Reproductive factors and pancreatic cancer risk: a Norwegian cohort study.

A cohort of 63,090 Norwegian women born 1886-1928 was followed more than 38 years, and relations between reproductive factors and risk of pancreatic cancer were explored; 449 cases were recorded at ages 50-89 years. Age at menopause showed a moderately positive association with risk (rate ratio (RR)=1.08 per 2 years delay in menopause; 95% confidence interval (CI)=1.00-1.17). Neither parity nor duration of breastfeeding showed significant associations with risk after adjusting only for demographic factors. With mutual adjustment, however, parity became positively associated (RR=1.13 per delivery; 95% CI=1.05-1.22) while duration of breastfeeding was inversely associated (RR=0.87 per 12 months; 95% CI=0.78-0.97). These associations lessened in magnitude with increasing age, and were essentially absent above age 80 years. Risk was raised among women reporting at least one abortion, but no trend was seen with number of abortions. Together with previous studies, the findings raise questions about the role of chance, but do not exclude hormonal factors related to breastfeeding and pregnancy from affecting pancreatic cancer risk.

Twin births, sex of children and maternal risk of ovarian cancer: a cohort study in Norway.

In a follow-up of 1,208,001 women aged 20-74 years, no significant association was found between twin births (112 cases) and risk, though those with twin girls had a non-significantly higher risk than those with singleton births; among the latter, those with girls only had a higher risk of endometrioid tumours (incidence rate ratio 1.35; 95% confidence interval 1.03-1.76, based on 475 cases) than women with boys only.

Breast cancer risk by age at birth, time since birth and time intervals between births: exploring interaction effects.

In a Norwegian, prospective study we investigated breast cancer risk in relation to age at, and time since, childbirth, and whether the timing of births modified the risk pattern after delivery. A total of 23,890 women of parity 5 or less were diagnosed with breast cancer during follow-up of 1.7 million women at ages 20-74 years. Results, based on Poisson regression analyses of person-years at risk, showed long-term protective effects of the first, as well as subsequent, pregnancies and that these were preceded by a short-term increase in risk. The magnitude and timing of this adverse effect differed somewhat by birth order, maternal age at delivery and birth spacing. No transient increase in risk was seen shortly after a first birth below age 25 years, but an early first birth did not prevent a transient increase in risk after subsequent births. In general, the magnitude of the adverse effect was strongest after pregnancies at age 30 years or older. A wide birth interval was also related to a more pronounced adverse effect. Increasing maternal age at the first and second childbirth was associated with an increase in risk in the long run, whereas no such long-term effect was seen with age at higher order births.

Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol.

BACKGROUND: Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis. OBJECTIVE: The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infarction (MI) on subsequent cardiac events and serum lipids. DESIGN: Three hundred patients with acute MI were randomly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil, administered in a double-blind manner over 12-24 mo. Median follow-up time was 1.5 y. Clinical follow-up, including the drawing of blood samples, was performed after 6 wk of treatment and later at 0.5-year intervals. RESULTS: Forty-two (28%) patients in the n-3 group and 36 (24%) in the corn oil group experienced at least one cardiac event (cardiac death, resuscitation, recurrent MI, or unstable angina). No significant difference in prognosis was observed between groups for single or combined cardiac events. Total cholesterol concentrations decreased in both groups, with no significant intergroup differences. On average, the monthly increase in HDL cholesterol was 1.11% in the n-3 group and 0.55% in the corn oil group (P = 0.0016). Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group, whereas they increased by 0.35%/mo in the corn oil group (P < 0.0001). CONCLUSION: No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids.

Patients' views on importance and usefulness of plain radiography for low back pain.

