Systematic Identification of Familial Hypercholesterolaemia in Primary Care-A Systematic Review.
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SUBMITTER: Silva L
PROVIDER: S-EPMC8071332 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVES:Heterozygous familial hypercholesterolaemia (FH) confers a significant risk for premature cardiovascular disease (CVD). However, the estimated prevalence of FH varies substantially among studies. We aimed to provide a summary estimate of FH prevalence in the general population and assess variations in frequency across different sociodemographic characteristics. SETTING, PARTICIPANTS AND OUTCOME MEASURES:We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO and PubMed for peer-reviewed literature using validated strategies. Results were limited to studies published in English between January 1990 and January 2017. Studies were eligible if they determined FH prevalence using clinical criteria or DNA-based analyses. We determined a pooled point prevalence of FH in adults and children and assessed the variation of the pooled frequency by age, sex, geographical location, diagnostic method, study quality and year of publication. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were investigated through subgroups, meta-regression and sensitivity analyses. RESULTS:The pooled prevalence of FH from 19 studies including 2 458 456 unique individuals was 0.40% (95% CI 0.29% to 0.52%) which corresponds to a frequency of 1 in 250 individuals. FH prevalence was found to vary by age and geographical location but not by any other covariates. Results were consistent in sensitivity analyses. CONCLUSIONS:Our systematic review suggests that FH is a common disorder, affecting 1 in 250 individuals. These findings underscore the need for early detection and management to decrease CVD risk.
| S-EPMC5588988 | biostudies-literature
Project description:Familial hypercholesterolaemia (FH) is a common inherited disorder, causing lifelong elevated low-density lipoprotein cholesterol (LDL-C). Most individuals with FH remain undiagnosed, precluding opportunities to prevent premature heart disease and death. Some machine-learning approaches improve detection of FH in electronic health records, though clinical impact is under-explored. We assessed performance of an array of machine-learning approaches for enhancing detection of FH, and their clinical utility, within a large primary care population. A retrospective cohort study was done using routine primary care clinical records of 4,027,775 individuals from the United Kingdom with total cholesterol measured from 1 January 1999 to 25 June 2019. Predictive accuracy of five common machine-learning algorithms (logistic regression, random forest, gradient boosting machines, neural networks and ensemble learning) were assessed for detecting FH. Predictive accuracy was assessed by area under the receiver operating curves (AUC) and expected vs observed calibration slope; with clinical utility assessed by expected case-review workload and likelihood ratios. There were 7928 incident diagnoses of FH. In addition to known clinical features of FH (raised total cholesterol or LDL-C and family history of premature coronary heart disease), machine-learning (ML) algorithms identified features such as raised triglycerides which reduced the likelihood of FH. Apart from logistic regression (AUC, 0.81), all four other ML approaches had similarly high predictive accuracy (AUC > 0.89). Calibration slope ranged from 0.997 for gradient boosting machines to 1.857 for logistic regression. Among those screened, high probability cases requiring clinical review varied from 0.73% using ensemble learning to 10.16% using deep learning, but with positive predictive values of 15.5% and 2.8% respectively. Ensemble learning exhibited a dominant positive likelihood ratio (45.5) compared to all other ML models (7.0-14.4). Machine-learning models show similar high accuracy in detecting FH, offering opportunities to increase diagnosis. However, the clinical case-finding workload required for yield of cases will differ substantially between models.
| S-EPMC7603302 | biostudies-literature
Project description:Effective treatments for familial hypercholesterolaemia (FH) offer patients the opportunity of normal life expectancy, but lifelong adherence to both lipid-lowering therapies and lifestyle measures is challenging, and thus, this is rarely achieved. The aim of this systematic review is to identify attributes of educational interventions that promote adherence to treatment in FH. A systematic literature search was undertaken using Medline, CINAHL, HMIC and Embase. Papers were included based upon pre-defined inclusion and exclusion criteria; the quality of each included paper was assessed using the MERSQI scoring system. Relevant data were extracted, and a narrative synthesis was created. Six relevant studies of varying methodological quality were found amongst 2963 papers identified during the search. In total, there were 619 patients with FH in the intervention arm of the relevant studies. All six studies showed a positive effect of education on adherence to FH treatment; however, only two papers observed a statistically significant effect. Assessment was limited to the short-term. Four themes were identified as important when using education to improve treatment adherence: involving family, patient empowerment, practical problem solving and use of information leaflets. Educational interventions improve short term treatment adherence in patients with FH. Successful interventions are those that involve the whole family, set practical problem solving tasks, and that use techniques to increase the patients self-efficacy. This should all be supported by contemporaneous provision of written, age-appropriate information. There were no studies looking at education and long-term adherence in FH patients, and more research is needed in this area.
