scholarly journals Double heterozygous familial hypercholesterolaemia: Case series, genetics and Cascade screening of families

2021 ◽  
Vol 35 ◽  
pp. 75-83
Author(s):  
Hoang Thi Yen ◽  
Vu Duc Anh ◽  
Le Thi Yen ◽  
Dang Thi Ngoc Dung
Keyword(s):  
Family Members ◽  
Case Series ◽  
Lipoprotein Metabolism ◽  
Incidence Rates ◽  
Ldlr Gene ◽  
Cascade Screening ◽  
Autosomal Dominant Disorder ◽  
Exon 9 ◽  
Complications Of Myocardial Infarction ◽  
Heterozygous Familial Hypercholesterolaemia

Background: Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism characterized by high levels of LDL-cholesterol (LDL-C) in the blood. Studies identified more than 1,000 mutations of the LDLR gene in FH patients with incidence rates between 1: 500 and 1: 300. The mutation that occurs primarily in: LDLR, apoB, PCSK9, LDLRAP1 genes, 80% of which were detected the LDLR gene mutation. Nowaday, FH disease has not been paid much attention, leading to a delay in treatment.  Objectives: identify mutations in other family members of the patient FH.  Subjects and Methods: 14 family members of FH patients were gene analyzed, identified mutations on exons 4, 9 LDLR genes. Results: 11/15 family members carrying heterozygous mutations on exon 4 and exon 9 of LDLR gene. Patient and 1 family member detected and treated late, leading to complications of myocardial infarction. Conclusion: Therefore, Cascade screening of patient's family members has an important role in early detection, genetic counseling and treatment, even in cases where pedigree members do not have xanthomas and no increase or slight increase in blood lipids. This is the basis for early counseling and treatment for members with mutations, reducing the risk of coronary artery diseases in the future.

TBE in Italy

2020 ◽  
Keyword(s):  
Surveillance System ◽  
Ad Hoc ◽  
National Level ◽  
Case Series ◽  
Incidence Rates ◽  
Mountainous Regions ◽  
North East ◽  
The North ◽  
Tick Borne Encephalitis ◽  
Low Incidence

Italy is considered a low-incidence country for tick-borne encephalitis (TBE) in Europe.1 Areas at higher risk for TBE in Italy are geographically clustered in the forested and mountainous regions and provinces in the north east part of the country, as suggested by TBE case series published over the last decade.2-5 A national enhanced surveillance system for TBE has been established since 2017.6 Before this, information on the occurrence of TBE cases at the national level in Italy was lacking. Both incidence rates and the geographical distribution of the disease were mostly inferred from endemic areas where surveillance was already in place, ad hoc studies and international literature.1

scholarly journals Cascade screening for glaucoma in high-risk family members of African-Caribbean glaucoma patients in an urban population in London

2020 ◽  
pp. bjophthalmol-2020-317373
Author(s):  
Anindyt Nagar ◽  
Sam Myers ◽  
Diana Kozareva ◽  
Mark Simcoe ◽  
Christopher Hammond
Keyword(s):  
High Risk ◽  
Genetic Diseases ◽  
Family Doctor ◽  
Family Members ◽  
Hospital Setting ◽  
High Risk Group ◽  
Cascade Screening ◽  
Specialist Referral ◽  
High Risk Family ◽  
African Caribbean

Background/aimsCascade screening has been used successfully in relatives of patients with inherited cancers and other genetic diseases to identify presymptomatic disease. This study was designed to examine if this approach would be successful in a high-risk group: first-degree relatives (FDR) of African-Caribbean glaucoma patients resident in London.MethodsAfrican-Caribbean patients (probands) with glaucoma from an inner London hospital setting in a deprived area were asked to disseminate personalised information to their FDR over the age of 30 and to arrange a free hospital-based screening. Data collected, including optical coherence tomography imaging, were reviewed by a glaucoma specialist and if glaucoma was diagnosed or suspected, local specialist referral via family doctor was made.Results203 probands were recruited from glaucoma clinics. 248 suitable FDR were identified as potentially eligible to attend screening. 57 (23%) FDR made contact with the research team of whom 18 (7%) attended a subsequent screening visit. No patients were diagnosed with glaucoma; one participant was diagnosed as glaucoma suspect. Reasons for poor uptake included reluctance by probands to involve their family members, and retirees spending significant time abroad.ConclusionCascade screening of FDR of African-Caribbean glaucoma patients in inner city London was unsuccessful. Research confidentiality guidance prohibiting research teams directly contacting family members was a barrier. Greater community engagement, community-based screening and permission to contact FDR directly might have improved uptake.

