Completeness Of Case Ascertainment Research Articles

Five-Year Incidence of Amyotrophic Lateral Sclerosis in British Columbia (2010-2015).

Amyotrophic lateral sclerosis (ALS) is a fatal degenerative neurological disease with significant effects on quality of life. International studies continue to provide consistent incidence values, though complete case ascertainment remains a challenge. The Canadian population has been understudied, and there are currently no quantitative data on the incidence of ALS in British Columbia (BC). The objectives of this study were to determine the five-year incidence rates of ALS in BC and to characterize the demographic patterns of the disease. The capture-recapture method was employed to estimate ALS incidence over a five-year period (2010-2015). Two sources were used to identify ALS cases: one database from an ALS medical centre and another from a not-for-profit ALS organization. During this time period, there were 690 incident cases within the two sources. The capture-recapture method estimated 57 unobserved cases, corresponding to a crude five-year incidence rate of 3.29 cases per 100,000 (CI 95%=3.05-3.53). The mean age of diagnosis was 64.6 (CI 95%=59.7-69.4), with 63.5 (CI 95%=56.9-70.1) for men and 65.7 (CI 95%=58.6-72.7) for women. There was a slight male preponderance in incidence, with a 1.05:1 ratio to females. Peak numbers in incidence occurred between the ages of 70 and 79. The incidence of ALS in BC was found to be consistent with international findings though nominally higher than that in other Canadian provinces to date.

Prenatal detection of major congenital heart disease – optimising resources to improve outcomes

IntroductionCongenital heart disease (CHD) is the most common major structural fetal abnormality and the benefits of prenatal detection are well described. The objective of this study was to evaluate the precision of prenatal diagnosis at a single tertiary referral unit over two three year periods (2006, 2007, 2008 and 2010, 2011, 2012), before and after a prenatal screening protocol for CHD was developed to include extended cardiac views, mandatory recall for suboptimal views, and a multidisciplinary Fetal Cardiac clinic was established. There exists a single national centre for paediatric cardiothoracic surgery in Ireland, a situation which facilitates near complete case ascertainment. Materials and methodsSurgery records of the National Children's Cardiac Centre were interrogated for all cases of major congenital heart defects requiring surgical intervention in the first six months of life. Minor procedures such as ligation of a patent ductus arteriosus and isolated atrial septal defect repairs were excluded. Analyses of the Fetal Medicine database at the Rotunda Hospital (a stand-alone tertiary level perinatology centre with 8500 deliveries per year) and the mortality data at the Perinatal Pathology department were conducted. The Cochrane–Armitage trend test was used to determine statistical significance in prenatal detection rates over time. Results51,822 women delivered during the study period, and the incidence of major congenital heart disease either that underwent surgical intervention or that resulted in perinatal mortality, was 238/51,822 (0.5%). Prenatal detection of major CHD increased from 31% to 91% (p<0.001). Detection of critical duct-dependant lesions rose from 19% to 100%. ConclusionWe attribute the dramatic improvement in prenatal detection rates to the multifaceted changes introduced during the study period. Improved prenatal detection for births that are geographically remote from the National Paediatric Cardiac Centre will require local replication of this prenatal programme.

Effect of Presymptomatic Body Mass Index and Consumption of Fat and Alcohol on Amyotrophic Lateral Sclerosis.

