High Incidence In Populations Research Articles

Medicaid Insurance is Associated With Decreased MRI Use for Ankle Sprains Compared With Private Insurance: A Retrospective Database Analysis.

Advanced imaging modalities are expensive, and access to advanced imaging services may vary by socioeconomic factors, creating the potential for unwarranted variations in care. Ankle sprains are a common injury for which variations in MRI use can occur, both via underuse of indicated MRIs (appropriate use) and overuse of nonindicated MRIs (inappropriate use). High-value, equitable healthcare would decrease inappropriate use and increase appropriate use of MRI for this common injury. It is unknown whether socioeconomic factors are associated with underuse of indicated MRIs and overuse of nonindicated MRIs for ankle sprains. Using ankle sprains as a paradigm injury, given their high population incidence, we asked: (1) Does MRI use for ankle sprains vary by insurance type? (2) After controlling for relevant confounding variables, did patients who received an MRI have higher odds of undergoing ankle surgery? Between 2011 and 2019, a total of 6,710,223 patients were entered into the PearlDiver Mariner Patient Records Database with a diagnosis of ankle sprain. We considered patients with continuous enrollment in the database for at least 1 year before and 2 years after the diagnosis as potentially eligible. Based on that, 68% (4,567,106) were eligible; a further 20% (1,372,478) were excluded because of age younger than 18 years, age at least 65 years with Medicaid insurance, or age < 65 years with Medicare insurance. Another 0.1% (9169) had incomplete data, leaving 47% (3,185,459) for analysis here. Patients with Medicaid insurance differed from patients with Medicare Advantage or private insurance with respect to age, gender, region, and comorbidity burden. The primary outcome was ankle MRI occurring within 12 months after diagnosis. The use of ankle surgery after MRI in each cohort was measured as a secondary outcome. We used multivariable logistic regression models to evaluate the association between insurance type and MRI use while adjusting for age, gender, region, and comorbidity burden. Separate multivariable regression models were created to evaluate the association between receiving an MRI and subsequent ankle surgery for each insurance type, adjusting for age, gender, region, and comorbidity burden. Within 12 months of an ankle sprain diagnosis, 1% (3522 of 339,457) of patients with Medicaid, 2% (44,793 of 2,627,288) of patients with private insurance, and 1% (1660 of 218,714) of patients with Medicare Advantage received an MRI. After controlling for age, gender, region, and comorbidity burden, patients with Medicaid had lower odds of receiving an MRI within 12 months after ankle sprain diagnosis than patients with private insurance (odds ratio 0.60 [95% confidence interval 0.57 to 0.62]; p < 0.001). Patients with Medicaid who received an MRI had higher adjusted odds of undergoing subsequent ankle surgery (OR 23 [95% CI 21 to 26]; p < 0.001) than patients with private insurance (OR 12.7 [95% CI 12 to 13]; p < 0.001). Although absolute MRI use was generally low, there was substantial relative variation by insurance type. Given the high incidence of ankle sprains in the general population, these relative differences can translate to tens of thousands of MRIs. Further studies are needed to evaluate the reasons for decreased appropriate MRI use in patients with Medicaid and overuse of MRI in patients with private insurance. The establishment of clinical practice guidelines by orthopaedic professional societies and more stringent gatekeeping for MRI use by health insurers could reduce unwarranted variations in MRI use. Level III, prognostic study.

Differential Cellular Interactome in Schizophrenia and Bipolar Disorder-Discriminatory Biomarker Role.

Schizophrenia (SCH) and bipolar disorder (BD) are two of the most important psychiatric pathologies due to their high population incidence and disabling power, but they also present, mainly in their debut, high clinical similarities that make their discrimination difficult. In this work, the differential oxidative stress, present in both disorders, is shown as a concatenator of the systemic alterations-both plasma and erythrocyte, and even at the level of peripheral blood mononuclear cells (PBMC)-in which, for the first time, the different affectations that both disorders cause at the level of the cellular interactome were observed. A marked erythrocyte antioxidant imbalance only present in SCH generalizes to oxidative damage at the plasma level and shows a clear impact on cellular involvement. From the alteration of protein synthesis to the induction of death by apoptosis, including proteasomal damage, mitochondrial imbalance, and autophagic alteration, all the data show a greater cellular affectation in SCH than in BD, which could be linked to increased oxidative stress. Thus, patients with SCH in our study show increased endoplasmic reticulum (ER)stress that induces increased proteasomal activity and a multifactorial response to misfolded proteins (UPR), which, together with altered mitochondrial activity, generating free radicals and leading to insufficient energy production, is associated with defective autophagy and ultimately leads the cell to a high apoptotic predisposition. In BD, however, oxidative damage is much milder and without significant activation of survival mechanisms or inhibition of apoptosis. These clear differences identified at the molecular and cellular level between the two disorders, resulting from progressive afflictions in which oxidative stress can be both a cause and a consequence, significantly improve the understanding of both disorders to date and are essential for the development of targeted and preventive treatments.