STUDY DESIGN: Quantitative and qualitative cross-sectional interview study. OBJECTIVES: To investigate how patients who are referred for plain radiography because of low back pain perceive the importance and usefulness of the examination. SUMMARY OF BACKGROUND DATA: Up to 50% of plain radiography examinations for low back pain may be unnecessary based on clinical criteria. However, many patients have great confidence in these examinations. A further exploration of the patients' views may indicate how their needs can be met without unnecessary use of radiography. METHODS: Ninety-nine patients (65 women, 34 men) 14-91 years of age who were referred from Norwegian general practitioners for plain radiography of the lumbosacral spine were asked to rate the examination as slightly/fairly or very important (93 responded). Chi-squared tests were used to evaluate differences in rating according to age, gender, clinical history, and clinical appropriateness of the examination, as determined by comparing information in the referral form with Norwegian (NR) and British (BR) recommendations for use of radiography. Each of the 99 patients also underwent a semistructured interview that was based on questions about importance, usefulness, and reasons for the radiography referral. Answers were categorized and described using a qualitative method (template analysis). RESULTS: Seventy-two percent (68 of 93) of patients rated radiography as very important. The proportion was higher for men than women (85% vs. 65%, P = 0.04), higher for those with worsening than those with improving/unchanged symptoms (86% vs. 65%, P = 0.03), and higher for inappropriately than appropriately referred patients (NR: 76% vs. 61%, P = 0.17; BR: 81% vs. 56%, P = 0.01). The qualitative analysis showed that the patients related their views on the importance and usefulness of receiving radiography to seven different issues: symptoms and clinical history, information and advice (especially from health care providers), need for emotional support from the physician, need for certainty and reassurance, need for symptom explanation and diagnosis, reliability of radiography compared with clinical evaluation, and expected practical consequences of the radiologic examination. CONCLUSIONS: The finding that inappropriately referred patients tended to rate their radiography referral as more important than appropriately referred patients indicates that the patient's view may be a substantial barrier to appropriate use of radiography. The study identified seven issues underlying the patients' views on importance and usefulness of receiving radiography. Strategies to prevent unnecessary use of plain radiography for low back pain that address these issues are suggested.

Psychosomatic Symptoms among Victims of School Bullying.

Associations between being a victim of bullying and psychosomatic health have been examined among 856 Norwegian school adolescents aged 13 to 15 years. Multiple logistic and linear regression analyses were applied. Pupils being bullied sometimes or more often during the previous term had significantly higher odds of every psychosomatic symptom except sleeplessness, compared to pupils who reported that they were never exposed to bullying. The highest odds ratio was observed in analysis of feeling low. No significant interactions with gender or age were seen, but the association with irritability, headache and backache tended to be strongest for boys, whereas the association with nervousness and sleeplessness was strongest for girls. Increasing exposure to bullying was associated with a highly significant increase in number of symptoms. The strong and consistent associations with different symptoms and the dose-response relationship suggest a causal relationship.

Risk of symptoms related to late effects of poliomyelitis.

OBJECTIVE: To compare the risk of developing symptoms related to late effects of poliomyelitis between polio patients and persons of similar age and sex without history of poliomyelitis. MATERIAL AND METHODS: The study comprised information on 148 patients with prior poliomyelitis and 115 persons with no history of poliomyelitis. Information was obtained by questionnaire and analyzed by multiple logistic regression method. RESULTS: The risk of experiencing two or more symptoms was significantly higher among the polio patients than among the persons without history of poliomyelitis. The elevation in risk was less pronounced in the nonparalytic group (OR = 2.35; 95% CI = 0.92-5.97) than the group with permanent muscular weakness (OR = 8.84; 95% CI =4.32-18.09). CONCLUSIONS: Although symptoms defined in the PPS are unspecific and may occur in the general population, the risk for developing such symptoms are higher among the polio victims. The difference in risk among nonparalytic and paralytic patients may depend on the extent of motor neuron damage in the acute stage.

Modeling effects of age at and time since delivery on subsequent risk of cancer.

We describe a simple model for examining the temporal effects of childbirth on cancer risk, considering data on uniparous and nulliparous women, from either a cohort or case-control study design. For uniparous women, the expression for risk includes terms for age at delivery and time since delivery. With a suitable definition of the effect of uniparity, no terms relating to delivery are needed for nulliparous women. If the pure age effect is assumed to be the same in all women, the effects of age at delivery and time since delivery are both estimable, despite the linear dependence involving attained age in uniparous women. Omitting terms for time since delivery and considering the heterogeneity of age-specific effects of uniparity provides a valid test for the effect of time since delivery, although risk estimates are biased. Tests based on linear interaction terms for age at delivery and attained age, as applied in recent case-control studies, are not appropriate for investigating the effect of time since delivery. We show how our basic model may be applied to the analysis of case-control data from a Norwegian study of breast cancer. We then compare these results with those from other models.

[Radiography of the lumbosacral spine--do the referrals conform to clinical recommendations?]. / Røntgen lumbosakralcolumna--er henvisningene i samsvar med kliniske anbefalinger?

