Staphylococcus aureus in the nose and throat of Iowan families.

The study objective was to determine the prevalence of Staphylococcus aureus colonisation in the nares and oropharynx of healthy persons and identify any risk factors associated with such S. aureus colonisation. In total 263 participants (177 adults and 86 minors) comprising 95 families were enrolled in a year-long prospective cohort study from one urban and one rural county in eastern Iowa, USA, through local newspaper advertisements and email lists and through the Keokuk Rural Health Study. Potential risk factors including demographic factors, medical history, farming and healthcare exposure were assessed. Among the participants, 25.4% of adults and 36.1% minors carried S. aureus in their nares and 37.9% of adults carried it in their oropharynx. The overall prevalence was 44.1% among adults and 36.1% for minors. Having at least one positive environmental site for S. aureus in the family home was associated with colonisation (prevalence ratio: 1.34, 95% CI: 1.07-1.66). The sensitivity of the oropharyngeal cultures was greater than that of the nares cultures (86.1% compared with 58.2%, respectively). In conclusion, the nares and oropharynx are both important colonisation sites for healthy community members and the presence of S. aureus in the home environment is associated with an increased probability of colonisation.

Examining sex differences in knee pain: the multicenter osteoarthritis study.

OBJECTIVE: To determine whether women experience greater knee pain severity than men at equivalent levels of radiographic knee osteoarthritis (OA). DESIGN AND METHODS: A cross-sectional analysis of 2712 individuals (60% women) without knee replacement or a recent steroid injection. Sex differences in pain severity at each Kellgren-Lawrence (KL) grade were assessed by knee using visual analog scale (VAS) scale and Western Ontario and McMaster Universities Arthritis Index (WOMAC) with and without adjustment for age, analgesic use, Body mass index (BMI), clinic site, comorbid conditions, depression score, education, race, and widespread pain (WSP) using generalized estimating equations. Effect sizes (Cohen's d) were also calculated. Analyses were repeated in those with and without patellofemoral OA (PFOA). RESULTS: Women reported higher VAS pain at all KL grades in unadjusted analyses (d = 0.21-0.31, P < 0.0001-0.0038) and in analyses adjusted for all covariates except WSP (d = 0.16-0.22, P < 0.0001-0.0472). Pain severity differences further decreased with adjustment for WSP (d = 0.10-0.18) and were significant for KL grade ≤2 (P = 0.0015) and 2 (P = 0.0200). Presence compared with absence of WSP was associated with significantly greater knee pain at all KL grades (d = 0.32-0.52, P < 0.0001-0.0008). In knees with PFOA, VAS pain severity sex differences were greater at each KL grade (d = 0.45-0.62, P = 0.0006-0.0030) and remained significant for all KL grades in adjusted analyses (d = 0.31-0.57, P = 0.0013-0.0361). Results using WOMAC were similar. CONCLUSIONS: Women reported greater knee pain than men regardless of KL grade, though effect sizes were generally small. These differences increased in the presence of PFOA. The strong contribution of WSP to sex differences in knee pain suggests that central sensitivity plays a role in these differences.

The relationship between quadriceps muscle weakness and worsening of knee pain in the MOST cohort: a 5-year longitudinal study.

OBJECTIVE: To determine whether quadriceps weakness is associated with elevated risk of worsening knee pain over 5 years. METHODS: The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of 50-79-year-old adults with knee osteoarthritis (OA) or known risk factors for knee OA. The predictor variable was baseline isokinetic quadriceps strength. Covariates included baseline body mass index (BMI), physical activity level, and history of knee surgery. The outcome was worsening pain reported on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale or knee replacement surgery between baseline and 5-year follow-up. Analyses were knee-based and used generalized estimating equations, stratified by sex to assess whether the lowest compared with the highest tertile of baseline quadriceps strength was associated with an increased risk of worsening knee pain at 5-year follow-up, controlling for age, BMI, history of knee surgery, and physical activity level as well as correlation between knees within participants. RESULTS: Analyses of worsening knee pain included 4,648 knees from 2,404 participants (61% female). Men with lower quadriceps strength did not have a higher risk of worsening knee pain (RR {95% CI} = 1.01 {0.78-1.32}, P = 0.9183). However, women in the lowest compared with the highest strength tertile had a 28% increased risk of worsening knee pain (RR {95% CI} = 1.28 {1.08-1.52}, P = 0.0052). CONCLUSION: Quadriceps weakness was associated with an increased risk of worsening of knee pain over 5 years in women, but not in men.