Incidence and characteristics of stroke in Zanzibar-a hospital-based prospective study in a low-income island population.

BackgroundStroke in adults is a critical clinical condition and a leading cause of death and disability globally. Epidemiological data on stroke in sub-Saharan Africa are limited. This study describes incidence rates, stroke types and antecedent factors among patients hospitalized with stroke in Zanzibar.MethodsThis was a prospective, observational study of stroke patients at hospitals in Unguja, Zanzibar. Socioeconomic and demographic data were recorded alongside relevant past medical history, medicine use and risk factors. The modified National Institute of Health Stroke Scale (mNIHSS) was used to assess admission stroke severity and, when possible, stroke was confirmed by neuroimaging.ResultsA total of 869 stroke admissions were observed from 1st October 2019 through 30th September 2020. Age-standardized to the World Health Organization global population, the yearly incidence was 286.8 per 100,000 adult population (95%CI: 272.4–301.9). Among these patients, 720 (82.9%) gave consent to participate in the study. Median age of participants was 62 years (53–70), 377 (52.2%) were women, and 463 (64.3%) had a first-ever stroke. Known stroke risk factors included hypertension in 503 (72.3%) patients, of whom 279 (55.5%) reported regularly using antihypertensive medication, of whom 161 (57.7%) had used this medication within the last week before stroke onset. A total of 460 (63.9%) participants had neuroimaging performed; among these there was evidence of intracerebral hemorrhage (ICH) in 140 (30.4%). Median stroke severity score using mNIHSS was 19 (10–27).ConclusionZanzibar has high incidence of hospitalization for stroke, indicating a very high population incidence of stroke. The proportion of strokes due to ICH is substantially higher than in high-income countries. Most stroke patients had been in contact with health care providers prior to stroke onset and been diagnosed with hypertension. However, few were using antihypertensive medication at the time of stroke onset.www.ClinicalTrial.gov registration NCT04095806.

QUALITY CONTROL MEASUREMENT AND IN VITRO BIOEQUIVALENCE OF VALSARTAN AND ATENOLOL TABLETS MARKETED IN UKRAINE

Background. The urgent issue of hypertension is determined by its high population incidence, significant burden of the disease, risk of disability and impact on life expectancy. Rational combinations of drugs of different pharmacological groups in case of ineffectiveness of monotherapy to achieve the clinical effect of pharmacotherapy are clearly recommended in the world and national recommendations for diagnosis and treatment of hypertension. Therefore, innovative pharmaceutical development of a combination of antihypertensive drugs and creation of domestic drugs with antihypertensive action is an urgent task of contemporary pharmacy.&#x0D; Objective. The aim of this study was to perform the quality control measurements and evaluation of dissolution tests for different brands of valsartan and atenolol tablets available in Ukraine. &#x0D; Methods. The concentrations of valsartan and atenolol in samples (drug content and dissolution study) were determined by the proposed HPLC method. &#x0D; Results. The results of the tests conducted for evaluation of the tablets were found to be in acceptable limits for all the selected brands. The correlation coefficient (R2) was 0.9991 and the regression equation was y=61.39x+0.3117. It has been established that the equivalence of dissolution profiles for all recommended dissolution media is observed (рН 1.2, 4.5, and 6.8) for the studied drugs. In all three dissolution media, the release rates of valsartan and atenolol of all dosage forms are more than 85% in 15 min. The dissolution profile of all the selected brands was within the standard limits and was acceptable.&#x0D; Conclusions. Analytical method development is an integral part of the quality control measurements and evaluation of dissolution tests. Our previously developed HPLC method is essential for quality control of a large number of samples in short time intervals. Therefore, the method developed by our group is suitable for a routine quality control analysis of any pharmaceutical preparation containing two tested drugs with the suggested chromatographic method advantages for checking quality during dissolution studies of their dosage forms.

