Cumulative Incidence Proportion Research Articles

Epilepsy after severe traumatic brain injury: frequency and injury severity

ABSTRACT Objective: To estimate national frequency of posttraumatic epilepsy (PTE) after severe traumatic brain injury (TBI) and assess injury severity (Glasgow Coma Scale (GCS) and posttraumatic amnesia (PTA)) as prognostic factors for PTE. Methods Data on patients ≥18 years surviving severe TBI 2004–2016 were retrieved from the Danish Head Trauma Database (n = 1010). The cumulative incidence proportion (CIP) was estimated using death as competing event. The association between injury severity and PTE was assessed using multivariable competing risk regressions. Results CIP of PTE 28 days and one year post-TBI was 6.8% (95% confidence interval (CI) 5.4–8.5) and 18.5% (95% CI 16.1–21.1%), respectively. Injury severity was not associated with PTE within 28 days post-TBI but indicated higher PTE-rates in less severely injured patients. PTA-duration >70 days was associated with PTE 29–365 days post-TBI (Adjusted sub-hazard ratio 4.23 (95% CI 1.79–9.99)). GCS was not associated with PTE 29–365 days post-TBI. Conclusion The PTE frequency was higher compared to previous estimates. Increasing injury severity was associated with PTE 29–365 days post-TBI when measured with PTA, but not with GCS. Though nonsignificant, the increased PTE-risk within 28 days in lower severity suggests an underdiagnosing of PTE.

Associations between biomechanical and clinical/anthropometrical factors and running-related injuries among recreational runners: a 52-week prospective cohort study

BackgroundThe purpose of this exploratory study was to investigate whether runners with certain biomechanical or clinical/anthropometrical characteristics sustain more running-related injuries than runners with other biomechanical or clinical/anthropometrical characteristics.MethodsThe study was designed as a prospective cohort with 52-weeks follow-up. A total of 224 injury-free, recreational runners were recruited from the Gothenburg Half Marathon and tested at baseline. The primary exposure variables were biomechanical and clinical/anthropometrical measures, including strength, lower extremity kinematics, joint range of motion, muscle flexibility, and trigger points. The primary outcome measure was any running-related injury diagnosed by a medical practitioner. Cumulative risk difference was used as measure of association. A shared frailty approach was used with legs as the unit of interest. A total of 448 legs were included in the analyses.ResultsThe cumulative injury incidence proportion for legs was 29.0% (95%CI = 24.0%; 34.8%). A few biomechanical and clinical/anthropometrical factors influence the number of running-related injuries sustained in recreational runners. Runners with a late timing of maximal eversion sustained 20.7% (95%CI = 1.3; 40.0) more injuries, and runners with weak abductors in relation to adductors sustained 17.3% (95%CI = 0.8; 33.7) more injuries, compared with the corresponding reference group.ConclusionsMore injuries are likely to occur in runners with late timing of maximal eversion or weak hip abductors in relation to hip adductors.

CrossFit and the Epidemiology of Musculoskeletal Injuries: A Prospective 12-Week Cohort Study.

Background:Despite the increasing international popularity of CrossFit, there is a paucity of scientific evidence on the risk of CrossFit-related musculoskeletal injuries (CRMIs).Purpose:To investigate the incidence (cumulative incidence proportion [IP] and incidence density [ID]) of CRMIs and the association of CRMIs with personal and training characteristics.Study Design:Descriptive epidemiology study.Methods:A prospective, 12-week descriptive epidemiology cohort study was conducted in a convenience sample of CrossFit facilities in a single Brazilian city. Printed baseline questionnaires were distributed to 13 CrossFit boxes. All participants who filled out the questionnaire and consented to participate in the study were invited to respond to an online follow-up questionnaire every 2 weeks to collect data on CrossFit training characteristics and CRMIs. A CRMI was defined as any self-reported musculoskeletal injury or pain that prevented an athlete from exercising for at least 1 day. The IP was defined as the number of new cases divided by the entire population at risk, while the ID was defined as new events divided by the total person-time exposure in hours. Logistic mixed models were developed to investigate the association of CRMIs with personal and training characteristics.Results:A total of 515 CrossFit participants filled out the baseline questionnaire and provided informed consent, and 406 (78.8%) completed at least 1 follow-up measure. There were 133 participants who reported at least 1 CRMI during the study, and a total of 247 unique and new CRMIs were reported over a total estimated person-time exposure to CrossFit of 13,041 hours. The IP was 32.8% (95% CI, 28.4%-37.5%). The ID was 18.9 (95% CI, 16.6-21.3) per 1000 hours of CrossFit exposure. The shoulders (19.0%; n = 47) and lumbar spine (15.0%; n = 37) were most affected. Muscle injuries (45.3%; n = 112) and joint pain (24.7%; n = 61) were the most common CRMI types reported. Switching between prescribed and scaled down training loads (odds ratio [OR], 3.5 [95% CI, 1.7-7.3]) and previous injuries (OR, 3.2 [95% CI, 1.4-7.7]) were risk factors for a CRMI, while CrossFit experience was identified as a protective factor (OR, 0.7 [95% CI, 0.5-1.0]).Conclusion:In this 12-week prospective study, the ID was 18.9 CRMIs per 1000 hours of exposure; switching between training loads and previous injuries was associated with 3.5- and 3.2-fold higher odds, respectively, of sustaining CRMIs.