The longitudinal relationship between thigh muscle mass and the development of knee osteoarthritis.

OBJECTIVE: Greater quadriceps strength has been found to reduce risk for symptomatic knee osteoarthritis (SxKOA) and knee joint space narrowing (JSN). However, this finding could relate to muscle mass or activation pattern. The purpose of this study was to assess whether greater thigh muscle mass protects against (1) incident radiographic (RKOA), (2) incident SxKOA or (3) worsening of knee JSN by 30-month follow-up. DESIGN: Multicenter Osteoarthritis (MOST) study participants, who underwent dual-energy X-ray absorptiometry (DXA) at the Iowa site were included. Thigh muscle mass was calculated from DXA image sub-regions. Sex-stratified, knee-based analyses controlled for incomplete independence between limbs within subjects. The effect of thigh lean mass and specific strength as predictors of ipsilateral RKOA, SxKOA and worsening of JSN were assessed, while controlling for age, body mass index (BMI), and history of knee surgery. RESULTS: A total of 519 men (948 knees) and 784 women (1453 knees) were included. Mean age and BMI were 62 years and 30 kg/m(2). Thigh muscle mass was not associated with risk for RKOA, SxKOA or knee JSN. However, in comparison with the lowest tertile, those in the highest and middle tertiles of knee extensor specific strength had a lower risk for SxKOA and JSN [odds ratio (OR) 0.29-0.68]. CONCLUSIONS: Thigh muscle mass does not appear to confer protection against incident or worsening knee OA. These findings suggest that future studies of risk for knee OA should focus on the roles of knee extensor neuromuscular activation and muscle physiology, rather than the muscle mass.

Elevated tibiofemoral articular contact stress predicts risk for bone marrow lesions and cartilage damage at 30 months.

OBJECTIVE: As cartilage loss and bone marrow lesions (BMLs) are associated with knee joint pain and structural worsening, this study assessed whether non-invasive estimates of articular contact stress may longitudinally predict risk for worsening of knee cartilage morphology and BMLs. DESIGN: This was a longitudinal cohort study of adults aged 50-79 years with risk factors for knee osteoarthritis. Baseline and follow-up measures included whole-organ magnetic resonance imaging score (WORMS) classification of knee cartilage morphology and BMLs. Tibiofemoral geometry was manually segmented on baseline magnetic resonance imaging (MRI), and three-dimensional (3D) tibiofemoral point clouds were registered into subject-specific loaded apposition using fixed-flexion knee radiographs. Discrete element analysis (DEA) was used to estimate mean and peak contact stresses for the medial and lateral compartments. The association of baseline contact stress with worsening cartilage and BMLs in the same subregion over 30 months was assessed using conditional logistic regression. RESULTS: Subjects (N = 38, 60.5% female) had a mean ± standard deviation (SD) age and body mass index (BMI) of 63.5 ± 8.4 years and 30.5 ± 3.7 kg/m2 respectively. Elevated mean articular contact stress at baseline was associated with worsening cartilage morphology and worsening BMLs by 30 months, with odds ratio (OR) [95% confidence interval (CI)] of 4.0 (2.5, 6.4) and 6.6 (2.7, 16.5) respectively. Peak contact stress also was significantly associated with worsening cartilage morphology and BMLs {1.9 (1.5, 2.3) and 2.3 (1.5, 3.6)}(all P < 0.0001). CONCLUSIONS: Detection of higher contact stress 30 months prior to structural worsening suggests an etiological role for mechanical loading. Estimation of articular contact stress with DEA is an efficient and accurate means of predicting subregion-specific knee joint worsening and may be useful in guiding prognosis and treatment.

Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study.