Is Re-introducing Major Open and Minimally Invasive Surgery during COVID-19 Safe for Patients and Healthcare Workers? An International, Multi-centre Cohort Study in the Field of Oesophago-gastric Surgery

IntroductionThe COVID-19 pandemic has resulted in unparalleled changes to patient care, including the suspension of cancer surgery. Concerns regarding COVID-19-related risks to patients and healthcare workers with the re-introduction of major complex minimally invasive and open surgery have been raised. This study examines the COVID-19 related risks to patients and healthcare workers following the re-introduction of major oesophago-gastric (EG) surgery.Patients and MethodsThis was an international, multi-centre, observational study of consecutive patients treated by open and minimally invasive oesophagectomy and gastrectomy for malignant or benign disease. Patients were recruited from nine European centres serving regions with a high population incidence of COVID-19 between 1 May and 1 July 2020. The primary endpoint was 30-day COVID-19-related mortality. All staff involved in the operative care of patients were invited to complete a health-related survey to assess the incidence of COVID-19 in this group.ResultsIn total, 158 patients were included in the study (71 oesophagectomy, 82 gastrectomy). Overall, 87 patients (57%) underwent MIS (59 oesophagectomy, 28 gastrectomy). A total of 403 staff were eligible for inclusion, of whom 313 (78%) completed the health survey. Approaches to mitigate against the risks of COVID-19 for patients and staff varied amongst centres. No patients developed COVID-19 in the post-operative period. Two healthcare workers developed self-limiting COVID-19.ConclusionsPrecautions to minimise the risk of COVID-19 infection have enabled the safe re-introduction of minimally invasive and open EG surgery for both patients and staff. Further studies are necessary to determine the minimum requirements for mitigations against COVID-19.

V3 Is re-introducing major open and minimally invasive surgery during COVID-19 safe for patients and healthcare workers? An international, multi-centre cohort study in the field of oesophago-gastric surgery

IntroductionThe Covid-19 pandemic has resulted in unprecedented and challenging changes to surgical practice, especially with the suspension of cancer surgery. There have been concerns regarding Covid-19 risk and infection to patients and healthcare workers, during major complex open surgical intervention, especially with minimally invasive surgery. This study examines the COVID-19 related risks to patients and healthcare workers following the re-introduction of major oesophago-gastric (OG) surgery.MethodsThis was an international, multi-centre, cohort study of open and minimally invasive oesophagectomy and gastrectomy procedures in specialist Upper GI centres, over a consecutive period of two months. Patients were recruited from nine European centres serving regions with a high population incidence of COVID-19 infections. 30-day operative morbidity and mortality data was collected for patients. All staff involved in the operative care of patients, were invited to complete a health-related survey.ResultsA total of 158 patients were included in the study (71 oesophagectomy, 82 gastrectomy), of which 87 patients (57%) underwent minimally invasive surgery (59 esophagectomy, 28 gastrectomy). A total of 403 staff were eligible for inclusion of which 313 (78%) completed the health survey. Non- standardised precautions to minimise against the risks of COVID for patients and staff were implemented at the centres. There were no cases of Covid-19 among patients in the post-operative period, however, two healthcare workers developed self-limiting COVID infection.ConclusionPrecautions to minimise COVID-19 infection risk to healthcare staff and patients, have allowed the safe and successful reintroduction of major open and minimally invasive OG surgery.

Effect of Endovascular Treatment Rate on Population Level Outcomes and Survival After Intact Abdominal Aortic Aneurysm Repair