Role of community-based active case finding in screening tuberculosis in Yunnan province of China

BackgroundThe barriers to access diagnosis and receive treatment, in addition to insufficient case identification and reporting, lead to tuberculosis (TB) spreads in communities, especially among hard-to-reach populations. This study evaluated a community-based active case finding (ACF) strategy for the detection of tuberculosis cases among high-risk groups and general population in China between 2013 and 2015.MethodsThis retrospective cohort study conducted an ACF in ten communities of Dongchuan County, located in northeast Yunnan Province between 2013 and 2015; and compared to 136 communities that had passive case finding (PCF). The algorithm for ACF was: 1) screen for TB symptoms among community enrolled residents by home visits, 2) those with positive symptoms along with defined high-risk groups underwent chest X-ray (CXR), followed by sputum microscopy confirmation. TB incidence proportion and the number needed to screen (NNS) to detect one case were calculated to evaluate the ACF strategy compared to PCF, chi-square test was applied to compare the incidence proportion of TB cases’ demography and the characteristics for detected cases under different strategies. Thereafter, the incidence rate ratio (IRR) and multiple Fisher’s exact test were applied to compare the incidence proportion between general population and high-risk groups. Patient and diagnostic delays for ACF and PCF were compared by Wilcoxon rank sum test.ResultsA total of 97 521 enrolled residents were visited with the ACF cumulatively, 12.3% were defined as high-risk groups or had TB symptoms. Sixty-six new TB patients were detected by ACF. There was no significant difference between the cumulative TB incidence proportion for ACF (67.7/100000 population) and the prevalence for PCF (62.6/100000 population) during 2013 to 2015, though the incidence proportion in ACF communities decreased after three rounds active screening, concurrent with the remained stable prevalence in PCF communities. The cumulative NNS were 34, 39 and 29 in HIV/AIDS infected individuals, people with positive TB symptoms and history of previous TB, respectively, compared to 1478 in the general population. The median patient delay under ACF was 1 day (Interquartile range, IQR: 0–27) compared to PCF with 30 days (IQR: 14–61).ConclusionsThis study confirmed that massive ACF was not effective in general population in a moderate TB prevalence setting. The priority should be the definition and targeting of high-risk groups in the community before the screening process is launched. The shorter time interval of ACF between TB symptoms onset and linkage to healthcare service may decrease the risk of TB community transmission. Furthermore, integrated ACF strategy in the National Project of Basic Public Health Service may have long term public health impact.

P827EXPLORE-J: Lipid management and 2-year long-term clinical outcome in Japanese patients with acute coronary syndrome

