Jonas Ranstam

Associations between smoking and beta-cell function in a non-hypertensive and non-diabetic population. Skaraborg Hypertension and Diabetes Project

Aims An increased risk for Type 2 diabetes in male and female smokers has been associated with insulin resistance. However, this might also be the result of an adverse effect on the β‐cell. The aim of the present study was to examine the association between smoking and β‐cell function.

Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50 302 women with breast cancer and 96 973 women without the disease

Background Although childbearing is known to protect against breast cancer, whether or not breastfeeding contributes to this protective effect is unclear. Methods Individual data from 47 epidemiological studies in 30 countries that included information on breastfeeding patterns and other aspects of childbearing were collected, checked, and analysed centrally, for 50 302 women with invasive breast cancer and 96 973 controls. Estimates of the relative risk for breast cancer associated with breastfeeding in parous women were obtained after stratification by fine divisions of age, parity, and womens ages when their first child was born, as well as by study and menopausal status. Findings Women with breast cancer had, on average, fewer births than did controls (2·2 vs 2·6). Furthermore, fewer parous women with cancer than parous controls had ever breastfed (71% vs 79%), and their average lifetime duration of breastfeeding was shorter (9·8 vs 15·6 months). The relative risk of breast cancer decreased by 4·3% (95% CI 2·9–5·8; p<0·0001) for every 12 months of breastfeeding in addition to a decrease of 7·0% (5·0–9·0; p<0·0001) for each birth. The size of the decline in the relative risk of breast cancer associated with breastfeeding did not differ significantly for women in developed and developing countries, and did not vary significantly by age, menopausal status, ethnic origin, the number of births a woman had, her age when her first child was born, or any of nine other personal characteristics examined. It is estimated that the cumulative incidence of breast cancer in developed countries would be reduced by more than half, from 6·3 to 2·7 per 100 women by age 70, if women had the average number of births and lifetime duration of breastfeeding that had been prevalent in developing countries until recently. Breastfeeding could account for almost two-thirds of this estimated reduction in breast cancer incidence. Interpretation The longer women breast feed the more they are protected against breast cancer. The lack of or short lifetime duration of breastfeeding typical of women in developed countries makes a major contribution to the high incidence of breast cancer in these countries. (Less)BACKGROUND Although childbearing is known to protect against breast cancer, whether or not breastfeeding contributes to this protective effect is unclear. METHODS Individual data from 47 epidemiological studies in 30 countries that included information on breastfeeding patterns and other aspects of childbearing were collected, checked, and analysed centrally, for 50302 women with invasive breast cancer and 96973 controls. Estimates of the relative risk for breast cancer associated with breastfeeding in parous women were obtained after stratification by fine divisions of age, parity, and womens ages when their first child was born, as well as by study and menopausal status. FINDINGS Women with breast cancer had, on average, fewer births than did controls (2.2 vs 2.6). Furthermore, fewer parous women with cancer than parous controls had ever breastfed (71% vs 79%), and their average lifetime duration of breastfeeding was shorter (9.8 vs 15.6 months). The relative risk of breast cancer decreased by 4.3% (95% CI 2.9-5.8; p<0.0001) for every 12 months of breastfeeding in addition to a decrease of 7.0% (5.0-9.0; p<0.0001) for each birth. The size of the decline in the relative risk of breast cancer associated with breastfeeding did not differ significantly for women in developed and developing countries, and did not vary significantly by age, menopausal status, ethnic origin, the number of births a woman had, her age when her first child was born, or any of nine other personal characteristics examined. It is estimated that the cumulative incidence of breast cancer in developed countries would be reduced by more than half, from 6.3 to 2.7 per 100 women by age 70, if women had the average number of births and lifetime duration of breastfeeding that had been prevalent in developing countries until recently. Breastfeeding could account for almost two-thirds of this estimated reduction in breast cancer incidence. INTERPRETATION The longer women breast feed the more they are protected against breast cancer. The lack of or short lifetime duration of breastfeeding typical of women in developed countries makes a major contribution to the high incidence of breast cancer in these countries.

Mammographic screening and mortality from breast cancer: the Malmö mammographic screening trial.

STUDY OBJECTIVE--To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN--Birth year cohorts of city population separately randomised into study and control groups. SETTING--Screening clinic outside main hospital. PATIENTS--Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS--Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT--Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS--All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS--In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS--Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.

Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial

BACKGROUND Balloon kyphoplasty is a minimally invasive procedure for the treatment of painful vertebral fractures, which is intended to reduce pain and improve quality of life. We assessed the efficacy and safety of the procedure. METHODS Adults with one to three acute vertebral fractures were eligible for enrolment in this randomised controlled trial at 21 sites in eight countries. We randomly assigned 300 patients by a computer-generated sequence to receive kyphoplasty treatment (n=149) or non-surgical care (n=151). The primary outcome was the difference in change from baseline to 1 month in the short-form (SF)-36 physical component summary (PCS) score (scale 0-100) between the kyphoplasty and control groups. Quality of life and other efficacy measurements and safety were assessed up to 12 months. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00211211. FINDINGS 138 participants in the kyphoplasty group and 128 controls completed follow-up at 1 month. By use of repeated measures mixed effects modelling, all 300 randomised participants were included in the analysis. Mean SF-36 PCS score improved by 7.2 points (95% CI 5.7-8.8), from 26.0 at baseline to 33.4 at 1 month, in the kyphoplasty group, and by 2.0 points (0.4-3.6), from 25.5 to 27.4, in the non-surgical group (difference between groups 5.2 points, 2.9-7.4; p<0.0001). The frequency of adverse events did not differ between groups. There were two serious adverse events related to kyphoplasty (haematoma and urinary tract infection); other serious adverse events (such as myocardial infarction and pulmonary embolism) did not occur perioperatively and were not related to procedure. INTERPRETATION Our findings suggest that balloon kyphoplasty is an effective and safe procedure for patients with acute vertebral fractures and will help to inform decisions regarding its use as an early treatment option.

A randomized trial of treatment for acute anterior cruciate ligament tears.

BACKGROUND The optimal management of a torn anterior cruciate ligament (ACL) of the knee is unknown. METHODS We conducted a randomized, controlled trial involving 121 young, active adults with acute ACL injury in which we compared two strategies: structured rehabilitation plus early ACL reconstruction and structured rehabilitation with the option of later ACL reconstruction if needed. The primary outcome was the change from baseline to 2 years in the average score on four subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS)--pain, symptoms, function in sports and recreation, and knee-related quality of life (KOOS(4); range of scores, 0 [worst] to 100 [best]). Secondary outcomes included results on all five KOOS subscales, the Medical Outcomes Study 36-Item Short-Form Health Survey, and the score on the Tegner Activity Scale. RESULTS Of 62 subjects assigned to rehabilitation plus early ACL reconstruction, 1 did not undergo surgery. Of 59 assigned to rehabilitation plus optional delayed ACL reconstruction, 23 underwent delayed ACL reconstruction; the other 36 underwent rehabilitation alone. The absolute change in the mean KOOS(4) score from baseline to 2 years was 39.2 points for those assigned to rehabilitation plus early ACL reconstruction and 39.4 for those assigned to rehabilitation plus optional delayed reconstruction (absolute between-group difference, 0.2 points; 95% confidence interval, -6.5 to 6.8; P=0.96 after adjustment for the baseline score). There were no significant differences between the two treatment groups with respect to secondary outcomes. Adverse events were common in both groups. The results were similar when the data were analyzed according to the treatment actually received. CONCLUSIONS In young, active adults with acute ACL tears, a strategy of rehabilitation plus early ACL reconstruction was not superior to a strategy of rehabilitation plus optional delayed ACL reconstruction. The latter strategy substantially reduced the frequency of surgical reconstructions. (Funded by the Swedish Research Council and the Medical Faculty of Lund University and others; Current Controlled Trials number, ISRCTN84752559.)

Risk Factors for Hip Fracture in Men from Southern Europe: The MEDOS Study

Abstract: The aims of this study were to identify risk factors for hip fracture in men aged 50 years or more. We identified 730 men with hip fracture from 14 centers from Portugal, Spain, France, Italy, Greece and Turkey during the course of a prospective study of hip fracture incidence and 1132 age-stratified controls selected from the neighborhood or population registers. The questionnaire examined aspects of work, physical activity past and present, diseases and drugs, height, weight, indices of co-morbidity and consumption of tobacco, alcohol, calcium, coffee and tea. Significant risk factors identified by univariate analysis included low body mass index (BMI), low sunlight exposure, a low degree of recreational physical activity, low consumption of milk and cheese, and a poor mental score. Co-morbidity including sleep disturbances, loss of weight, impaired mental status and poor appetite were also significant risk factors. Previous stroke with hemiplegia, prior fragility fractures, senile dementia, alcoholism and gastrectomy were associated with significant risk, whereas osteoarthrosis, nephrolithiasis and myocardial infarction were associated with lower risks. Taking medications was not associated with a difference in risk apart from a protective effect with the use of analgesics independent of co-existing osteoarthrosis and an increased risk with the use of anti-epileptic agents. Of the potentially ‘reversible’ risk factors, BMI, leisure exercise, exposure to sunlight and consumption of tea and alcohol and tobacco remained independent risk factors after multivariate analysis, accounting for 54% of hip fractures. Excluding BMI, 46% of fractures could be explained on the basis of the risk factors sought. Of the remaining factors low exposure to sunlight and decreased physical activity accounted for the highest attributable risks (14% and 9% respectively). The use of risk factors to predict hip fractures had relatively low sensitivity and specificity (59.6% and 61.0% respectively). We conclude that lifestyle factors are associated with significant differences in the risk of hip fracture. Potentially remediable factors including a low degree of physical exercise and a low BMI account for a large component of the total risk.

Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden.