| S-EPMC9947204 | biostudies-literature
Project description:BackgroundThe vast majority of individuals with familial hypercholesterolaemia in the general population remain unidentified worldwide. Recognising patients most likely to have the condition, to enable targeted specialist assessment and treatment, could prevent major coronary morbidity and mortality. We aimed to evaluate a clinical case-finding algorithm, the familial hypercholesterolaemia case ascertainment tool (FAMCAT), and compare it with currently recommended methods for detection of familial hypercholesterolaemia in primary care.MethodsIn this external validation study, FAMCAT regression equations were applied to a retrospective cohort of patients aged 16 years or older with cholesterol assessed, who were randomly selected from 1500 primary care practices across the UK contributing to the QResearch database. In the main analysis, we assessed the ability of FAMCAT to detect familial hypercholesterolaemia (ie, its discrimination) and compared it with that of other established clinical case-finding approaches recommended internationally (Simon Broome, Dutch Lipid Clinic Network, Make Early Diagnosis to Prevent Early Deaths [MEDPED] and cholesterol concentrations higher than the 99th percentile of the general population in the UK). We assessed discrimination by area under the receiver operating curve (AUROC; ranging from 0·5, indicating pure chance, to 1, indicating perfect discrimination). Using a probability threshold of more than 1 in 500 (prevalence of familial hypercholesterolaemia), we also assessed sensitivity, specificity, positive predictive values, and negative predictive values in the main analysis.FindingsA sample of 750 000 patients who registered in 1500 UK primary care practices that contribute anonymised data to the QResearch database between Jan 1, 1999, and Sept 1, 2017, was randomly selected, of which 747 000 patients were assessed. FAMCAT showed a high degree of discrimination (AUROC 0·832, 95% CI 0·820-0·845), which was higher than that of Simon Broome criteria (0·694, 0·681-0·703), Dutch Lipid Clinic Network criteria (0·724, 0·710-0·738), MEDPED criteria (0·624, 0·609-0·638), and screening cholesterol concentrations higher than the 99th percentile (0·581, 0·570-0·591). Using a 1 in 500 probability threshold, FAMCAT achieved a sensitivity of 84% (1028 predicted vs 1219 observed cases) and specificity of 60% (443 949 predicted vs 745 781 observed non-cases), with a corresponding positive predictive value of 0·84% and a negative predictive value of 99·2%.InterpretationFAMCAT identifies familial hypercholesterolaemia with greater accuracy than currently recommended approaches and could be considered for clinical case finding of patients with the highest likelihood of having hypercholesterolaemia in primary care.FundingUK National Institute for Health Research School for Primary Care Research.
| S-EPMC6506568 | biostudies-literature
Project description:ObjectiveFamilial hypercholesterolaemia (FH) is a common inherited disorder causing premature coronary heart disease (CHD) and death. We have developed the novel Familial Hypercholesterolaemia Case Ascertainment Tool (FAMCAT 1) case-finding algorithm for application in primary care, to improve detection of FH. The performance of this algorithm was further improved by including personal history of premature CHD (FAMCAT 2 algorithm). This study has evaluated their performance, at 95% specificity, to detect genetically confirmed FH in the general population. We also compared these algorithms to established clinical case-finding criteria.MethodsProspective validation study, in 14 general practices, recruiting participants from the general adult population with cholesterol documented. For 260 participants with available health records, we determined possible FH cases based on FAMCAT thresholds, Dutch Lipid Clinic Network (DLCN) score, Simon-Broome criteria and recommended cholesterol thresholds (total cholesterol >9.0 mmol/L if ≥30 years or >7.5 mmol/L if <30 years), using clinical data from electronic and manual extraction of patient records and family history questionnaires. The reference standard was genetic testing. We examined detection rate (DR), sensitivity and specificity for each case-finding criteria.ResultsAt 95% specificity, FAMCAT 1 had a DR of 27.8% (95% CI 12.5% to 50.9%) with sensitivity of 31.2% (95% CI 11.0% to 58.7%); while FAMCAT 2 had a DR of 45.8% (95% CI 27.9% to 64.9%) with sensitivity of 68.8% (95% CI 41.3% to 89.0%). DLCN score ≥6 points yielded a DR of 35.3% (95% CI 17.3% to 58.7%) and sensitivity of 37.5% (95% CI 15.2% to 64.6%). Using recommended cholesterol thresholds resulted in DR of 28.0% (95% CI 14.3% to 47.6%) with sensitivity of 43.8% (95% CI 19.8% to 70.1%). Simon-Broome criteria had lower DR 11.3% (95% CI 6.0% to 20.0%) and specificity 70.9% (95% CI 64.8% to 76.5%) but higher sensitivity of 56.3% (95% CI 29.9% to 80.2%).ConclusionsIn primary care, in patients with cholesterol documented, FAMCAT 2 performs better than other case-finding criteria for detecting genetically confirmed FH, with no prior clinical review required for case finding.Trial registration numberNCT03934320.