The aim was to study outcomes of endovascular aneurysm repair (EVAR) and open surgical repair (OSR) of abdominal aortic aneurysms (AAAs) in four geographically adjacent populations with identical demographics and variable EVAR rates. This was a multicentre cohort study based on local and national registry data from an area of 815000 inhabitants. The study involved 527 consecutive patients with an intact AAA treated with EVAR (n=327) or OSR (n=200) between 2010 and 2016. The catchment area was divided into four health care districts (populations A, B, C, and D) with one central hospital in each district. Each hospital decided independently between OSR and EVAR for patients within their population; OSR was performed in all hospitals while EVAR was centralised in one of them. Patient demographics and treatment outcomes were extracted from local registries. Population demographics, overall AAA incidence, and mortality data were retrieved from a national database. The rate of new intact AAA diagnosis varied between 20 and 29 per 100000 inhabitants/year with the highest incidence in population D (p<.001). The intact AAA repair rates were 9.8, 8.9, 9.9, and 8.7 per 100000 inhabitants/year for populations A, B, C, and D, respectively (p=.64). There were no significant differences in mean age (73.6±8.0 years) or mean aortic diameter (62±13mm) between the treated patient populations. Groups A and B had high EVAR rates (74% and 72%, respectively) whereas the EVAR rates were lower in groups C and D (50% and 38%, respectively) (p<.001). The 30 day mortality rates were 2%, 2%, 4%, and 1% (p=.55), and complication rates were 17%, 12%, 15%, and 11% (p=.39) for A, B, C and D, respectively. There were no significant differences in mortality, complication or re-intervention rates between the groups during the mean follow up of 3.3±2.0 years. At population level, high EVAR rates had no measurable effect compared with lower EVAR rates on the outcomes in patients with intact AAA.

Incidence of Second Anterior Cruciate Ligament Tears (1990-2000) and Associated Factors in a Specific Geographic Locale

Background: Second anterior cruciate ligament (ACL) tears after reconstruction occur at a reported rate of 20% to 30%. This high frequency indicates that there may be factors that predispose an athlete to graft failure and ACL tears of the contralateral knee. Purpose: To determine the incidence of second ACL injuries in a geographic population-based cohort over a 10-year observation period. Study Design: Descriptive epidemiological study. Methods: International Classification of Diseases, 9th Revision (ICD-9) codes relevant to the diagnosis of an ACL tear and the procedure code for ACL reconstruction were searched across the Rochester Epidemiology Project, a multidisciplinary county database, between the years of 1990 and 2000. This cohort of patients was tracked for subsequent ACL injuries through December 31, 2015. The authors identified 1041 patients with acute, isolated ACL tears. These patients were stratified by primary and secondary tears, sex, age, activity level, side of injury, sex by side of injury, and graft type. Results: Of the 1041 unique patients with a diagnosed ACL tear in Olmsted County, Minnesota, from 1990 to 2000, there were 66 (6.0%) second ACL tears; 66.7% of these tears occurred on the contralateral side. A second ACL injury was influenced by graft type (P < .0001), election of ACL reconstruction (P = .0060), and sex by side of injury (P = .0072). Nonparametric analysis of graft disruption by graft type demonstrated a higher prevalence of second ACL tears with allografts compared with hamstring (P = .0499) or patellar tendon autografts (P = .0012). Conclusion: The incidence of second ACL tears in this population-based cohort was 6.0%, with 66.7% of these tears occurring on the contralateral side from the original injury. There was a high population incidence of second ACL injuries in female patients younger than age 20 years. The utilization of patellar tendon autografts significantly reduced the risk of second ACL injuries compared with allografts or hamstring autografts in this cohort.

β-Thalassemia Distribution in the Old World: an Ancient Disease Seen from a Historical Standpoint.

BackgroundHaemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. β-thalassaemia is characterised by the reduced synthesis (β+) or absence (βo) of the β-globin chains in the HbA molecule, resulting in accumulation of excess unbound α-globin chains that precipitate in erythroid precursors in the bone marrow and in the mature erythrocytes, leading to ineffective erythropoiesis and peripheral haemolysis. Approximately 1.5% of the global population are heterozygotes (carriers) of the β-thalassemias; there is a high incidence in populations from the Mediterranean basin, throughout the Middle East, the Indian subcontinent, Southeast Asia, and Melanesia to the Pacific Islands.AimThe principal aim of this paper is to review, from a historical standpoint, our knowledge about an ancient disease, the β-thalassemias, and in particular, when, how and in what way β-thalassemia spread worldwide to reach such high incidences in certain populations.ResultsMutations involving the β-globin gene are the most common cause of genetic disorders in humans. To date, more than 350 β-thalassaemia mutations have been reported. Considering the current distribution of β- thalassemia, the wide diversity of mutations and the small number of specific mutations in individual populations, it seems unlikely that β-thalassemia originated in a single place and time.ConclusionsVarious processes are known to determine the frequency of genetic disease in human populations. However, it is almost impossible to decide to what extent each process is responsible for the presence of a particular genetic disease. The wide spectrum of β-thalassemia mutations could well be explained by looking at their geographical distribution, the history of malaria, wars, invasions, mass migrations, consanguinity, and settlements. An analysis of the distribution of the molecular spectrum of haemoglobinopathies allows for the development and improvement of diagnostic tests and management of these disorders.