Abstract Background The cardiovascular event rate in Japan is much lower than that in Western countries. However, the incidence of atherosclerotic CV disease and its burden are expected to increase in the Japanese society with rapid aging, westernization of lifestyles and metabolic derangement. An increase in patients with CAD has been remarkable in spite of various preventive measures. The positive linear correlation of LDL-C level with CAD incidence along with LDL-C lowering and CAD event reduction is established by large-scale studies in Western countries, but data in Japan are limited. EXPLORE-J, observational study, was conducted to gain insights into the relationship between LDL-C management and CV events in the Japanese ACS patients. Purpose The primary objective was to evaluate the status of post-ACS lipid management and CV events in Japan. Method ACS patients aged ≥20 years were enrolled and followed up for 2 years. The primary endpoint was the incidence proportion of major adverse cardiovascular events (MACE), including CV death (death associated with MI/stroke and other CV deaths), non-fatal ACS/stroke requiring hospitalization during the observation period. Other endpoints were medications and metabolic parameters. Additional stratified analyses of MACE incidence proportions by median LDL-C reduction category (above/below absolute or % reduction) from the first measurement after ACS to V1 (Day 1 + 14 days) was also conducted. Result Of the 2016 registered patients, 1944 were analyzed. The mean age and BMI were 66.0 years and 24.2 kg/m2, respectively. At 2-year follow up, the cumulative incidence proportion of MACE was 6.8%. The cumulative incidence proportions of CV death, non-fatal ACS and stroke were 0.7%, 4.5% and 1.7%, respectively. Statin, intensive statin, and ezetimibe were prescribed, respectively, to 93.6%, 8.2%, and 3.9% at V1, and 92.3%, 10.5%, and 11.6% at V5 (Day 730±30 days). The mean LDL-C levels were 121.2, 99.4, 80.9, and 79.8 mg/dL at the first measurement after ACS, V1, V2 (Day 30±7 days) and V5, respectively. The proportions of patients who achieved LDL-C <70 and <100 mg/dL at V1 and V5 were 14.4% to 34.6% and 56.5% to 82.8%, respectively. The incidence rate of MACE was lower among patients with larger than median absolute reduction in LDL-C level than among those with smaller reduction (median −17.0 mg/dL; 5.5% vs 8.3%, p=0.0435). The same trend was observed in patients with higher LDL-C reduction rate (median −15.36%; 6.3% vs 7.6%, p=0.4302). Kaplan-Meier estimates of MACE incidence Conclusion The results show the status of medical management and CV event rates in post-ACS Japanese patients. It also shows that half of the ACS patients did not achieve the recommended LDL-C levels of <70 mg/dL per guidelines, indicating the need to intensify lipid lowering therapy. To further characterize and quantify the patient population and the benefit of lipid management, we plan to conduct additional analyses with risk stratification of the population. Acknowledgement/Funding This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.

Incidence of Morphea following Adjuvant Irradiation of the Breast in 2,268 Patients

Background: Morphea of the breast is an autoimmune reaction of the subcutaneous connective tissue which can be triggered by exposure to ionizing radiation. The literature suggests incidence rates of 1:500 to 1:3,000 which, however, do not seem to match the very small number of cases reported. Objectives: The aim of the present study was to determine the incidence of morphea following irradiation of the breast in order to generate more evidence about the frequency of this serious and mutilating complication. Method: Retrospective analysis of patient data who underwent adjuvant radiotherapy in the period 2009–2018 following breast-conserving surgery and who made use of the recommended radiooncology follow-up examinations in 2018. Analysis was done by descriptive statistics. Results: Of a total of 5,129 patients who had undergone radiotherapy over a 10-year period, follow-up data were available in 2,268 patients. In 2,236 patients (98.6%) the breast had been irradiated using conventional fractionation schemes with a total dose of 50–50.4 Gy; 32 (1.4%) were given a total dose of 40.05 Gy in 15 fractions. During the observation period, 6 patients were diagnosed with morphea (4 unilateral and 2 bilateral) by punch biopsies resulting in a cumulative incidence proportion of 0.26% (95% CI: 0.24–0.28), translating into 1 case for every 378 irradiated patients. Conclusions: In the case studies reported to date, morphea is described as a very rare complication. In contrast, our data suggest a cumulative incidence of 1:378, which is higher than other authors have estimated. This leads us to suspect that in a large number of patients, morphea is incorrectly diagnosed as an infection (in the early stages) and radiation-induced fibrosis (in later stages).

Family recurrence risk of alopecia areata in the Faroe Islands.

Reports of a positive family history of alopecia areata (AA) have led to the assumption of a genetic component. The Faroe Islands population is small, has been isolated until the 20th century, and is served by only one dermatology clinic, making it highly suitable for genealogical studies. To determine the incidence of AA and to estimate the recurrence risk ratio (RRR) in five generations and in a nationwide dermatologist-based AA cohort using the Faroese genealogy database. All registered cases of AA during the period 1973-2011 were identified from the Faroese national dermatology clinics. The AA cases were linked with the genealogy database covering the entire Faroese population, and the probability of AA among first-, second- and third-degree relatives was calculated. In total, 178 cases of AA were identified, giving a crude incidence of 10.1 per 100000 person-years (10.9 for women and 9.4 for men). The cumulative incidence proportion over life was 0.8%. There was no apparent trend in the probabilities for AA in first-degree family members compared with second- and third-degree relatives. RRR was >1 in second-degree family members only. A lower prevalence rate of AA was found than previously published. The genealogical study failed to identify any apparent trend in the RRR estimates, questioning the role of genetic factors in AA in the Faroe Islands. However, it is possible that the trend is masked by bias and low power; larger studies are therefore warranted to estimate the heritability of AA.

