Invasive Dental Treatment and Risk for a First Myocardial Infarction.

Invasive dental treatment is suggested to be associated with an increased risk for the development of cardiovascular events. We tested the hypothesis that the incidence of a first myocardial infarction (MI) within 4 wk after invasive dental treatments is increased. A registry-based case-control study within nationwide health care and population registries in Sweden was performed. The case patients included 51,880 individuals with a first fatal or nonfatal MI between January 2011 and December 2013. For each case, 5 control subjects, free from prior MI and matched for age, sex, and geographic area of residence, were randomly selected from the national population registry through risk set sampling with replacement, resulting in 246,978 control subjects. Information on dental treatments was obtained from the Dental Health Register, and the procedures were categorized into invasive dental treatments or other dental treatments. Conditional logistic regression was used to estimate odds ratios (ORs) for MI with corresponding 95% confidence intervals (CIs). In addition to the matching variables, adjustments were made for the following confounders: diabetes, previous cardiovascular disease (CVD), CVD drug treatment, education, and income. The mean age for case patients and controls subjects was 72.6 ± 13.0 y and 72.3 ± 13.0 y, respectively. Case patients more often had previous CVD (49% vs. 23%; P < 0.001) and diabetes (19% vs. 11%; P < 0.001) and received more treatment with CVD drugs (68% vs. 56%; P < 0.001) than control subjects. There was no association between invasive dental treatments during the 4 wk preceding the MI index date (crude OR = 0.99; 95% CI, 0.92 to 1.06; adjusted for confounders OR = 0.98; 95% CI, 0.91 to 1.06). This study did not support the hypothesis of an increased incidence of MI after recent invasive dental treatment.

Estimated drinking water fluoride exposure and risk of hip fracture: a cohort study.

The cariostatic benefit from water fluoridation is indisputable, but the knowledge of possible adverse effects on bone and fracture risk due to fluoride exposure is ambiguous. The association between long-term (chronic) drinking water fluoride exposure and hip fracture (ICD-7-9: '820' and ICD-10: 'S72.0-S72.2') was assessed in Sweden using nationwide registers. All individuals born in Sweden between January 1, 1900 and December 31, 1919, alive and living in their municipality of birth at the time of start of follow-up, were eligible for this study. Information on the study population (n = 473,277) was linked among the Swedish National In-Patient Register (IPR), the Swedish Cause of Death Register, and the Register of Population and Population Changes. Estimated individual drinking water fluoride exposure was stratified into 4 categories: very low, < 0.3 mg/L; low, 0.3 to 0.69 mg/L; medium, 0.7 to 1.49 mg/L; and high, ≥ 1.5 mg/L. Overall, we found no association between chronic fluoride exposure and the occurrence of hip fracture. The risk estimates did not change in analyses restricted to only low-trauma osteoporotic hip fractures. Chronic fluoride exposure from drinking water does not seem to have any important effects on the risk of hip fracture, in the investigated exposure range.

Use of serotonin reuptake inhibitors in patients with psoriasis is associated with a decreased need for systemic psoriasis treatment: a population-based cohort study.

OBJECTIVE: To investigate whether psoriasis is affected by the use of serotonin reuptake inhibitors (SSRIs). DESIGN: A population-based cohort study. SETTING: The general adult population with plaque psoriasis in Sweden between 1997 and 2006. SUBJECTS: A total of 69 830 patients with plaque psoriasis were identified in the National Patient Register. Whether study subjects were exposed to SSRIs was identified through the Swedish Prescribed Drug Register. The SSRI-exposed subjects (n = 1282) had a prescription for SSRIs dispensed twice during 6 months at a Swedish pharmacy between 1 July 2006 and 1 April 2008, with a wash-out period of 1 year or longer. The reference subjects (n = 1282), who were not exposed to SSRIs, were matched for age, county of residence, sex, psoriasis severity and seasonal variation. MAIN OUTCOME MEASURE: Change in psoriasis severity defined by switching between nonsystemic and systemic psoriasis treatments 6 months after exposure to SSRIs. RESULTS: The risk of switching from nonsystemic to systemic psoriasis treatments was significantly decreased in the SSRI-exposed group (odds ratio 0.44, 95% confidence interval 0.28-0.68). CONCLUSION: SSRI use in patients with psoriasis is associated with a decreased need for systemic psoriasis treatment.

