caused by biallelic pathogenic variants in the AGK gene, which encodes the... (Review)
Review
Sengers syndrome (OMIM# 212350) is a rare autosomal recessive mitochondrial disease caused by biallelic pathogenic variants in the AGK gene, which encodes the acylglycerol kinase enzyme. The syndrome was originally defined as a "triad" of hypertrophic cardiomyopathy, cataracts, and lactic acidosis, with or without skeletal myopathy. The clinical manifestation of Sengers Syndrome exhibits substantial heterogeneity, with mild and severe/infantile forms reported. Further, biallelic AGK pathogenic variants have also been identified in a familial case of non-syndromic isolated cataract (OMIM# 614691), expanding our understanding of the gene's influence beyond the originally defined syndrome. In this study, we provide a systematic review of molecularly confirmed cases with biallelic AGK pathogenic variants (Supplementary Table 1). Our analysis demonstrates the variable expressivity and penetrance of the central features of Sengers syndrome, as follows: cataracts (98%), cardiomyopathy (88%), lactic acidosis (adjusted 88%), and skeletal myopathy (adjusted 74%) (Table 1). Furthermore, we investigate the associations between genotype, biochemical profiles, and clinical outcomes, with a particular focus on infantile mortality. Our findings reveal that patients carrying homozygous nonsense variants have a higher incidence of infant mortality and a lower median age of death (p = 0.005 and p = 0.02, Table 2a). However, the location of pathogenic variants within the AGK domains was not significantly associated with infantile death (p = 0.62, Table 2b). Additionally, we observe a borderline association between the absence of lactic acidosis and longer survival (p = 0.053, Table 2c). Overall, our systematic review sheds light on the diverse clinical manifestations of AGK-related disorders and highlights potential factors that influence its prognosis. These provide important implications for the diagnosis, treatment, and counseling of affected individuals and families.
Topics: Infant; Humans; Acidosis, Lactic; Cardiomyopathies; Cataract; Muscular Diseases; Biological Variation, Population; Phosphotransferases (Alcohol Group Acceptor)
PubMed: 37354892
DOI: 10.1016/j.ymgme.2023.107626 -
Frontiers in Genetics 2023To analyze the phenotypes, genotypes, and the relationship of phenotypes and genotypes for Chinese patients with Bardet-Biedl syndrome (BBS). The Chinese Wanfang and...
To analyze the phenotypes, genotypes, and the relationship of phenotypes and genotypes for Chinese patients with Bardet-Biedl syndrome (BBS). The Chinese Wanfang and Weipu data, and PubMed were searched up to December 2022. Patients with detailed clinical feature data were involved in the analysis. A total of 153 Chinese patients, including 87 males, 53 females, and 12 unknown, were enrolled. Their ages ranged from 1.2 to 44 years old with a mean of 16.70 ± 9.90 years old. Among these patients, 80 (52.29%) were reported by ophthalmologists, and only 24 (15.68%) reported by pediatricians. Most patients (132/137, 96.35%) had visual problems; 131/153 (85.62%) had polydactyly; 124/132 (93.93%) were overweight or obese; 63/114 (55.26%) had renal abnormalities; kidney dysfunction was found in 33 (21.57%); 83/104 (79.81%) had hypogonadism and/or genital hypoplasia; and 111/136 (81.62%) had mental retardation. In this series, genetic analysis was performed in 90 (58.82%) patients, including 22 (24.71%), 20 (22.73%), and 10 (11.24%) patients. Moreover, 11 fetuses were diagnosed prenatally in the last 4 years except for one patient in 2004 year. It was noted that had higher penetrance. had higher hearing impairment and lower renal abnormality penetrance. also had lower renal abnormality penetrance as well. Misdiagnosis or miss diagnosis of BBS may be common in China. In patients with polydactyly, visual impairment, obesity, renal abnormalities, hypogonadism, and mental retardation, or in fetuses with polydactyly and/or renal abnormalities, BBS should be considered in the differential diagnosis. Other deformities should be evaluated carefully and genetic analysis should be performed as early as possible.