Coronary CT Angiographic and Flow Reserve-Guided Management of Patients With Stable Ischemic Heart Disease

BackgroundClinical outcomes following coronary computed tomography–derived fractional flow reserve (FFRCT) testing in clinical practice are unknown. ObjectivesThis study sought to assess real-world clinical outcomes following a diagnostic strategy including first-line coronary computed tomography angiography (CTA) with selective FFRCT testing. MethodsThe study reviewed the results of 3,674 consecutive patients with stable chest pain evaluated with CTA and FFRCT testing to guide downstream management in patients with intermediate stenosis (30% to 70%). The composite endpoint (all-cause death, myocardial infarction, hospitalization for unstable angina, and unplanned revascularization) was determined in 4 patient groups: 1) CTA stenosis <30%, optimal medical treatment (OMT), and no additional testing; 2) FFRCT >0.80, OMT, no additional testing; 3) FFRCT ≤0.80, OMT, no additional testing; and 4) FFRCT ≤0.80, OMT, and referral to invasive coronary angiography. Patients were followed for a median of 24 (range 8 to 41) months. ResultsFFRCT was available in 677 patients, and the test result was negative (>0.80) in 410 (61%) patients. In 75% of the patients with FFRCT >0.80, maximum coronary stenosis was ≥50%. The cumulative incidence proportion (95% confidence interval [CI]) of the composite endpoint at the end of follow-up was comparable in groups 1 (2.8%; 95% CI: 1.4% to 4.9%) and 2 (3.9%; 95% CI: 2.0% to 6.9%) (p = 0.58) but was higher (when compared with group 1) in groups 3 (9.4%; p = 0.04) and 4 (6.6%; p = 0.08). Risk of myocardial infarction was lower in group 4 (1.3%) than in group 3 (8%; p < 0.001). ConclusionsIn patients with intermediate-range coronary stenosis, FFRCT is effective in differentiating patients who do not require further diagnostic testing or intervention (FFRCT >0.80) from higher-risk patients (FFRCT ≤0.80) in whom further testing with invasive coronary angiography and possibly intervention may be needed. Further studies assessing the risk and optimal management strategy in patients undergoing first-line CTA with selective FFRCT testing are needed.

The long-term impact of multiple sclerosis on the risk of divorce

BackgroundSeveral studies have investigated the impact of multiple sclerosis (MS) on the risk of divorce. However, current evidence is inconclusive and limited by e.g. small sample populations, short follow-up, and/or lack of a control group. The objective of this retrospective, observational study was to estimate the long-term impact of MS on the risk of divorce. MethodsSwedish patients diagnosed with MS between 1975 and 2012 were identified in a nationwide disease-specific register (the Swedish Multiple Sclerosis Registry) and matched with general population controls based on age, sex, region of residency, and marital status. We used survival analysis to estimate the cumulative incidence proportion of divorce after index (i.e. the MS diagnosis date). ResultsOur final sample comprised 3998 patients and 15,992 general population controls (mean age 44 years; 73% female). Mean follow-up was 10 years (range: 1–37 years). Unadjusted Kaplan-Meier failure functions revealed no significant differences in the cumulative incidence proportion of divorce between patients and controls (log-rank test, p = 0.902), or women with MS and female controls (p = 0.157). In contrast, men with MS were estimated to have a notably higher incidence of divorce compared with male controls (p = 0.040). Cox proportional-hazards model outcomes showed that men with MS had a 21% higher risk (HR: 1.21, p = 0.032) of divorce across follow-up compared with male controls when controlling for age, region of residency, and year of diagnosis. No significant adjusted risk increase was found for women with MS. ConclusionsWe show that MS is associated with an increased risk of divorce among men, but not women. Our result should be helpful to inform health policy and clinical interventions, such as relationship counselling programs, and highlight the socio-economic burden of the disease.

