Prediabetes and incident heart failure in hypertensive patients: Results from the Swedish Primary Care Cardiovascular Database.

BACKGROUNDS AND AIMS: The cardiovascular risk conferred by concomitant prediabetes in hypertension is unclear. We aimed to examine the impact of prediabetes on incident heart failure (HF) and all-cause mortality, and to describe time in therapeutic blood pressure range (TTR) in a hypertensive real-world primary care population. METHODS AND RESULTS: In this retrospective cohort study, 9628 hypertensive individuals with a fasting plasma glucose (FPG) in 2006-2010 but no diabetes, cardiovascular or renal disease were followed to 2016; median follow-up was 9 years. Prediabetes was defined as FPG 5.6-6.9 mmol/L, and in a secondary analysis as 6.1-6.9 mmol/L. Study outcomes were HF and all-cause mortality. Hazard ratios (HR) were compared for prediabetes with normoglycemia using Cox regression. All blood pressure values from 2001 to the index date (first FPG in 2006-2010) were used to calculate TTR. At baseline, 51.4% had prediabetes. The multivariable-adjusted HR (95% confidence intervals) was 0.86 (0.67-1.09) for HF and 1.06 (0.90-1.26) for all-cause mortality. For FPG defined as 6.1-6.9 mmol/L, the multivariable-adjusted HR were 1.05 (0.80-1.39) and 1.42 (1.19-1.70), respectively. The prediabetic group had a lower TTR (p < 0.05). CONCLUSIONS: Prediabetes was not independently associated with incident HF in hypertensive patients without diabetes, cardiovascular or renal disease. However, prediabetes was associated with all-cause mortality when defined as FPG 6.1-6.9 mmol/L (but not as 5.6-6.9 mmol/L). TTR was lower in the prediabetic group, suggesting room for improved blood pressure to reduce incident heart failure in prediabetes.

Plasma albumin and calcium concentrations, and long-term mortality in primary health care patients in Sweden.

OBJECTIVE: Low plasma (p)-albumin and p-calcium concentrations are associated with increased mortality in hospitalised patients. There are few studies addressing this in primary care. Low p-calcium has been associated with mortality, but it is not known whether this applies to p-albumin. Could p-albumin and p-calcium be used as markers of an increased risk of mortality? PURPOSE: To study p-albumin and p-calcium at baseline and their association with mortality after 10-14 years. DESIGN: Prospective cohort study using data from a large primary health care area and the National Swedish Cause of Death Register. SETTING: Primary health care in Skaraborg, Sweden. SUBJECTS: 43,052 patients (39.1% men), ≥18 years, 60.7 ± 18.4 years with p-albumin and p-calcium concentrations registered in 2001-2005. MAIN OUTCOME MEASURES: P-albumin and p-calcium concentrations at baseline and their association with mortality after a mean follow-up period of 10.3 ± 4.0 years. RESULTS: Low p-albumin was associated with total mortality compared with normal p-albumin, greatest at lower ages (18-47 years). The hazard ratios for women and men were 3.12 (95% CI 1.27-7.70) and 4.09 (95% CI 1.50-11.14), respectively. The increased mortality was seen in both cardiovascular and malignant diseases in both women and men. In contrast, low p-calcium was not associated with increased mortality, 1.00 (95% CI 0.96-1.05). Elevated p-calcium was associated with increased mortality, 1.17 (95% CI 1.13-1.22). CONCLUSIONS: Low p-albumin could be a marker of an increased risk of mortality, especially in patients of younger ages. This finding should prompt diagnostic measures in order to identify underlying causes. KEY POINTS Low p-albumin and calcium concentrations have been associated with increased mortality in hospitalised patients, but this is unexplored in primary care patients. A low p-albumin concentration at baseline was a risk marker for mortality; highest in the younger age groups. Increased mortality in both cardiovascular and malignant diseases was seen in both men and women with low compared with normal p-albumin concentrations. Elevated but not low p-calcium concentrations were associated with increased mortality after 10-14 years of follow-up.

