Increased risk for tooth extraction in primary hyperparathyroidism and hypercalcemia: a population study.

The aim of this study was to analyze dental comorbidities in untreated primary hyperparathyroidism (pHPT). Patients with pHPT subjected to parathyroidectomy (PTX) at Karolinska University Hospital, Stockholm, during 2011-2016 (n = 982) were selected from the Scandinavian Quality Register of Thyroid, Parathyroid and Adrenal surgery and compared to a general population cohort (n = 2944), matched for age and gender. Dental data was obtained from the Swedish Dental Health Registry for the 3 years prior to PTX. The incidence rate ratios (IRRs) of tooth loss by extraction, periodontal interventions, and dental visit rate were analyzed by Poisson regression models. In order to analyze the impact of disease severity, the PHPT cohort was sub-grouped based on preoperative serum levels of ionized calcium (S-Ca2+). The total number of tooth extractions, periodontal interventions, and number of visits were similar in the cohorts. PHPT patients belonging to the quartile with the highest S-Ca2+ (≥ 1.51 mmol/L) had increased risk for tooth extraction (IRR 1.85; 95% CI 1.39-2.46). Female gender independently amplified the risk (IRR 1.341, P < 0.027). This study indicates an association between pHPT and oral disorders reflected by increased tooth loss by extraction related to high S-Ca2. Increased awareness of dental comorbidity in primary hyperparathyroidism may benefit a large group of patients with a common disease through earlier detection and prevention.

Comorbidities, risk factors and outcomes in patients with heart failure and an ejection fraction of more than or equal to 40% in primary care- and hospital care-based outpatient clinics.

OBJECTIVE: The aim of this study is to describe patients with heart failure and an ejection fraction (EF) of more than or equal to 40%, managed in both Primary- and Hospital based outpatient clinics separately with their prognosis, comorbidities and risk factors. Further to compare the heart failure medication in the two groups. DESIGN: We used the prospective Swedish Heart Failure Registry to include 9654 out-patients who had HF and EF ≥40%, 1802 patients were registered in primary care and 7852 in hospital care. Descriptive statistical tests were used to analyze base line characteristics in the two groups and multivariate logistic regression analysis to assess mortality rate in the groups separately. SETTING: The prospective Swedish Heart Failure Registry. SUBJECTS: Patients with heart failure and an ejection fraction (EF) of more than or equal to 40%. MAIN OUTCOME MEASURES: Comorbidities, risk factors and mortality. RESULTS: Mean-age was 77.5 (primary care) and 70.3 years (hospital care) p < 0.0001, 46.7 vs. 36.3% women respectively (p < 0.0001) and EF ≥50% 26.1 vs. 13.4% (p < 0.0001). Co-morbidities were common in both groups (97.2% vs. 92.3%), the primary care group having more atrial fibrillation, hypertension, ischemic heart disease and COPD. According to the multivariate logistic regression analysis smoking, COPD and diabetes were the most important independent risk factors in the primary care group and valvular disease in the hospital care group. All-cause mortality during mean follow-up of almost 4 years was 31.5% in primary care and 27.8% in hospital care. One year-mortality rates were 7.8%, and 7.0% respectively. CONCLUSION: Any co-morbidity was noted in 97% of the HF-patients with an EF of more than or equal to 40% managed at primary care based out-patient clinics and these patients had partly other independent risk factors than those patients managed in hospital care based outpatients clinics. Our results indicate that more attention should be payed to manage COPD in the primary care group. KEY POINTS 97% of heart failure patients with an ejection fraction of more than or equal to 40% managed at primary care based out-patient clinics had any comorbidity. Patients in primary care had partly other independent risk factors than those in hospital care. All-cause mortality during mean follow-up of almost 4 years was higher in primary care compared to hospital care. In matched HF-patients RAS-antagonists, beta-blockers as well as the combination of the two drugs were more seldom prescribed when managed in primary care compared with hospital care.

Severe Periodontitis Is Associated with Myocardial Infarction in Females.