Incisional hernia and its impact on health-related quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a national prospective cohort study

BackgroundTo evaluate the incidence of incisional hernia (IH) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and its impact on health-related quality of life (HRQoL).MethodFrom June 2006 until June 2016, 152 patients were followed after CRS + HIPEC at Aarhus University Hospital, a single national center. Patients were seen postoperatively in an outpatient clinic at 3, 6, 12, 18, 24, 36 48, and 60 months. Clinical examinations at these follow-up visits were used to evaluate IH events prospectively. The incidence of IH was estimated using competing risk analysis and is presented as the cumulative incidence proportion (CIP). We expected the incidence to be 15% at 12 months. HRQoL was assessed at 12 months by the Short Form (SF-36) questionnaire, which we used to compare patients with an IH to patients without an IH.ResultsThe median follow-up time was 16.6 months [range 0.9–62.0]. During this period, 14/152 (9.2%) patients developed an IH. The 1-year CIP was 5.9% [95% CI 2.9; 10.4] (n = 8), and the 2-year CIP was 9.2% [95% CI 5.3; 14.5] (n = 14). Patients with an IH were significantly older (67 years [range 48–72]) compared to patients without IH (60 years [range 24–75], p ≤ 0.01). The rate of postoperative complications between patients with and without IH was comparable, except that a greater proportion of patients with IH had a fascial dehiscence (21.4%) compared to patients without an IH (3.6%). Reponses to the SF-36 show that patients with an IH report lower HRQoL with regard to Role-physical (mean difference − 32.9 [95% CI − 60.6; − 5.3]) and Role-emotional (mean difference − 20.2 [95% CI − 43.4; 3.1]), meaning a reduction in work and daily activities due to their physical and psychological health. We found no general decrease in HRQoL.ConclusionCRS + HIPEC do not increase the risk of IH as measured within 12 months postoperatively, contrary to expectations. However, patients with an IH report a limitation in daily activities, which can best be explained by changes in physical and psychological health. A larger cohort from multiple centres is necessary to verify our findings.

Fistula recurrence, pregnancy, and childbirth following successful closure of female genital fistula in Guinea: a longitudinal study.

SummaryBackgroundFemale genital fistula is a devastating maternal complication of delivery in developing countries. We sought to analyse the incidence and proportion of fistula recurrence, residual urinary incontinence, and pregnancy after successful fistula closure in Guinea, and describe the delivery-associated maternal and child health outcomes.MethodsWe did a longitudinal study in women discharged with a closed fistula from three repair hospitals supported by EngenderHealth in Guinea. We recruited women retrospectively (via medical record review) and prospectively at hospital discharge. We used Kaplan-Meier methods to analyse the cumulative incidence, incidence proportion, and incidence ratio of fistula recurrence, associated outcomes, and pregnancy after successful fistula closure. The primary outcome was recurrence of fistula following discharge from repair hospital in all eligible women who consented to inclusion and could provide follow-up data.Findings481 women eligible for analysis were identified retrospectively (from Jan 1, 2012, to Dec 31, 2014; 348 women) or prospectively (Jan 1 to June 20, 2015; 133 women), and followed up until June 30, 2016. Median follow-up was 28·0 months (IQR 14·6–36·6). 73 recurrent fistulas occurred, corresponding to a cumulative incidence of 71 per 1000 person-years (95% CI 56·5–89·3) and an incidence proportion of 18·4% (14·8–22·8). In 447 women who were continent at hospital discharge, we recorded 24 cases of post-repair residual urinary incontinence, equivalent to a cumulative incidence of 23·1 per 1000 person-years (14·0–36·2), and corresponding to 10·3% (5·2–19·6). In 305 women at risk of pregnancy, the cumulative incidence of pregnancy was 106·0 per 1000 person-years, corresponding to 28·4% (22·8–35·0) of these women. Of 50 women who had delivered by the time of follow-up, only nine delivered by elective caesarean section. There were 12 stillbirths, seven delivery-related fistula recurrences, and one maternal death.InterpretationRecurrence of female genital fistula and adverse pregnancy-related maternal and child health outcomes were frequent in women after fistula repair in Guinea. Interventions are needed to safeguard the health of women after fistula repair.FundingBelgian Development Cooperation (DGD), Institute of Tropical Medicine of Antwerp (ITM), and Maferinyah Training and Research Center in Rural Health (Guinea).