scholarly journals Epidemiologic Study of the Discoid Meniscus: Investigating Demographic-Based Predictors in Large-Scale Claims Database

2021 ◽  
Vol 9 (7_suppl3) ◽  
pp. 2325967121S0008
Author(s):  
Sahej S Randhawa ◽  
Emily P Tran ◽  
Nicole A Segovia ◽  
Theodore J Ganley ◽  
Marc Tompkins ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Total Population ◽  
Clinical Care ◽  
Epidemiologic Study ◽  
Case Series ◽  
Incidence Rates ◽  
National Database ◽  
Discoid Meniscus ◽  
Racial Categories ◽  
Claims Database

Background: Discoid meniscus epidemiology remains poorly defined for race and sex, in part, due to limitations of retrospective studies and small case series. A better understanding of epidemiology may improve clinical care and diagnostic precision. Purpose: Our purpose is to better define the epidemiology of discoid meniscus by analyzing a large, national database for incidence rates by sex and race. Methods: Analysis was conducted on the national-scale Clinformatics Data Mart Database by Optum. Proportions of the database’s racial categories (Asian, Black, Hispanic, White, and Unknown) in the total population of diagnosed discoid meniscus cases (n = 1,006) were calculated and compared via chi-squared tests to the total database population (n = 65,759,970). This analysis was repeated for the population of patients who received knee arthroscopies (81,205). Incidence rates were calculated from these populations as well. Finally, a multivariable logistic regression analysis based on the population of arthroscopy-receiving patients was performed to control for age, reported gender, and income. Results: Proportions of Asian, Black, Hispanic, and White racial categories in the discoid meniscus group were 5.7%, 7.3%, 20.6%, 66.4%, respectively; the proportions of each racial category in the total population were 5.2%, 10.3%, 13.5%, 71.0%, respectively. Incidence rates (per 10,000) for these groups in the arthroscopy population were 72.9, 25.6, 49.2, 25.6, respectively. Our logistic regression model indicated that race was not a statistically significant predictor for our dataset after income adjusting. Adjusting for other covariates, the odds of a discoid meniscus diagnosis decreased by 6% for each increase in age (p < 0.001) and were 41% lower for males compared to females (p < 0.001). Conclusion: Prior studies have suggested that race (Asian and Hispanic, is a predictor of higher incidence of discoid meniscus – this study did not show a difference in incidence based upon race. Patient sex and age was identified as significant predictors for discoid meniscus, and increasing age showed a decreasing incidence of this condition. This study’s analysis of a large, national claims database allows for a comprehensive epidemiological study on this topic, offering proportions and incidence rates by race appropriate for application to the US population. Its conclusions promote patient sex and age as significant predictors and question the beliefs on race-associated incidence often based on comparing results from the corpus of single-site cohort studies. Tables/Figures: [Table: see text]

scholarly journals Case series: Breast and ovarian cancer syndrome

2016 ◽  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Brca Mutation ◽  
Family Members ◽  
Case Series ◽  
Second Primary ◽  
Time Interval ◽  
Breast And Ovarian Cancer ◽  
Ovarian Carcinomas ◽  
Increased Risk

Aims and Objectives: To report a series of cases with breast and ovarian carcinomas either in same patient or in a family and identifying the importance of BRCA 1,2 genetic testing in such individuals. Materials and Methods: The medical records of breast and ovarian cancer patients operated over past 3 years at a single institute were reviewed retrospectively and their clinical profile, family history, final pathological reports and follow up data was collected. Results: 8 patients were found to have breast and ovarian malignancies, out of which 3 had synchronous breast and ovarian cancers, 4 had metachronous and 1 patient with ovarian cancer had history of breast cancer in family. Median age of presentation to the hospital was 47 years and median time interval in metachronous disease patients was 5.5 years. Conclusion: About 5% of people who have breast cancer and about 10% of women who have ovarian cancer have HBOC, caused by germline mutation in BRCA1, 2 gene. These individuals have increased risk of developing breast cancer at younger age, TNBC, or developing a second primary in breast or ovary plus an overall risk of breast/ovarian/prostate/pancreatic malignancies in other family members due to inheritable mutation. Identification of BRCA mutation in such individuals can help family members to undergo genetic counseling and follow different screening and prevention guidelines from general population thus reducing the cancer risks.

scholarly journals Enablers and barriers to treatment adherence in heterozygous familial hypercholesterolaemia: a qualitative evidence synthesis

