National Knowledge-Driven Management of Obstructive Sleep Apnea-The Swedish Approach.

INTRODUCTION: This paper describes the development of "Swedish Guidelines for OSA treatment" and the underlying managed care process. The Apnea Hypopnea Index (AHI) is traditionally used as a single parameter for obstructive sleep apnea (OSA) severity classification, although poorly associated with symptomatology and outcome. We instead implement a novel matrix for shared treatment decisions based on available evidence. METHODS: A national expert group including medical and dental specialists, nurses, and patient representatives developed the knowledge-driven management model. A Delphi round was performed amongst experts from all Swedish regions (N = 24). Evidence reflecting treatment effects was extracted from systematic reviews, meta-analyses, and randomized clinical trials. RESULTS: The treatment decision in the process includes a matrix with five categories from a "very weak"" to "very strong" indication to treat, and it includes factors with potential influence on outcome, including (A) OSA-related symptoms, (B) cardiometabolic comorbidities, (C) frequency of respiratory events, and (D) age. OSA-related symptoms indicate a strong incitement to treat, whereas the absence of symptoms, age above 65 years, and no or well-controlled comorbidities indicate a weak treatment indication, irrespective of AHI. CONCLUSIONS: The novel treatment matrix is based on the effects of treatments rather than the actual frequency of respiratory events during sleep. A nationwide implementation of this matrix is ongoing, and the outcome is monitored in a prospective evaluation by means of the Swedish Sleep Apnea Registry (SESAR).

Newly initiated opioid treatment and the risk of fall-related injuries. A nationwide, register-based, case-crossover study in Sweden.

BACKGROUND: There is growing epidemiological evidence that opioids may increase the risk of unintentional injuries and it is plausible that the time of initiation is most critical in that respect. Studies on fall-related injuries remain few, limited and mostly focused on specific groups of elderly patients. OBJECTIVE: The objective of this study was to assess the short-term effects of newly prescribed opioids on the risk of fall-related injuries in the general adult population. METHODS: A case-crossover design was applied on national register data linking, at the individual level, fall-injury information involving adults aged 18 years and above identified in the Swedish National Inpatient Register (during the period 1 May 2006 to 31 December 2009) and dispensed drugs from the Swedish Prescribed Drug Register (n=167,257 cases with a first fall-related injury). All types of opioid substances were considered, classified according to the Anatomical Therapeutic Chemical (ATC) classification system. We investigated newly dispensed opioids 28 days preceding the injury, compared with an earlier, and equally long, control period following a 3-month washout period. Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI). The analyses were also conducted stratified by age group, by type of fall and for each period of 1 week during the 28-day period. RESULTS: From among the fall-injured patients, 7,450 patients (4.5%) had a new opioid dispensation within 28 days prior to the injury, of which the most frequent types were tramadol (2.0%) and codeine (1.1%). Consistently increased risks of fall-related injuries associated with a new prescription of any opioid were found and they were most pronounced among young adults, 18-29 years of age (OR, 7.17; 95% CI 5.04-10.2). The closer the dispensation date to the injury, the higher the odds: an OR of 5.14 (95% CI 4.76-5.55) during the first week of opioid treatment and 1.23 (95% CI 1.10-1.38) for the fourth week. Of the documented falls, the risk was most pronounced for falls from 'another, high level' (OR, 5.33; 95% CI 3.99-7.10). CONCLUSIONS: Newly prescribed opioids may trigger injurious falls. The effect lowers over time and is less pronounced with increasing age. The risk is also higher for fall from height.

Parental autoimmune diseases associated with autism spectrum disorders in offspring.

BACKGROUND: Autism spectrum disorders are often idiopathic. Studies have suggested associations between immune response and these disorders. We explored associations between parental autoimmune disorders and children's diagnosis of autism by linking Swedish registries. METHODS: Data for each participant were linked across 3 Swedish registries. The study includes 1227 cases and 25 matched controls for each case (30,693 controls with parental linkage). Parental diagnoses comprised 19 autoimmune disorders. We estimated odds ratios (ORs) using multivariable conditional logistic regression. RESULTS: Parental autoimmune disorder was weakly associated with autism spectrum disorders in offspring (maternal OR = 1.6 [95% confidence interval = 1.1-2.2]; paternal OR = 1.4 [1.0-2.0]). Several maternal autoimmune diseases were correlated with autism. For both parents, rheumatic fever was associated with autism spectrum disorders. CONCLUSIONS: These data support previously reported associations between parental autoimmune disorders and autism spectrum disorders. Parental autoimmune disorders may represent a critical pathway that warrants more detailed investigation.

