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The Cochrane Database of Systematic... Nov 2020Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second...
BACKGROUND
Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal haemoglobin polymerisation leading to a symptomatic disorder. Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review.
OBJECTIVES
The objectives of this review are: - to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease; - to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings. We also searched online trial registries, Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 September 2020.
SELECTION CRITERIA
All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting.
DATA COLLECTION AND ANALYSIS
No trials of gene therapy for sickle cell disease were found.
MAIN RESULTS
No trials of gene therapy for sickle cell disease were reported.
AUTHORS' CONCLUSIONS
No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.
Topics: Anemia, Sickle Cell; Genetic Therapy; Humans
PubMed: 33251574
DOI: 10.1002/14651858.CD007652.pub7 -
Journal of the Peripheral Nervous... Jun 2022Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy characterised by a high clinical and genetic heterogeneity. While most cases were... (Review)
Review
BACKGROUND AND AIMS
Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy characterised by a high clinical and genetic heterogeneity. While most cases were described in populations with Caucasian ancestry, genetic research on CMT in Africa is scant. Only a few cases of CMT have been reported, mainly from North Africa. The current study aimed to summarise available data on CMT in Africa, with emphasis on the epidemiological, clinical, and genetic features.
METHODS
We searched PubMed, Scopus, Web of Sciences, and the African Journal Online for articles published from the database inception until April 2021 using specific keywords. A total of 398 articles were screened, and 28 fulfilled our selection criteria.
RESULTS
A total of 107 families totalling 185 patients were reported. Most studies were reported from North Africa (n = 22). The demyelinating form of CMT was the commonest subtype, and the phenotype varied greatly between families, and one family (1%) of CMT associated with hearing impairment was reported. The inheritance pattern was autosomal recessive in 91.2% (n = 97/107) of families. CMT-associated variants were reported in 11 genes: LMNA, GDAP1, GJB1, MPZ, MTMR13, MTMR2, PRX, FGD4/FRABIN, PMP22, SH3TC2, and GARS. The most common genes reported are LMNA, GDAP1, and SH3TC2 and have been found mostly in Northern African populations.
INTERPRETATION
This study reveals that CMT is not rare in Africa, and describes the current clinical and genetic profile. The review emphasised the urgent need to invest in genetic research to inform counselling, prevention, and care for CMT in numerous settings on the continent.
Topics: Africa; Charcot-Marie-Tooth Disease; Genes, Recessive; Humans; Microfilament Proteins; Mutation; Phenotype; Proteins
PubMed: 35383421
DOI: 10.1111/jns.12489 -
Nefrologia 2023The irreversible progression of autosomal dominant polycystic kidney disease (ADPKD) to end-stage renal disease (ESRD) is delayed by tolvaptan. Therefore, we aim to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The irreversible progression of autosomal dominant polycystic kidney disease (ADPKD) to end-stage renal disease (ESRD) is delayed by tolvaptan. Therefore, we aim to systematically estimate and evaluate the efficacy and safety of tolvaptan in the treatment of ADPKD.
METHODS
Two reviewers independently searched all published randomized controlled trials studies in PubMed, EMBASE, Web of Science and Cochrane databases, extracted data, assessed bias risk and rated the quality of evidence. Data were analyzed by the RevMan software.
RESULTS
We identified 8 trials including 2135 patients. Both of the decline of estimated glomerular filtration rate (eGFR) [MD=1.89, 95% CI (0.74, 3.04), P=0.001] and total kidney volume (TKV) [MD=-3.32, 95% CI (-4.57, -2.07), P<0.001] were delayed in tolvaptan group compared with placebo group in ADPKD patients. The use of tolvaptan delayed TKV progression in the different-month subgroups [MD=-69.99, 95% CI (-91.05, -48.94), P<0.001]. Tolvaptan reduced renal pain [RR=0.66, 95% CI (0.54, 0.81), P<0.001] and hematuria events [RR=0.55, 95% CI (0.41, 0.74), P<0.001] in ADPKD patients. However, the prevalence of thirst [RR=2.75, 95% CI (2.34, 3.24), P<0.001] and nocturia events [RR=3.01, 95% CI (1.27, 7.11), P=0.01] were increased in tolvaptan group. There is no significant difference of hypertension events [RR=0.92, 95% CI (0.82, 1.03), P=0.13] in tolvaptan group compared placebo group.
CONCLUSIONS
This meta-analysis suggests that tolvaptan may improve clinical progression in patients with ADPKD without significantly increasing the risk of adverse reactions.