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e030290 ◽  
Author(s):  
Fiona J Kinnear ◽  
Elaine Wainwright ◽  
Rachel Perry ◽  
Fiona E Lithander ◽  
Graham Bayly ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Treatment Adherence ◽  
Familial Hypercholesterolaemia ◽  
Family Members ◽  
Personal Control ◽  
Qualitative Studies ◽  
Cochrane Library ◽  
Barriers To Treatment ◽  
Thematic Synthesis ◽  
Heterozygous Familial Hypercholesterolaemia

ObjectivesIndividuals with heterozygous familial hypercholesterolaemia (FH) are at high risk of developing cardiovascular disease (CVD). This risk can be substantially reduced with lifelong pharmacological and lifestyle treatment; however, research suggests adherence is poor. We synthesised the qualitative research to identify enablers and barriers to treatment adherence.DesignThis study conducted a thematic synthesis of qualitative studies.Data sourcesMEDLINE, Embase, PsycINFO via OVID, Cochrane library and CINAHL databases and grey literature sources were searched through September 2018.Eligibility criteriaWe included studies conducted in individuals with FH, and their family members, which reported primary qualitative data regarding their experiences of and beliefs about their condition and its treatment.Data extraction and synthesisQuality assessment was undertaken using the Critical Appraisal Skills Programme for qualitative studies. A thematic synthesis was conducted to uncover descriptive and generate analytical themes. These findings were then used to identify enablers and barriers to treatment adherence for application in clinical practice.Results24 papers reporting the findings of 15 population samples (264 individuals with FH and 13 of their family members) across 8 countries were included. Data captured within 20 descriptive themes were considered in relation to treatment adherence and 6 analytical themes were generated: risk assessment; perceived personal control of health; disease identity; family influence; informed decision-making; and incorporating treatment into daily life. These findings were used to identify seven enablers (eg, ‘commencement of treatment from a young age’) and six barriers (eg, ‘incorrect and/or inadequate knowledge of treatment advice’) to treatment adherence. There were insufficient data to explore if the findings differed between adults and children.ConclusionsThe findings reveal several enablers and barriers to treatment adherence in individuals with FH. These could be used in clinical practice to facilitate optimal adherence to lifelong treatment thereby minimising the risk of CVD in this vulnerable population.PROSPERO registration numberCRD42018085946.

scholarly journals POS0774 INFLUENZA INFECTION AS A TRIGGER FOR SYSTEMIC LUPUS ERYTHEMATOSUS FLARES RESULTING IN HOSPITALIZATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 641.1-641
Author(s):  
Y. B. Joo ◽  
Y. J. Park
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Confidence Interval ◽  
Lupus Erythematosus ◽  
Influenza Infection ◽  
Age Groups ◽  
Case Series ◽  
Incidence Rates ◽  
Systemic Lupus ◽  
Control Interval ◽  
The Impact

Background:Infections have been associated with a higher risk of systemic lupus erythematosus (SLE) flares, but the impact of influenza infection on SLE flares has not been evaluated.Objectives:We evaluated the association between influenza infection and SLE flares resulting in hospitalization.Methods:SLE flares resulting in hospitalization and influenza cases were ascertained from the Korean national healthcare insurance database (2014-2018). We used a self-controlled case series design. We defined the risk interval as the first 7 days after the influenza index date and the control interval was defined as all other times during the observation period of each year. We estimated the incidence rates of SLE flares resulting in hospitalization during the risk interval and control interval and compared them using a Poisson regression model.Results:We identified 1,624 influenza infections among the 1,455 patients with SLE. Among those, there were 98 flares in 79 patients with SLE. The incidence ratio (IR) for flares during the risk interval as compared with the control interval was 25.75 (95% confidence interval 17.63 – 37.59). This significantly increased the IRs for flares during the risk interval in both women (IR 27.65) and men (IR 15.30), all age groups (IR 17.00 – 37.84), with and without immunosuppressive agent (IR 24.29 and 28.45, respectively), and with and without prior respiratory diseases (IR 21.86 and 26.82, respectively).Conclusion:We found significant association between influenza infection and SLE flares resulting in hospitalization. Influenza infection has to be considered as a risk factor for flares in all SLE patients regardless of age, sex, medications, and comorbidities.References:[1]Kwong, J. C. et al. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N Engl J Med 2018:378;345-353.Table 1.Incidence ratios for SLE flares resulting in hospitalization after influenza infectionRisk intervalIncidence ratio95% CIDuring risk interval for 7 days / control interval25.7517.63 – 37.59Days 1-3 / control interval21.8114.71 – 32.35Days 4-7 / control interval7.563.69 – 15.47SLE, systemic lupus erythematosus; CI, confidence intervalDisclosure of Interests:None declared

scholarly journals MP13: Injuries presenting to the ED following jumps from bridges into water: a multi-agency retrospective case series