Because dietary intake may influence pathophysiologic mechanisms in sporadic amyotrophic lateral sclerosis (ALS), the association between premorbid dietary intake and the risk of sporadic ALS will provide insight into which mechanisms are possibly involved in ALS pathophogenesis. To systematically determine the association between premorbid dietary intake and the risk of sporadic ALS. A population-based case-control study was conducted in a general community setting in the Netherlands from January 1, 2006, to September 30, 2011. Analysis was conducted April 1, 2013, to November 15, 2014. All patients with a new diagnosis of possible, probable (laboratory supported), or definite ALS according to the revised El Escorial criteria were included and multiple sources were used to ensure complete case ascertainment. Of 986 eligible patients, 674 gave informed consent and returned a complete questionnaire; 2093 controls randomly selected from the general practitioners' registers and frequency matched to the patients for sex and age were included. We studied the premorbid intake of nutrients in association with the risk of ALS by using a 199-item food frequency questionnaire adjusted for confounding factors and corrected for multiple comparisons while minimizing recall bias. Presymptomatic total daily energy intake in patients, reported as mean (SD), was significantly higher compared with controls (2258 [730] vs 2119 [619] kcal/day; P < .01), and presymptomatic body mass index (calculated as weight in kilograms divided by height in meters squared) was significantly lower in patients (25.7 [4.0] vs 26.0 [3.7]; P = .02). With values reported as odds ratio (95% CI), higher premorbid intake of total fat (1.14; 1.07-1.23; P < .001), saturated fat (1.43; 1.25-1.64; P < .001), trans-fatty acids (1.03; 1.01-1.05; P < .001), and cholesterol (1.08; 1.05-1.12; P < .001) was associated with an increased risk of ALS; higher intake of alcohol (0.91; 0.84-0.99; P = .03) was associated with a decreased risk of ALS. These associations were independent of total energy intake, age, sex, body mass index, educational level, smoking, and lifetime physical activity. No significant associations between dietary intake and survival were found. The combination of independent positive associations of a low premorbid body mass index and a high fat intake together with prior evidence from ALS mouse models transgenic for SOD1 and earlier reports on premorbid body mass index support a role for increased resting energy expenditure before clinical onset of ALS.

HLA Associations and Risk of Posttransplant Lymphoproliferative Disorder in a Danish Population-Based Cohort.

Posttransplant lymphoproliferative disorder (PTLD) is a feared complication to organ transplantation, associated with substantial morbidity and inferior survival. Risk factors for PTLD include T cell-depleting induction therapy and primary infection or reactivation of Epstein-Barr virus. Possible associations between certain HLA types and the risk of developing PTLD have been reported by other investigators; however, results are conflicting. We conducted a retrospective, population-based study on 4295 Danish solid organ transplant patients from the Scandiatransplant database. Having identified 93 PTLD patients in the cohort, we investigated the association of HLA types with PTLD, Epstein-Barr virus status and time to PTLD onset. The outcomes survival and PTLD were evaluated using Cox regression; mismatching, and the PTLD-specific mortality were evaluated in a competing risk analysis. Risk of PTLD was associated with male sex (odds ratio, 1.70; 95% confidence interval, 1.07-2.71), and, in women, HLA-DR13 conferred an increased risk (odds ratio, 3.22; 95% confidence interval, 1.41-7.31). In multivariate analysis, HLA-B45 and HLA-DR13 remained independent predictive factors of PTLD. Mismatching in the B locus was associated with a reduced risk of PTLD (P < 0.001). Overall survival was poor after a PTLD diagnosis and was significantly worse than that in the remaining transplant cohort (P < 0.001). Our data indicate risk-modifying HLA associations, which can be clinically useful after transplantation in personalized monitoring schemes. Given the strong linkage disequilibrium in the HLA region, the associations must be interpreted carefully. The large size, virtually complete ascertainment of cases and no loss to follow-up remain important strengths of the study.

Completeness and validity in a national clinical thyroid cancer database: DATHYRCA

BackgroundAlthough a prospective national clinical thyroid cancer database (DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of data quality has been performed. The purpose of the study was to evaluate completeness and data validity in the Danish national clinical thyroid cancer database: DATHYRCA. Study design and settingNational prospective cohort. Denmark; population 5.5 million. Completeness of case ascertainment was estimated by the independent case ascertainment method using three governmental registries as a reference. The reabstracted record method was used to appraise the validity. For validity assessment 100 cases were randomly selected from the DATHYRCA database; medical records were used as a reference. ResultThe database held 1934 cases of thyroid carcinoma and completeness of case ascertainment was estimated to 90.9%. Completeness of registration was around or above 90% in most instances. Perfect agreement on the diagnosis of thyroid carcinoma was found, both inter- and intra-observer, and κ values of selected variables showed overall good to excellent agreement. ConclusionIn a setup with public health insurance, personal identity numbers and extended governmental databases, it is possible to establish national clinical cancer databases with a satisfactory completeness and validity. The DATHYRCA database is considered reliable in terms of describing thyroid carcinoma at a national level.

Who needs selection bias?