The aim of this study was to evaluate how referrals from Norwegian general practitioners for plain radiography of the lumbosacral spine conform to clinical recommendations. The clinical information given in 274 referral letters was compared with Norwegian and British recommendations. We also interviewed 99 of the patients about symptoms and prior radiographs, and performed a new comparison using all available information. Only 27% (43%) of the 274 referrals conformed to the Norwegian (British) recommendations, 36% (41%) did not conform, and 37% (16%) were considered uncertain, mainly because of lack of pertinent information in the referral letters. Of 143 referrals which were in disagreement with the Norwegian and/or the British recommendations, only four resulted in "important" findings (osteoporotic fractures in two patients, uncertain sacroiliac joint arthritis in one patient, and probably benign bony sclerosis in one patient). In the interview group, the proportion of non-conforming referrals decreased from 40% (47%) to 31% (29%) when the additional clinical information was considered. Nevertheless, we conclude that a substantial proportion of referrals for plain radiography of the lumbosacral spine do not conform to clinical recommendations. Referrals outside the advised criteria yield few relevant findings and could probably be cancelled.

Effect of bupivacaine on pain after tonsillectomy: a randomized clinical trial.

Several authors have found that pre-incisional injection of local anaesthetics reduces postoperative pain. In the present double-blind study, comprising 126 inpatients aged 6-42 (mean 19) years, we investigated whether pre-incisional injection of bupivacaine during general anaesthesia reduces the pain experienced after tonsillectomy. The patients were randomized into three treatment groups: 43 patients were injected with 5 ml of bupivacaine (2.5 mg/ml)+ epinephrine (5 microg/ml) solution in both tonsillar fossa, 41 had epinephrine (5 microg/ml) + saline (9 mg/ml) and 42 patients received saline (9 mg/ml) only. Self-assessment of pain during the first postoperative week (repeated measures) was recorded. Use of analgetics, experience of the surgeons, peroperative bleeding and several other clinical parameters were assessed. Analyses of covariance with repeated measures was carried out for each pain score. In general there was no statistical significant difference in pain scores, represented by a visual analogue scale (VAS) between the three treatment groups. However, injection of bupivacaine into the tonsillar fossa seemed to reduce pain shortly after the operation in the age group 19-24 years. Further, females and older patients reported more pain and used more analgetics than males and younger patients. Increasing experience of the surgeon was related to a lower score for baseline pain shortly after the operation. Epinephrine in bupivacaine or saline reduced peroperative bleeding. We conclude that bupivacaine does not provide significant postoperative analgesia after tonsillectomy in an unselected group of patients.

Joint effects on cancer risk of age at childbirth, time since birth and attained age: circumventing the problem of collinearity.

In previous studies of female cancer risk, we introduced a new method for circumventing the problem of collinearity in age-adjusted analysis of the joint effects of age at birth and time since birth. The basic idea was to estimate the pure age effect considering nulliparous women, assuming that the age effect is common to all women. However, risk estimates for attained age obtained in this manner may suffer from bias, in particular in small data sets, which may in turn influence risk estimates for reproductive factors among parous women. Certain factors possibly affecting cancer risk among nulliparous women only, for instance biological infertility, might also introduce bias. The purpose of this paper is to investigate the accuracy of risk estimates obtained by the joint approach, and to reveal the extent of bias in traditional separate age-adjusted analyses of age at birth or time since birth among parous women. Results are based on analyses of simulated data sets reflecting reproductive and demographic characteristics of a cohort of 1.1 million Norwegian women. Incidence rate ratios are calculated in Poisson regression analyses of person-years at risk. Our simulations show that the joint analysis in general yields unbiased risk estimates, but the number of cases must be rather high to achieve reliable results. Risk estimates from separate analyses can be seriously biased, although the amount of bias depends on the strength and direction of associations with cancer risk. With a total of 5500 cancer cases, the estimators for age at last birth and time since last birth were 13-78 per cent and 5-66 per cent more efficient in the joint than in the separate analysis, respectively. Significance levels were close to the nominal 5 per cent in the joint analysis, but about twice as high in the separate analysis. Adding an effect of biological infertility on cancer risk among nulliparous women, without taking it into account in the analyses, did not seriously affect risk estimates in the joint model.

Use of pelvic surface coil MR imaging for assessment of clinically localized prostate cancer with histopathological correlation.

