Wilson's disease and diagnostic conundrum in a low income country.
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ABSTRACT:
SUBMITTER: Patra PK
PROVIDER: S-EPMC5491743 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:(1) Introduction: Wilson's disease (WND) is an autosomal recessive disorder of copper metabolism. The WND gene is ATP7B, located on chromosome 13. WND is characterized by high clinical variability, which causes diagnostic difficulties. (2) Methods: The PubMed, Science Direct, and Wiley Online Library medical databases were reviewed using the following phrases: "Wilson's disease", "ATP7B genotype", "genotype-phenotype", "epigenetics", "genetic modifiers", and their combinations. Publications presenting the results of experimental and clinical studies, as well as review papers, were selected, which concerned: (i) the diversity of genetic strategies and tests used in WND diagnosis; (ii) the difficulties of genetic diagnosis, including uncertainty as to the pathogenicity of variants; (iii) genetic counseling; (iv) phenotypic effects of ATP7B variants in patients with WND and in heterozygous carriers (HzcWND); (v) genetic and epigenetics factors modifying the clinical picture of the disease. (3) Results and conclusions: The genetic diagnosis of WND is carried out using a variety of strategies and tests. Due to the large number of known variants in the ATP7B gene (>900), the usefulness of genetic tests in routine diagnostics is still relatively small and even analyses performed using the most advanced technologies, including next-generation sequencing, require additional tests, including biochemical evidence of abnormal copper metabolism, to confirm the diagnosis of WND. Pseudodominant inheritance, the presence of three various pathogenic variants in the same patient, genotypes indicating the possibility of segmental uniparental disomy, have been reported. Genotype-phenotype relationships in WND are complex. The ATP7B genotype, to some extent, determines the clinical picture of the disease, but other genetic and epigenetic modifiers are also relevant.
| S-EPMC10093728 | biostudies-literature
Project description:ImportancePopulation-based screening for chronic kidney disease (CKD) is sometimes recommended based on the assumption that detecting CKD is associated with beneficial changes in treatment. However, the treatment of CKD is often similar to the treatment of hypertension or diabetes, which commonly coexist with CKD.ObjectiveTo determine the frequency with which population-based screening for CKD is associated with a change in recommended treatment compared with a strategy of measuring blood pressure and assessing glycemia.Design, setting, and participantsThis cohort study was conducted using data obtained from studies that evaluated CKD in population-based samples from China (2007-2010), India (2010-2014), Mexico (2007-2008), Senegal (2012), and the United States (2009-2014), including a total of 126 242 adults screened for CKD. Data were analyzed from January 2020 to March 2021.Main outcomes and measuresThe primary definition of CKD was estimated glomerular filtration rate less than 60 mL/min/1.73 m2. For individuals with CKD, the need for a treatment change was defined as not taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker or having blood pressure levels of 140/90 mm Hg or greater. For individuals with CKD who also had diabetes, the need for a treatment change was also defined as having hemoglobin A1c levels of 8% or greater or fasting glucose levels of 178.4 mg/dL (9.9 mmol/L) or greater. Case finding was defined as testing for CKD only in adults with hypertension or diabetes.ResultsAmong 126 242 adults screened for CKD, there were 47 204 patients in the China cohort, 9817 patients in the India cohort, 51 137 patients in the Mexico cohort, 2441 patients in the Senegal cohort, and 15 643 patients in the US cohort. The mean age of participants was 49.6 years (95% CI, 49.5-49.7 years) in the China cohort, 42.9 years (95% CI, 42.6-43.2 years) in the India cohort, 51.6 years (95% CI, 51.5-51.7 years) in the Mexico cohort, 48.2 years (95% CI, 47.5-48.9 years) in the Senegal cohort, and 47.3 years (95% CI, 46.6-48.0 years) in the US cohort. The proportion of women was 57.3% (95% CI, 56.9%-57.7%) in the China cohort, 53.4% (95% CI, 52.4%-54.4%) in the India cohort, 68.8% (95% CI, 68.4%-69.2%) in the Mexico cohort, 56.0% (95% CI, 54.0%-58.0%) in the Senegal cohort, and 51.9% (51.0%-52.7%) in the US cohort. The prevalence of CKD was 2.5% (95% CI, 2.4%-2.7%) in the China cohort, 2.3% (95% CI, 2.0%-2.6%) in the India cohort, 10.6% (95% CI, 10.3%-10.9%) in the Mexico cohort, 13.1% (95% CI, 11.7%-14.4%) in the Senegal cohort, and 6.8% (95% CI, 6.2%-7.5%) in the US cohort. Screening for CKD was associated with the identification of additional adults whose treatment would change (beyond those identified by measuring blood pressure and glycemia) per 1000 adults: China: 8 adults (95% CI, 8-9 adults); India: 5 adults (95% CI, 4-7 adults); Mexico: 26 adults (95% CI, 24-27 adults); Senegal: 59 adults (95% CI, 50-69 adults); and the US: 19 adults (95% CI, 16-23 adults). Case finding was associated with the identification of 46.2% (95% CI, 45.1%-47.4%) to 86.4% (95% CI, 85.4%-87.3%) of individuals with CKD depending on the country, an increase in the proportion of individuals requiring a treatment change by as much 89.6% (95% CI, 80.4%-99.3%) in the US, and a decrease in the proportion of individuals needing GFR measurements by as much as 57.8% (95% CI, 56.3%-59.3%) in the US.Conclusions and relevanceThis study found that most additional individuals with CKD identified by population-based screening programs did not need a change in treatment compared with a strategy of measuring blood pressure and assessing glycemia and that case finding was more efficient than screening for early detection of CKD.