Subacute cutaneous lupus erythematosus and its association with drugs: a population-based matched case-control study of 234 patients in Sweden.

BACKGROUND: Numerous case reports about drug-induced (DI) subacute cutaneous lupus erythematosus (SCLE) have been published. Various drug types with different latencies has been proposed as triggers for this autoimmune skin disease. OBJECTIVES: To evaluate the association between exposure to certain suspected drugs (previously implicated to induce SCLE) and a subsequent diagnosis of SCLE. METHODS: We performed a population-based matched case-control study in which all incident cases of SCLE (n=34) from 2006 to 2009 were derived from the National Patient Register. The control group was selected from the general population, matched (1:10) for gender, age and county of residence. The data were linked to the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the association between exposures to certain suspected drugs and the development of SCLE. RESULTS: During the 6 months preceding SCLE diagnosis, 166 (71%) of the patients with SCLE had at least one filled prescription of the suspected drugs. The most increased ORs were found for terbinafine (OR 52.9, 95% CI 6.6-∞), tumour necrosis factor-α inhibitors (OR 8.0, 95% CI 1.6-37.2), antiepileptics (OR 3.4, 95% CI 1.9-5.8) and proton pump inhibitors (OR 2.9, 95% CI 2.0-4.0). CONCLUSIONS: We found an association between drug exposure and SCLE. More than one third of the SCLE cases could be attributed to drug exposure. No significant OR was found for thiazides, which might be due to longer latency and therefore missed with this study design. DI-SCLE is reversible once the drug is discontinued, indicating the importance of screening patients with SCLE for potentially triggering drugs. A causal relationship cannot be established from this study and the underlying pathogenesis remains unclear.

Increased risk of cancer among 3663 patients with cutaneous lupus erythematosus: a Swedish nationwide cohort study.

BACKGROUND: Other autoimmune diseases have been associated with higher risks for cancer, and numerous case reports of cutaneous lupus erythematosus (CLE) and different cancer types are available. OBJECTIVES: To estimate the overall and specific cancer risks in a nationwide cohort study of patients diagnosed with CLE in Sweden and compare that risk with that in a control cohort without CLE. METHODS: A cohort of 3663 individuals with CLE and a matched control cohort from the general population (three controls to each CLE case) without a diagnosis of CLE were derived from the Swedish National Patient Register, 1997-2007, and were electronically linked to the Swedish Cancer Register and the Swedish Cause of Death Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to compare the observed vs. the expected numbers of cancers. RESULTS: A total of 183 incident cancers occurred within the observation interval, yielding a HR of 1·8 (95% CI 1·5-2·2) for cancer overall. Median follow-up was 4·1 years. About a fourfold risk increase was seen for buccal cancer, lymphomas, respiratory cancer and nonmelanoma skin cancer. CONCLUSIONS: Patients with CLE appear to have an elevated risk for certain cancer types, an increase that remains when excluding patients also diagnosed with systemic lupus erythematosus. Our findings point to the importance of counselling about not smoking and sun avoidance, and underscore the need for specialized monitoring of this patient group along with bench-to-bedside research efforts to clarify pathogenesis.

Cutaneous lupus erythematosus and the association with systemic lupus erythematosus: a population-based cohort of 1088 patients in Sweden.