PubMed: 38034494
DOI: 10.3389/fgene.2023.1247557 -
Expert Review of Clinical Immunology Aug 2021: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare inborn immune error characterized by a triad of chronic mucocutaneous candidiasis...
: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare inborn immune error characterized by a triad of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (HP), and adrenal insufficiency (ADI).: Literature search was conducted in PubMed, Web of Science, and Scopus databases using related keywords, and included studies were systematically evaluated.: We reviewed 938 APECED patients and the classic triad of APECED was detected in 57.3% (460 of 803) of patients. CMC (82.5%) was reported as the earliest, HP (84.2%) as the most prevalent, and ADI (72.2%) as the latest presentation within the classic triad. A broad spectrum of non-triad involvements has also been reported; mainly included ectodermal dystrophy (64.5%), infections (58.7%), gastrointestinal disorders (52.0%), gonadal failure (42.0%), neurologic involvements (36.4%), and ocular manifestations (34.3%). A significant positive correlation was detected between certain tissue-specific autoantibodies and particular manifestations including ADI and HP. Neutralizing autoantibodies were detected in at least 60.0% of patients. Nonsense and/or frameshift insertion-deletion mutations were detected in 73.8% of patients with CMC, 70.9% of patients with HP, and 74.6% of patients with primary ADI.: Besides penetrance diversity, our review revealed a diverse affected ethnicity (mainly from Italy followed by Finland and Ireland). APECED can initially present in adolescence as 5.2% of the patients were older than 18 years at the disease onset. According to the variety of clinical conditions, which in the majority of patients appear gradually over time, clinical management deserves a separate analysis.
Topics: Adolescent; Autoantibodies; Frameshift Mutation; Humans; Mutation; Polyendocrinopathies, Autoimmune; Transcription Factors
PubMed: 33957837
DOI: 10.1080/1744666X.2021.1925543 -
Hernia : the Journal of Hernias and... Apr 2013Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies... (Review)
Review
BACKGROUND
Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias.
METHODS
A literature search in the MEDLINE and Embase databases was performed with the following search terms: genetics, heredity, multifactorial inheritance, inheritance patterns, sibling relations, family relations, and abdominal hernia. Only English human clinical or register-based studies describing the inheritance of groin hernias, family history of groin hernias, or familial accumulation of groin hernias were included.
RESULTS
Eleven studies evaluating 37,166 persons were included. The overall findings were that a family history of inguinal hernia was a significant risk factor for the development of a primary hernia. A family history of inguinal hernia showed a tendency toward increased hernia recurrence rate and significantly earlier recurrence. The included studies did not agree on the possible inheritance patterns differing between polygenic inheritance, autosomal dominant inheritance, and multifactorial inheritance. Furthermore, the studies did not agree on the degree of penetrance.
CONCLUSION
The literature on the inheritance of groin hernias indicates that groin hernia is most likely an inherited disease; however, neither the extent of familial accumulation nor a clear inheritance pattern has yet been found. In order to establish whether groin hernias are accumulated in certain families and to what extent, large register studies based on hernia repair data or clinical examinations are needed. Groin hernia repair (inguinal and femoral hernia) is among the most commonly performed gastrointestinal surgical procedures [1]. Emergency groin hernia surgery is associated with increased mortality, increased patient-related morbidity, and increased hospital stay compared with elective groin hernia procedures [2, 3]. Identifying patients at high risk of developing groin hernia would therefore provide the possibility of timely elective surgical intervention, thus reducing the rate of emergency procedures. It could also potentially make way for individualized surgical methods in the future.
