The Impact of Second Primary Malignancies on Head and Neck Cancer Survivors: A Nationwide Cohort Study

Background

Head and neck cancer (HNC) is associated with a high rate of developing second primary malignancies(SPMs). But the impact on survival remains poorly understood before. Therefore, we want to estimate the impact of SPMs on HNC survivors.

Methods and Findings

Between 1986 and 2008, a total of 9,996 SPMs were recorded for 93,891 patients with an initial diagnosis of HNC by the Taiwan Cancer Registry. Patients were followed with national death registry database to 2011.Using the Kaplan–Meier method, a time-dependent covariate was employed to compare the survival rates between patients with and without SPMs. A Cox proportional hazards model that treated age and sex as confounders was used to examine the hazard ratios of SPMs. The relative survival rates were calculated using age- and sex-specific life tables for the population. Parametric mixture cure fraction models were then employed to estimate the percentage of cancer survivors who would be cured. Use of the Kaplan–Meier method showed that the crude survival rates differed significantly for patients with and patients without SPMs (log-rank test <0.01). For the results of Cox proportional hazards regression analysis, SPMs had a significant influence on survival rates with univariate (HR 2.59,95% CI 2.53to 2.65) and multivariate analysis (HR 2.34, 2.28 to 2.40). Patients with SPMs of nasopharyngeal carcinoma (NPC) had the highest cure rate at 39%, where as esophageal and lung cancer had the worst prognosis, with a cure rate of 11%.

Conclusions

A worse prognosis was found for second primary cancer such as esophageal or lung cancer. Patients and healthcare providers must strongly consider and have a high clinical suspicion of these SPMs.     

Impact of Pacemaker Lead Characteristics on Pacemaker Related Infection and Heart Perforation: A Nationwide Population-Based Cohort Study

Background

Several risk factors for pacemaker (PM) related complications have been reported. However, no study has investigated the impact of lead characteristics on pacemaker-related complications.

Methods and Results

Patients who received a new pacemaker implant from January 1997 to December 2011 were selected from the Taiwan National Health Insurance Database. This population was grouped according to the pacemaker lead characteristics in terms of fixation and insulation. The impact of the characteristics of leads on early heart perforation was analyzed by multivariable logistic regression analysis, while the impact of the lead characteristics on early and late infection and late heart perforation over a three-year period were analyzed using Cox regression. This study included 36,104 patients with a mean age of 73.4±12.5 years. In terms of both early and late heart perforations, there were no significant differences between groups across the different types of fixation and insulations. In the multivariable Cox regression analysis, the pacemaker-related infection rate was significantly lower in the active fixation only group compared to either the both fixation (OR, 0.23; 95% CI, 0.07–0.80; P = 0.020) or the passive fixation group (OR, 0.26; 95% CI, 0.08–0.83; P = 0.023).

Conclusions

There was no difference in heart perforation between active and passive fixation leads. Active fixation leads were associated with reduced risk of pacemaker-related infection.     

Pre-Eclampsia Increases the Risk of Postpartum Haemorrhage: A Nationwide Cohort Study in The Netherlands

Background

Postpartum haemorrhage is a leading cause of maternal morbidity and mortality worldwide. Identifying risk indicators for postpartum haemorrhage is crucial to predict this life threatening condition. Another major contributor to maternal morbidity and mortality is pre-eclampsia. Previous studies show conflicting results in the association between pre-eclampsia and postpartum haemorrhage. The primary objective of this study was to investigate the association between pre-eclampsia and postpartum haemorrhage. Our secondary objective was to identify other risk indicators for postpartum haemorrhage in the Netherlands.

Methods

A nationwide cohort was used, containing prospectively collected data of women giving birth after 19 completed weeks of gestation from January 2000 until January 2008 (n =  1 457 576). Data were extracted from the Netherlands Perinatal Registry, covering 96% of all deliveries in the Netherlands. The main outcome measure, postpartum haemorrhage, was defined as blood loss of ≥1000 ml in the 24 hours following delivery. The association between pre-eclampsia and postpartum haemorrhage was investigated with uni- and multivariable logistic regression analyses.

Results

Overall prevalence of postpartum haemorrhage was 4.3% and of pre-eclampsia 2.2%. From the 31 560 women with pre-eclampsia 2 347 (7.4%) developed postpartum haemorrhage, compared to 60 517 (4.2%) from the 1 426 016 women without pre-eclampsia (odds ratio 1.81; 95% CI 1.74 to 1.89). Risk of postpartum haemorrhage in women with pre-eclampsia remained increased after adjusting for confounders (adjusted odds ratio 1.53; 95% CI 1.46 to 1.60).