Nationwide population-based cohort study to assess risk of surgery for adhesive small bowel obstruction following open or laparoscopic rectal cancer resection

BackgroundLaparoscopic surgery has been reported to reduce the formation of adhesions following colorectal surgery. The aim of this nationwide cohort study was to investigate the risk of surgery for adhesive small bowel obstruction (SBO) following open and laparoscopic rectal cancer resection.MethodsPatients undergoing rectal cancer resection between 2005 and 2013 were identified in the Danish Colorectal Cancer Group database. The primary outcome of surgery for adhesive SBO was identified in the Danish National Patient Registry. The risk of surgery for adhesive SBO was estimated as the cumulative incidence proportion, treating death as a competing risk. Cox proportional hazards regression analysis with multivariable adjustment was used to compute hazard ratios (HRs). The secondary outcome was 30‐day mortality after surgery for adhesive SBO.ResultsOf 7657 patients, 340 (4·4 per cent) underwent surgery for adhesive SBO. The 5‐year risk of surgery for adhesive SBO was 4·5 per cent among 4472 patients undergoing open resection and 3·0 per cent among 3185 patients having a laparoscopic resection. Laparoscopic rectal resection was associated with a lower risk of subsequent operation for adhesive SBO (adjusted HR 0·65, 95 per cent c.i. 0·50 to 0·86; P = 0·002). The adjusted HR of mortality after adhesive SBO was 0·84 (0·37 to 1·91; P = 0·671) comparing patients with previous laparoscopic and open resection.ConclusionLaparoscopic rectal cancer resection was associated with a decreased risk of surgery for adhesive SBO. There was a substantial difference in 30‐day mortality after surgery for adhesive SBO based on the surgical approach used at the time of rectal resection.

Perceived stress as a risk factor for dyspepsia: a register-based cohort study.

Dyspepsia is a common condition and has a huge impact on quality of life and working capacity, but its causes are not well understood. An association between stress and dyspepsia has been debated for decades, but the issue has not been resolved. We examined the 3-year risk of redeeming a proton-pump inhibitor or an H2-receptor antagonist as a proxy of dyspepsia according to the level of perceived stress. Perceived stress was measured in a general health survey of 16 124 Danes aged older than 16 years of age in 2010 using Cohen's Perceived Stress Scale. Data were linked individually to national registries, including the Danish National Prescription Registry. The risk of redeeming a proton-pump inhibitor or an H2-receptor antagonist for quintiles of stress level was estimated using Cox proportional hazard regression. In total, 2703 redeemed one of these drugs during the 33 months of follow-up. The cumulative incidence proportion of dyspepsia increased gradually, from 11.6 to 24.9%, with quintiles of stress. After full model adjustment, the four highest stress quintiles had a statistically significantly increased risk of redeeming a drug compared with the lowest stress quintile. The hazard ratios were 1.16 [95% confidence interval (CI): 1.00-1.34] for the second quintile, 1.21 (95% CI: 1.06-1.39) for the third quintile, 1.20 (95% CI: 1.05-1.38) for the fourth quintile, and 1.30 (95% CI: 1.12-1.50) for the fifth quintile. Higher levels of self-reported perceived everyday life stress increased the risk of redeeming a drug for dyspepsia significantly during 33 months of follow-up.

Perceived stress as a risk factor for peptic ulcers: a register-based cohort study.

BackgroundThe association between stress and peptic ulcers has been questioned since the discovery of helicobacter pylori. This study examined whether high perceived everyday life stress was associated with an increased risk of either receiving a triple treatment or being diagnosed with a peptic ulcer.MethodsCohen’s perceived stress scale measured the level of stress in a general health survey in 2010 of 17,525 residents of northern Jutland, Denmark, and was linked with National Danish registers on prescription drugs and hospital diagnoses. Cox proportional hazard regression was used to estimate the risk of either receiving a triple treatment or being diagnosed in a hospital with a peptic ulcer, in relation to quintiles of stress levels.ResultsA total of 121 peptic ulcer incidents were recorded within 33 months of follow-up. The lowest stress group had a cumulative incidence proportion of either receiving triple treatment or being diagnosed with peptic ulcer of approximately 0.4%, whereas the highest stress group had a cumulative incidence proportion of approximately 1.2%. Compared with that of the lowest stress group, those in the highest stress group had a 2.2-fold increase in risk of either receiving triple treatment or being diagnosed with peptic ulcer (HR 2.24; CI 95% 1.16:4.35) after adjustment for age, gender, socioeconomic status, non-steroid anti-inflammatory drug use, former ulcer and health behaviours. There was no difference in risk between the four least stressed quintiles. Subgroup analysis of diagnosed peptic ulcer patients revealed the same pattern as the main analysis, although the results were not significant.ConclusionThe highest level of perceived everyday life stress raised the risk of either receiving triple treatment or being diagnosed with peptic ulcer during the following 33 months more than twice compared with that of the lowest level of perceived stress.