The aim of the present study was to test the hypothesis that there is a sex difference in the association between periodontitis (PD) and a first myocardial infarction (MI). The analysis in the case-control study was based on 785 patients (147 females and 638 males) with a first MI and 792 matched controls (147 females and 645 males), screened for cardiovascular risk factors and subjected to a panoramic dental X-ray. Periodontal status was defined by alveolar bone loss and diagnosed as no PD (≥80% remaining alveolar bone), mild to moderate PD (66% to 79%), or severe PD (<66%). Logistic regression was used when analyzing PD as a risk factor for MI, adjusting for age, smoking, diabetes, education, and marital status. The mean age was 64 ± 7 y for females and 62 ± 8 y for males. Severe PD was more common in female patients than female controls (14 vs. 4%, P = 0.005), with an increased risk for severe PD among female patients with a first MI (odds ratio [OR] = 3.92, 95% confidence interval [CI] =1.53 to 10.00, P = 0.005), which remained (OR = 3.72, 95% CI = 1.24 to 11.16, P = 0.005) after adjustments. Male patients had more severe PD (7% vs. 4%; P = 0.005) than male controls and an increased risk for severe PD (OR = 1.88, 95% CI = 1.14 to 3.11, P = 0.005), but this association did not remain following adjustment (OR = 1.67, 95% CI = 0.97 to 2.84, NS). Severe PD was associated with MI in both females and males. After adjustments for relevant confounders, this association did, however, remain only in females. These data underline the importance of considering poor dental health when evaluating cardiovascular risk, especially in females.

Randomized Clinical Trials on Deep Carious Lesions: 5-Year Follow-up.

Deep caries presents a dilemma in terms of which treatment that will render an optimal prognosis by maintaining pulp vitality with absence of apical pathology. Previously, 2 randomized clinical trials were performed testing the short-term effects of stepwise carious tissue removal versus nonselective carious removal to hard dentin with or without pulp exposure. The aim of this article was to report the 5-y outcome on these previously treated patients having radiographically well-defined carious lesions extending into the pulpal quarter of the dentin but with a well-defined radiodense zone between the carious lesion and the pulp. In this long-term study, 239 of 314 (76.2%) patients were analyzed. The stepwise removal group had a significantly higher proportion of success (60.2%) at 5-y follow-up compared with the nonselective carious removal to hard dentin group (46.3%) ( P = 0.031) when pulp exposures per se were included as failures. Pulp exposure rate was significantly lower in the stepwise carious removal group (21.2% vs. 35.5%; P = 0.014). Irrespective of pulp exposure status, the difference (13.3%) was still significant when sustained pulp vitality without apical radiolucency and unbearable pain was considered (95% confidence interval, 3.1-26.3, P = 0.045). After pulp exposure, only 9% ( n = 4) of the analyzed patients were assessed as successful, indicating that the prognosis is highly dubious following conventional pulp-capping procedures (direct pulp capping or partial pulpotomy) in deep carious lesions in adults. In conclusion, the stepwise carious removal group had a significantly higher proportion of pulps with sustained vitality without apical radiolucency versus nonselective carious removal of deep carious lesions in adult teeth at 5-y follow-up ( ClinicalTrials.gov NCT00187837 and NCT00187850).

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.

Autologous hematopoietic stem cell transplantation in multiple myeloma and lymphoma: an analysis of factors influencing stem cell collection and hematological recovery.

Autologous stem cell transplantation is standard treatment for newly diagnosed younger patients with multiple myeloma and for relapsed or refractory Hodgkin or non-Hodgkin lymphoma. Patient characteristics influencing the yield from stem cell collection and time from transplant to platelet recovery were retrospectively analyzed in 630 consecutive patients, attempting to define adequate amounts of CD34+ cells to collect and reinfuse; 509/630 patients (81%) mobilized the requested CD34+ cell number. Factors influencing the harvest yield were age (P < 0.001) and gender, where 85% of men and 78% of women (P < 0.02) attained the requested stem cell amount. Time to platelet recovery was significantly faster for multiple myeloma patients compared to all other diagnoses (14.6 days compared to 19.8, P < 0.0001). Multiple myeloma patients were older than lymphoma patients but received stem cell transplant up-front as opposed to second line therapy for other patient groups. Multivariate analysis revealed that the most important factor influencing platelet recovery was diagnosis, followed by the amount of reinfused CD34+ cells (P < 0.001, P < 0.05). Blood group O+ had the fastest platelet recovery, whereas blood group A harvested the highest cell amounts. In conclusion, we demonstrate a significant importance of the number of reinfused CD34+ cells on the time to platelet recovery.