Present day low participation rates in certain parts of research is concerning. It is not unusual that half (or even more) of those invited to participate in a research project decline the invitation. Many think this will always lead to selection bias regardless of the type of study in question. That is fortunately not the case. Selection bias is a reason for concern in studies that aim to obtain a representative sample concerning risk factors or outcomes. Those who decline participation will often have a higher risk profile (lower social status, smokers etc) and more chronic disorders. Selection bias of the most serious type is related to the specific hypothesis when the hypothesis is known to participants. Being asked to participate in a study on oral contraceptives (OC) and breast cancer, for example, may be more appealing to women with breast cancer who have used OC. Selection is therefore often of concern in case–control studies. Non-response and selection bias is of less concern in follow-up studies where the outcome is not known at the time of recruitment. The reason for limited interest in “representativeness” is that scientific inference addresses a potential cause–effect relation in general, not in a specific population. Whether an established cause–effect relation is present in a specific population with a given effect estimate is a matter of effect measure modification and the distribution of component causes in that population at that given time period. Non-response in a follow-up study is expected to affect the structure of the population and influence the confounder distribution, often by producing less confounding because those with health problems and extreme lifestyle factors are more likely to decline participation. Since these factors may act as confounders, selection may change effect sizes without bias but just because effect sizes are population-specific. One should, however, be aware of a selection bias that would not be present with complete case ascertainment as illustrated in figure 1. Without selection (S), C 3 would not cause bias, but S (conditioned upon) will link C 3 to E, and establish the backdoor E-C 3 -D that can be closed by adjusting for C 3 . In a like manner, C 1 and C 2 have confounding potential because conditioning on S will produce the backdoor paths C 1 -C 3 -D and C 1 -C 2 -D. Adjustments for C 2 and C 3 will be needed. This will happen even in situations where S is not directly linked to D (because D has not occurred at the time of recruitment). Direct selection bias relating S to both E and D is only expected if D can be predicted by study participants (eg, by using the family history of disease occurrence). Selection in a cohort will not in itself lead to selection bias but will often produce a different confounder structure and therefore call for a different strategy when deciding on which confounders to include and how to treat them in the analysis.

Uncontrolled Hypertension in a Group of Hypertensive Patients in Erbil

Background: Hypertension is a powerful risk factor for fatal and non-fatal cardiovascular disease events, and many randomized trials showed that hypertension control is associated with a decrease in incidence of stroke and coronary heart disease. Objective: This study was carried out to identify the prevalence of, and factors associated with, uncontrolled hypertension in a group of hypertensive patients in Erbil. Patients and methods: A cross sectional study was carried out. A convenience sample of 400 hypertensive patients attended outpatient clinics at Rizgary teaching hospital in Erbil city was included. This study was extended of 1st April 2011 through 31st March 2012. The data were obtained by a direct interview with the patients using a questionnaire a specially designed questionnaire. The statistical package for social sciences (SPSS, version 18.0) was used for data entry and analysis. Results: The prevalence of uncontrolled hypertension was (58.8%). The prevalence of uncontrolled hypertension among males hypertensive patients were 61.8%.and among females were 57.5%. The Logistic regressions analysis of uncontrolled hypertension showed a statistically significant association between uncontrolled hypertension with current smoker (OR=8.77), regularity of treatment (OR=0.296), exercise (OR= 0.414) and type of antihypertensive drugs: diuretics (OR=11.938), ACEI (OR=7.907) beta blockers (OR=7.096), and CCB (OR=7.169). Conclusions: More than half of the hypertensive patients were uncontrolled. The factors associated with uncontrolled hypertension were smoking, lack of exercise, irregularity of treatment (non adherence to treatment). Recommendations: There is a need to stimulate researches and further studies, such as complete community-based case ascertainment.