| S-EPMC8491102 | biostudies-literature
Project description:PurposeMeasurement of serum ceruloplasmin level is the first step in screening for Wilson's disease (WD). Despite the rarity of WD in the general population, ceruloplasmin levels are routinely measured through hepatitis screening in both adults and children. Herein, we evaluated the diagnostic value of ceruloplasmin for the diagnosis of WD among children with hepatitis.MethodsWe retrospectively reviewed data on serum ceruloplasmin levels measured as a serologic marker for patients with hepatitis at Asan Medical Center (Seoul, Korea) between from January 2004 to November 2013. The diagnosis of WD was confirmed by the identification of pathogenic variants in the ATP7B gene. To determine the diagnostic accuracy of ceruloplasmin, receiver operation characteristic (ROC) curves were constructed and the area under curve (AUC) were calculated.ResultsMeasurements of serum ceruloplasmin were performed in 2,834 children who had hepatitis. Among these, 181 (6.4%) children were diagnosed with WD. The sensitivity, specificity, and accuracy of a ceruloplasmin level of <20 mg/dL in the discrimination of WD were 93.4%, 84.2%, and 84.8%, respectively. In this study, 418 (14.7%) false-positive cases and 12 (0.4%) false-negative cases were noted. Using a ROC curve, a ceruloplasmin level of ≤16.6 mg/dL showed the highest AUC value (0.956) with a sensitivity of 91.2%, a specificity of 94.9%, and an accuracy of 94.7%.ConclusionThe measurement of serum ceruloplasmin was frequently used for the screening of WD in children, despite a low positive rate. The diagnostic value of ceruloplasmin may be strengthened by adopting a new lower cut-off level.
| S-EPMC4600703 | biostudies-literature
Project description: Not available
| S-EPMC7365372 | biostudies-literature
Project description:BackgroundCardiovascular disease disproportionately affects persons living in low- and middle-income countries and heart failure (HF) is thought to be a leading cause. Population-based studies characterizing the epidemiology of HF in these settings are lacking. We describe the age-standardized prevalence, survival, subtypes, risk factors, and 1-year mortality of HF in the population-based Haiti Cardiovascular Disease Cohort.MethodsParticipants were recruited using multistage cluster-area random sampling in Port-au-Prince, Haiti. A total of 2981 completed standardized history and exam, laboratory measures, and cardiac imaging. Clinical HF was defined by Framingham criteria. Kaplan-Meier and Cox proportional hazard regression assessed mortality among participants with and without HF; logistic regression identified associated factors.ResultsAmong all participants, the median age was 40 years (interquartile range, 27-55), and 58.2% were female. Median follow-up was 15.4 months (interquartile range, 9-22). The age-standardized HF prevalence was 3.2% (93/2981 [95% CI, 2.6-3.9]). The average age of participants with HF was 57 years (interquartile range, 45-65), and 67.7% were female. The first significant increase in HF prevalence occurred between 30 to 39 and 40 to 49 years (1.1% versus 3.7%, P=0.003). HF with preserved ejection fraction was the most common HF subtype (71.0%). Age (adjusted odds ratio, 1.36 [1.12-1.66] per 10-year increase), hypertension (2.14 [1.26-3.66]), obesity (3.35 [95% CI, 1.99-5.62]), poverty (2.10 [1.18-3.72]), and renal dysfunction (5.42 [2.94-9.98]) were associated with HF. One-year HF mortality was 6.6% versus 0.8% (hazard ratio, 7.7 [95% CI, 2.9-20.6]; P<0.0001).ConclusionsThe age-standardized prevalence of HF in this low-income setting was alarmingly high at 3.2%-5-fold higher than modeling estimates for low- and middle-income countries. Adults with HF were two decades younger and 7.7× more likely to die at 1 year compared with those in the community without HF. Further research characterizing the population burden of HF in low- and middle-income countries can guide resource allocation and development of pragmatic HF prevention and treatment interventions, ultimately reducing global cardiovascular disease health disparities.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT03892265.