In osteoarthritis (OA) the synovium is often inflamed and inflammatory cytokines contribute to cartilage damage. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory effects whereas omega-6 polyunsaturated fatty acids (n-6 PUFAs) have, on balance, proinflammatory effects. The goal of our study was to assess the association of fasting plasma phospholipid n-6 and n-3 PUFAs with synovitis as measured by synovial thickening on contrast enhanced (CE) knee MRI and cartilage damage among subjects in the Multicenter Osteoarthritis Study (MOST). MOST is a cohort study of individuals who have or are at high risk of knee OA. An unselected subset of participants who volunteered obtained CE 1.5T MRI of one knee. Synovitis was scored in six compartments and a summary score was created. This subset also had fasting plasma, analyzed by gas chromatography for phospholipid fatty acid content, and non-CE MRI, read for cartilage morphology according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) method. The association between synovitis and cartilage morphology and plasma PUFAs was assessed using logistic regression after controlling for the effects of age, sex, and BMI. 472 out of 535 subjects with CE MRI had complete data on synovitis, cartilage morphology and plasma phospholipids. Mean age was 60 years, mean BMI 30, and 50% were women. We found an inverse relation between total n-3 PUFAs and the specific n-3, docosahexaenoic acid with patellofemoral cartilage loss, but not tibiofemoral cartilage loss or synovitis. A positive association was observed between the n-6 PUFA, arachidonic acid, and synovitis. In conclusion, systemic levels of n-3 and n-6 PUFAs which are influenced by diet, may be related to selected structural findings in knees with or at risk of OA. Future studies manipulating the systemic levels of these fatty acids may be warranted to determine the effects on structural damage in knee OA.

Relation of MRI-Detected Features of Patellofemoral Osteoarthritis to Pain, Performance-Based Function, and Daily Walking: The Multicenter Osteoarthritis Study.

OBJECTIVE: The study objective was to determine the relationship of magnetic resonance imaging (MRI)-detected features of patellofemoral joint osteoarthritis to pain and functional outcomes. METHODS: We sampled 1,099 participants from the 60-month visit of the Multicenter Osteoarthritis Study (mean ± SD age: 66.8 ± 7.5 years; body mass index: 29.6 ± 4.8; 65% female). We determined the prevalence of MRI-detected features of patellofemoral joint osteoarthritis (eg, cartilage damage, bone marrow lesions, and osteophytes) and assessed the relationship between these features and knee pain severity, knee pain on stairs, chair stand time, and walking less than 6,000 steps per day. We evaluated the relationship of MRI features to each outcome using logistic and linear regression, adjusting for potential covariates. RESULTS: Participants with cartilage damage in 3-4 subregions had the highest mean pain severity (22.0/100; 95% confidence interval [CI]: 17.6-26.4 mm). They also showed higher odds of having at least mild pain on stairs (odds ratio [OR]: 3.3; 95% CI: 1.7-6.5) and of walking less than 6,000 steps per day (OR: 2.3; 95% CI: 1.1-4.4) compared with those without cartilage damage. Participants with bone marrow lesions in 3-4 subregions had higher odds of at least mild pain on stairs than those without (OR: 3.3; 95% CI: 2.2-5.2). Participants with osteophytes in 3-4 subregions also had higher odds of walking less than 6,000 steps/day (OR 2.1, 95% CI: 1.3-3.5, respectively). CONCLUSION: MRI-detected features of osteoarthritis of the patellofemoral joint are related to pain and functional performance. This knowledge highlights the need to develop treatments for those with patellofemoral joint osteoarthritis to improve pain and maximize function.

Cyst-like lesions of the knee joint and their relation to incident knee pain and development of radiographic osteoarthritis: the MOST study.

OBJECTIVE: To determine whether intra- and periarticular cyst-like lesions of the knee are associated with incident knee pain and incident radiographic knee osteoarthritis (OA). DESIGN: The Multicenter Osteoarthritis (MOST) Study is a cohort of individuals who have or are at high risk for knee OA. Using a nested case-control study design, we investigated the associations of cyst-like lesions (Baker's, meniscal and proximal tibiofibular joint (PTFJ) cysts, and prepatellar and anserine bursitides) with (1) incident pain at 15- or 30-month follow-up and (2) incident radiographic OA at 30-month follow-up. Baseline cyst-like lesions were scored semiquantitatively using the Whole Organ Magnetic Resonance Imaging Score (WORMS). Conditional logistic regression models were used to assess the relation between these lesions and the outcomes, adjusting for potential confounding factors (i.e., cartilage loss, meniscal damage, bone marrow lesions, synovitis and joint effusion, which were also scored using WORMS). RESULTS: Incident knee pain study included 157 cases and 336 controls. Prevalence of meniscal and PTFJ cysts in the case group was twice that in the control group [9 (6%) vs 9 (3%) and 9 (6%) vs 10 (3%), respectively]. Incident radiographic OA study included 149 cases and 298 controls. Prevalence of grade 2 Baker's cysts and PTFJ cysts in the case group was approximately four times that in the control group [16(11%) vs 9 (3%) and 6 (4%) vs 3 (1%), respectively]. However, none of the cyst-like lesions was associated with incident pain or radiographic OA after fully adjusted logistic regression analyses and correction of P-values for multiple comparisons. CONCLUSION: None of the analyzed lesions was an independent predictor of incident knee pain or radiographic OA. Intra- and periarticular cyst-like lesions are likely to be a secondary phenomenon seen in painful or OA-affected knees, rather than a primary trigger for incident knee pain or radiographic OA.