Parenteral nutrition associated cholestasis

Parenteral nutrition (PN) is life saving for many preterm infants and other neonates with severe illness, but prolonged use of PN can lead to intrahepatic cholestasis, referred to as parenteral nutrition–associated cholestasis (PNAC). It is defined as direct bilirubin greater than 2.0 mg/dL persistent for at least 2 consecutive tests duringthe administration of PN, not associated with other known causes of cholestasis [1-3]. With the increasing survival of preterm infants and neonates requiring intensive care, PNAC has become a more common clinical challenge. The incidence of PNAC varywidely depending on the population studied, with high incidencein populations carrying several risk factors for PNAC. It increases with duration of PN and ranges from 10% to 85% in infants [4-8]. A multifactorial aetiology has been proposed for the development of PNAC. Recognized risk factors for PNAC include low birth weight, low gestational age, necrotizing enterocolitis, intestinal malformations, and intestinal surgery. A further risk factor is the occurrence ofsevere infections, due to the requirement for central line for infusion of PN, and bacterial overgrowth caused by enteralstarvation and immature immune function[9-13]. However, exposure to PN is demonstratedas the main factor in the development of PNAC. Intravenous hyper-alimentationhas been implicated, such as thetotal caloric overload, the quality of aminoacid solutions, the cumulative amount and the quality of lipid infusion, the presence of excessivealuminium in the PN solution, and the high manganese intake with PN [1,14-17]. Ursodeoxycholic acid, cyclic PN, light protection for PN, tapering the soybean-based lipid emulsion, and antibiotics to decontaminate bacterial overgrowth are used to treat PNAC [18-21]. In recent years, increasing attention has been paid to the lipid content in PN. It has been found that fish oil–containing lipid emulsions could be useful in infants to reverse PNAC for whom enteral feeding is intolerable. However, no evidence supports the use of fish oil–containing lipid emulsions to prevent PNAC in neonates, including preterm infants [22]. Enteral feeding remains the best strategy to reverse and prevent PNAC, with as little as 10% of caloric intake showing beneficial effects [5,22].

Venous thrombosis – the importance of cardiovascular disease as a risk factor

Cardiologia CROATICA Objectives: The aim of the study was to reveal demographic data, laboratory and vein duplex findings in patients hospitalized for venous thrombosis and thromboembolism. Specific interest was focused on usual laboratory findings such as D-dimer, coagulation cascade parameters and thrombophilia investigation and its relationship with the severity of deep vein thrombosis (DVT). Risk factors such as cardiovascular diseases, malignancy, trauma, metabolic parameters and other well known data were analyzed. The increasing incidence of venous thrombosis in ageing population has changed the priority list and the importance of usual risk factors. Patients and Methods: The study included all patients with clinical suspicion for DVT and or/pulmonary embolism (PE), treated in the University Hospital Centre Zagreb through the period of 52 months. Three hundred twenty-four patients with venous thrombosis and/or pulmonary embolism were analyzed. Antropometric, biochemical and lipid parameters, hypercoagulability factors, malignancy, trauma or surgery, cardiovascular disease, DVT family history, previous DVT or PE were evaluated. Patients were grouped according to the vein thrombosis location. Diagnosis of DVT was done with duplex scan. PE was diagnosed on MSCT pulmonary angiography or lung ventilation-perfusion scintigraphy. Results: DVT was diagnosed in 264 (81.5%) and PE in 80 patients (24.7%). Only 46 patients suffering from PE had evidence of venous thrombosis on the limb duplex scan. The femoral and popliteal veins were the most common sites of thrombi. The frequency of patients older than 55 years was 68.2%. Similar incidence was found in both sexes. The evidence of cardiovascular disease was the most frequent risk factor (47.8%). Malignancy was found in 62 patients (19.2%). The incidence of previous surgery or any trauma was 17%. Thrombophilia as the only risk for venous thrombosis was revealed in 63 patients. Proximal DVT was most extensive in the older age group (P<0.0001). D-dimer values had significant positive correlation with thrombosis severity (P<0.0001). Conclusion: Cardiovascular disease had the highest incidence in population suffering from venous thromboembolism. This finding emphasized the importance of careful preventive strategies in patients with cardiovascular disease. In clinical settings, higher levels of D-dimer could implicate proximal deep venous thrombosis.