Topics: Humans; Tolvaptan; Polycystic Kidney, Autosomal Dominant; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Kidney
PubMed: 37150675
DOI: 10.1016/j.nefroe.2023.04.002 -
Endocrine Oct 2021Familial hyperaldosteronism type 1 (FH-1) is a rare autosomal dominant form of primary aldosteronism, which features a marked phenotypic heterogeneity, ranging from mild... (Review)
Review
PURPOSE
Familial hyperaldosteronism type 1 (FH-1) is a rare autosomal dominant form of primary aldosteronism, which features a marked phenotypic heterogeneity, ranging from mild to severe forms of arterial hypertension that can be complicated by stroke and cardiovascular events at a young age. As affected patients usually reach the fertile age, transmission of the disease to offspring is common. Notwithstanding this, reports of FH-1 in pregnancy are limited and there is a lack of treatment guidelines.
METHODS AND RESULTS
We searched the PubMed and EuropePMC databases with a PICO strategy to retrieve available information on management of FH-1 patients during pregnancy. We could identify seven relevant articles, which are herein reviewed.
CONCLUSION
Based on available information on pathophysiology and treatment of FH-1 in pregnancy, recommendations for the rational management of FH-1 in pregnancy are provided.
Topics: Female; Humans; Hyperaldosteronism; Hypertension; Pregnancy; Stroke
PubMed: 34043182
DOI: 10.1007/s12020-021-02763-5 -
PharmacoEconomics Apr 2022Spinal muscular atrophy (SMA) is a severe neuromuscular disease that is inherited in an autosomal recessive manner with an estimated incidence of 1 in 10,000 live...
BACKGROUND
Spinal muscular atrophy (SMA) is a severe neuromuscular disease that is inherited in an autosomal recessive manner with an estimated incidence of 1 in 10,000 live births. The traditional classification of SMA includes five types (Types 0-4 SMA) based on patient age at disease onset and the highest motor milestone achieved. Spinal muscular atrophy leads to progressive muscle denervation, skeletal muscle atrophy and loss of motor function and ambulation, though phenotypes vary along a disease continuum. Regardless of disease severity, or access to treatment, a multidisciplinary approach to care is required to ease the burden of disease. To date, limited global data exist regarding the cost and resource use associated with SMA management.
OBJECTIVE
We planned to perform a systematic literature review to identify studies on cost and healthcare resource use associated with SMA.
METHODS
A comprehensive search was conducted in 2019 using several electronic databases in addition to supplementary sources and updated in 2021 in order to capture recently published studies. Electronic searches performed in Embase, MEDLINE, Evidence-Based Medicine Reviews and EconLit via the Ovid platform were supplemented by searches of the grey literature (reference lists, conference proceedings, global Health Technology Assessment body websites and other relevant sources). Study eligibility criteria were based on the population, interventions, comparators and outcomes (PICO) framework. Quality assessment of full-text publications was evaluated with reference to a published checklist. To accommodate heterogeneity across studies including countries, currencies, populations, time units and methods of reporting used, costs were reported in Euros in 2019.
RESULTS
A total of 51 publications, comprising 49 unique studies of patients with SMA that met all eligibility criteria were included in the final selection. The publications comprised data from 14 countries and seven additional studies that reported multi-national data. Because of the heterogeneity between the different types of SMA, data were frequently reported separately for individuals with Type 1 or early-onset SMA and for Types 2, 3, and 4 SMA or later-onset SMA. Generally, direct medical costs and resource use were reported to be highest for patients with Type 1 SMA, decreasing incrementally for patients with Type 2 and Type 3 disease. Where cost categories were similar, direct costs were much lower in Europe than in the USA. Indirect costs were primarily associated with informal care, which was a substantial burden on patients and families in terms of both cost and time. Cost drivers were generally found to be dependent on SMA type.
CONCLUSIONS
Long-term robust studies are required to fully elucidate the economic burden of SMA. Considering that motor function can vary broadly, especially in Type 2 SMA, it would be beneficial to understand how costs and resource use are affected by different degrees of ambulation. Reporting data in terms of achieved motor function could also mitigate the challenges of comparing global data studies of small populations. Global, regional, and/or local data collection platforms and disease registry networks could play an important role in helping to address current data gaps.
Topics: Costs and Cost Analysis; Europe; Humans; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Technology Assessment, Biomedical
PubMed: 34761360
DOI: 10.1007/s40273-021-01105-7 -
Neurology. Clinical Practice Dec 2020Migraine is a common and often refractory feature for individuals with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy... (Review)
Review
BACKGROUND
Migraine is a common and often refractory feature for individuals with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) without consensus guidelines for treatment. Migraine treatment poses a theoretical risk within this unique population with precarious cerebrovascular autoregulation, given the vasomodulatory influence of many antimigraine medications. In this systematic review and meta-analysis, we evaluate the frequency and efficacy of treatments for migraine in individuals with CADASIL.