Topics: Genetic Predisposition to Disease; Hernia, Inguinal; Humans; Inheritance Patterns; Risk Factors; Twin Studies as Topic
PubMed: 23423330
DOI: 10.1007/s10029-013-1060-4 -
The British Journal of Ophthalmology Mar 2009This study describes, in detail, the phenotype of late-onset retinal macular degeneration (L-ORMD) an inherited condition affecting both the retina and anterior segment.... (Review)
Review
AIM
This study describes, in detail, the phenotype of late-onset retinal macular degeneration (L-ORMD) an inherited condition affecting both the retina and anterior segment. A staging based on clinical characteristics is proposed, and the relevance of this condition to current understanding of age-related macular degeneration is discussed.
METHODS
A systematic review of the literature regarding this condition supports a detailed description of the natural history. Clinical experiences in identifying, monitoring and managing patients are also presented.
RESULTS
L-ORMD is a rare fully penetrant autosomal dominant condition resulting from a mutation in the C1QTNF5 gene on chromosome 11. Affected individuals develop bilateral loss of vision, dark-adaptation abnormalities, fundus drusen-like yellow spots, midperipheral pigmentation, choroidal neovascularisation, chorioretinal atrophy and long anteriorly inserted lens zonules. Patients may benefit from treatment with high-dose vitamin A.
CONCLUSIONS
Raised awareness of L-ORMD should lead to earlier diagnosis and improved care for patients. New antivascular endothelial growth factor treatment may provide a new possibility for management. A deeper insight into molecular and genetic mechanisms of L-ORMD may suggest avenues to explore new treatments of this disorder.
Topics: Adult; Aged; Aged, 80 and over; Collagen; Female; Fundus Oculi; Humans; Macular Degeneration; Male; Middle Aged; Mutation; Retina; Vitamin A; Vitamins
PubMed: 19098033
DOI: 10.1136/bjo.2008.150151 -
Chemosphere Nov 2022Number of research on molecular simulation and design has emerged recently but there is currently a lack of review to present these studies in an organized manner to...
Number of research on molecular simulation and design has emerged recently but there is currently a lack of review to present these studies in an organized manner to highlight the advances and feasibility. This paper aims to review the development, structural, physical properties and separation performance of hybrid membranes using molecular simulation approach. The hybrid membranes under review include ionic liquid membrane, mixed matrix membrane, and functionalized hybrid membrane for understanding of the transport mechanism of molecules through the different structures. The understanding of molecular interactions, and alteration of pore sizes and transport channels at atomistic level post incorporation of different components in hybrid membranes posing impact to the selective transport of desired molecules are also covered. Incorporation of molecular simulation of hybrid membrane in related fields such as carbon dioxide (CO) removal, wastewater treatment, and desalination are also reviewed. Despite the limitations of current molecular simulation methodologies, i.e., not being able to simulate the membrane operation at the actual macroscale in processing plants, it is still able to demonstrate promising results in capturing molecule behaviours of penetrants and membranes at full atomic details with acceptable separation performance accuracy. From the review, it was found that the best performing ionic liquid membrane, mixed matrix membrane and functionalized hybrid membrane can enhance the performance of pristine membrane by 4 folds, 2.9 folds and 3.3 folds, respectively. The future prospects of molecular simulation in hybrid membranes are also presented. This review could provide understanding to the current advancement of molecular simulation approach in hybrid membranes separation. This could also provide a guideline to apply molecular simulation in the related sectors.