Revisiting the Effect of Acute P. falciparum Malaria on Epstein-Barr Virus: Host Balance in the Setting of Reduced Malaria Endemicity

Burkitt's lymphoma (BL), an EBV-associated tumour, occurs at high incidence in populations where malaria is holoendemic. Previous studies in one such population suggested that acute P.falciparum infection impairs EBV-specific T-cell surveillance, allowing expansion of EBV infected B-cells from which BL derives. We re-examined the situation in the same area, The Gambia, after a reduction in malaria endemicity. Cellular immune responses to EBV were measured in children with uncomplicated malaria before (day 0) and after treatment (day 28), comparing EBV genome loads in blood and EBV-specific CD8+ T-cell numbers (assayed by MHC Class I tetramers and IFNγ ELISPOTS) with those seen in age- and sex-matched healthy controls. No significant changes were seen in EBV genome loads, percentage of EBV-specific CD8+ T-cells and IFNγ producing T-cells in acute versus convalescent samples, nor any difference versus controls. Regression assays performed also no longer detected any impairment of EBV-specific T-cell surveillance. Acute uncomplicated malaria infection no longer alters EBV-specific immune responses in children in The Gambia. Given the recent decline in malaria incidence in that country, we hypothesise that gross disturbance of the EBV-host balance may be a specific effect of acute malaria only in children with a history of chronic/recurrent malaria challenge.

Low creatine kinase is associated with a high population incidence of fainting

ObjectiveVasoconstrictor capacity, skeletal muscle tone, and renal sodium retention are involved in the pathogenesis of fainting. As muscle contractility and ion transport are highly energy-demanding processes, we hypothesized that a low activity of the energy-generating enzyme creatine kinase (CK) is associated with a higher risk of fainting. The aim of this observational study was to explore the association of vasovagal syncope with low CK.MethodsA random sample of 1,000 subjects aged 34–60 years was drawn from the general population, with 442 subjects eventually included in the study. Data on fainting history were collected with the investigators blinded to participants’ CK level. We prepared this report according to the “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) statement. The main outcome was the lifetime cumulative incidence of vasovagal syncope in subjects with low versus high-normal serum CK after a 3 days rest. ResultsThe proportion of fainters within the high CK group was 29 out of 130 (22%) versus 121 out of 312 (39%) in the low CK group; a 73% greater occurrence of fainting with low CK (P = 0.0005). This finding was consistent across recurrent fainters, and in men and women. InterpretationLow CK is associated with a 73% higher incidence of fainting in a random population sample. The association is biologically plausible, as CK enhances cardiovascular and skeletal muscle contractility and salt retention. The presented data suggest that low CK activity is a potential new risk factor for vasovagal syncope.

Detection of CAG repeats in pre-eclampsia/eclampsia using the repeat expansion detection method

Pre-eclampsia/eclampsia is a serious disorder of human pregnancy that has a worldwide incidence of 2-10% and carries a severe morbidity and mortality risk for both mother and child. Its precise cause remains unknown. However, there is increasing evidence of an underlying complex maternal genetic susceptibility. Its high population incidence in the face of strong negative selection pressure suggests that the gene(s) involved have a selective advantage and/or a high mutation rate. One class of genetic diseases that involve a high mutation rate are the trinucleotide repeat expansion diseases. Thus, the aim of this study was to determine whether there is an association between a trinucleotide (CAG) repeat expansion and pre-eclampsia/eclampsia. We have used the repeat expansion detection (RED) method, which was developed to directly identify clinically significant repeat expansions, to analyse genomic DNA from an Australian and New Zealand population. The maximal CAG repeat length for each individual was recorded and the Mann-Whitney U and Wilcoxon rank sum test for independent samples were used to compare distributions for CAG/CTG repeats between two populations. There were no statistically significant differences between the distribution of CAG repeats in normotensive (n = 59) and severe pre-eclampsia (n = 69) (Mann-Whitney U = 1732; P = 0.14), and normotensive (n = 59) and eclamptic (n = 15) populations (Mann-Whitney U = 417, P = 0.726). Therefore, these RED results do not support a role for a large CAG expansion in pre-eclampsia/eclampsia. However, these data do not preclude the possibility that a small CAG expansion is associated with the disorder nor do they negate the hypothesis that a highly mutable gene contributes to the genetic component of pre-eclampsia/eclampsia.