| S-EPMC8506870 | biostudies-literature
Project description:Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that causes marked elevation in plasma low-density lipoprotein (LDL) cholesterol concentrations and premature coronary heart disease. There are at least 45,000 people with FH in Australia and New Zealand, but most remain unrecognised and those diagnosed remain inadequately treated. To bridge this gap in coronary prevention the FH Australasia Network has developed a model of care for FH. An executive summary of the model of care is presented, with a commentary on its recommendations and the key role of the clinical biochemistry laboratory.
| S-EPMC3284341 | biostudies-literature
Project description:BackgroundPrimary care physicians (PCP) play an important role in detecting Familial Hypercholesterolaemia (FH) early. However, knowledge, awareness and practice (KAP) regarding FH among Malaysian PCP are not well established, and there was no validated tool to assess their FH KAP. Thus, the aim of this study was to adapt an FH KAP questionnaire and determine its validity and reliability among Malaysian PCP.MethodsThis cross-sectional validation study involved Malaysian PCP with ≥ 1-year work experience in the primary care settings. In Phase 1, the original 19-item FH KAP questionnaire underwent content validation and adaptation by 7 experts. The questionnaire was then converted into an online survey instrument and was face validated by 10 PCP. In Phase 2, the adapted questionnaire was disseminated through e-mail to 1500 PCP. Data were collected on their KAP, demography, qualification and work experience. The construct validity was tested using known-groups validation method. The hypothesis was PCP holding postgraduate qualification (PCP-PG-Qual) would have better FH KAP compared with PCP without postgraduate qualification (PCP-noPG-Qual). Internal consistency reliability was calculated using Kuder Richardson formula-20 (KR-20) and test-retest reliability was tested on 26 PCP using kappa statistics.ResultsDuring content validation and adaptation, 10 items remained unchanged, 8 items were modified, 1 item was moved to demography and 7 items were added. The adapted questionnaire consisted of 25 items (11 knowledge, 5 awareness and 9 practice items). A total of 130 out of 1500 PCP (response rate: 8.7%) completed the questionnaire. The mean percentage knowledge score was found to be significantly higher in PCP-PG-Qual compared with PCP-noPG-Qual (53.5, SD ± 13.9 vs. 35.9, SD ± 11.79), t(128) = 6.90, p < 0.001. The median percentage awareness score was found to be significantly higher in PCP-PG-Qual compared with PCP-noPG-Qual (15.4, IqR ± 23.08 vs. 7.7, IqR ± 15.38), p = 0.030. The mean percentage practice score was significantly higher in PCP-PG-Qual compared with PCP-noPG-Qual (69.2, SD ± 17.62 vs. 54.4, SD ± 19.28), t(128) = 3.79, p < 0.001. KR-20 value was 0.79 (moderate reliability) and average Kappa was 0.796 (substantial agreement).ConclusionThis study has proven that the 25-item adapted FH KAP questionnaire is valid and reliable. It can be used to measure and establish FH KAP among PCP in Malaysia.