METHODS
A search protocol was designed to include all available publications reporting antimigraine therapies for CADASIL. Individual responses to medications were categorized as unfavorable, neutral, or favorable. Responses across medication classes were compared using the Mann-Whitney test.
RESULTS
Thirteen studies were included, yielding a cohort of 123 individuals with a median age of 53 years (range: 23-83 years), with 61% (75/123) being women. No controlled trials were identified. Simple analgesics (35.8%, 44/123) and beta-blockers (22.0%, 27/123) were the most common abortive and prophylactic strategies, respectively. Over half (54.4%) of all patients had used more than 1 medication sequentially or concomitantly. Beta-blockers were significantly associated with a neutral or unfavorable response (13.5%, 22/163, = 0.004). We found no significant associations among other medication categories.
CONCLUSIONS
Migraine in CADASIL remains a formidable therapeutic challenge, with patients often tried on several medications. Antimigraine prophylaxis with beta-blockers may be contraindicated relative to other common therapies in CADASIL. Controlled studies are needed to rigorously evaluate the safety and efficacy of antimigraine therapies in this population.
PubMed: 33520412
DOI: 10.1212/CPJ.0000000000000769 -
Andrologia Feb 2022Reciprocal translocation and Robertsonian translocation are known to be causative factors of male infertility. However, the association between autosomal reciprocal...
Reciprocal translocation and Robertsonian translocation are known to be causative factors of male infertility. However, the association between autosomal reciprocal translocation, Robertsonian translocation and semen parameters remains controversial. We performed a retrospective study and systematic review to investigate semen parameters in patients with autosomal reciprocal translocation or Robertsonian translocation. We recruited a total of 1,033 controls, 723 reciprocal translocation carriers and 326 Robertsonian translocation carriers. Men in the control, reciprocal translocation and Robertsonian translocation groups had a median age of 32.0 (95% CI, 32.0-33.0), 32.0 (95% CI, 32.0-33.0) and 33.0 (95% CI, 32.0-33.0) years respectively. Results showed that sperm concentration, total number per ejaculate, total motility, progressive motility of autosomal reciprocal translocation and Robertsonian translocation carriers were statistically lower than controls (p < .001). Eleven studies featuring 794 patients were enrolled in this systematic review. Compared with controls, autosomal reciprocal translocation and Robertsonian translocation carriers showed lower sperm concentration, total motility, progressive motility and normal morphology. Our results support the conclusion that sperm concentration, total number per ejaculate, total motility and progressive motility are significantly lower in autosomal reciprocal translocation and Robertsonian translocation carriers than in controls.
Topics: Humans; Infertility, Male; Male; Retrospective Studies; Semen; Sperm Count; Spermatozoa; Translocation, Genetic
PubMed: 34599520
DOI: 10.1111/and.14262 -
The Cochrane Database of Systematic... Nov 2021Cystic fibrosis (CF) is one of the most common life-shortening autosomal-recessive genetic conditions with around 100,000 people affected globally. CF mainly affects... (Review)
Review
BACKGROUND
Cystic fibrosis (CF) is one of the most common life-shortening autosomal-recessive genetic conditions with around 100,000 people affected globally. CF mainly affects the respiratory system, but cystic fibrosis-related diabetes (CFRD) is a common extrapulmonary co-morbidity and causes excess morbidity and mortality in this population. Continuous glucose monitoring systems (CGMS) are a relatively new technology and, as yet, the impact of these on the monitoring and subsequent management of CFRD remains undetermined.
OBJECTIVES
To establish the impact of insulin therapy guided by continuous glucose monitoring compared to insulin therapy guided by other forms of glucose data collection on the lives of people with CFRD.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of latest search: 23 September 2021. We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 23 September 2021.
SELECTION CRITERIA
Randomised controlled studies comparing insulin regimens led by data from CGMS (including real-time or retrospective data, or both) with insulin regimens guided by abnormal blood glucose measurements collected through other means of glycaemic data collection in people with CFRD. Studies with a cross-over design, even with a washout period between intervention arms, are not eligible for inclusion due to the potential long-term impact of each of the interventions and the potential to compromise the outcomes of the second intervention.
DATA COLLECTION AND ANALYSIS
No studies were included in the review, meaning that no data were available to be collected for analysis.