BACKGROUND: Studies reporting the incidence of isolated cutaneous lupus erythematosus (CLE) are rare. OBJECTIVES: To examine in a population-based cohort study the incidence of CLE and its subsets in Sweden. The short-term probability of receiving an additional diagnosis of systemic lupus erythematosus (SLE) is also assessed. METHODS: A population-based open cohort study including all patients with CLE [International Classification of Diseases (ICD) code, ICD-10: L93] in Sweden, 2005-2007. Patients (n=1088) were identified in the Swedish National Patient Register. RESULTS: The incidence of CLE was 4·0/100,000; the female/male ratio was 3:1. Mean age at disease onset was 54 years. The most common subset was discoid lupus erythematosus (DLE) (80%, n = 868). A quarter of the patients (24%, n=260) were already diagnosed with SLE at the time they were diagnosed with CLE. During the whole observation period (2005-2007), an additional 18% (n = 107) were diagnosed with SLE, the probability of receiving an additional SLE diagnosis being highest for the subacute CLE (SCLE) subset. CONCLUSIONS: This is the first nationwide epidemiological study on CLE. We found the incidence of CLE to be about equal to that of SLE, and found a higher short-term probability for receiving an additional diagnosis with SLE than previously described for CLE. Subsets other than DLE and SCLE were rarely reported in our system; an update of the ICD codes for this diagnostic group could increase reporting of these more unusual cases. Our study clarifies that monitoring and follow-up are called for in this patient group due to the risk for SLE, and underscores the need for clear criteria for risk assessment in the large group of patients with CLE who also fulfil criteria for SLE.

No survival benefit from early-start dialysis in a population-based, inception cohort study of Swedish patients with chronic kidney disease.

OBJECTIVE: To investigate how the timing of dialysis initiation is associated with mortality. DESIGN: Population-based, prospective, observational cohort study. SETTING: Clinical laboratories (n = 69) provided information on all patients in Sweden whose serum creatinine level for the first time and exceeded 3.4 mg dL(-1) (men) or 2.8 mg dL(-1) (women) between 20 May 1996 and 31 May 1998. SUBJECTS: All patients (n = 901), aged 18-74 years, in whom the cause of serum creatinine elevation was chronic kidney disease, were included in the study; participants were interviewed and followed for 5-7 years. MAIN OUTCOME MEASURES: Information on date of death was obtained from a national Swedish population register. Early-start dialysis [estimated glomerular filtration rate from serum creatinine (eGFR) ≥7.5 mL min(-1) per 1.73 m(2)] was compared to late start of dialysis (eGFR <7.5 mL min(-1) per 1.73 m(2)), and no dialysis. Relative risk [hazard ratio (HR)] of death was modelled with time-dependent multivariate Cox proportional hazards regression. RESULTS: Mean eGFR was 16.1 mL min(-1) per 1.73 m(2) at inclusion and 7.6 mL min(-1) per 1.73 m(2) at the start of dialysis. Among the 385 patients who started dialysis late, 36% died during follow-up compared to 52% of 323 who started early. The adjusted HR for death was 0.84 [95% confidence interval (CI) 0.64, 1.10] among late versus early starters. The mortality among nondialysed patients increased significantly at eGFR below 7.5 mL min(-1) per 1.73 m(2) (HR 4.65; 95% CI 2.28, 9.49; compared to eGFR 7.5-10 mL min(-1) per 1.73 m(2)). After the start of dialysis, the mortality rate further increased. Compared to nondialysed patients with eGFR ≤15 mL min(-1) per 1.73 m(2), adjusted HR was 2.65 (95% CI 1.80, 3.89) for patients receiving dialysis. CONCLUSION: We found no survival benefit from early initiation of dialysis.

Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders.