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S47-S47
Author(s):  
D. Stephanian ◽  
D. Shearer ◽  
N. Bandara ◽  
J. Brubacher
Keyword(s):  
Injury Severity ◽  
Cold Water ◽  
Mild Hypothermia ◽  
Water Immersion ◽  
Case Series ◽  
Incidence Rates ◽  
Coast Guard ◽  
Injury Incidence ◽  
Injury Patterns ◽  
Retrospective Case

Introduction: Suicidal jumps from bridges into water are a unique blunt trauma mechanism. Impact into water produces substantial variation in injuries as compared to falls onto hard surfaces. Outcomes can be further complicated by submersion injuries. We identified cases through a multi-agency review in order to analyze injury patterns seen in EDs. Methods: Cases in British Columbia's Lower Mainland of jumps from bridges >12m into water between 2006 and 2017 were identified by retrospective review of Coast Guard and Police records. Records pertaining to identified incidents were located in ambulance and then hospital records. This multi-agency approach was necessary to generate a comprehensive case series, as case identification was not possible at the hospital level. Patient hospital charts were abstracted and injury incidence rates were analyzed. Results: Records were available for 41 of 52 patients. The population was 63% (26/41) male, median age 37 (IQR 29-48). Thirty-two cases were admitted to hospital, seven were deceased in the ED, one was discharged, and disposition is unknown for one. Most patients (85%) presented to Level One trauma centers. Bridge heights ranged from 15m to 70m; the mean fall height was 40.1m. Pulmonary injuries were nearly universal, including pneumothorax (51%), haemothorax (22%), and pulmonary infiltrate (34%). The primary cardiovascular concern was cardiac arrhythmia (51%). A quarter of cases had intraabdominal lacerations or ruptures (27%). Vertebral fractures at all levels were frequent (59%), although there was only one case each of cord transection and contusion. Neurological injuries were rare; 59% of patients presented to the ED with GCS ≥14 and the incidence of intracranial bleeding was low (7%). Rib fractures were commonly reported (37%) along with other fractures (32%). Body temperature was reported in 24 cases with 3 reports of moderate and 6 reports of mild hypothermia. Conclusion: This case series is the first to characterize injury patterns of jumps from bridges into water in Canada. Patterns are similar to reports in the literature from other countries. However, we found lower injury severity, and higher incidences of spinal fractures and cardiac arrhythmias. The low injury severity reflects the survivorship bias inherent to the sample: data was only obtained from patients who survived to be assessed the ED. These results suggest that patients with this mechanism of injury should be treated for both suspected trauma and cold-water immersion injuries.

scholarly journals A Novel Frameshift Mutation of SCNN1G Causing Liddle Syndrome with Normokalemia

2019 ◽  
Vol 32 (8) ◽  
pp. 752-758
Author(s):  
Peng Fan ◽  
Yu-Mo Zhao ◽  
Di Zhang ◽  
Ying Liao ◽  
Kun-Qi Yang ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Frameshift Mutation ◽  
Stop Codon ◽  
Single Gene ◽  
Family Members ◽  
Premature Stop Codon ◽  
Chinese Family ◽  
Autosomal Dominant Disorder ◽  
Liddle Syndrome ◽  
Genetic Sequencing

Abstract BACKGROUND Liddle syndrome (LS) is an autosomal dominant disorder caused by single-gene mutations of the epithelial sodium channel (ENaC). It is characterized by early-onset hypertension, spontaneous hypokalemia and low plasma renin and aldosterone concentrations. In this study, we reported an LS pedigree with normokalemia resulting from a novel SCNN1G frameshift mutation. METHODS Peripheral blood samples were collected from the proband and eight family members for DNA extraction. Next-generation sequencing and Sanger sequencing were performed to identify the SCNN1G mutation. Clinical examinations were used to comprehensively evaluate the phenotypes of two patients. RESULTS Genetic analysis identified a novel SCNN1G frameshift mutation, p.Arg586Valfs*598, in the proband with LS. This heterozygous frameshift mutation generated a premature stop codon and deleted the vital PY motif of ENaC. The same mutation was present in his elder brother with LS, and his mother without any LS symptoms. Biochemical examination showed normokalemia in the three mutation carriers. The mutation identified was not found in any other family members, 100 hypertensives, or 100 healthy controls. CONCLUSIONS Our study identified a novel SCNN1G frameshift mutation in a Chinese family with LS, expanding the genetic spectrum of SCNN1G. Genetic testing helped us identify LS with a pathogenic mutation when the genotypes and phenotype were not completely consistent because of the hypokalemia. This case emphasizes that once a proband is diagnosed with LS by genetic testing, family genetic sequencing is necessary for early diagnosis and intervention for other family members, to protect against severe cardiovascular complications.