| S-EPMC9974582 | biostudies-literature
Project description:BackgroundPrior research has demonstrated that low- and low-middle-income countries (LLMICs) bear a higher burden of critical illness and have a higher rate of mortality from critical illness than high-income countries (HICs). There is a pressing need for improved critical care delivery in LLMICs to reduce this inequity. This systematic review aimed to characterise the range of critical care interventions and services delivered within LLMIC health care systems as reported in the literature.MethodsA search strategy using terms related to critical care in LLMICs was implemented in multiple databases. We included English language articles with human subjects describing at least one critical care intervention or service in an LLMIC setting published between 1 January 2008 and 1 January 2020.ResultsA total of 1620 studies met the inclusion criteria. Among the included studies, 45% of studies reported on pediatric patients, 43% on adults, 23% on infants, 8.9% on geriatric patients and 4.2% on maternal patients. Most of the care described (94%) was delivered in-hospital, with the remainder (6.2%) taking place in out-of-hospital care settings. Overall, 49% of critical care described was delivered outside of a designated intensive care unit. Specialist physicians delivered critical care in 60% of the included studies. Additional critical care was delivered by general physicians (40%), as well as specialist physician trainees (22%), pharmacists (16%), advanced nursing or midlevel practitioners (8.9%), ambulance providers (3.3%) and respiratory therapists (3.1%).ConclusionsThis review represents a comprehensive synthesis of critical care delivery in LLMIC settings. Approximately 50% of critical care interventions and services were delivered outside of a designated intensive care unit. Specialist physicians were the most common health care professionals involved in care delivery in the included studies, however generalist physicians were commonly reported to provide critical care interventions and services. This study additionally characterised the quality of the published evidence guiding critical care practice in LLMICs, demonstrating a paucity of interventional and cost-effectiveness studies. Future research is needed to understand better how to optimise critical care interventions, services, care delivery and costs in these settings.RegistrationPROSPERO CRD42019146802.
| S-EPMC10691174 | biostudies-literature
Project description:ImportanceMost of the global morbidity and mortality in chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries (LMICs), with significant economic effects.ObjectiveTo assess the discriminative accuracy of 3 instruments using questionnaires and peak expiratory flow (PEF) to screen for COPD in 3 LMIC settings.Design, setting, and participantsA cross-sectional analysis of discriminative accuracy, conducted between January 2018 and March 2020 in semiurban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda, using a random age- and sex-stratified sample of the population 40 years or older.ExposuresThree screening tools, the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE; range, 0-6; high risk indicated by a score of 5 or more or score 2-5 with low PEF [<250 L/min for females and <350 L/min for males]), the COPD in LMICs Assessment questionnaire (COLA-6; range, 0-5; high risk indicated by a score of 4 or more), and the Lung Function Questionnaire (LFQ; range, 0-25; high risk indicated by a score of 18 or less) were assessed against a reference standard diagnosis of COPD using quality-assured postbronchodilator spirometry. CAPTURE and COLA-6 include a measure of PEF.Main outcomes and measuresThe primary outcome was discriminative accuracy of the tools in identifying COPD as measured by area under receiver operating characteristic curves (AUCs) with 95% CIs. Secondary outcomes included sensitivity, specificity, positive predictive value, and negative predictive value.ResultsAmong 10 709 adults who consented to participate in the study (mean age, 56.3 years (SD, 11.7); 50% female), 35% had ever smoked, and 30% were currently exposed to biomass smoke. The unweighted prevalence of COPD at the 3 sites was 18.2% (642/3534 participants) in Nepal, 2.7% (97/3550) in Peru, and 7.4% (264/3580) in Uganda. Among 1000 COPD cases, 49.3% had clinically important disease (Global Initiative for Chronic Obstructive Lung Disease classification B-D), 16.4% had severe or very severe airflow obstruction (forced expiratory volume in 1 second <50% predicted), and 95.3% of cases were previously undiagnosed. The AUC for the screening instruments ranged from 0.717 (95% CI, 0.677-0.774) for LFQ in Peru to 0.791 (95% CI, 0.770-0.809) for COLA-6 in Nepal. The sensitivity ranged from 34.8% (95% CI, 25.3%-45.2%) for COLA-6 in Nepal to 64.2% (95% CI, 60.3%-67.9%) for CAPTURE in Nepal. The mean time to administer the instruments was 7.6 minutes (SD 1.11), and data completeness was 99.5%.Conclusions and relevanceThis study demonstrated that screening instruments for COPD were feasible to administer in 3 low- and middle-income settings. Further research is needed to assess instrument performance in other low- and middle-income settings and to determine whether implementation is associated with improved clinical outcomes.