Association of dairy intake with cardiovascular disease and mortality in 21 countries from five continents (PURE): a prospective cohort study.

BACKGROUND: Dietary guidelines recommend minimising consumption of whole-fat dairy products, as they are a source of saturated fats and presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Evidence for this contention is sparse and few data for the effects of dairy consumption on health are available from low-income and middle-income countries. Therefore, we aimed to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease. METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35-70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre. FINDINGS: Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9·1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0·84, 95% CI 0·75-0·94; ptrend=0·0004), total mortality (0·83, 0·72-0·96; ptrend=0·0052), non-cardiovascular mortality (0·86, 0·72-1·02; ptrend=0·046), cardiovascular mortality (0·77, 0·58-1·01; ptrend=0·029), major cardiovascular disease (0·78, 0·67-0·90; ptrend=0·0001), and stroke (0·66, 0·53-0·82; ptrend=0·0003). No significant association with myocardial infarction was observed (HR 0·89, 95% CI 0·71-1·11; ptrend=0·163). Higher intake (>1 serving vs no intake) of milk (HR 0·90, 95% CI 0·82-0·99; ptrend=0·0529) and yogurt (0·86, 0·75-0·99; ptrend=0·0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0·88, 0·76-1·02; ptrend=0·1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1·09, 95% CI 0·90-1·33; ptrend=0·4113). INTERPRETATION: Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

The quality of the sickness certificate. A case control study of patients with symptom and disease specific diagnoses in primary health care in Sweden.

Objective: To compare information in sickness certificates and rehabilitation activities for patients with symptom diagnoses vs patients with disease specific diagnoses. Design: Retrospective case control study 2013-2014. Setting: Primary health care, Sweden. Subjects. Patients with new onset sickness certificates with symptom diagnoses n = 222, and disease specific diagnoses (controls), n = 222. Main outcome measures: Main parameters assessed were: information about body function and activity limitation in certificates, duration of sick leave, certificate renewals by telephone, diagnostic investigations, health care utilisation, contacts between patients, rehabilitation coordinators, social insurance officers, employers and occurrence of rehabilitation plans. Results: Information about body function and activity limitation was sufficient according to guidelines in half of all certificates, less in patients with symptom diagnoses compared to controls (44% vs. 56%, p = 0.008). Patients with symptom diagnoses had shorter sick leave than controls (116 vs. 151 days p = 0.018) and more certificates issued by telephone (23% vs. 15% p = 0.038). Furthermore, they underwent more diagnostic investigations (32% vs. 18%, p < 0.001) and the year preceding sick leave they had more visits to health care (82% vs. 68%, p < 0.001), but less follow-up (16% vs. 26%, p < 0.008). In both groups contacts related to rehabilitation and with employers were scarce. Conclusion: Certificates with symptom diagnoses compared to disease specific diagnoses could be used as markers for insufficient certificate quality and for patients with higher health care utilisation. Overall, the information in half of the certificates was insufficient and early contacts with employers and rehabilitation activities were in practice missing. KEY POINTS Symptom diagnoses are proposed as markers of sickness certification quality. We investigated this by comparing certificates with and without symptom diagnoses. Certificates with symptom diagnoses lacked information to a higher degree compared to certificates with disease specific diagnoses. Regardless of diagnoses, early contacts between patients, rehabilitation coordinators and social insurance officers were rare and contacts with employers were absent.

Drug adherence in treatment resistant and in controlled hypertension-Results from the Swedish Primary Care Cardiovascular Database (SPCCD).