We evaluated the ability of magnetic resonance imaging (MRI) operating at 1.0 Tesla with a Helmholz pelvic surface coil to predict the pathological stage of prostate carcinoma. Radiological diagnosis was based on fast spin-echo axial T2-weighted images with and without frequency selective fat-suppression and fast spin-echo coronal T2-weighted images. Thirty-one consecutive patients (mean age 61 years, range 49 to 71 years) underwent pelvic MRI before radical prostatectomy. Correlation with whole-mount step-sections of the surgical specimens showed that the tumours were correctly localized in all but one prostate gland in which the tumour could not be seen on pelvic MRI. The transverse diameter of the visible tumour at pelvic MRI appeared to represent an approximate estimate of the true tumour dimension. Based on histopathologic whole-mount step-sections of the surgical specimens, 22 of 31 patients (71%) had tumours extending beyond the confines of the prostatic capsule. The specificity for MRI to predict capsular penetration and seminal vesicle invasion was relatively high (0.80 and 0.86, respectively). The sensitivity was acceptable for capsular penetration (0.62) but poor for seminal vesicle invasion (0.30).

MRI with an endorectal coil for staging of clinically localised prostate cancer prior to radical prostatectomy.

The purpose of this study was to evaluate the ability of MR imaging with an endorectal coil (erMRI) to predict the local pathological stage of prostatic carcinoma prior to radical prostatectomy. Thirty-one consecutive patients (median age 61 years, range 40-71 years) with clinically localised prostate cancer were assessed preoperatively by endorectal MRI (at 1.0 T). The pulse sequences consisted of fast spin-echo axial and coronal T2-weighted images and inversion recovery with two echoes for axial fat-suppressed images. The assessment of tumour stage and measurement of tumour dimension by erMRI were compared with the corresponding findings on whole-mount step sections of the surgical specimens. Postoperatively, 14 of the 31 patients (45 %) were found to have extracapsular extension, 7 with capsular penetration (CP) only, and 7 had a combination of CP and seminal vesicle invasion (SVI). Capsular penetration was detected by erMRI with a sensitivity of 0.71 and specificity of 0.47, whereas the sensitivity for SVI detection was 0.71 and the specificity 0.83. Endorectal MRI for staging clinically localised prostatic carcinoma gives a good prediction of invasion of the seminal vesicles but is unreliable in predicting capsular penetration.

Plain radiography of the lumbosacral spine. An audit of referrals from general practitioners.

PURPOSE: To evaluate how referrals from Norwegian general practitioners for plain radiography of the lumbosacral spine conform to clinical recommendations, and whether non-conforming referrals yield important findings. MATERIAL AND METHODS: The clinical information reported in referral letters of 323 patients was compared with recommendations given in a Norwegian and in a British "guide". Additional clinical data were obtained by interviewing 100 of the patients. Using all available information, a new comparison was performed. Radiological findings were obtained from the routine reports. RESULTS: Of the 323 referrals, 24% (37%) conformed to the Norwegian (British) "guide", 34% (46%) did not conform, and 42% (18%) were considered uncertain, mainly because of lack of pertinent information in the referral letters. A total of 182 examinations were in disagreement with one or both "guides". Only 4 of these examinations revealed potentially important findings (osteoporotic fractures in 2 patients, uncertain sacroiliac joint arthritis in 1 patient, and "probably benign" sclerotic densities in 1 patient). In the interview group, the proportion of non-conforming referrals was 40% (48%) based on the referral letters, and 31% (30%) when the interview data were taken into account. CONCLUSION: A great proportion of referrals for plain radiography of the lumbosacral spine do not conform to recent clinical recommendations. Referrals outside the advised criteria yield few relevant findings and could probably be cancelled. They require at least supplementary information to justify radiography.

School-related stress and psychosomatic symptoms among school adolescents.

Associations between psychosomatic symptoms and school-induced stress, and personal and social resources were analyzed among 862 Norwegian adolescents ages 13-15 years participating in the WHO project, "Health Promoting Schools." Stress-related factors were represented by the average of scores of 3-12 items. Both in combined and separate analyses of each psychosomatic symptom, increasing school distress, the most direct measure of stress experience, was associated with increased risk. A similar relationship was found with school alienation, though not significant for all symptoms. Social support from the teacher decreased the risk among girls, whereas social support from other pupils reduced the risk among both genders, but in particular among boys. No consistent associations were seen between psychosomatic complaints and general or school-related self-efficacy or decision control. In some analyses, however, these factors seemed to modify the association with school distress or school alienation.

Observer variation in plain radiography of the lumbosacral spine.