Conclusion

Women with pre-eclampsia have a 1.53 fold increased risk for postpartum haemorrhage. Clinicians should be aware of this and use this knowledge in the management of pre-eclampsia and the third stage of labour in order to reach the fifth Millenium Developmental Goal of reducing maternal mortality ratios with 75% by 2015.     

Recurrence of Preeclampsia in Northern Tanzania: A Registry-Based Cohort Study

Objective

Preeclampsia occurs in about 4 per cent of pregnancies worldwide, and may have particularly serious consequences for women in Africa. Studies in western countries have shown that women with preeclampsia in one pregnancy have a substantially increased risk of preeclampsia in subsequent pregnancies. We estimate the recurrence risks of preeclampsia in data from Northern Tanzania.

Methods

A prospective cohort study was designed using 19,811 women who delivered singleton infants at a hospital in Northern Tanzania between 2000and2008. A total of 3,909 women were recorded with subsequent deliveries in the hospital with follow up through 2010. Adjusted recurrence risks of preeclampsia were computed using regression models.

Results

The absolute recurrence risk of preeclampsia was25%, which was 9.2-fold (95% CI: 6.4 - 13.2) compared with the risk for women without prior preeclampsia. When there were signs that the preeclampsia in a previous pregnancy had been serious either because the baby was delivered preterm or had died in the perinatal period, the recurrence risk of preeclampsia was even higher. Women who had preeclampsia had increased risk of a series of adverse pregnancy outcomes in future pregnancies. These include perinatal death (RR= 4.3), a baby with low birth weight (RR= 3.5), or a preterm birth (RR= 2.5). These risks were only partly explained by recurrence of preeclampsia.

Conclusions

Preeclampsia in one pregnancy is a strong predictor for preeclampsia and other adverse pregnancy outcomes in subsequent pregnancies in Tanzania. Women with previous preeclampsia may benefit from close follow-up during their pregnancies.     

Peptic Ulcer Disease in Healthcare Workers: A Nationwide Population-Based Cohort Study

Health care workers (HCWs) in Taiwan have heavy, stressful workloads, are on-call, and have rotating nightshifts, all of which might contribute to peptic ulcer disease (PUD). We wanted to evaluate the PUD risk in HCWs, which is not clear. Using Taiwan’s National Health Insurance Research Database, we identified 50,226 physicians, 122,357 nurses, 20,677 pharmacists, and 25,059 other HCWs (dieticians, technicians, rehabilitation therapists, and social workers) as the study cohort, and randomly selected an identical number of non-HCW patients (i.e., general population) as the comparison cohort. Conditional logistical regression analysis was used to compare the PUD risk between them. Subgroup analysis for physician specialties was also done. Nurses and other HCWs had a significantly higher PUD risk than did the general population (odds ratio [OR]: 1.477; 95% confidence interval [CI]: 1.433–1.521 and OR: 1.328; 95% CI: 1.245–1.418, respectively); pharmacists had a lower risk (OR: 0.884; 95% CI: 0.828–0.945); physicians had a nonsignificantly different risk (OR: 1.029; 95% CI: 0.987–1.072). In the physician specialty subgroup analysis, internal medicine, surgery, Ob/Gyn, and family medicine specialists had a higher PUD risk than other physicians (OR: 1.579; 95% CI: 1.441–1.731, OR: 1.734; 95% CI: 1.565–1.922, OR: 1.336; 95% CI: 1.151–1.550, and OR: 1.615; 95% CI: 1.425–1.831, respectively). In contrast, emergency physicians had a lower risk (OR: 0.544; 95% CI: 0.359–0.822). Heavy workloads, long working hours, workplace stress, rotating nightshifts, and coping skills may explain our epidemiological findings of higher risks for PUD in some HCWs, which might help us improve our health policies for HCWs.     

Long-Term Prognosis of Patients with Carbon Monoxide Poisoning: A Nationwide Cohort Study

Background

Carbon monoxide poisoning (COP) often produces severe complications and can be fatal. Because this topic has not been well delineated, we investigated long-term prognoses of patients with COP (COP^[+]).

Methods

In this retrospective nationwide cohort study, 441 COP^[+] patients and 8820 COP^[−] controls (120) from 1999 to 2010 were selected from Taiwan’s National Health Insurance Research Database.