Economic evaluation in Sweden of epoetin beta with intravenous iron supplementation in anaemic patients with lymphoproliferative malignancies not receiving chemotherapy.

BACKGROUND AND OBJECTIVE: Functional iron deficiency is one reason for lack of response to erythropoietin treatment. Concomitant intravenous (IV) iron supplementation has the potential to improve response to erythropoietin, allowing a decrease in erythropoietin dose requirements. In a recent study of anaemic, iron-replete patients with lymphoproliferative malignancies (Leukemia, 21, 2007, 627), the haemoglobin (Hb) increase and response rate were significantly greater in patients receiving epoetin beta with concomitant IV iron compared with patients receiving epoetin beta without IV iron (P < 0.05). The present analysis aimed to investigate whether a combination of epoetin beta and IV iron is cost-effective compared with epoetin beta without IV iron. METHODS: This analysis was performed from a Swedish societal perspective as a within-trial evaluation of overall costs (based on differences in drug costs and resource use between groups) and effect (differences in Hb increases) during 16 weeks' treatment with epoetin beta with or without concomitant IV iron. RESULTS AND DISCUSSION: There was an improved response to epoetin beta with IV iron therapy and an almost 2-fold greater increase in Hb levels. Overall mean cost per patient in the epoetin beta with IV iron group was euro5558 and in the epoetin beta without IV iron group was euro6228. Thus, treatment with epoetin beta with IV iron resulted in overall cost savings of about 11% compared with epoetin beta without iron, mainly due to reduced erythropoietin dosages. CONCLUSION: Epoetin beta with concomitant IV iron in anaemic patients with lymphoproliferative malignancies not receiving chemotherapy resulted in better outcomes at lower cost compared with epoetin beta without iron. This suggests that epoetin beta with IV iron is a dominant therapy from a Swedish perspective.

Values and beliefs about consequences related to smoking among pregnant and non-pregnant women.

The purpose of the study was to test a model based on the product of value and belief, called expected utility (EU), on the addictive behaviour of smoking. A total of 40 pregnant and 40 non-pregnant women over a period of 2 weeks performed judgements on values and beliefs about consequences related to smoking for the conditions of continuing and stopping smoking. There were no differences between pregnant and non-pregnant women in the EU of smoking. Differences in expected utility between the conditions of continuing and stopping smoking were larger for health consequences compared with psychological and social consequences and consequences related to pregnancy. Expected utility gives a good description of judgements over time. Values as well as beliefs related to health consequences should be stressed in smoking cessation programmes, especially among pregnant women.

Perceived consequences among pregnant and non-pregnant women of continuing or ceasing to smoke.

OBJECTIVE: To examine the perception of risk of smoking-related psychological and social outcomes, and the effect of pregnancy and intention to stop smoking on the perceived risk. METHODS: Eighty women were asked to make judgments about the probability of outcomes for smoking-related consequences. Four subgroups were created using the variables of pregnancy (pregnant versus not pregnant) and cessation of smoking (intention to stop versus no intention to stop). Judgments were based on the decision to stop and not stop smoking. RESULT: Intention to stop smoking affected the estimated probabilities for the occurrence of consequences for both continuing and stopping smoking, whereas pregnancy did not affect the estimated probabilities. The estimated effect of stopping smoking was statistically significant. CONCLUSION: Health messages about smoking for all population groups should consider both future risk of mortality and immediate quality-of-life effects of smoking.

Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study.

This randomized study assessed if intravenous iron improves hemoglobin (Hb) response and permits decreased epoetin dose in anemic (Hb 9-11 g/dl), transfusion-independent patients with stainable iron in the bone marrow and lymphoproliferative malignancies not receiving chemotherapy. Patients (n=67) were randomized to subcutaneous epoetin beta 30 000 IU once weekly for 16 weeks with or without concomitant intravenous iron supplementation. There was a significantly (P<0.05) greater increase in mean Hb from week 8 onwards in the iron group and the percentage of patients with Hb increase >or=2 g/dl was significantly higher in the iron group (93%) than in the no-iron group (53%) (per-protocol population; P=0.001). Higher serum ferritin and transferrin saturation in the iron group indicated that iron availability accounted for the Hb response difference. The mean weekly patient epoetin dose was significantly lower after 13 weeks of therapy (P=0.029) and after 15 weeks approximately 10 000 IU (>25%) lower in the iron group, as was the total epoetin dose (P=0.051). In conclusion, the Hb increase and response rate were significantly greater with the addition of intravenous iron to epoetin treatment in iron-replete patients and a lower dose of epoetin was required.