Accuracy of International Classification of Diseases, 9th Revision, Clinical Modification codes for upper gastrointestinal complications varied by position and age: a validation study in a cohort of nonsteroidal anti‐inflammatory drugs users in Friuli Venezia Giulia, Italy

To validate the International Classification of Diseases, 9th Revision, Clinical Modification discharge codes used to identify cases of upper gastrointestinal complications (UGICs) in hospitals of Friuli Venezia Giulia, Italy. Cohort study on the risk of UGIC in users of nonsteroidal anti-inflammatory drugs conducted in Friuli Venezia Giulia between 2001 and 2008. Cases were identified through primary and secondary International Classification of Diseases, 9th Revision Clinical specific codes 531 (gastric ulcer), 532 (duodenal ulcer), 533 (peptic ulcer), 534 (gastrojejunal ulcer), and nonspecific code 578 (gastrointestinal hemorrhage). Potential cases were confirmed through hospital chart review. The chart retrieval percentage was 98.4%.The positive predictive value (PPV) was 94.3% for primary codes 531 and 532, 79.5% for code 533, 83.1% for code 534, 40.2% for code 578. The PPV for secondary codes was 34.7% but increased to 88.9% and 79.2% when the primary code was for peritonitis or acute post-hemorrhagic anemia, respectively. Validation of secondary codes increased case ascertainment by 4.9%. Endoscopy confirmed 79.4% of cases but only 67.2% of those above age 84 years. The PPV was high for specific primary codes and moderate to low for nonspecific primary and secondary codes. The inclusion of confirmed cases identified by nonspecific and secondary codes can be of value in studies that need a complete ascertainment of cases occurring in the study population. In this cohort, not including these cases would underestimate the incidence of UGICs. A potential for case misclassification exists in particular in eldest ages.

Completeness of case ascertainment at the Irish National Cancer Registry

Cancer registries play a major role in cancer control, including quantifying the burden of cancer in the population, informing health service planning, and evaluating service provision. Registries must achieve a high level of completeness of case ascertainment. Completeness of case ascertainment for the National Cancer Registry (NCR) in Ireland was estimated. For all invasive cancers, and the four most common sites, we used two quantitative methods which use information from death certificates to obtain estimates of completeness of registration-the Lincoln-Petersen (LP) estimator (which provides a lower bound estimate) and the flow method (which estimates completeness at a fixed time-point, in this case 5 years). Data were extracted at the end of 2010. Independent case ascertainment was used to assess completeness of breast cancer registration in the 50-64 age group and of rectal cancer in surgical patients diagnosed in 2007. Completeness of case ascertainment was >99 % for the breast screening age-group and for surgical rectal cancer cases. A lower bound on completeness of case ascertainment for all invasive cancers excluding non-melanoma skin cancers is 94.3 % using the LP estimator. The estimate from the flow method is 97 % after 5 years, [95 % confidence interval (96.2 %, 97.7 %)]. Five-year levels of completeness for the four commonest cancers using the flow method were: colorectal, 97.4 %; lung, 98.7 %; prostate, 95.8 % and breast, 98.0 %. The estimated levels of completeness for the NCR are satisfactory. Further work is required to compare the methods used.

The Incidence of Amyotrophic Lateral Sclerosis in Friuli Venezia Giulia, Italy, from 2002 to 2009: A Retrospective Population-Based Study

Background: We conducted a retrospective population-based study to estimate the incidence of amyotrophic lateral sclerosis (ALS) in Friuli Venezia Giulia, Italy, from 2001 to 2009. Methods: Multiple sources were used for case ascertainment: Health databases, archives of the neurology departments and of the regional chapter of the Italian ALS Association. The diagnosis was validated through clinical documentation review. Crude and standardized incidence rates (IRs) per 100,000 person-years were calculated. Results: We identified 262 incident ALS cases, 50.4% men, 4.2% familial. Half of the patients had spinal onset (56.8% in men) and 25.2% bulbar (29% in women). Bulbar onset had a similar frequency in women (31.7%) and men (31.5%) aged 67 or above at diagnosis. The crude IR was 2.72 (95% confidence interval, 95% CI, 2.39-3.05) and the male:female ratio 1.08. The IR peaked in the 65-74 age group, with a second increase in men 85 years and older. The IR standardized to the 2001 Italian population was 2.38 (95% CI 2.13-2.63) and to the 2000 European population 2.58 (95% CI 2.34-2.81). Conclusions: This retrospective study found IRs of ALS in the range of Italian and European prospective population-based registries, suggesting an almost complete case ascertainment.