Some thoughts about the etiopathogenesis of temporal arteritis - a review

The three most striking features of temporal arteritis (TA) are the high incidence in populations of Nordic origins, the remarkable rarity of the disease among persons younger than 50 years, and the predilection for the superficial temporal arteries. At present, neither genetic susceptibility, environmental factors nor occurrence of specific infections offer complete explanations to why Scandinavians are at increased risk of contracting TA. Similarly, recent developments in immunology and pathology of inflamed arteries cannot explain the preference of TA for this particular medium-size artery or why the disease almost exclusively affects persons older than 50 years. Although significant contributions regarding the pathogenesis of TA during the last decade are encouraging, the etiology of this disease still remains an enigma.

Finding genes influencing susceptibility to complex diseases in the post-genome era.

During the last decade, hundreds of genes that harbor mutations causing simple Mendelian disorders have been identified using a combination of linkage analysis and positional cloning techniques. Traditional approaches to gene mapping have been largely unsuccessful in mapping genes influencing so-called 'complex' genetic diseases, however, because of low power and other factors. Complex genetic diseases do not display simple Mendelian patterns of inheritance, although genes do have an influence and close relatives of probands consequently have an increased risk. These disorders are thought to be due to the combined effects of variation at multiple interacting genes and the environment. Complex diseases have a significant impact on human health because of their high population incidence (unlike simple Mendelian disorders, which tend to be rare). New techniques are being developed aimed specifically at mapping genes conferring susceptibility to complex diseases. A project aimed at mapping genes influencing susceptibility to a complex disease may be undertaken in several stages: establishing a genetic basis for the disease in one or more populations; measuring the distribution of gene effects; studying statistical power using models; carrying out marker-based mapping studies using linkage or association. Quantitative genetic models can be used to estimate the heritability of a complex (polygenic) disease, as well as to predict the distribution of gene effects and to test whether one or more quantitative trait loci (QTLs) exist. Such models can be used to predict the power of different mapping approaches, but are often unrealistic and therefore provide only approximate predictions. Linkage analyses, association studies and family-based association tests are all hindered by low power and other specific problems. Association studies tend to be more powerful but can generate spurious associations due to population admixture. Alternative strategies for association mapping include the use of recent founder populations or unique isolated populations that are genetically homogeneous, and the use of unlinked markers (so-called genomic controls) to assign different regions of the genome of an admixed individual to particular source populations. Linkage disequilibrium observed in a sample of unrelated affected and normal individuals can also be used to fine-map a disease susceptibility locus in a candidate region. New Bayesian strategies make use of an annotated human genome sequence to further refine the position of a candidate disease susceptibility locus.

Giant cell arteritis. Epidemiology, etiology and pathogenesis.

Giant cell arteritis (GCA) is a chronic inflammatory disorder targeting large and medium-sized arteries, which predominantly affects postmenopausal women. Its high incidence in populations with Scandinavian lineage, some familial accumulation, and the association with the HLA-DR4 haplotype indicate a genetic predisposition. Epidemiological observations, as well as the symptomatology, may indicate an infectious origin, but so far GCA has not been shown to be a truly infectious form of vasculitis. Immunological research indicates an antigen-driven disease with local T-cell and macrophage activation in the vessel wall. Morphologically, the inflammatory process appears to be initiated by a foreign-body giant-cell attack on calcified internal elastic membrane in arteries and on calcified atrophic parts of the aortic media. The ensuing diffuse chronic inflammation leads to vessel dilatation and extensive intimal thickening. The latter, which relates to the production of promoting factors by the inflammatory cells, causes arterial stenosis and ischemic complications. The possible role of female sex hormones in GCA requires further investigation. Mononuclear and giant cells in GCA display the cytoplasmic accumulation of estrogen receptor (ER) alpha. Cytoplasmic ER-alpha is also seen in media smooth-muscle cells in GCA and in non-GCA controls, but nucleotide sequence analysis of the ER-alpha gene revealed no differences between GCA patients and controls. In the future, comprehensive morphological, cell biological and immunological research will be required for a better understanding of the complex etiology and pathogenesis of GCA.