The Inaccuracy of Patient Recall for COPD Exacerbation Rate Estimation and Its Implications: Results from Central Adjudication

COPD exacerbation incidence rates are often ascertained retrospectively through patient recall and self-reports. We compared exacerbation ascertainment through patient self-reports and single-physician chart review to central adjudication by a committee and explored determinants and consequences of misclassification. Self-reported exacerbations (event-based definition) in 409 primary care patients with COPD participating in the International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts (ICE COLD ERIC) cohort were ascertained every 6months over 3 years. Exacerbations were adjudicated by single experienced physicians and an adjudication committee who had information from patient charts. We assessed theaccuracy (sensitivities and specificities) of self-reports and single-physician chart reviewagainst a central adjudication committee (AC) (reference standard). We used multinomial logistic regression and bootstrap stability analyses to explore determinants of misclassifications. The AC identified 648 exacerbations, corresponding to an incidence rate of 0.60±0.83 exacerbations/patient-year and a cumulative incidence proportion of 58.9%. Patients self-reported 841 exacerbations (incidence rate, 0.75 ± 1.01; incidence proportion, 59.7%). The sensitivity and specificity of self-reports were 84%and 76%, respectively, those of single-physician chart review were between 89%and 96%and 87%and 99%, respectively. The multinomial regression model and bootstrap selection showed that having experienced more exacerbations was the only factor consistently associated with underreporting andoverreporting of exacerbations (underreporters: relative risk ratio [RRR], 2.16; 95%CI, 1.76-2.65 and overreporters: RRR, 1.67; 95%CI, 1.39-2.00). Patient 6-month recall of exacerbation events are inaccurate. This may lead to inaccurate estimates of incidence measures and underestimation of treatment effects. The use of multiple data sources combined with event adjudication could substantially reduce sample size requirements and possibly cost of studies. www.ClinicalTrials.gov, NCT00706602.

Research round-up

Research round-up

The incidence of metastatic basal cell carcinoma (mBCC) in Denmark, 1997-2010.

Few data exist on the occurrence of metastatic basal cell carcinoma (mBCC). To identify all cases of mBCC in Denmark over a 14-year period. We searched the Danish National Patient Registry covering all Danish hospitals, the Danish Cancer Registry, the National Pathology Registry and the Causes of Death Registry during the period 1997 to 2010 for potential cases of mBCC registered according to the International classification of diseases ICD-10 and the International Systemized Nomenclature of Medicine (SNOMED). We identified 126,627 patients with a history of primary basal cell carcinoma (BCC) in the registries during the 14-year study period. Using case identifications from the four registries, a total of 170 potential mBCC cases were identified. However, after a pathology review, only five cases could be confirmed, of which three were basosquamous carcinomas. The 14-year cumulative incidence proportion of mBCC was 0.0039% (95% CI 0.0016-0.0083) among individuals with a history of previous BCC (n = 126,627) and 0.0001% (95% CI 0.0000-0.0002) in the general population. MBCC is a rare disease and only a small proportion of potential cases identified in automated clinical databases or registries can be confirmed by pathology and medical record review.

Hip Osteoarthritis and the Risk of All-Cause and Disease-Specific Mortality in Older Women: A Population-Based Cohort Study.