In-hospital falls and fall-related injuries: a protocol for a cost of fall study

BackgroundIn-hospital falls are common and pose significant economic burden on the healthcare system. To date, few studies have quantified the additional cost of hospitalisation associated with an in-hospital fall or...

Risk of upper gastrointestinal complications in a cohort of users of nimesulide and other nonsteroidal anti‐inflammatory drugs in Friuli Venezia Giulia, Italy

Information on the risk of upper gastrointestinal complications (UGIC) in users of nimesulide, the most used nonsteroidal anti-inflammatory drug (NSAID) in Italy, is scarce. In the context of the European regulatory review on nimesulide, we estimated and compared the risk associated with nimesulide and other individual NSAIDs with the risk in nonusers. We used 2001-2008 data from regional health databases in Friuli Venezia Giulia (FVG), Italy, to conduct a cohort and nested case-control study of users of NSAIDs. Cases were identified by specific and nonspecific hospital discharge diagnoses in primary and secondary position and validated through hospital records. Ten controls per case were selected using density-based sampling from the cohort. Conditional logistic regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). The cohort included 588,827 NSAIDs users and 3031 UGIC cases. Nonspecific codes contributed to 23% of cases and secondary codes to 5%. Among current users, IR per 1000 person-years decreased from 4.45 cases in 2001 to 2.21 cases in 2008. The RR (95%CI) for current use of NSAIDs was 3.28 (2.86, 3.76). RR was <2 for rofecoxib, celecoxib, and nimesulide; 2 to <5 for naproxen, ibuprofen, diclofenac, etoricoxib, and meloxicam; and ≥ 5 for ketoprofen, piroxicam, and ketorolac. IRs of UGIC in FVG decreased about 50% between 2001 and 2008. Nimesulide was in the low-medium range of RR. A complete ascertainment of UGIC cases in databases may require validation of nonspecific codes, secondary codes, and additional codes such as peritonitis and acute posthemorrhagic anemia.

Systemic lupus erythematosus in an African Caribbean population: incidence, clinical manifestations, and survival in the Barbados National Lupus Registry.

To assess the epidemiology, clinical features, and outcomes of systemic lupus erythematosus (SLE) in the predominantly African Caribbean population of Barbados. A national registry of all patients diagnosed with SLE was established in 2007. Complete case ascertainment was facilitated by collaboration with the island's sole rheumatology service, medical practitioners, and the lupus advocacy group. Informed consent was required for inclusion. Between January 1, 2000 and December 31, 2009, there were 183 new cases of SLE (98% African Caribbean) affecting 172 women and 11 men for unadjusted annual incidence rates of 12.21 (95% confidence interval [95% CI] 10.46-14.18) and 0.84 (95% CI 0.42-1.51) per 100,000 person-years, respectively. Excluding pediatric cases (ages <18 years), the unadjusted incidence rate among women was 15.14 per 100,000 person-years. The principal presenting manifestations were arthritis (84%), nephritis (47%), pleuritis (41.5%), malar rash (36.4%), and discoid lesions (33.1%). Antinuclear antibody positivity was 95%. The overall 5-year survival rate was 79.9% (95% CI 69.6-87.1), decreasing to 68% in patients with nephritis. A total of 226 persons with SLE were alive at the end of the study for point prevalences of 152.6 (95% CI 132.8-174.5) and 10.1 (95% CI 5.4-17.2) per 100,000 among women and men, respectively. Rates of SLE in Barbadian women are among the highest reported to date, with clinical manifestations similar to African American women and high mortality. Further study of this population and similar populations of West African descent might assist our understanding of environmental, genetic, and health care issues underpinning disparities in SLE.

Completeness of case ascertainment for surveillance of autism spectrum disorders using the autism developmental disabilities monitoring network methodology

BackgroundThe Autism and Developmental Disabilities Monitoring Network (ADDM), sponsored by the Centers for Disease Control and Prevention, is the largest-scale project ever undertaken to identify the prevalence of Autism Spectrum Disorders (ASD) in the United States. ObjectiveThe objective of the present study was to examine the accuracy of the ADDM methodology in terms of completeness of case ascertainment; that is, to assess the success of the ADDM Network in identifying and accurately classifying all existing cases of ASD among 8-year-old children in the target study areas. MethodsTo accomplish this objective, the ADDM methodology was applied to a selected region of South Carolina for 8-year olds in 2000 (birth year 1992) and again seven years later for the same region and birth year. ResultsFor this region and birth year, completeness of case ascertainment was high, with prevalence estimates of 7.6 per 1000 at both ages 8- and 15-years. For children common to both surveillance years, concordance in case status was also high (82%). ConclusionsGiven that prevalence did not change within this region and birth year, continued research is needed to better understand the changes in prevalence estimates being found by the ADDM network across surveillance groups.