Overweight, obesity and risk of haematological malignancies: a cohort study of Swedish and Finnish twins.

BACKGROUND: Obesity is related to an increased risk of several forms of cancer. However, findings from studies on haematological malignancies are inconsistent. METHODS: We used prospectively collected data from two Swedish twin cohorts and the Finnish Twin Cohort (in total 70,067 persons) to study the effects of overweight and obesity on the development of leukaemia, non-Hodgkin lymphoma, Hodgkin's lymphoma and myeloma. The cohorts were followed from baseline through 2002 (Sweden) and through 2004 (Finland). RESULTS: We found a risk increase of myeloma with a relative risk (RR) of 2.1 (95% confidence interval [CI] 1.1-3.7) among obese persons, a RR of 2.5 (1.0-6.2) for chronic myeloid leukaemia and a RR of 2.7 (0.8-9.6) for acute lymphoblastic leukaemia among overweight persons as compared to normal-weighted ones. CONCLUSIONS: Our results add further evidence suggesting that overweight and obesity may have an impact on some haematological malignancies, in particular myeloma.

Co-twin control and cohort analyses of body mass index and height in relation to breast, prostate, ovarian, corpus uteri, colon and rectal cancer among Swedish and Finnish twins.

Associations between anthropometric measures and cancer have been studied previously, but relatively few studies have had the opportunity to control for genetic and early shared environmental factors. In this study, we analyzed 2 twin cohorts from Sweden born 1886-1925 (n = 21,870) and 1926-1958 (n = 30,279) and 1 from Finland born 1880-1958 (n = 25,882) including in total 78,031 twins, and studied the association between BMI and height and risk of prostate, breast, ovarian, corpus uteri, colon and rectal cancer. The cohorts were both analyzed through a co-twin control method and as traditional cohorts. In co-twin control analyses, older obese (BMI > or = 30 kg/m(2)) subjects (median age 56 years at baseline) were at higher risk of cancer of the corpus uteri (OR = 3.0; 95% CI 0.9-10.6), colon (OR = 1.9; 95% CI 0.8-4.5) and breast (OR = 2.5; 95% CI 1.3-4.2). For younger obese women (median age 30 years at baseline), an inverse tendency was observed for breast cancer (OR = 0.6; 95% CI 0.3-1.5, p for trend = 0.05). The tallest women had an increased risk of breast (OR = 1.8; 95% CI 1.3-2.7) and ovarian cancer (OR = 1.7; 95% CI 0.8-3.5). No consistent associations were found for prostate cancer either for BMI or height. There are some suggestions in our study that uncontrolled genetic or early shared environmental factors may affect risk estimates in studies of anthropometric measures and cancer risk, but do not explain observations of increased cancer risks related to BMI or height.

Autoimmune diseases, asthma and risk of haematological malignancies: a nationwide case-control study in Sweden.

To investigate potential associations between several autoimmune diseases and haematological malignancies, we studied 39,908 cases of leukaemia, Hodgkin's disease, non-Hodgkin's lymphoma and myeloma that occurred during 1987-1999 in Sweden, and 149,344 controls. Hospital discharge diagnoses of psoriasis, Sjögren's syndrome, autoimmune haemolytic anaemia, idiopathic thrombocytopenic purpura, pernicious anaemia, multiple sclerosis, rheumatic fever or asthma from 1969 to 1999 were retrieved from the Swedish Hospital Discharge Registry. Psoriasis was positively associated with leukaemia, excluding chronic lymphocytic leukaemia, (odds ratio [OR]=1.6, 95% confidence interval [CI] 1.1-2.3) and non-Hodgkin's lymphoma (OR=1.6, 95% CI 1.3-2.1). Sjögren's syndrome increased the risks of all haematological malignancies combined (OR=4.0, 95% CI 2.3-7.0), and of non-Hodgkin's lymphoma (OR=6.4, 95% CI 3.5-12). These findings, together with increased risks of several haematological malignancies in autoimmune haemolytic anaemia and idiopathic thrombocytopenic purpura but not in asthma, suggest chronic autoimmunity and immune stimulation as mechanisms contributing to the development of haematological malignancies.