Results

Thirty-seven (8.39%) COP^[+] patients and 142 (1.61%) controls died (P<0.0001) during follow-up. Incidence rate ratios (IRR) of death were 5.24 times higher in COP^[+] patients than in controls (P<0.0001). The risk of death was particularly high in the first month after COP (IRR: 308.78; 95% confidence interval [CI]: 40.79–2337.56), 1 to 6 months after (IRR: 18.92; 95% CI: 7.69–46.56), and 6–12 months after (IRR: 4.73; 95% CI: 1.02–21.90). After adjusting for age, gender, and selected comorbidities, the hazard ratio of death for COP^[+] patients was still 4.097 times higher than for controls. Moreover, older age (≥30 years old), male gender, diabetes mellitus, hypertension, and low income were also independent mortality predictors.

Conclusions

COP significantly increases the risk for long-term mortality. Early follow-up and secondary prevention of death are needed for patients with COP.     

Effect of Alcoholic Intoxication on the Risk of Inflammatory Bowel Disease: A Nationwide Retrospective Cohort Study

PurposeThis study investigated whether alcoholic intoxication (AI) increases the risk of inflammatory bowel disease (IBD) by using a population-based database in Taiwan.MethodsThis retrospective matched-cohort study included 57 611 inpatients with new-onset AI (AI cohort) and 230 444 randomly selected controls (non-AI cohort). Each patient was monitored for 10 years to individually identify those who were subsequently diagnosed with Crohn disease (CD) and ulcerative colitis (UC) during the follow-up period. Cox proportional hazard regression analysis was conducted to determine the risk of IBD in patients with AI compared with controls without AI.ResultsThe incidence rate of IBD during the 10-year follow-up period was 2.69 per 1 000 person-years and 0.49 per 1 000 person-years in the AI and non-AI cohorts, respectively. After adjustment for age, sex, and comorbidity, the AI cohort exhibited a 3.17-fold increased risk of IBD compared with the non-AI cohort (hazard ratio [HR] = 3.17, 95% confidence interval [CI] = 2.19–4.58). Compared with the non-AI cohort, the HRs of CD and UC were 4.40 and 2.33 for the AI cohort, respectively. After stratification for the severity of AI according to the duration of hospital stay, the adjusted HRs exhibited a significant correlation with the severity; the HRs of IBD were 1.76, 6.83, and 19.9 for patients with mild, moderate, and severe AI, respectively (p for the trend < .0001).ConclusionThe risk of IBD was higher in patients with AI and increased with the length of hospital stay.     

Retinitis Pigmentosa Reduces the Risk of Proliferative Diabetic Retinopathy: A Nationwide Population-Based Cohort Study

Purpose

To study the association between retinitis pigmentosa (RP) and the progression of diabetic retinopathy (DR).

Methods

Using the Longitudinal Health Insurance Database 2000 of Taiwan, we identified individuals with an initial diagnosis for RP during the period of 1997–2008. A non-RP comparison group, 10-fold frequency matched by sex, age, index year and the year of diabetes diagnosed, were randomly selected from the same database. The occurrence of DR was observed for all subjects until the end of 2009. The Kaplan-Meier curves were used to illustrate the cumulative probability of developing DR for the RP group and comparison groups. The hazard ratio (HR) of DR for the RP group relative to the comparison group was estimated using Cox proportional hazards model after adjusting for potential confounders.

Results

The Kaplan-Meier curves were not statistically significant different between the RP group and the comparison group. However, the RP group had a higher cumulative probability of developing DR during the first six to seven years. The cumulative probability kept increasing and became higher in the comparison group but remained unchanged in the RP group. The HR for the RP patients comparing with the comparison group was 0.96 (95% confidence interval (CI) = 0.43–2.14). Stratified by severity, RP was associated with a non-statistically significant reduced risk of proliferative DR (PDR) (HR = 0.70, 95% CI = 0.16–3.14). The HR for non-proliferative DR (NPDR) was 1.08 (95% CI = 0.40–2.86).

Conclusion

In this study, RP was not statistically significant associated with the incidence of DR.     

Risk of Psychiatric Disorders following Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study

Background

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A higher prevalence of psychiatric comorbidities, including depressive disorder, anxiety disorder, and bipolar disorder has been proved in patients with PCOS. However, a clear temporal causal relationship between PCOS and psychiatric disorders has not been well established.

Objective

We explored the relationship between PCOS and the subsequent development of psychiatric disorders including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder.

Methods

We identified patients who were diagnosed with PCOS by an obstetrician-gynecologist in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without PCOS who were matched according to age and sex. The occurrence of subsequent new-onset psychiatric disorders was evaluated in both cohorts based on diagnoses made by psychiatrists.