Favourable long term prognosis in stable angina pectoris: an extended follow up of the angina prognosis study in Stockholm (APSIS).

OBJECTIVE: To evaluate the long term prognosis of patients with stable angina pectoris. DESIGN: Registry based follow up (median 9.1 years) of patients participating in the APSIS (angina prognosis study in Stockholm), which was a double blind, single centre trial of antianginal drug treatment. PATIENTS: 809 patients (31% women) with stable angina pectoris < 70 (mean (SD) 59 (7) years at inclusion) and an age and sex matched reference population from the same catchment area. INTERVENTIONS: Double blind treatment with metoprolol or verapamil during 3.4 years (median), followed by referral for usual care with open treatment. MAIN OUTCOME MEASURES: Cardiovascular (CV) death and non-fatal myocardial infarction (MI) in the APSIS cohort and total mortality in comparison with reference subjects. RESULTS: 123 patients died (41 MI, 36 other CV causes) and 72 had non-fatal MI. Mortality (19% v 6%, p < 0.001) and fatal MI (6.6% v 1.6%, p < 0.001) were increased among male compared with female patients. Diabetes, previous MI, hypertension, and male sex independently predicted CV mortality (p < 0.001). Diabetes greatly increased the risk in a small subgroup of female patients. Male patients had higher mortality than men in the reference population during the first three years (cumulative absolute difference 3.8%) but apparently not thereafter. Female patients had similar mortality to women in the reference population throughout the 9.1 years of observation. CONCLUSIONS: Female patients with stable angina had similar mortality to matched female reference subjects but male patients had an increased risk. Diabetes, previous MI, hypertension, and male sex were strong risk factors for CV death or MI.

Effect of intravenous nimodipine on blood pressure and outcome after acute stroke.

BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.

Epoetin beta in the treatment of anemia in patients with advanced gastrointestinal cancer.

PURPOSE: The possibility that epoetin beta (EPO) could increase hemoglobin (B-Hb) levels and improve quality of life (QoL) in patients with advanced gastrointestinal cancers was investigated. PATIENTS AND METHODS: One hundred patients with gastric, pancreatic, biliary, or colorectal cancers and subnormal B-Hb levels were included in a randomized study to test low-dose EPO (2,000 U subcutaneously thrice weekly [2,000 group]) against a higher dose (10,000 U times three [10,000 group]). Eighty-four patients were treated with chemotherapy. QoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 instrument. RESULTS: At baseline, mean B-Hb was 108 g/L with no difference between the groups. In the 10,000 group, an increase in B-Hb (>10 g/L) was seen in 30 (73%) patients treated with chemotherapy, after a median of 4 weeks, whereas a corresponding increase in the 2,000 group was seen in 15 (30%) patients after a median of 10 weeks (P < .001). A difference in the proportion of responders (five of eight v one of eight) was also seen in the group of patients not treated with chemotherapy. The proportion of responders was independent of baseline endogenous serum EPO level or observed/predicted log10 serum (S)-EPO levels. Patients who demonstrated improved B-Hb levels also showed improvements in QoL parameters. Tumor response was usually also associated with QoL improvements. CONCLUSION: Treatment with EPO at a dose of 10,000 U thrice weekly can rapidly and safely increase B-Hb levels in a high proportion of patients with advanced gastrointestinal cancers. QoL is influenced by the B-Hb increase, but also by the course of the underlying malignancy. It is therefore difficult to define clearly the clinical relevance of the B-Hb increase as such.