Psychophysically determined thresholds for thermal perception and pain perception in healthy women across the menstrual cycle.

OBJECTIVES: Several studies have indicated changes in sensation and/or pain sensitivity among women across the menstrual cycle, but the pattern of the changes varies considerably. One reason for the reported discrepancies could reside in lack of biochemical definition of menstrual cycle phase. The aim was to quantify temperature and temperature pain thresholds at biochemically defined stages of the menstrual cycle. METHODS: Nineteen healthy women were included in the study. Temperature and temperature pain thresholds were evaluated by quantitative sensory testing, performed at 3 occasions during the menstrual cycle (early follicular phase, late follicular phase, and mid-luteal phase). At each test session, serum concentrations of estradiol and progesterone were assessed. RESULTS: Thermal cold perception threshold at the mammilla was significantly lower in the late follicular and mid-luteal phases, compared with the early follicular phase (P<0.05, respectively). For the remaining test sites, no cycle related differences in thermal perception or thermal thresholds could be documented. CONCLUSIONS: The present study has indicated no major changes in thermal pain thresholds related to phase of the menstrual cycle for the tested locations, although thermal cold perception threshold at the mammilla was a significantly lower in the late follicular and mid-luteal phases, compared with the early follicular phase. The findings of the present study further underlines the need for strict criteria for menstrual cycle phase when studying pain sensitivity in relation to hormonal events in women.

Prior hospitalization for epilepsy, diabetes, and stroke and subsequent glioma and meningioma risk.

We conducted a case-control study to evaluate the preclinical association between epilepsy, diabetes, and stroke and primary adult brain tumors. We first identified all 1,501 low-grade glioma, 4,587 high-grade glioma (HGG), and 4,193 meningioma cases reported to the Swedish Cancer Registry from 1987 to 1999. Next, controls (137,485) were randomly selected from the continuously updated Swedish Population Registry and matched to cases diagnosed that year on age and sex. Finally, cases and controls were linked to the Swedish Hospital Discharge Registry (1969-1999). We found that > or =8 years before HGG diagnosis (or control reference year) there was an elevated risk of HGG among people discharged with epilepsy [odds ratio (OR), 3.01; 95% confidence interval (95% CI), 1.73-5.22]. Two to 3 years before HGG diagnosis, this risk increased (OR, 5.33; 95% CI, 3.58-7.93) and was especially strong among people ages <55 years (OR, 13.49; 95% CI, 6.99-25.94). During this 2- to 3-year prediagnostic period, we also found an increased risk of HGG among people discharged with meningitis (OR, 3.02; 95% CI, 1.06-8.59) or viral encephalitis (OR, 12.64; 95% CI, 2.24-71.24). Results are similar for glioblastoma multiforme, low-grade glioma, and meningioma. In contrast, risk of HGG among people discharged with diabetes or stroke does not increase until year of brain tumor diagnosis. The occurrence of excess epilepsy > or =8 years before HGG diagnosis suggests a relatively long preclinical phase, but excess diabetes or stroke appear late in HGG development.

Allergic conditions and risk of hematological malignancies in adults: a cohort study.

BACKGROUND: Two contradictory hypotheses have been proposed to explain the relationship between allergic conditions and malignancies, the immune surveillance hypothesis and the antigenic stimulation hypothesis. The former advocates that allergic conditions may be protective against development of cancer, whereas the latter proposes an increased risk. This relationship has been studied in several case-control studies, but only in a few cohort studies. METHODS: The association between allergic conditions and risk of developing leukemia, Hodgkin's disease, non-Hodgkin's lymphoma and myeloma was investigated in a cohort of 16,539 Swedish twins born 1886-1925. Prospectively collected, self-reported information about allergic conditions such as asthma, hay fever or eczema was obtained through questionnaires administered in 1967. The cohort was followed 1969-99 and cancer incidence was ascertained from the Swedish Cancer Registry. RESULTS: Hives and asthma tended to increase the risk of leukemia (relative risk [RR] = 2.1, 95% Confidence Interval [CI] 1.0-4.5 and RR = 1.6, 95% CI 0.8-3.5, respectively). There was also an indication of an increased risk of non-Hodgkin's lymphoma associated with eczema during childhood (RR = 2.3, 95% CI 1.0-5.3). CONCLUSION: In contrast to most previous studies, our results do not indicate a protective effect of allergic conditions on the risk of developing hematological malignancies. Rather, they suggest that allergic conditions might increase the risk of some hematological malignancies.