PURPOSE: To assess drug adherence in patients treated with ≥3 antihypertensive drug classes, with both controlled and uncontrolled blood pressure and describe associated factors for nonadherence. METHODS: Patients with hypertension, without cardiovascular comorbidity, aged >30 years treated with ≥3 antihypertensive drug classes were followed for 2 years. Both patients with treatment resistant hypertension (TRH) and patients with controlled hypertension were included. Clinical data were derived from a primary care database. Pharmacy refill data from the Swedish Prescribed drug registry was used to calculate proportion of days covered (PDC). Patients with a PDC level ≥ 80% were included. RESULTS: We found 5846 patients treated ≥3 antihypertensive drug classes, 3508 with TRH (blood pressure ≥ 140/90), and 2338 with controlled blood pressure (<140/90 mm Hg). TRH patients were older (69.1 vs 65.8 years, P < .0001) but had less diabetes (28.5 vs 31.7%, P < .009) compared with patients with controlled blood pressure. The proportion of patients with PDC ≥ 80% declined with 11% during the first year in both groups. Having diabetes was associated with staying adherent at 1 year (RR 0.82; 95% CI, 0.68-0.98) whilst being born outside Europe was associated with nonadherence at one and (RR 2.05; 95% CI, 1.49-2.82). CONCLUSIONS: Patients with multiple antihypertensive drug therapy had similar decline in adherence over time regardless of initial blood pressure control. Diabetes was associated with better adherence, which may imply that the structured caregiving of these patients enhances antihypertensive drug treatment.

Bone mineral density in primary care patients related to serum calcium concentrations: a longitudinal cohort study from Sweden.

OBJECTIVE: Elevated calcium concentration is a commonly used measure in screening analyses for primary hyperparathyroidism (pHPT) and cancer. Low bone mineral density (BMD) and osteoporosis are common features of pHPT and strengthen the indication for parathyroidectomy. It is not known whether an elevated calcium concentration could be a marker of low BMD in suspected pHPT patients with a normal parathyroid hormone concentration. PURPOSE: To study if low BMD and osteoporosis are more common after ten years in patients with elevated compared with normal calcium concentrations at baseline. DESIGN: Prospective case control study. SETTING: Primary care, southern Sweden. SUBJECTS: One hundred twenty-seven patients (28 men) with baseline elevated, and 254 patients (56 men) with baseline normal calcium concentrations, mean age 61 years, were recruited. After ten years, 77% of those still alive (74 with elevated and 154 with normal calcium concentrations at baseline) participated in a dual energy x-ray absorptiometry measurement for BMD assessment and analysis of calcium and parathyroid hormone concentrations. MAIN OUTCOME MEASURES: Association between elevated and normal calcium concentration at base-line and BMD at follow-up. Correlation between calcium and parathyroid hormone concentrations and BMD at follow-up. RESULTS: A larger proportion of the patients with elevated baseline calcium concentrations who participated in the follow-up had osteoporosis (p value = 0.036), compared with the patients with normal concentrations. In contrast, no correlation was found between calcium or parathyroid hormone concentrations and BMD at follow-up. CONCLUSIONS: In this study, patients with elevated calcium concentrations at baseline had osteoporosis ten years later more often than controls (45% vs. 29%), which highlights the importance of examining these patients further using absorptiometry, even when their parathyroid hormone level is normal. Key Points Osteoporosis is common, difficult to detect and usually untreated. It is not known whether elevated calcium concentrations, irrespective of the PTH level, could be a marker of low bone mineral density. No correlation was found between calcium or parathyroid hormone concentrations and bone mineral density at follow-up. In this study, patients with elevated calcium concentrations at baseline had osteoporosis ten years later more often than controls (45% vs. 29%).

Which instruments to support diagnosis of depression have sufficient accuracy? A systematic review.