Completeness of Cancer Case Ascertainment in Korea Radiation Effect and Epidemiology Cohort Study

The aim of this study was to evaluate whether the completeness of case ascertainment during the follow-up of a cohort differed between the exposed and the nonexposed groups in Korea Radiation Effect and Epidemiology Cohort (KREEC). The completeness was defined as the proportion of the number of detected cases to the number of estimated cases, in which the estimation was performed by capture-recapture method. Data were obtained from the cancer registries, death certificates, and medical records during years 2004-2007. Among 11,367 subjects in the exposed group and 24,809 subjects in the unexposed group, the completeness of cancer case ascertainment were 88.2% vs 87.2% in cancer registry, 38.2% vs 41.1% in death certificate and 57.9% vs 62.0% in medical records data, 96.9% vs 97.1% for all combined sources and were not statistically different between the two groups. In conclusion, the method of ascertaining the cases in the KREEC was not biased depending on the exposure status, and thus adds credibility to the outcomes of the KREEC study as well as confirming the incident cases in the two groups.

The Spectrum Captured: A Methodological Approach to Studying Incidence and Outcomes of Traumatic Brain Injury on a Population Level

Objective: Drawing on the experience of conducting the Brain Injury Incidence and Outcomes New Zealand in the Community study, this article aims to identify the issues arising from the implementation of proposed guidelines for population-based studies of incidence and outcomes in traumatic brain injury (TBI). Study Design and Setting: All new cases of TBI (all ages and severities) were ascertained over a 1-year period, using overlapping prospective and retrospective sources of case ascertainment in New Zealand. All eligible TBI cases were invited to participate in a comprehensive assessment at baseline and at 1-month follow-up. Results: Our experience to date has revealed the feasibility of case ascertainment methods. Consultation with community health services and professionals resulted in feasible referral pathways to support the identification of TBI cases. ‘Hot pursuit’ methods of recruitment were essential to ensure complete case ascertainment for this population with few additional cases of TBI identified through cross-checks. Conclusion: This review of proposed guidelines in relation to practical study methodology provides a framework for future comparable population-based epidemiological studies of TBI incidence and outcomes in developed countries.

Comparison of racial differences in childhood cancer risk in case-control studies and population-based cancer registries

Introduction: Although selection bias in case-control studies has been studied extensively, little is known about selection of cases and controls among various ethnic groups. This study compares racial differences in childhood cancer rates as estimated by case-control studies with various design features. It also compares estimates of racial distribution among cases as reported by case-control studies to those observed for an ideal case series with complete ascertainment of cases for these studies or in population-based cancer registries in corresponding geographic regions and calendar periods. Methods: Peer-reviewed publications on childhood leukemia and brain tumors from North America, published between 1980 and 2007, were reviewed. Incidence data by race/ethnicity were compiled from research publications, federal cancer statistics, and cancer registries. Meta-analysis was conducted to assess racial/ethnic differences by study characteristics. Racial distributions of cases from published case-control studies were compared to those of a presumably noncensored case distribution (i.e. include both participating and non-participating cases in a case-control study) or cases recorded by cancer registries. Results: In interview-based case-control studies of childhood cancer, the proportion of Whites compared to non-Whites tended to be higher among controls than among cases; however, the opposite was true for record-based case-control studies. Additionally, the proportion of Whites tended to be higher among the participating cases in the published case-control studies compared to the proportion of Whites among the non-participating cases or in cancer registries. Conclusions: Investigators need to consider differential participation by racial group as a potential source of bias in the interpretation of case-control study results.