Topics: Carbon Dioxide; Ionic Liquids; Membranes; Membranes, Artificial; Water Purification
PubMed: 35952794
DOI: 10.1016/j.chemosphere.2022.135844 -
Familial Cancer Oct 2018Around 5% of colorectal cancers are due to mutations within DNA mismatch repair genes, resulting in Lynch syndrome (LS). These mutations have a high penetrance with... (Meta-Analysis)
Meta-Analysis
Around 5% of colorectal cancers are due to mutations within DNA mismatch repair genes, resulting in Lynch syndrome (LS). These mutations have a high penetrance with early onset of colorectal cancer at a mean age of 45 years. The mainstay of surgical management is either a segmental or extensive colectomy. Currently there is no unified agreement as to which management strategy is superior due to limited conclusive empirical evidence available. A systematic review and meta- analysis to evaluate the risk of metachronous colorectal cancer (MCC) and mortality in LS following segmental and extensive colectomy. A systematic review of the PubMed database was conducted. Studies were included/ excluded based on pre-specified criteria. To assess the risk of MCC and mortality attributed to segmental or extensive colectomies, relative risks (RR) were calculated and corresponding 95% confidence intervals (CI). Publication bias was investigated using funnel plots. Data about mortality, as well as patient ascertainment [Amsterdam criteria (AC), germline mutation (GM)] were also extracted. Statistical analysis was conducted using the R program (version 3.2.3). The literature search identified 85 studies. After further analysis ten studies were eligible for inclusion in data synthesis. Pooled data identified 1389 patients followed up for a mean of 100.7 months with a mean age of onset of 45.5 years of age. A total 1119 patients underwent segmental colectomies with an absolute risk of MCC in this group of 22.4% at the end of follow-up. The 270 patients who had extensive colectomies had a MCC absolute risk of 4.7% (0% in those with a panproctocolecomy). Segmental colectomy was significantly associated with an increased relative risk of MCC (RR = 5.12; 95% CI 2.88-9.11; Fig. 1), although no significant association with mortality was identified (RR = 1.65; 95% CI 0.90-3.02). There was no statistically significant difference in the risk of MCC between AC and GM cohorts (p = 0.5, Chi-squared test). In LS, segmental colectomy results in a significant increased risk of developing MCC. Despite the choice of segmental or extensive colectomies having no statistically significant impact on mortality, the choice of initial surgical management can impact a patient's requirement for further surgery. An extensive colectomy can result in decreased need for further surgery; reduced hospital stays and associated costs. The significant difference in the risk of MCC, following segmental or extensive colectomies should be discussed with patients when deciding appropriate management. An individualised approach should be utilised, taking into account the patient's age, co-morbidities and genotype. In order to determine likely germline-specific effects, or a difference in survival, larger and more comprehensive studies are required.
Topics: Adult; Aged; Aged, 80 and over; Colectomy; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Female; Humans; Male; Middle Aged; Mutation; Risk Factors
PubMed: 29189962
DOI: 10.1007/s10689-017-0062-2 -
Polymorphisms of progesterone receptor and ovarian cancer risk: a systemic review and meta-analysis.The Journal of Obstetrics and... Feb 2015Growing bodies of studies have investigated the associations between three progesterone receptor (PGR) polymorphisms, +331G/A, Alu insertion and Val660Leu, and... (Meta-Analysis)
Meta-Analysis Review
AIM
Growing bodies of studies have investigated the associations between three progesterone receptor (PGR) polymorphisms, +331G/A, Alu insertion and Val660Leu, and susceptibility to ovarian cancer, but the results remain controversial and inconclusive. Thus, we conducted a meta-analysis to derive a more precise estimation of the associations.
METHODS
A total of 21 case-control studies from 16 publications that included analyses of Alu insertion (981 cases, 2136 controls), Val660Leu (2205 cases, 3222 controls) and +331G/A (2842 cases, 4305 controls) polymorphisms were identified.
RESULTS
Significantly increased risks of ovarian cancer were found for Alu insertion (T2 T2 + T1 T2 vs T1 T1 ; odds ratio [OR], 1.504; 95% confidence interval [CI], 1.206-2.203) and Val660Leu (TT vs GT; OR, 1.524; 95% CI, 1.013-2.293). No significant association was found between +331G/A polymorphism and ovarian cancer.
CONCLUSION
This meta-analysis suggests that the two polymorphisms of PGR, Alu insertion and Val660Leu, may contribute to ovarian cancer susceptibility as low-penetrance risk factors.
Topics: Female; Genetic Predisposition to Disease; Humans; Ovarian Neoplasms; Penetrance; Polymorphism, Single Nucleotide; Receptors, Progesterone; Risk Factors
PubMed: 25228088
DOI: 10.1111/jog.12519