BACKGROUND: Instruments are frequently used in case finding, diagnosis and severity grading of major depression, but the evidence supporting their utility is weak. AIM: To systematically review the specificity and sensitivity of instruments used to diagnose and grade the severity of depression. METHODS: MEDLINE, PsycInfo, Embase and the Cochrane Library databases were searched until April 2014. Fifty studies fulfilled the inclusion criteria. Risk of bias was assessed with QUADAS. The average sensitivity and specificity of each instrument was estimated with hierarchical summary receiver operating characteristics analyses and the confidence in the estimates was evaluated using GRADE. Minimum acceptable sensitivity/specificity, with structured interview as the reference, was 80%/80% for structured interviews and 80%/70% for case-finding instruments. The minimum acceptable standard for severity measures was a correlation of 0.7 with DSM-IV classification. RESULTS: Twenty instruments were investigated. The average sensitivity/specificity was 85%/92% for the Structured Clinical Interview for DSM-IV-Axis-I Disorders (SCID-I), 95%/84% for the Mini International Neuropsychiatric Interview (MINI), < 70%/85% for the Primary Care Evaluation of Mental Disorders (PRIME-MD), 88%/78% for the Patient Health Questionnaire-9 (PHQ-9) with a cut-off score of 10, 69%/95% for PHQ-9 as a diagnostic algorithm and 70%/83% for the Hospital Anxiety and Depression Scale (HADS) with a cut-off score of 7. The confidence in the estimates for the other instruments was very low. CONCLUSIONS: Only the SCID-I, MINI and PHQ-9 with a cut-off score of 10 fulfilled the minimum criteria for sensitivity and specificity. The use of the PRIME-MD and HADS is not supported by current evidence.

The prognosis of diabetic retinopathy in patients with type 2 diabetes since 1996-1998: the Skaraborg Diabetes Register.

Diabetes mellitus is the main reason for visual impairment among patients of working ages. The aim of this paper was to investigate the prognosis of eye complications in patients with diabetes during 10 years of follow-up and contributing risk factors. Data from ophthalmological records (occurrence of retinopathy and laser treatment and visual acuity), and clinical data (blood pressure, glycosylated hemoglobin (HbA1c), body mass index (BMI), and antihypertensive treatment) from the Skaraborg Diabetes Register were retrieved in the Skaraborg Screening Program of 1,258 patients diagnosed during 1996-1998. Kaplan Meyer survival analysis and Log Rank test were used to analyze eye complications in 773 patients with type 2 diabetes and ≤70 years at diagnosis. Visual acuity was above the limit for driving license in 96 % of 548 patients and only nineteen patients were treated by laser. At diagnosis of diabetes, mean HbA1c was 6.7 ± 1.7 % (59 ± 7.1 mmol/mol), and systolic blood pressure was 142.9 ± 0.7 mmHg; neither changed significantly during follow-up. Retinopathy appeared about 1 year, and maculopathy 2 years earlier, if HbA1c ≥ 7 % (63 mmol/mol) at diagnosis (p < 0.001 and p < 0.006). Antihypertensive treatment, higher BMI, and higher age at diagnosis were associated with less retinopathy during follow-up. Most patients with diabetes develop little retinopathy for the first 10 years after diagnosis. High HbA1c at baseline was associated with retinopathy and maculopathy during follow-up. Antihypertensive treatment, probably a proxy for regular controls and early detection of diabetes, was associated with less retinopathy.

Quality of life and health care consumption in primary care patients with elevated serum calcium concentrations in - a prospective, case control, study.

BACKGROUND: Patients with elevated calcium concentrations have an increased morbidity due to various underlying illnesses. However, there is a lack of studies of quality of life and health care consumption in patients with hypercalcaemia per se. The study aims to investigate quality of life and health care consumption, as measured by, sick leave, drug prescriptions and the number of visits and admissions to health care centres and hospitals, in primary care patients with elevated calcium concentrations. METHODS: A prospective, case control, study in primary care centre, in Sweden. Patients with elevated, (n=127, 28 men), and normal calcium concentrations, (n=254, 56 men), mean age 61.4 year, were recruited in the study and followed during 10 years. Eighty-six percent of those alive at the time of follow up participated in a follow up visit. The study participants completed a quality of life survey, SF-36, which also were compared with the Swedish SF-36 national normative database. RESULTS: Patients with elevated calcium concentrations had significantly lower quality of life both compared with the control group (patients with normal calcium concentrations) and compared with age and gender-matched reference material from the Swedish SF-36 national normative database. The group with elevated calcium concentrations had significantly more hospitalisations (p=0.017), subsequently cancer diagnoses (p<0.003), sick leave (p=0.007) and medication (p=0.002) compared with patients with normal calcium concentrations. Men with elevated calcium concentrations had more contacts with the psychosocial team (p=0.02) at the health care centre. CONCLUSIONS: Elevated calcium concentrations are associated with significantly reduced quality of life and increased health care consumption and should therefore be an important warning flag that should alert the physician to further investigate and care for the patient. This is the first study in this field and the results need to be confirmed in further studies.