Effects of metoprolol vs verapamil in patients with stable angina pectoris. The Angina Prognosis Study in Stockholm (APSIS)

OBJECTIVE: To study long-term treatment effects of metoprolol or verapamil on combined cardiovascular end points and psychological variables in patients with stable angina pectoris. DESIGN: Randomized, double-blind, double-dummy trial. PATIENTS: The study included 809 patients under 70 years of age with stable angina pectoris. The mean age of the patients was 59 +/- 7 years and 31% were women. Exclusion criteria were myocardial infarction within the previous 3 years and contraindications to beta-blockers and calcium antagonists. The patients were followed between 6 and 75 months (median 3.4 years and a total of 2887 patient years). INTERVENTION: The patients were treated with either metoprolol (Seloken ZOC 200 mg o.d.) or verapamil (Isoptin Retard 240 b.i.d.). Acetylsalicylic acid, ACE inhibitors, lipid lowering drugs and long acting nitrates were allowed in the study. END POINTS: Death, non-fatal cardiovascular events including acute myocardial infarction, incapacitating or unstable angina, cerebrovascular or peripheral vascular events. Psychological variables reflecting quality of life i.e. psychosomatic symptoms, sleep disturbances and an evaluation of overall life satisfaction. RESULTS: Combined cardiovascular events did not differ and occurred in 30.8% and 29.3% of metoprolol and verapamil treated patients respectively. Total mortality in metoprolol and verapamil treated patients was 5.4 and 6.2%, respectively. Cardiovascular mortality was 4.7% in both groups. Non-fatal cardiovascular events occurred in 26.1 and 24.3% of metoprolol and verapamil-treated patients, respectively. Psychosomatic symptoms and sleep disturbances were significantly improved in both treatment groups. The magnitudes of change were small and did not differ between treatments. Life satisfaction did not change on either drug. Withdrawals due to side effects occurred in 11.1 and 14.6% respectively. CONCLUSION: This long term study indicates that both drugs are well tolerated and that no difference was shown on the effect on mortality, cardiovascular end points and measures of quality of life.

Regular hypnotic drug treatment in a sample of 32,679 Swedes: associations with somatic and mental health, inpatient psychiatric diagnoses and suicide, derived with automated record-linkage.

We studied Swedish survey responders who reported regular treatment with hypnotic drugs, to find associations to perceived health problems, inpatient psychiatric diagnoses, and subsequent suicide. Among 32,679 sampled Swedes, 26,952 (83%) participated, 500 of which (2%) reported regular hypnotic drug treatment. The rate of treatment was higher in women, and increased by age in both sexes. The major findings were high odds of concurrent psychoactive drug treatments, nervous symptoms and insomnia, as well as high rates of circulatory and musculoskeletal conditions in both sexes, with indicators of disability and sleep-disturbing symptoms. During a 15-year period, 35% of the men and 21% of the women who reported regular hypnotic drug treatment had also been admitted to inpatient psychiatric care. Substance abuse was diagnosed in 20% of the men and 4.3% of the women reporting hypnotic drug treatment. In multiple logistic regression models, the highest odds for regular hypnotic drug treatment were incurred by recent/current insomnia, nervous symptoms, and other psychoactive drug treatment. We conclude that therapy was principally given according to some current peer guidelines. Yet, further research is needed into the risk/benefit ratio of sustained hypnotic drug therapy in patients with qualifying somatic and psychiatric disorders to obtain a more uniformly based consensus.

Clinical significance of mucosal inflammation of the vermiform appendix.

In 942 emergency appendectomies, the clinical data of 77 patients with inflammatory changes confined to the mucosa of the vermiform appendix were compared with data from 622 patients with diffuse acute appendicitis and 243 patients without evidence of inflammation in the appendix. In all cases, routine histologic sections of the specimens were reviewed. Of the 77 patients with mucosal appendiceal inflammation, 50 were female and 50% were under 17 years of age. In several clinical aspects, such as incidence of nausea, vomiting, migration of pain, and localized muscular rigidity, there existed significant differences between patients with mucosal inflammation and patients with diffuse appendicitis. Conversely, no statistically significant differences were found between patients with mucosal inflammation and patients without evident appendiceal inflammation. These results in addition to the frequent finding of histologically indistinguishable changes in appendices removed incidentally suggest that the condition is not responsible for the actual complaint.

Impurities of 99mTc-generators.

The impurities present after use in 99Mo- 99mTc-generators produced by four different manufacturers were investigated by means of the energy spectrum and half-life measurements. The generators produced with fission contained only a few impurities, and the half-lives of their nuclides were relatively short. The only generator manufactured using neutron bombardment contained several nuclides whose half-lives were in a range of a few months, but also a 60Co nuclide whose long half-life may give rise to difficulties in destroying the generator.