PURPOSE Recent studies indicate that BRCA1 breast and ovarian tumors may have an advantageous survival. In this population-based study, the survival of carriers of a mutated BRCA1 gene was investigated. PATIENTS AND METHODS The survival of 71 BRCA1-associated cancer patients (33 breast cancer, seven breast and ovarian cancer, and 31 ovarian cancer patients from 21 families with BRCA1 germline mutations) diagnosed after 1958 was compared with that of a population-based comparison group that consisted of all other invasive breast (n = 28,281) and ovarian (n = 7,011) cancers diagnosed during 1958 to 1995, as well as an age- and stage-matched control group. RESULTS No apparent survival advantage was found for BRCA1-associated breast cancers upon direct comparison. After adjustment for age and calendar year of diagnosis, survival was equal to or worse than that of the comparison group (hazards ratio [HR], 1.5; 95% confidence interval [CI], 0.9 to 2.4). In comparison with an age- and stage-matched control group, survival again appeared equal or worse (HR, 1.5; 95% CI, 0.6 to 3.7). For BRCA1-associated ovarian cancers, an initial survival advantage was noted that disappeared with time. Due to this time dependency, multivariate analyses cannot adequately be analyzed. Compared with the age- and stage-matched control group, survival again appeared equal or worse (HR, 1.2; 95% CI, 0.5 to 2.8). CONCLUSION The results suggest that survival for carriers of a BRCA1 mutation may be similar, or worse than, that for breast and ovarian cancer in general. This finding is in accordance with the adverse histopathologic features observed in BRCA1 tumors and underlines the need for surveillance in families that carry a BRCA1 mutation.

Polymorphism in the beta(1)-adrenergic receptor gene and hypertension

Background—The Arg389 variant of the &bgr;1-adrenergic receptor gene mediates a higher isoproterenol-stimulated adenylate cyclase activity than the Gly389 variant in vitro. We investigated whether the Arg389Gly or the Ser49Gly polymorphism is associated with hypertension in Scandinavians. Methods and Results—A total of 292 unrelated, nondiabetic, hypertensive patients and 265 unrelated healthy control subjects were included in a case-control association study. From 118 families, 102 nondiabetic sibling pairs without antihypertensive medication who were discordant for the Arg389Gly polymorphism were selected for a sibling study. Allele and genotype frequencies of the Arg389Gly and Ser49Gly polymorphisms were compared between hypertensive patients and normotensive control subjects. Blood pressure and heart rate were compared between carriers of the different genotypes. In the case-control study, the age- and body mass index-adjusted odds ratio for hypertension in subjects homozygous for the Arg389 allele was 1.9 (95% confidence interval, 1.3 to 2.7;P =0.0005) when compared with carriers of 1 or 2 copies of the Gly389 allele. The genotype-discordant sibling pair analysis revealed that siblings homozygous for the Arg389 allele had significantly higher diastolic blood pressures (79.4±9.9 versus 76.0±10.1 mm Hg;P =0.003) and higher heart rates (68.3±11.0 versus 65.1±9.4 bpm;P =0.02) than siblings carrying 1 or 2 copies of the Gly389 allele. The Ser49Gly polymorphism was not associated with hypertension. Conclusion—Our data suggest that individuals homozygous for the Arg389 allele of the &bgr;1-adrenergic receptor gene are at increased risk to develop hypertension.

Validity of register data on acute myocardial infarction and acute stroke: The Skaraborg Hypertension Project

In the evaluation of a hypertension treatment program, the end-point surveillance included incidence of acute myocardial infarction and acute stroke identified from hospital in-patient registers and the national mortality register. To ascertain the validity, in-patient records containing the ICD-codes 410–411 and 430–438 were validated. First event of acute myocardial infarction and acute stroke suggested in the in-patient register could be confirmed in 96% and 94%, respectively. In-patient diagnoses of suspected acute myocardial infarction or other acute or subacute ischemic heart diseases, transient ischemic attack and unspecified cerebrovascular disease revealed high proportions of what in fact turned out to be definite events (11%, 24% and 53% respectively). It is concluded that disease ascertainment for this cohort study claims validation of register data with hospital records.

Treatment for acute anterior cruciate ligament tear: five year outcome of randomised trial.

STUDY QUESTION In young active adults with an acute anterior cruciate ligament (ACL) rupture, do patient reported or radiographic outcomes after five years differ between those treated with rehabilitation plus early ACL reconstruction and those treated with rehabilitation and optional delayed ACL reconstruction? SUMMARY ANSWER At five years, patients assigned to rehabilitation plus early ACL reconstruction did not differ significantly in patient reported or radiographic outcomes from those assigned to initial rehabilitation with the option of having a later reconstruction if needed. WHAT IS KNOWN AND WHAT THIS PAPER ADDS The relative efficacy of surgical reconstruction and rehabilitation for short and long term outcomes of ACL rupture is debated. Clinicians and young active adult patients should consider rehabilitation as a primary treatment option following an acute ACL tear.