Increased registration of hypertension and cancer diagnoses after the introduction of a new reimbursement system.

OBJECTIVE: To investigate the impact on ICD coding behaviour of a new case-mix reimbursement system based on coded patient diagnoses. The main hypothesis was that after the introduction of the new system the coding of chronic diseases like hypertension and cancer would increase and the variance in propensity for coding would decrease on both physician and health care centre (HCC) levels. DESIGN: Cross-sectional multilevel logistic regression analyses were performed in periods covering the time before and after the introduction of the new reimbursement system. SETTING: Skaraborg primary care, Sweden. SUBJECTS: All patients (n = 76 546 to 79 826) 50 years of age and older visiting 468 to 627 physicians at the 22 public HCCs in five consecutive time periods of one year each. MAIN OUTCOME MEASURES: Registered codes for hypertension and cancer diseases in Skaraborg primary care database (SPCD). RESULTS: After the introduction of the new reimbursement system the adjusted prevalence of hypertension and cancer in SPCD increased from 17.4% to 32.2% and from 0.79% to 2.32%, respectively, probably partly due to an increased diagnosis coding of indirect patient contacts. The total variance in the propensity for coding declined simultaneously at the physician level for both diagnosis groups. CONCLUSIONS: Changes in the healthcare reimbursement system may directly influence the contents of a research database that retrieves data from clinical practice. This should be taken into account when using such a database for research purposes, and the data should be validated for each diagnosis.

No physician gender difference in prescription of sick-leave certification: a retrospective study of the Skaraborg Primary Care Database.

OBJECTIVE: The primary objective was to investigate how physicians' gender and level of experience affects the rate and length of sick-leave certificate prescription. The secondary objective was to study the physicians' gender and professional experience in relation to the diagnoses on the certificates. DESIGN: Retrospective, cross-sectional study of computerized medical records from 24 health care centres in 2005. SETTING: Primary care in Sweden. SUBJECTS: Primary care physicians (n = 589) and patients (n = 88 780) aged 18-64 years. MAIN OUTCOME MEASURES: Rate and duration of sick leave certified by different categories of physicians and for different diagnoses and gender of patients. RESULTS: Sick leave was certified in 9.0% (musculoskeletal (3%) and psychiatric (2.3%) diagnoses were most common) of all contacts and the mean duration was 32.2 days. Overall there was no difference between male and female physicians in the sick-leave certification prescription rate (9.1% vs. 9.0%) or duration of sick leave (32.1 vs. 32.6 days). The duration of sick leave was associated with the physician's level of professional experience in general practice (GPs (Distriktläkare) 37, GP trainees (ST-läkare) 26, interns (AT-läkare) 20 and locum (vikarier) 19 days, p < 0.001). CONCLUSION: Contrary to earlier studies we found no difference in sick-leave certification prescription rate and length between male and female physicians.

Understanding adherence to therapeutic guidelines: a multilevel analysis of statin prescription in the Skaraborg Primary Care Database.