| S-EPMC7814747 | biostudies-literature
Project description:AimsFamilial hypercholesterolaemia (FH) is a vastly under-diagnosed genetic disorder, associated with early development of coronary heart disease and premature mortality which can be substantially reduced by effective treatment. Patents have recently expired on high-intensity statins, reducing FH treatment costs. We build a model using UK data to estimate the cost effectiveness of DNA testing of relatives of those with monogenic FH.Methods and resultsA Markov model was used to estimate the cost effectiveness of cascade testing, using data from UK cascade services. The estimated incremental cost effectiveness ratio (ICER) was £5806 and the net marginal lifetime cost per relative tested was £2781. More than 80% of lifetime costs were diagnosis-related and incurred in the 1st year. In UK services, 23% of 6396 index cases were mutation-positive. For each mutation-positive index case, 1.33 relatives were tested, resulting overall in a rate of 0.31 tested relatives per tested index case. If the number of relatives tested per tested index case rose to 3.2 (projected by National Institute for Health and Care Excellence in 2008) the ICER would reduce to £2280 and lifetime costs to £1092.ConclusionCascade testing of relatives of those with suspected FH is highly cost effective. The current Europe-wide high levels of undiagnosed FH, and associated morbidity and mortality, mean adoption of cascade services should yield substantial quality of life and survival gains.
| S-EPMC5837803 | biostudies-literature
Project description:BackgroundPatients attend primary care with many types of problems and to achieve a range of possible outcomes. There is currently a lack of patient-reported outcome measures (PROMs) designed to capture these diverse outcomes. The objective of this systematic review was to identify, describe and appraise generic PROMs suitable for measuring outcomes from primary care.MethodsWe carried out a systematic Medline search, supplemented by other online and hand-searches. All potentially relevant PROMs were itemised in a long-list. Each PROM in the long-list which met inclusion criteria was included in a short-list. Short-listed PROMs were then described in terms of their measurement properties and construct, based on a previously published description of primary care outcome as three constructs: health status, health empowerment and health perceptions. PROMs were appraised in terms of extent of psychometric testing (extensive, moderate, low) and level of responsiveness (high, medium, low, unknown).ResultsMore than 5000 abstracts were identified and screened to identify PROMs potentially suitable for measuring outcomes from primary care. 321 PROMs were long-listed, and twenty PROMs were catalogued in detail. There were five PROMs which measured change directly, without need for a baseline. Although these had less strong psychometric properties, they may be more responsive to change than PROMs which capture status at a point in time. No instruments provided coverage of all three constructs. Of the health status questionnaires, the most extensively tested was the SF-36. Of the health empowerment instruments, the PEI, PAM and heiQ provided the best combination of responsiveness and psychometric testing. The health perceptions instruments were all less responsive to change, and may measure a form of health perception which is difficult to shift in primary care.ConclusionsThis systematic review is the first of its kind to identify papers describing the development and validation of generic PROMs suitable for measuring outcomes from primary care. It identified that: 1) to date, there is no instrument which comprehensively covers the outcomes commonly sought in primary care, and 2) there are different benefits both to PROMs which measure status at a point in time, and PROMs which measure change directly.
| S-EPMC5856382 | biostudies-literature
Project description:This systematic review evaluated the effectiveness of strategies to identify and manage patients with familial risk of breast, ovarian, colorectal and prostate cancer in primary care to improve clinical outcomes. MEDLINE, EMBASE, CINAHL and Cochrane library were searched from January 1980 to October 2017. We included randomised controlled trials (RCT) and non-randomised studies of interventions (NRSI). Primary outcomes were cancer incidence, cancer-related clinical outcomes or the identification of cancer predisposition; secondary outcomes were the appropriateness of referral, uptake of preventive strategies and cognitive and psychological effect. From 11,842 abstracts, 111 full texts were reviewed and three eligible studies (nine articles) identified. Two were cluster RCTs and one NRSI; all used risk assessment software. No studies identified our primary outcomes, with no consistent outcome across the three studies. In one RCT, intervention improved the proportion of genetic referrals meeting referral guidelines for breast cancer (OR 4.5, 95% CI 1.6 to 13.1). In the other RCT, there was no difference in screening adherence between the intervention and control group. However, there was borderline increased risk perception (OR 1.89, 95% CI 0.99 to 3.59) in the subgroup that under-estimated their colon cancer risk. In the NRSI, there was no change in psychological distress in patients at increased familial breast cancer risk, but population risk patients had reduced anxiety after intervention (state anxiety mean change - 3, 95% CI - 5 to - 2). Future studies should have better-defined comparator groups and longer follow-up and assess outcomes using validated tools.
| S-EPMC6962422 | biostudies-literature