Results

The PCOS cohort consisted of 5431 patients, and the comparison cohort consisted of 21,724 matched control patients without PCOS. The incidence of depressive disorder (hazard ratio [HR] 1.296, 95% confidence interval [CI] 1.084–.550), anxiety disorder (HR 1.392, 95% CI 1.121–1.729), and sleep disorder (HR 1.495, 95% CI 1.176–1.899) were higher among the PCOS patients than among the patients in the comparison cohort. In addition, a higher incidence of newly diagnosed depressive disorder, anxiety disorder, and sleep disorder remained significantly increased in all of the stratified follow-up durations (0–1, 1–5, ≥5 y).

Conclusions

PCOS might increase the risk of subsequent newly diagnosed depressive disorder, anxiety disorder, and sleep disorder. The risk of newly diagnosed bipolar disorder, which has often been reported in the literature to be comorbid with PCOS, was not significantly elevated.     

New-Onset Atrial Fibrillation Is a Predictor of Subsequent Hyperthyroidism: A Nationwide Cohort Study

Aims

To examine the long-term risk of hyperthyroidism in patients admitted to hospital with new-onset AF. Hyperthyroidism is a well-known risk factor for atrial fibrillation (AF), but it is unknown whether new-onset AF predicts later-occurring hyperthyroidism.

Methods and Results

All patients admitted with new-onset AF in Denmark from 1997–2009, and their present and subsequent use of anti-thyroid medication was identified by individual-level linkage of nationwide registries. Patients with previous thyroid diagnosis or thyroid medication use were excluded. Development of hyperthyroidism was assessed as initiation of methimazole or propylthiouracil up to a 13-year period. Risk of hyperthyroidism was analysed by Poisson regression models adjusted for important confounders such as amiodarone treatment. Non-AF individuals from the general population served as reference. A total of 145,623 patients with new-onset AF were included (mean age 66.4 years [SD ±13.2] and 55.3% males) of whom 3% (4,620 events; 62.2% women) developed hyperthyroidism in the post-hospitalization period compared to 1% (48,609 events; 82% women) in the general population (n = 3,866,889). In both women and men we found a significantly increased risk of hyperthyroidism associated with new-onset AF compared to individuals in the general population. The highest risk was found in middle-aged men and was consistently increased throughout the 13-year period of observation. The results were confirmed in a substudy analysis of 527,352 patients who had thyroid screening done.

Conclusion

New-onset AF seems to be a predictor of hyperthyroidism. Increased focus on subsequent risk of hyperthyroidism in patients with new-onset AF is warranted.     

Long-Term Mortality in Patients Diagnosed with Meningococcal Disease: A Danish Nationwide Cohort Study

Background

In contrast to the case fatality rate of patients diagnosed with meningococcal disease (MD) the long-term mortality in these patients is poorly documented.

Methodology/Principal Findings

We performed a nationwide, population-based cohort study including all Danish patients diagnosed with MD from 1977 through 2006 and alive one year after diagnosis. Data was retrieved from the Danish National Hospital Register, the Danish Civil Registration System and the Danish Register of Causes of Death. For each patient four age- and gender-matched individuals were identified from the population cohort. The siblings of the MD patients and of the individuals from the population cohort were identified. We constructed Kaplan-Meier survival curves and used Cox regression analysis, cumulative incidence function and subdistribution hazard regression to estimate mortality rate ratios (MRR) and analyze causes of death. We identified 4,909 MD patients, 19,636 individuals from the population cohort, 8,126 siblings of MD patients and 31,140 siblings of the individuals from the population cohort. The overall MRR for MD patients was 1.27 (95% confidence interval (CI), 1.12–1.45), adjusted MRR, 1.21 (95% CI, 1.06–1.37). MD was associated with increased risk of death due to nervous system diseases (MRR 3.57 (95% CI, 1.82–7.00). No increased mortality due to infections, neoplasms or cardiovascular diseases was observed. The MRR for siblings of MD patients compared with siblings of the individuals from the population cohort was 1.17 (95% CI, 0.92–1.48).

Conclusions

Patients surviving the acute phase of MD have increased long-term mortality, but the excess risk of death is small and stems mainly from nervous system diseases.     

Educational Inequalities in Acute Myocardial Infarction Incidence in Norway: A Nationwide Cohort Study

Background

Increasing differences in cardiovascular disease (CVD) mortality across levels of education have been reported in Norway. The aim of the study was to investigate educational inequalities in acute myocardial infarction (AMI) incidence and whether such inequalities have changed during the past decade using a nationwide longitudinal study design.

Methods

Data on 141 332 incident (first) AMIs in Norway during 2001–2009 were obtained through the Cardiovascular Disease in Norway (CVDNOR) project. Educational inequalities in AMI incidence were assessed in terms of age-standardised incidence rates stratified on educational level, incidence rate ratios (IRR), relative index of inequality (RII) and slope index of inequality (SII). All calculations were conducted in four gender and age strata: Men and women aged 35–69 and 70–94 years.