INTRODUCTION: Although it has been hypothesised that metal welding and flame cutting are associated with an increased risk for Parkinson's disease due to manganese released in the welding fume, few rigorous cohort studies have evaluated this risk. METHODS: The authors examined the relation between employment as a welder and all basal ganglia and movement disorders (ICD-10, G20-26) in Sweden using nationwide and population based registers. All men recorded as welders or flame cutters (n = 49,488) in the 1960 or 1970 Swedish National Census were identified and their rates of specific basal ganglia and movement disorders between 1964 and 2003 were compared with those in an age and geographical area matched general population comparison cohort of gainfully employed men (n = 489,572). RESULTS: The overall rate for basal ganglia and movement disorders combined was similar for the welders and flame cutters compared with the general population (adjusted rate ratio (aRR) = 0.91 (95% CI 0.81 to 1.01). Similarly, the rate ratio for PD was 0.89 (95% CI 0.79 to 0.99). Adjusted rate ratios for other individual basal ganglia and movement disorders were also not significantly increased or decreased. Further analyses of Parkinson's disease by attained age, time period of follow up, geographical area of residency, and educational level revealed no significant differences between the welders and the general population. Rates for Parkinson's disease among welders in shipyards, where exposures to welding fumes are higher, were also similar to the general population (aRR = 0.95; 95% CI 0.70 to 1.28). CONCLUSION: This nationwide record linkage study offers no support for a relation between welding and Parkinson's disease or any other specific basal ganglia and movement disorders.

Swedish registers to examine drug safety and clinical issues in RA.

Data from several different monitoring systems are examined. The potential for registers based on data obtained from clinical practice, and linkage of such data to national health and population registers, is discussed. The approach described is a possible prototype for long term surveillance systems needed for the safe introduction of new treatments.

Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists.

BACKGROUND: Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s. OBJECTIVE: To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials. METHODS: A population based study of three RA cohorts (one prevalent, admitted to hospital 1990-2003 (n = 53,067), one incident, diagnosed 1995-2003 (n = 3703), and one treated with TNF antagonists 1999-2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003. RESULTS: With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20-50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (-20%) and colorectal cancer (-25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA. CONCLUSION: The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.

Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists.

BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear. OBJECTIVE: To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA. METHODS: A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53,067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed. RESULTS: Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas. CONCLUSION: Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.

Results from a nationwide postmarketing cohort study of patients in Sweden treated with etanercept.

OBJECTIVES: To describe a nationwide system for postmarketing follow up of new antirheumatic drugs in Sweden, and to analyse safety and effectiveness in an etanercept treated patient cohort. METHODS: Etanercept became available in Sweden for prescribing on a named patient basis in 1999. All patients treated were included in a follow up of intensified adverse event reporting and recording of clinical outcome during 24 months, according to the EULAR core set. RESULTS: The mean (SD) disease activity score (DAS 28) value at inclusion among 820 patients recruited on a named patient basis during year 1 was 5.99 (1.19). After two years, 21% (n = 172) of these patients had discontinued the treatment. Of the remaining 648 patients, 68% (n = 442) responded to the treatment. However, in 55% of the responders, the disease activity was intermediate or high (mean DAS 28, 3.37 (1.20)). In all, 540 adverse events were reported in 421 adverse drug reaction (ADR) reports, in 294 patients. The events in 80 reports (19%) were serious. Twenty two per cent of the events were infections, of which 24% (n = 29) were serious. The incidence of serious adverse events remained constant over time. CONCLUSIONS: At start of etanercept treatment, patients had high disease activity. Activity remained high in a large proportion of the responding patients. Although serious ADRs occurred during late phases of treatment, no unexpected safety problems arose. No specific indicators of ADR risk were found. The monitoring system that was established may be useful in future postmarketing surveillance.

Acetaminophen, aspirin, and chronic renal failure.