MAIN RESULTS
Review authors screened 14 studies at the full-text stage against the review's inclusion criteria. Consequently, seven were excluded due to the study type being ineligible (not randomised), two studies were excluded due to their cross-over design, and two studies was excluded since the intervention used was not eligible and one was a literature review. One study in participants hospitalised for a pulmonary exacerbation is ongoing. Investigators are comparing insulin dosing via insulin pump with blood sugar monitoring by a CGMS to conventional diabetes management with daily insulin injections (or on an insulin pump if already on an insulin pump in the outpatient setting) and capillary blood glucose monitoring. The participants in the control arm will wear a blinded continuous glucose monitoring system for outcome assessment. In addition to this, one further study is still awaiting classification, and will be screened to determine whether it is eligible for inclusion, or is to be excluded, in an update of this review.
AUTHORS' CONCLUSIONS
No studies were included in the review, indicating that there is currently insufficient evidence to determine the impact of insulin therapy guided by CGMS compared to insulin therapy guided by other forms of glucose data collection on the lives of people with CFRD, nor on potential adverse effects of continuous glucose monitoring in this context. Randomised controlled studies are needed to generate evidence on the efficacy and safety of continuous glucose monitoring in people with CFRD. There is one relevant ongoing study that may be eligible for inclusion in a future update of this Cochrane Review, and whose results may help answer the review question.
Topics: Blood Glucose; Blood Glucose Self-Monitoring; Cystic Fibrosis; Diabetes Mellitus; Humans; Retrospective Studies
PubMed: 34844283
DOI: 10.1002/14651858.CD013755.pub2 -
Clinical Genetics Aug 2023Huntington Disease (HD) is an incurable autosomal dominant single gene neurodegenerative disorder. Typical onset is between 30 and 40 years and characterised by motor... (Review)
Review
Huntington Disease (HD) is an incurable autosomal dominant single gene neurodegenerative disorder. Typical onset is between 30 and 40 years and characterised by motor difficulties, cognitive impairment, and behavioural and personality changes. The availability of reproductive testing means that affected and at-risk individuals can make reproductive decisions with genetic risk in mind. We aimed to summarise the literature on reproductive decision-making in the context of HD risk in terms of outcomes and the subjective experiences of at-risk individuals. Five databases were searched. Findings were synthesised using Framework analysis to identify common factors across results of quantitative and qualitative studies. Twenty five studies met inclusion criteria. Framework analysis identified the following key areas: 'The relationship between reproductive intentions and HD genetic risk', 'Views on assistive options', 'Complexity and challenges in reproductive decision-making', 'Actual reproductive outcomes', and 'Other factors influencing reproductive decision-making'. Quality of included studies was mixed. Reproductive decision making in the context of HD risk was found to be a complex and emotionally challenging process. Further research is required into reproductive decision-making and outcomes among those not utilising assistive options, and in developing a model of reproductive decision-making in HD.
Topics: Humans; Huntington Disease; Reproduction; Risk Factors; Decision Making
PubMed: 37095632
DOI: 10.1111/cge.14345 -
Journal of Neurology May 2024Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is characterised by...
BACKGROUND
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is characterised by early onset stroke and dementia. Most strokes are lacunar ischaemic strokes, but intracerebral haemorrhage (ICH) has also been reported, although there are limited published data on its frequency and characteristics.
METHODS
A retrospective review of a prospectively recruited CADASIL register from the British National Referral clinic was performed to identify acute ICH cases and their characteristics. In addition, a systematic review of ICH in CADASIL was performed. MEDLINE (Pubmed), Embase, and Web of Science were searched for articles published from inception until 31/05/2023.
RESULTS
Ten cases of ICH were identified from the National clinic register of 516 symptomatic patients, giving an estimated point prevalence of 1.9%. An additional 119 cases were identified from the systematic review, comprising 129 cases and 142 ICH events in total. Including all identified cases, the mean age at onset of ICH was 56.6 ± 15.7 (SD) years, and 74 (57.4%) were male. ICH was the first manifestation of the disease in 32 patients (38.1%), and ICH recurrence occurred in 16 (12.4%). Most ICHs were subcortical, with the thalamus, 58 (40.8%), and basal ganglia, 34 (23.9%), being the commonest sites. Anticoagulation, but not antiplatelet agents, was associated with an increased risk of ICH (20.0% vs. 1.9%, p = 0.006).
CONCLUSIONS
ICH is a relatively rare manifestation of CADASIL, occurring in about 2% of symptomatic cases. Most of the haemorrhages occurred in the subcortical regions.
Topics: Humans; CADASIL; Cerebral Hemorrhage; Middle Aged; Male; Prevalence; Risk Factors; Female; Aged; Adult; Retrospective Studies
PubMed: 38217707
DOI: 10.1007/s00415-023-12177-0