| S-EPMC8753498 | biostudies-literature
Project description:BackgroundRespiratory syncytial virus (RSV) is globally ubiquitous, and infection during the first six months of life is a major risk for severe disease and hospital admission; consequently RSV is the most important viral cause of respiratory morbidity and mortality in young children. Development of vaccines for young infants is complicated by the presence of maternal antibodies and immunological immaturity, but vaccines targeted at older children avoid these problems. Vaccine development for young infants has been unsuccessful, but this is not the case for older children (> 6 m). Would vaccinating older children have a significant public health impact? We developed a mathematical model to explore the benefits of a vaccine against RSV.Methods and findingsWe have used a deterministic age structured model capturing the key epidemiological characteristics of RSV and performed a statistical maximum-likelihood fit to age-specific hospitalization data from a developing country setting. To explore the effects of vaccination under different mixing assumptions, we included two versions of contact matrices: one from a social contact diary study, and the second a synthesised construction based on demographic data. Vaccination is assumed to elicit an immune response equivalent to primary infection. Our results show that immunisation of young children (5-10 m) is likely to be a highly effective method of protection of infants (<6 m) against hospitalisation. The majority benefit is derived from indirect protection (herd immunity). A full sensitivity and uncertainty analysis using Latin Hypercube Sampling of the parameter space shows that our results are robust to model structure and model parameters.ConclusionsThis result suggests that vaccinating older infants and children against RSV can have a major public health benefit.
| S-EPMC4577090 | biostudies-literature
Project description:BackgroundMigration among skilled labour has been noted as one of the major issues in recent times, especially among health workers. Data from the United Nations show that almost two thirds of people migrating are labor migrants and international migrants constitute 3.5% of the global migration population. Out of the millions of people who migrate across the globe, health workers, especially nurses form a greater portion of these numbers. This study explored nursing students' intention to migrate to other countries after completing their programs.MethodA descriptive cross-sectional design approach was adopted using self-administered questionnaire that contain aspects of open-ended questions. A sample size of 226 nursing students were recruited using convenient sampling technique.ResultsThe results overall, revealed that 226 nursing students participated in the study. Out of this, most of the respondents 42.5% were aged between 25 and 30 years with majority 53.1% being males. Also, 35% of the participants were married with more than half 59.7% of the respondents being Christians. The results further revealed that most of the participants 64.2% had intention of migrating to other countries. Among those who intended to migrate, 11.7% identified lack of jobs, 39.3% identified low salaries in Ghana while 50.3% identified bad working conditions. The rest 2.8% attributed their intentions to migrate to educational opportunities. Common places of destination included Canada, USA, UK and Australia.ConclusionThe outcome of this study points to the urgent need for low-income countries such as Ghana to urgently put in measures to curb the menace of brain drain among nurses. Improvement in working condition of nurses must be prioritized to motivate their stay.
| S-EPMC11256540 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide. Despite this, there has been little progress so far in terms of disease-modifying therapies over the last few decades and this is in part due to poor understanding of the definition and mechanisms surrounding early disease before it becomes established and increasingly complex. In this review, the nuances and difficulty in defining early disease in COPD are discussed. There are clear benefits in identifying patients early; however, usually diagnosis is made in the presence of significant lung damage. We consider what can be learned of early disease from COPD studies and highlight the lack of inclusion of young smokers (who may be at risk of COPD) or those with mild disease. We discuss promising clinical measures that are being used in an effort to detect early disease. These include symptom assessment, lung physiology measures and computed tomography (CT) imaging modalities. There is emerging evidence for the role of neutrophils and their proteinases in early COPD. This may form an important biomarker to investigate the pathophysiological processes of early COPD. Given the importance of the early disease, it is recommended that future COPD studies focus on capturing the earliest manifestations of disease, to understand the initiating mechanisms and to identify novel treatment targets.
| S-EPMC8053524 | biostudies-literature