BACKGROUND: Several epidemiologic studies have demonstrated an association between heavy consumption of nonnarcotic analgesics and the occurrence of chronic renal failure, but it is unclear which is the cause and which is the effect METHODS: In a nationwide, population-based, case-control study of early-stage chronic renal failure in Sweden, face-to-face interviews were conducted with 926 patients with newly diagnosed renal failure and 998 control subjects, of whom 918 and 980, respectively, had complete data. We used logistic-regression models to estimate the relative risks of disease-specific types of chronic renal failure associated with the use of various analgesics RESULTS: Aspirin and acetaminophen were used regularly by 37 percent and 25 percent, respectively, of the patients with renal failure and by 19 percent and 12 percent, respectively, of the controls. Regular use of either drug in the absence of the other was associated with an increase by a factor of 2.5 in the risk of chronic renal failure from any cause. The relative risks rose with increasing cumulative lifetime doses, rose more consistently with acetaminophen use than with aspirin use, and were increased for most disease-specific types of chronic renal failure. When we disregarded the recent use of analgesics, which could have occurred in response to antecedents of renal disease, the associations were only slightly attenuated CONCLUSIONS: Our results are consistent with the existence of exacerbating effects of acetaminophen and aspirin on chronic renal failure. However, we cannot rule out the possibility of bias due to the triggering of analgesic consumption by predisposing conditions.

Comparison of surrogate with self-respondents regarding medical history and prior medication use.

BACKGROUND: The self-report of medical history and medication use is a common feature of epidemiological research. METHODS: In a unique re-interview study, we evaluated the concordance of medical conditions and past medication use reported in two similar interviews 5 years apart. RESULTS: In 196 re-interviews with the subjects themselves, and in 107 with next-of-kin of subjects who died after the first interview, agreement was good or excellent (kappa > or =0.40) for 90% (9/10) of the conditions asked about in the personal medical history for both next-of-kin and self-respondents. Agreement was excellent (kappa >0.75) for two conditions, high blood pressure and hysterectomy, among self-respondents. Self- and surrogate respondents also showed similar reproducibility for prescription medications, but next-of-kin respondents tended to have poor agreement (kappa <0.40) for over-the-counter (OTC) medications such as antacids, antihistamines, and analgesics. Next-of-kin also less reliably reported a family history of cancer. When analyses were stratified by type of surrogate respondent, concordance between the two interviews was generally higher for spouses than for other surrogate respondents. CONCLUSIONS: This research demonstrates that personal medical history and prescription medication use may be as reliably reported by next-of-kin as self-respondents, but suggests that additional information may be needed to validate measures of OTC medication use and family history of cancer for next-of-kin respondents, possibly through the review of hospital records.

Area under the serum creatinine time-curve is a strong predictor of chronic renal allograft rejection.

BACKGROUND: A number of risk factors for chronic renal allograft rejection have been identified; in particular the number and severity of acute rejections, hypertension, hyperlipidemia, and insufficient immunosuppression. METHODS: In a retrospective case control study, all histologically confirmed cases of chronic rejection (n=45) that occurred between 1985 and 1993 among patients transplanted at Huddinge Hospital were compared with twice as many controls. Determinants such as donor age and sex, HLA-mismatch, cold ischemia time, recipient age and sex, body mass index, cause of renal disease, time undergoing dialysis, condition of blood vessels at surgery, time of onset, number of acute rejection episodes during the first 3 months, area under the serum creatinine versus time curve (AUC(Creatinine)), blood pressure, blood lipids, and cyclosporine concentrations at various times after the transplantation were also compared. Additional data were obtained from a questionnaire, concerning 79% of the cases and controls. RESULTS: Cases and controls were similar with regard to most determinants, that is, blood pressure, blood lipids, and average cyclosporine concentrations. The main outstanding risk factor for chronic rejection was the time-averaged creatinine (AUC(Creatinine)) value between day 22 and 3 months after transplantation. The adjusted odds ratio for chronic rejection increased stepwise from 1.1 to 9.2, when AUC(Creatinine) increased from < 150 to >300 micromol/l. The number of acute rejection episodes and number of HLA-mismatches also had a significant effect on the risk of chronic rejection. CONCLUSIONS: To reduce the risk of developing chronic rejection after renal transplantation acute rejection episodes during the first 3 months should be avoided as much as possible.