In this study, interobserver and intraobserver variations in the interpretation of plain radiographs of the lumbosacral spine were evaluated. Three radiologists independently interpreted the radiographs from 200 consecutive outpatients, aged 13-93 years, mostly referred from general practitioners. Interobserver agreement was best for vertebral fractures, osteopenia, spondylolisthesis at L5-S1, lumbosacral junctional vertebra, reduced disc height at L4-S1 and osteophytes at L2-S1 (kappa 0.61-0.95), and poorest for spina bifida of S1, degenerative spondylolisthesis and facet joint arthrosis at T12-L4, sacroiliac joint arthrosis, narrow central spinal canal, film quality, and for decisions concerning evaluation of facet joints and spinal canal (kappa < 0.34). For several diagnoses, the number of abnormal findings differed significantly between observers (p < 0.05, McNemar's test), indicating different diagnostic thresholds. Intraobserver agreement in 36 reevaluated patients was fair to excellent for almost all variables (kappa > 0.46). Although some diagnoses related to low back pain were quite consistently evaluated, the substantial disagreement on many findings should alert clinicians and radiologists against overestimating the validity and usefulness of the examinations. To improve diagnostic consistency, it is important to reduce variation caused by different thresholds for abnormality.

Lymphangiography combined with biopsy and computer tomography to detect lymph node metastases in localized prostate cancer.

To evaluate the efficacy of lymphangiography combined with fine needle aspiration biopsy and computer tomography (CT) for lymph node staging in clinically localized prostate cancer. Prospective evaluation of nodal involvement was carried out using standard bipedal lymphangiography combined with fine needle aspiration biopsy (FNAB) in 70 patients (aged 47 to 75 years, mean age 63 years) with apparently locally confined prostate cancer before intended radical prostatectomy. Sixty-four patients also underwent computer tomography. Seventeen withdrew the decision to undergo a radical prostatectomy, leaving 53 patients with pathologic examination of the lymph nodes eligible for analysis. Lymph node metastases were diagnosed in 8 patients (8/53 = 15.1%). Three were diagnosed preoperatively by FNAB, 3 peroperatively by lymph node dissection and frozen section biopsy and an additional 2 at the final pathologic assessment. The sensitivity, specificity, positive and negative predictive values for lymphangiography and lymphangiography combined with FNAB in predicting nodal disease, based on the analysis of the 53 patients with known pathologic results, were 0.63, 0.76, 0.31, 0.92 and 0.38, 1.00, 1.00, 0.90, respectively. The corresponding values for CT staging were 0.25, 0.98, 0.67 and 0.87, respectively. The efficacy of bipedal lymphangiography alone or combined with FNAB or CT alone for assessment of nodal metastases is too low to be worthwhile for lymph node staging in localized prostate cancer patients with expected low or intermediate probability of nodal disease.

Poorer survival of nulliparous women with endometrial carcinoma.

BACKGROUND: Several epidemiologic studies have shown an inverse relationship between parity and the incidence of endometrial carcinoma. A prognostic influence of reproductive factors has been reported for carcinomas of the breast and uterine cervix; but no such independent influence has been reported for endometrial carcinoma, to the authors' knowledge. Therefore, the authors investigated the prognostic importance of parity in an unselected group of patients. METHODS: Clinical and histopathologic data on all 316 patients treated for endometrial carcinoma during the period 1981-1990 in Hordaland County, Norway, were related to cause specific death in univariate (Kaplan-Meier) and multivariate (Cox proportional hazards regression model) analyses. The median follow-up for the survivors was 9 years (range, 4-16 years). No patients were lost due to insufficient follow-up information. RESULTS: Nulliparous women had a poorer 5-year survival rate compared with patients who had had 1 or more deliveries (57% vs. 81%, P = 0.0001), and they were significantly older and had more advanced disease at the time of primary surgery than the parous women. After adjustment for traditional risk factors, a hazard ratio of 2.81 (95% confidence interval, 1.55-5.06) was found for nulliparous versus parous women. International Federation of Gynecology and Obstetrics stage, curative treatment, and tumor differentiation grade were also identified as independent prognostic factors, whereas age and menopausal status had prognostic significance in the univariate analysis only. CONCLUSIONS: The decreased survival among nulliparous women reported herein may reflect biologic differences between parous and nulliparous endometrial carcinoma patients. It may also be due in part to a greater delay in diagnosing the women in the nulliparous group.