PURPOSE: In Skaraborg, Sweden, the economic responsibility for tax-financed prescription drug costs was transferred from the regional administrative level to the local level (health care centre; HCC) in 2003. The aim of this study was to investigate the impact of this decentralization of economic responsibility on adherence to guidelines for prescribing lipid-lowering drugs. METHODS: Data from all 24 public HCCs in Skaraborg on prescriptions for lipid-lowering drugs during 2003 and 2005 were extracted from the Skaraborg Primary Care Database (SPCD). Multilevel regression analysis (MLRA) was used to disentangle the variances at different levels of data (patient, physician, HCC). The outcome variable on the patient level was the prescription of the recommended statin (yes/no). Sex and age of the patients and sex, age and occupational status of the physician were included as fixed effects. The variance was expressed as the median odds ratio (MOR). RESULTS: The prevalence of adherence to guidelines for the prescription of statins increased from 77% in 2003 to 84% in 2005. The MLRA showed that in 2003 the variance was equally distributed between the HCC and physician levels (MOR(HCC2003)=1.89 vs. MOR(PHYSICIAN2003)=1.88). The variance between physicians and between HCCs decreased considerably between 2003 and 2005. The inclusion of individual and physician characteristics did not explain any of the remaining variance. CONCLUSION: The decentralized budget appears to have increased adherence to guidelines and reduced inefficient variation in prescribing.

Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study.

OBJECTIVE: To evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD). DESIGN: Prospective cohort study. SETTING: 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China). PARTICIPANTS: 116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years. MAIN OUTCOME MEASURES: The main outcome was development of IBD, including Crohn's disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals. RESULTS: Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn's disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with <1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn's disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD. CONCLUSIONS: Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods. STUDY REGISTRATION: ClinicalTrials.gov NCT03225586.

Variation in plasma calcium analysis in primary care in Sweden--a multilevel analysis.

BACKGROUND: Primary hyperparathyroidism (pHPT) is a common disease that often remains undetected and causes severe disturbance especially in postmenopausal women. Therefore, national recommendations promoting early pHPT detection by plasma calcium (P-Ca) have been issued in Sweden. In this study we aimed to investigate variation of P-Ca analysis between physicians and health care centres (HCCs) in primary care in county of Skaraborg, Sweden. METHODS: In this cross sectional study of patients' records during 2005 we analysed records from 154 629 patients attending 457 physicians at 24 HCCs. We used multilevel logistic regression analysis (MLRA) and adjusted for patient, physician and HCC characteristics. Differences were expressed as median odds ratio (MOR). RESULTS: There was a substantial variation in number of P-Ca analyses between both HCCs (MORHCC 1.65 [1.44-2.07]) and physicians (MORphysician 1.95 [1.85-2.08]). The odds for a P-Ca analysis were lower for male patients (OR 0.80 [0.77-0.83]) and increased with the number of diagnoses (OR 25.8 [23.5-28.5]). Sex of the physician had no influence on P-Ca test ordering (OR 0.93 [0.78-1.09]). Physicians under education ordered most P-Ca analyses (OR 1.69 [1.35-2.24]) and locum least (OR 0.73 [0.57-0.94]). More of the variance was attributed to the physician level than the HCC level. Different mix of patients did not explain this variance between physicians. Theoretically, if a patient were able to change both GP and HCC, the odds of a P-Ca analysis would in median increase by 2.45. Including characteristics of the patients, physicians and HCCs in the MLRA model did not explain the variance. CONCLUSIONS: The physician level was more important than the HCC level for the variation in P-Ca analysis, but further exploration of unidentified contextual factors is crucial for future monitoring of practice variation.

Very low calorie diet (VLCD) followed by a randomized trial of corset treatment for obesity in primary care.

OBJECTIVE: The primary objective was to investigate the feasibility and cost-effectiveness of weight reduction using very low calorie diet (VLCD) in groups. The secondary objective was to investigate whether subsequent corset treatment could maintain the weight reduction long term. DESIGN: Participants, consecutively included in groups of 8-14 subjects, underwent three months of VLCD with lifestyle advice at group meetings. Subjects attaining > or = 8 kg reduction were randomized to corset (A) or no corset (B) treatment for nine months. Weight was registered at all meetings and after 24 months. Costs were calculated using current salaries and anti-obesity drug prices as at 2008. SETTINGS: Primary care in Skaraborg, Sweden. Subjects. A total of 26 men and 65 women aged 30-60 years with BMI > or = 30-< 45 kg/m2. MAIN OUTCOME MEASURES: Weight changes and costs of treatment. RESULTS: VLCD (dropout n = 14) resulted in a mean weight reduction of 20.1+/-6.6 kg (20 men) and 15.7+/-4.7 kg (57 women). These 77 subjects were randomized to treatment A (n = 39) or B (n = 38). Compliance with corset was only 20% after three months. After one year (dropout n = 17) weight loss was 11.7+/-8.1 kg (A) and 9.3+/-6.9 kg (B), p = 0.23 and after two years (dropout n = 22) 6.1+/-7.0 kg and 4.4+/-7.3 kg respectively, p = 0.94. Serum glucose and lipids were altered favourably. The cost per participant of treatments A and B was SEK 4440 and SEK 1940 respectively. CONCLUSIONS: VLCD in groups was feasible and reduced weight even after one year. The cost of treatment was lower than drug treatment. Corset treatment suffered from poor compliance and could therefore not be evaluated.

Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes.

An important question in human genetics is the extent to which genes causing monogenic forms of disease harbor common variants that may contribute to the more typical form of that disease. We aimed to comprehensively evaluate the extent to which common variation in the six known maturity-onset diabetes of the young (MODY) genes, which cause a monogenic form of type 2 diabetes, is associated with type 2 diabetes. Specifically, we determined patterns of common sequence variation in the genes encoding Gck, Ipf1, Tcf2, and NeuroD1 (MODY2 and MODY4-MODY6, respectively), selected a comprehensive set of 107 tag single nucleotide polymorphisms (SNPs) that captured common variation, and genotyped each in 4,206 patients and control subjects from Sweden, Finland, and Canada (including family-based studies and unrelated case-control subjects). All SNPs with a nominal P value <0.1 for association to type 2 diabetes in this initial screen were then genotyped in an additional 4,470 subjects from North America and Poland. Of 30 nominally significant SNPs from the initial sample, 8 achieved consistent results in the replication sample. We found the strongest effect at rs757210 in intron 2 of TCF2, with corrected P values <0.01 for an odds ratio (OR) of 1.13. This association was observed again in an independent sample of 5,891 unrelated case and control subjects and 500 families from the U.K., for an overall OR of 1.12 and a P value <10(-6) in >15,000 samples. We combined these results with our previous studies on HNF4alpha and TCF1 and explicitly tested for gene-gene interactions among these variants and with several known type 2 diabetes susceptibility loci, and we found no genetic interactions between these six genes. We conclude that although rare variants in these six genes explain most cases of MODY, common variants in these same genes contribute very modestly, if at all, to the common form of type 2 diabetes.

Interaction between the angiotensin-converting enzyme gene insertion/deletion polymorphism and obstructive sleep apnoea as a mechanism for hypertension.

OBJECTIVE: Obstructive sleep apnoea (OSA) confers a risk of hypertension and cardiovascular complications. Both the renin-angiotensin-aldosterone system and OSA are important determinants of blood pressure, but it is not fully known how they interact. The aim of this study was to explore the interaction between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and OSA in the association with hypertension. DESIGN: A community-based, case-control design with hypertensive patients in primary care (n = 157) and normotensive population controls (n = 181). METHODS: All subjects underwent ambulatory polysomnography during one night. OSA was defined by a minimum of 10 apnoea/hypopnoea events per hour. Office blood pressure was measured and hypertension status was assessed. The genotypes were determined using polymerase chain reaction. RESULTS: An interaction analysis including sex, ACE I/D polymorphism (DD and ID versus II), and OSA identified a significant interaction between OSA and the ACE I/D polymorphism: odds ratio (OR) 6.3, 95% confidence interval (CI) 1.8-22.5, P = 0.004 as well as between OSA and sex: OR 3.3, 95% CI 1.1-9.6, P = 0.033. OSA was significantly associated with hypertension in men but not in women. CONCLUSION: The interaction between the ACE gene I/D polymorphism and OSA appears to be an important mechanism in the development of hypertension, particularly in men.

Prevalence of treatment-resistant hypertension and important associated factors-results from the Swedish Primary Care Cardiovascular Database.