Monitoring drug safety with registries: useful components of postmarketing pharmacovigilance systems

ObjectiveAt the time of licensing by regulatory agencies, the full range of risks and possible adverse drug reactions associated with a medication is rarely fully realized. This commentary aims to describe the role of registries as useful components of postmarketing pharmacovigilance systems for monitoring highly specialized medications associated with significant financial costs. Study Design and SettingWe consider the limitations of traditional pharmacovigilance programs and discuss the strengths, limitations, and uses of registries in postmarketing pharmacovigilance systems. ResultsRegistries have become increasingly appealing in postmarketing surveillance of medications; however, their exact role continues to evolve. Key registry projects, including the Prospective Immunogenicity Surveillance Registry, British Society for Rheumatology Biologics Register, Australian Rheumatology Association Database, the Haemostasis Registry, and the Bosentan Patient Registry highlight the value of registries for monitoring the incidence of rare adverse events. ConclusionAlthough often limited by lack of a control group and the need for complete case ascertainment to maintain data integrity, registries are a useful component of postmarketing pharmacovigilance systems for monitoring highly specialized medications associated with significant financial costs.

How high are carrier frequencies of rare recessive syndromes? Contemporary estimates for Fanconi Anemia in the United States and Israel

For many recessive genetic syndromes, carrier frequencies have been assessed through screening studies in founder populations but remain unclear in heterogeneous populations. One such syndrome is Fanconi Anemia (FA). FA is a model disease in cancer research, yet there are no contemporary data on carrier frequency or prevalence in the general United States (US) population or elsewhere. We inferred carrier frequency from birth incidence using the Hardy-Weinberg law. We estimated prevalence using birth incidence and survival data. We defined "plausible ranges" to incorporate uncertainty about completeness of case ascertainment. We made estimates for the US and Israel using demographic data from the Fanconi Anemia Research Fund and Israeli Fanconi Anemia Registry. In the US, a plausible range for the carrier frequency is 1:156-1:209 [midpoint 1:181]; we estimate that 550-975 persons were living with FA in 2010. For Israel, a plausible range for the carrier frequency is 1:66-1:128 [midpoint 1:93] in line with founder screening studies; we estimate that 40-135 Israelis were living with FA in 2008. The estimated US FA carrier frequency of 1:181 is significantly higher than the historical estimate of 1:300; hence, the gap may be narrower than previously recognized between the US carrier frequency and higher carrier frequencies of around 1:100 in several founder groups including Ashkenazi Jews. Assessment of cancer risks in heterozygous carriers merits further study. Clinical trials in FA will require co-ordination and innovative design because the number of living US patients is probably less than 1,000.

Completeness of case ascertainment and survival time error in English cancer registries: impact on 1-year survival estimates.

Background:It has been suggested that cancer registries in England are too dependent on processing of information from death certificates, and consequently that cancer survival statistics reported for England are systematically biased and too low.Methods:We have linked routine cancer registration records for colorectal, lung, and breast cancer patients with information from the Hospital Episode Statistics (HES) database for the period 2001–2007. Based on record linkage with the HES database, records missing in the cancer register were identified, and dates of diagnosis were revised. The effects of those revisions on the estimated survival time and proportion of patients surviving for 1 year or more were studied. Cases that were absent in the cancer register and present in the HES data with a relevant diagnosis code and a relevant surgery code were used to estimate (a) the completeness of the cancer register. Differences in survival times calculated from the two data sources were used to estimate (b) the possible extent of error in the recorded survival time in the cancer register. Finally, we combined (a) and (b) to estimate (c) the resulting differences in 1-year cumulative survival estimates.Results:Completeness of case ascertainment in English cancer registries is high, around 98–99%. Using HES data added 1.9%, 0.4% and 2.0% to the number of colorectal, lung, and breast cancer registrations, respectively. Around 5–6% of rapidly fatal cancer registrations had survival time extended by more than a month, and almost 3% of rapidly fatal breast cancer records were extended by more than a year. The resulting impact on estimates of 1-year survival was small, amounting to 1.0, 0.8, and 0.4 percentage points for colorectal, lung, and breast cancer, respectively.Interpretation:English cancer registration data cannot be dismissed as unfit for the purpose of cancer survival analysis. However, investigators should retain a critical attitude to data quality and sources of error in international cancer survival studies.