Cardiovascular risk in patients receiving ranibizumab for exudative age-related macular degeneration: a nationwide self-controlled case-series study

2020 ◽  
pp. bjophthalmol-2020-316373
Author(s):  
Ha-Lim Jeon ◽  
Seong Jun Byun ◽  
Nicole L Pratt ◽  
Janet Sultana ◽  
Sang Jun Park ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Macular Degeneration ◽  
Case Series ◽  
Haemorrhagic Stroke ◽  
Incidence Rates ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Case Series Study ◽  
Risk Patients ◽  
Rate Ratios

AimsTo identify the association between ranibizumab and risk of stroke and acute myocardial infarction (AMI) in patients with exudative age-related macular degeneration (AMD).MethodsWe identified patients aged ≥45 years who received ranibizumab for exudative AMD from the Korean National Health Insurance database. Of these, we selected patients suffering stroke or AMI for the self-controlled case series. We estimated incidence rate ratios (IRR) for stroke or AMI by comparing incidence rates of ranibizumab-exposed periods to that of baseline using conditional Poisson regression. The risks of haemorrhagic and ischaemic strokes were also calculated separately.ResultsAmong 33 134 patients receiving ranibizumab, 2397 patients had stroke or AMI. The risk of stroke (IRR=0.83, 95% CI 0.75 to 0.91) was not increased during the overall exposed period; however, there was a marginally elevated risk in ≥57 days exposed period (IRR=1.14, 95% CI 1.001 to 1.31). When analysing by the types of stroke, no increased risks of haemorrhagic (IRR=1.01, 95% CI 0.80 to 1.26) and ischaemic stroke (IRR=0.78, 95% CI 0.71 to 0.86) were observed during the exposed period, although the risks of ischaemic and haemorrhagic stroke were slightly elevated during ≥57 days exposed period. We could not find an association between ranibizumab and AMI.ConclusionsRanibizumab intravitreal injections did not increase the overall risk of stroke or AMI. Although the cardiovascular risk in patient receiving ranibizumab seems to be low, continuous monthly use of ranibizumab for high-risk patients should be judged carefully.

Recent advances in the understanding and care of familial hypercholesterolaemia: significance of the biology and therapeutic regulation of proprotein convertase subtilisin/kexin type 9

2015 ◽  
Vol 129 (1) ◽  
pp. 63-79 ◽  
Author(s):  
Michael M. Page ◽  
Claudia Stefanutti ◽  
Allan Sniderman ◽  
Gerald F. Watts
Keyword(s):  
Genetic Testing ◽  
Familial Hypercholesterolaemia ◽  
Lipoprotein Metabolism ◽  
New Drugs ◽  
High Density Lipoproteins ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Statin Intolerance ◽  
Cascade Screening ◽  
Recent Advances

Familial hypercholesterolaemia (FH) is an autosomal co-dominant disorder that markedly raises plasma low-density lipoprotein-cholesterol (LDL-C) concentration, causing premature atherosclerotic coronary artery disease (CAD). FH has recently come under intense focus and, although there is general consensus in recent international guidelines regarding diagnosis and treatment, there is debate about the value of genetic studies. Genetic testing can be cost-effective as part of cascade screening in dedicated centres, but the full mutation spectrum responsible for FH has not been established in many populations, and its use in primary care is not at present logistically feasible. Whether using genetic testing or not, cholesterol screening of family members of index patients with an abnormally raised LDL-C must be used to determine the need for early treatment to prevent the development of CAD. The metabolic defects in FH extend beyond LDL, and may affect triacylglycerol-rich and high-density lipoproteins, lipoprotein(a) and oxidative stress. Achievement of the recommended targets for LDL-C with current treatments is difficult, but this may be resolved by new drug therapies. Lipoprotein apheresis remains an effective treatment for severe FH and, although expensive, it costs less than the two recently introduced orphan drugs (lomitapide and mipomersen) for homozygous FH. Recent advances in understanding of the biology of proprotein convertase subtilisin/kexin type 9 (PCSK9) have further elucidated the regulation of lipoprotein metabolism and led to new drugs for effectively treating hypercholesterolaemia in FH and related conditions, as well as for treating many patients with statin intolerance. The mechanisms of action of PCSK9 inhibitors on lipoprotein metabolism and atherosclerosis, as well as their impact on cardiovascular outcomes and cost-effectiveness, remain to be established.

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