Population-based study of unintentional injuries in the home.

There is little current understanding of the risk for occurrence of unintentional injury in the home. The authors estimated the incidence of unintentional home injuries for an entire community, adjusting for actual time spent awake in the home and, in addition, analyzed the costs of these injuries. Cases of unintentional home injuries occurring from 1990 to 1993 among the residents of Stavanger, Norway (approximately 100,000 population) were identified through a prospective, ongoing injury registration system. Age- and sex-specific per-population incidence and incidence per time spent awake at home were estimated. Time exposure data for adults were obtained from the Norwegian Time Budget Survey and were estimated directly for children. The cost of injuries was estimated based on a random sample of 289 patients. A total of 8,580 persons received medical treatment for unintentional injuries in the home (22.0 per 1,000 population annually, 71.9 per 10 million hours awake at home). The per-population incidence was highest among children age 6 years or younger and among people aged 65 or older (51.0 and 32.7 respectively, per 1,000 population annually). The high population incidence for children was not accounted for by time spent awake at home. For people aged 65-74 years, however, increased incidence was primarily a function of greater time spent awake at home. For persons aged 75 years or older, the high population incidence was due to both high exposure-adjusted incidence and greater time spent awake at home. The male-female ratio of age-standardized per-population incidence was 1.07 (95% confidence interval 1.04-1.10), and the ratio of age-standardized exposure-adjusted incidence was 1.22 (95% confidence interval 1.17-1.28). The estimated cost (direct and indirect) per injury was $1,300 during the first year after injury. Persons aged 75 years or older accounted for 12% of the injuries but 50% of the total medical costs.

High population incidence of the 15p marker D15Z1 mapping to the short arm of one homologue 14

We have read with interest the paper by Smeets et al. (1991), reporting a "Frequent occurrence of translocation of the short arm of chromosome 15 to other D-group chromosomes" . We have per formed a similar population study of 100 subjects using the satellite-III probe D15Z1 obtained f rom the same source (Higgins et al. 1985), which is in fact a repetit ive human 1.8 kb KpnI sequence and not an alphoid sequence. Under high stringency conditions, this p robe has previously been thought to map exclusively to the DA/DAPI-pos i t ive juxta centromeric heterochromatic region of 15p, but 12 of our 100 subjects showed an additional hybridization spot on an acrocentric chromosome other than 15 (Fig. 1). In contrast to the observation by Smeets et al. (1991) we found the additional hybridization restricted to the p arm of one homologue 14, as identified by pre-G-banding, co-hybridization with the whole chromosome pBS14 and pBS15 probes, sequential D A / D A P I staining and D15Z1 hybridization. None of our cases showed hybridization to the p arm of chromosome 13. It will be interesting to see if this represents a true population difference between the British and the Dutch, or is merely due to chance variation. Family studies (two families) demonstrated that the 14p marker is an inherited character. The high incidence of this marker obviously restricts the value of D15Z1 as a diagnostic tool for the identification of 15p, particularly when used in interphase. We are still uncertain about the origin of this common constitutional marker . We suggest that it is premature to call it a chromosomal translocation, implying chromosome breakage and rearrangement. To-date there are no reasons to believe that this heritable polymorphism could not have originated by other means, e.g., selective amplification of sequences common to 15p and 14p.

Hereditary Factors in Cancer

MENDELIAN autosomal inheritance patterns have been demonstrated in familial aggregations of polyposis coli, retinoblastoma, xeroderma pigmentosum, neurofibromatosis,1Gardner's syndrome2and the basal cell nevus syndrome.3In addition, an increased familial incidence of carcinoma of the breast,4lung,5stomach and colon,6and prostate,7as well as leukemia,8multiple myeloma,9Waldenstrom's macroglobulinemia,10pheochromocytoma,11multiple endocrine tumors,12cerebellar hemangioblastoma,13and malignant melanoma14has been observed. However, the mode of inheritance is not clear in these latter conditions. In appraising these data, it must be kept in mind that only those families showing a high incidence of carcinoma are "selected" for publication. When one considers the high population incidence of carcinoma, "... it is bound to occur in excess in some families according to the operation of the laws of probability.15" The purpose of this paper is to present the findings in two large midwestern kindreds in which a high frequency of