To determine the risk of all-cause and disease-specific mortality among older women with hip osteoarthritis (OA) and to identify mediators in the causal pathway. Data were from the Study of Osteoporotic Fractures, a US population-based cohort study of 9,704 white women age ≥65 years. The analytic sample included women with hip radiographs at baseline (n = 7,889) and year 8 (n = 5,749). Mortality was confirmed through October 2013 by death certificates and hospital discharge summaries. Radiographic hip OA (RHOA) was defined as a Croft grade of ≥2 in at least 1 hip (definite joint space narrowing or osteophytes plus 1 other radiographic feature). The mean ± SD followup time was 16.1 ± 6.2 years. The baseline and year 8 prevalence of RHOA were 8.0% and 11.0%, respectively. The cumulative incidence (proportion of deaths during the study period) was 67.7% for all-cause mortality, 26.3% for cardiovascular disease (CVD) mortality, 11.7% for cancer mortality, 1.9% for gastrointestinal disease mortality, and 27.8% for all other mortality causes. RHOA was associated with an increased risk of all-cause mortality (hazard ratio 1.14 [95% confidence interval 1.05-1.24]) and CVD mortality (hazard ratio 1.24 [95% confidence interval 1.09-1.41]) adjusted for age, body mass index, education, smoking, health status, diabetes, and stroke. These associations were partially explained by the mediating variable of physical function. RHOA was associated with an increased risk of all-cause and CVD mortality among older white women followed up for 16 years. Dissemination of evidence-based physical activity and self-management interventions for hip OA in community and clinical settings can improve physical function and might also contribute to lower mortality.

The impact of ventilation tubes in otitis media on the risk of cholesteatoma on a national level

ObjectiveTo estimate the impact of treatment with middle ear ventilation tube insertion (VTI) in children with otitis media (OM) on the risk of cholesteatoma on a national level. MethodsData were obtained from the Danish National Patient Register, the National Health Service Register and Statistics Denmark. Cumulative incidence proportions were estimated by the Kaplan–Meier method and hazard ratios with Cox regression analysis. The first surgically treated middle ear cholesteatoma in a child (STMEC1) was considered an event. ResultsA total of 217,206 children, born after December 31, 1996, who had VTI from January 1, 1997 to August 31, 2011 were identified. Of these, 374 subsequently had a STMEC1.A corresponding 36,981 children without any VTI were identified for comparison using a random 5% sample of the Danish population. Of these, 5 had a STMEC1.The cumulative incidence proportion with STMEC1 at 12 years of age for children with 0, 1, 2, 3, and ≥4 VTI's was 0.04% (95% confidence interval 0.02–0.12%), 0.21% (0.18–0.26%), 0.35% (0.28–0.43%), 0.40% (0.30–0.54%), and 0.55% (0.44–0.70%), respectively.In the regression model each additional year of age before the first VTI increased the risk of STMEC1 by 54% (47–63%), while each additional year between two successive tube insertions increased the risk by 28% (15–43%). ConclusionWe found that prolonged OM requiring multiple VTIs was associated with an increased risk of STMEC1. Early age at first VTI and short time between two VTIs was associated with a lower risk of STMEC1. This may be the result of reduced time with negative middle ear pressure and OM. However, these findings may be susceptible to selection bias, as age at first VTI and time between VTIs, as well as the outcome variable, STMEC1, may all depend on the underlying indication for VTI.In short the present study suggests that treatment with VTI in children with OM reduces the risk of STMEC1 on a population level. However, for the individual child the absolute risk reduction is very small, and the decision of treatment with VTI must always rely on the symptoms and clinical findings in the individual child.

Cholesteatoma in Danish children – A national study of changes in the incidence rate over 34 years

ObjectiveTo describe temporal trends in the incidence rate of surgically treated middle ear cholesteatoma in Danish children from 1977 to 2010. MethodsData on surgically treated middle ear cholesteatoma was drawn from the Danish National Patient Register.A change in incidence rate over time was examined using Poisson regression analysis, while the cumulative incidence proportion was estimated using life-tables. ResultsA total of 5850 cases of surgically treated middle ear cholesteatoma distributed among 3874 children aged 0–15 years were identified.From 1977 to 2002 the age-standardized incidence rates for first-time surgically treated middle ear cholesteatoma increased from 8 to 15 per 100,000 person-years with an estimated annual increase of 1.8% (95% confidence interval (CI) 1.3–2.2%).From 2002 to 2010 the rates decreased from 15 to 10 per 100,000 person-years with an annual decrease of 5.4% (95% CI 3.2–7.5%).Age-specific incidence rates were at maximum around the age of 9 years during the whole period.The estimated cumulative incidence proportion at age 16 years based on the 2010 age-specific incidence rates was 0.16% (95% CI 0.09–0.32%) compared with 0.20% (95% CI 0.11–0.37%) based on the 2000 age-specific incidence rates. ConclusionFrom 2002 to 2010 there was a decrease in the incidence rate of first-time surgically treated middle ear cholesteatoma. The decrease was preceded by a significant increase in the incidence rate of middle ear ventilation tube insertion. However, further studies are needed to find possible explanations for the decrease.