We aimed to describe the prevalence, treatment, and associated comorbidity of treatment-resistant hypertension (TRH). This registry-based cohort study from The Swedish Primary Care Cardiovascular Database assessed 53,090 hypertensive patients attending primary care. Patients adherent to antihypertensive treatment measured by pharmacy fills and with proportion of days covered ≥80% were included. The prevalence of TRH was 17% when considering all current TRH definitions. Adherence to mineralocorticoid receptor antagonists differed between TRH- and non-TRH patients (8 vs. 4%). Higher frequencies (prevalence ratio and 95% confidence intervals) of diabetes mellitus (1.59, 1.53-1.66), heart failure (1.55, 1.48-1.64), atrial fibrillation (1.33, 1.27-1.40), ischemic heart disease (1.25, 1.20-1.30), and chronic kidney disease (1.38, 1.23-1.54) were seen in patients with TRH compared to patients without TRH. These findings, in a population with valid data on medication adherence, emphasize a broad preventive approach for these high-risk patients.

Persistence to antihypertensive drug classes: A cohort study using the Swedish Primary Care Cardiovascular Database (SPCCD).

The aim was to study persistence to, and switching between, antihypertensive drug classes and to determine factors associated with poor persistence.This was an observational cohort study. The Swedish Primary Care Cardiovascular Database includes data from medical records, socioeconomic data, filled prescriptions, and hospitalizations from national registries for 75,000 patients with hypertension. Patients included in the study were initiated on antihypertensive drug treatment in primary healthcare in 2006 to 2007. We defined class persistence as the proportion remaining on the initial drug class, including 30 days of gap. Patients with a filled prescription of another antihypertensive drug class after discontinuation of the initial drug, including 30 days of gap, were classified as switchers. Persistence to the various drug classes were compared with that for diuretics.We identified 4997 patients (mean age 60 ±â€Š12 years in men and 63 ±â€Š13 years in women). Out of these, 95 (2%) filled their first prescription for fixed combination therapy and 4902 (98%) for monotherapy, including angiotensin converting enzyme inhibitors (37%), angiotensin receptor blockers (4%), beta blockers (21%), calcium channel blockers (8%), and diuretics (28%). Persistence to the initial drug class was 57% after 1 year and 43% after 2 years. There were no differences in persistence between diuretics and any of the other antihypertensive drug classes, after adjustment for confounders. Discontinuation (all adjusted) was more common in men (P = 0.004), younger patients (P < 0.001), those with mild systolic blood pressure elevation (P < 0.001), and patients born outside the Nordic countries (P < 0.001). Among 1295 patients who switched drug class after their first prescription, only 21% had a blood pressure recorded before the switch occurred; and out them 69% still had high blood pressures.In conclusion, there appears to be no difference in drug class persistence between diuretics and other major antihypertensive drug classes, when factors known to be associated with poor persistence are taken into account.

Gender differences in antihypertensive drug treatment: results from the Swedish Primary Care Cardiovascular Database (SPCCD).

There are gender differences in antihypertensive treatment. This study aimed to investigate if gender differences in treatment could be explained by comorbidities. In addition, we aimed to study whether blood pressure control is different in women and men, and whether women interrupt treatment more often with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) compared with men.This cohort study within the Swedish Primary Care Cardiovascular Database included 40,825 patients with hypertension attending primary health care from 2007 to 2008. Cardiovascular comorbidities, with the exception of heart failure, were more common in men. Women were more often treated with diuretics, and men with ACEI, as were hypertensive patients with diabetes. Comorbidities could not entirely explain gender differences in antihypertensive treatment in a regression model. Women had higher systolic and lower diastolic blood pressure; this was also true in subgroups with cardiovascular comorbidity. Men more often than women were prescribed ACEIs/ARBs and interrupted treatment. Women and men are treated with different antihypertensive drugs, and this is not fully explained by differences in comorbidities. Women have higher systolic blood pressures, irrespective of comorbidity. Men have interrupted treatment more often with ACEIs/ARBs. These gender differences could affect outcome and warrant further investigation.