Results

AMI Incidence rates decreased during 2001–2009 for all educational levels except in women aged 35–69 among whom only those with basic education had a significant decrease. In all gender and age groups; those with the highest educational level had the lowest rates. The strongest relative difference was found among women aged 35–69, with IRR (95% CI) for basic versus tertiary education 3.04 (2.85–3.24)) and RII (95% CI) equal to 4.36 (4.03–4.71). The relative differences did not change during 2001–2009 in any of the four gender and age groups, but absolute inequalities measured as SII decreased among the oldest men and women.

Conclusions

There are substantial educational inequalities in AMI incidence in Norway, especially for women aged 35–69. Relative inequalities did not change from 2001 to 2009.     

Rheumatoid Arthritis Risk Associated with Periodontitis Exposure: A Nationwide,Population-Based Cohort Study

Background

The risk of periodontitis (PD) is increased in the patient group of rheumatoid arthritis (RA). RA and PD also shared some pathological mechanism. The aim of this study is to investigate the risk of RA associated with PD exposure.

Methods and Findings

This study identified 3 mutually exclusive cohorts using the 1999–2010 Taiwanese National Health Insurance Research Database (NHIRD) to investigate the association between PD and the risk of incident RA. All patients with PD in 2000 were identified from the database of all enrollees as the PD cohort. From the representative database of 1,000,000 enrollees randomly selected in 2010 (LHID2010), individuals without any periodontal disease (PO) during 1999–2010 were selected as the non-PO cohort. Individuals who were not included in the non-PO cohort and received dental scaling (DS) no more than two times per year during 1999–2010 were selected as the DS cohort from LHID2010. Using cox proportional regression analysis, hazard ratios (HRs) with 95% confidence intervals (Cis) were calculated to quantify the association between PD exposure and RA development. In the three-group comparison using the non-PO cohort as reference, we found that the risk of RA was higher in the PD and DS cohorts (HRs, 1.89 and 1.43; 95% CIs, 1.56–2.29 and 1.09–1.87, respectively). For comparisons between two cohorts, the PD cohort had a higher risk of RA than the non-PO and DS cohorts (HRs, 1.91 and 1.35; 95% CIs, 1.57–2.30 and 1.09–1.67, respectively).

Conclusion

PD was associated with an increased risk of RA development.     

The Long-Term Effects of Organophosphates Poisoning as a Risk Factor of CVDs: A Nationwide Population-Based Cohort Study

Background

Organophosphorus pesticides are widely used throughout the world. Because of their ease of availability, organophosphorus compounds are commonly used for self-poisoning in developing countries. The acute effects of exposure to organophosphorus pesticides are well known, but the chronic effects are unclear. Recent studies suggest that abnormalities of the central and peripheral nervous systems persisted for up to 5 years after acute poisoning due to a single large dose of organophosphates (OPs). However, the long-term effects on cardiovascular diseases are poorly understood.

Methodology/Principal Findings

An OPs-exposed cohort (N = 7,561) and an age- and gender-matched control cohort (N = 30,244), both identified from the National Health Insurance Research Database, were compared. We utilized the multivariable Cox proportional model to estimate the risks of developing arrhythmia, coronary artery disease (CAD) and congestive heart failure (CHF). The patients with acute poisoning from OPs had higher incidence rates of arrhythmia (5.89 vs. 3.61 per 1,000 person-years), CAD (9.10 vs. 6.88 per 1,000 person-years), and CHF (3.89 vs. 2.98 per 1,000 person-years) compared with that of the non-OPs poisoning cohort, with a crude subhazard ratio (SHR) of 1.40, 1.13, and 1.12, respectively. Additionally, a significantly higher risk of arrhythmia was observed in the OPs poisoning cohort (adjusted SHR = 1.25) compared with the non-OPs poisoning cohort, particularly in male patients (adjusted SHR = 1.33) and those under 49 years of age (adjusted SHR = 3.16). After accounting for the competing risks of death, there was a higher risk of arrhythmia and CAD during a three year follow-up period (adjusted SHR = 1.50 for arrhythmia; adjusted SHR = 1.10 for CAD). We also found an adjusted SHR of 1.36 associated with developing CHF after 6 years of follow-up for OPs poisoning cohort.

Conclusions

Acute OPs poisoning may continuously impact human health through mechanisms that are unclear. Any supportive measurements that could contribute to a reduction in the risk of heart disease may be beneficial in cases of OPs poisoning survivors.