Cohort studies of association between self-reported allergic conditions, immune-related diagnoses and glioma and meningioma risk.

An inverse association between self-reported allergies and glioma and meningioma risk, has been previously observed in case-control studies. Approximately 27% (median) of the information on both glioma and meningioma in these studies, however, is collected from proxy respondents. In fact, the odds ratios (OR) among previous brain tumor studies are inversely related to the proportion of proxy respondents (Pearson correlation coefficient = -0.94; 95% CI = -1.00 to -0.65); this correlation suggests bias. We therefore constructed 3 cohorts based on the Swedish Twin, Hospital Discharge, and Cancer Registries. In Cohorts I (14,535 people developed 37 gliomas and 41 meningiomas) and II (29,573 people developed 42 gliomas and 26 meningiomas) median time from self-report of allergies to brain tumor diagnosis was 15.4 years. Cohort III, which overlaps with Cohorts I and II (52,067 people developed 68 gliomas and 63 meningiomas), was linked to the Swedish Hospital Discharge Registry where pre-brain tumor immune-related discharge diagnoses were recorded. Allergies are inversely associated with glioma risk in Cohort I (Hazard ratio [HR] = 0.45; 95% CI = 0.19-1.07) and among high grade (III and IV, HR = 0.45; 95% CI = 0.11-1.92) but not low grade (I and II, HR = 2.60; 95% CI = 0.86-7.81) gliomas in Cohort II. In Cohort III, immune-related discharge diagnoses are also inversely associated with glioma (HR = 0.46; 95% CI = 0.14-1.49). There is no strong evidence against (and some for) the hypothesis that allergies reduce glioma risk.

Comparative study of the high-pressure behavior of As, Sb, and Bi.

The high-pressure behavior of the heavier group 15 elements As, Sb, and Bi was investigated by means of ab initio density functional calculations employing pseudopotentials and a plane wave basis set. The high-pressure structural sequence of these elements is distinguished by the occurrence of the Bi-III structure, which is a complex, incommensurately modulated, host-guest structure. We approximated this structure by a supercell which reproduced the experimentally established pressure stability ranges of the host-guest structure for the different elements extremely well. With pressure we find an increasing admixture of d states (s-d hybridization) in the occupied levels of the electronic structure of As, Sb, and Bi. However, the s-d mixing remains at a low level. Thus, the emergence of a complex intermediate pressure structure cannot be explained by a pressure-induced altered valence state for these elements. Instead, it is argued that the Bi-III structure is a consequence of a delicate interplay between the electrostatic and the band energy contribution to the total energy. In the intermediate pressure range of heavier group 15 elements, both important parts of the total energy account equally for structural stability.

Childhood leukemia and magnetic fields in infant incubators.

In studies of magnetic field exposure and childhood leukemia, power lines and other electrical installations close to the children's homes constitute the most extensively studied source of exposure. We conducted a study to assess whether exposure to magnetic fields in infant incubators is associated with an increased leukemia risk. We identified all children with leukemia born in Sweden between 1973 and 1989 from the national Cancer Registry and selected at random one control per case, individually matched by sex and time of birth, from the study base. We retrieved information about treatment in infant incubators from medical records. We made measurements of the magnetic fields inside the incubators for each incubator model kept by the hospitals. Exposure assessment was based on measurements of the magnetic field level inside the incubator, as well as on the length of treatment. For acute lymphoblastic leukemia, the risk estimates were close to unity for all exposure definitions. For acute myeloid leukemia, we found a slightly elevated risk, but with wide confidence intervals and with no indication of dose response. Overall, our results give little evidence that exposure to magnetic fields inside infant incubators is associated with an increased risk of childhood leukemia.