Baseline NIH stroke scale responses estimate the probability of each particular stroke subtype.

BACKGROUND: Emergency treatment of ischemic stroke should ideally be mechanism specific, but acute subtype diagnosis is problematic. Since different subtypes often are associated with specific patterns of neurological deficits, we hypothesize that scores on baseline NIH stroke scale (NIHSS) items may help emergently stratify patients by their probability of having a particular stroke subtype. METHODS: We performed multivariate polytomous logistic regression analyses on 1,281 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). We tested the predictive value of individual items to the baseline NIHSS exam, and syndromic combinations of those items, in anticipating the TOAST stroke subtype at 3 months adjusting for atrial fibrillation. We then used the most significant NIHSS items to construct a predictive model. RESULTS: The NIHSS items that discriminate between stroke subtypes are language, neglect, visual field and brachial predominance of weakness. Among patients without atrial fibrillation, a normal score for these 4 variables conveys a 46% chance of lacunar stroke, 12% of atherothrombotic stroke and 10% of cardioembolism. This pattern gradually reverses with increased numbers of abnormal responses. Those with abnormalities in all 4 items have a 0.1% chance of lacunar stroke, 50% of atherothrombotic stroke and 39% of cardioembolism. CONCLUSIONS: Language, neglect, visual fields and brachial predominance of weakness in the baseline NIHSS help discriminate between subtypes, particularly between lacunar and nonlacunar strokes. Clinical trials testing interventions aimed to particular stroke mechanisms may use these NIHSS items to emergently stratify patients based on their probability of having a particular stroke subtype.

Subjective and objective measures of physical activity in relationship to bone mineral content during late childhood: the Iowa Bone Development Study.

OBJECTIVE: This study compared accelerometry to self-report for the assessment of physical activity (PA) in relation to bone mineral content (BMC). In addition, we compared the ability of these measures to assess PA in boys versus girls. METHODS: Participants in this cross-sectional study included 449 children (mean age 11 years) from the Iowa Bone Development Study. PA was measured via 3-5 days of accelerometry using the Actigraph and 7 day self-report questionnaire using the Physical Activity Questionnaire for Children (PAQ-C). Hip, spine, and whole body BMC were measured via dual energy x ray absorptiometry (DXA). RESULTS: Partial correlation analysis (controlling for height, weight, and maturity) showed the Actigraph was significantly associated with hip (r = 0.40), spine (r = 0.20), and whole body (r = 0.33) BMC in boys, as was the PAQ-C (r = 0.28 hip, r = 0.19 spine, and r = 0.22 whole body). Among girls, only the Actigraph was significantly associated with hip (r = 0.18) and whole body (r = 0.16) BMC. Both the Actigraph and PAQ-C were significant in hip, spine, and whole body multivariable linear regression models (after controlling for body size and maturity) in boys. Only the Actigraph entered hip BMC regression model in girls. CONCLUSIONS: Our study supports previous work showing associations between everyday PA and BMC in older children. These associations are more likely to be detected with an objective versus subjective measure of PA, particularly in girls.

Correlations of Medial Joint Space Width on Fixed-Flexed Standing Computed Tomography and Radiographs With Cartilage and Meniscal Morphology on Magnetic Resonance Imaging.

OBJECTIVE: To assess whether medial tibiofemoral joint space width (JSW) on 3-dimensional (3-D) standing computed tomography (SCT) correlates more closely with magnetic resonance imaging cartilage morphology (CM) and meniscal scores than does radiographic 2-D JSW. METHODS: Participants in the Multicenter Osteoarthritis Study, who had standing fixed-flexion posteroanterior knee radiographs, were recruited. Medial tibiofemoral 3-D JSW on SCT and 2-D JSW on fixed-flexion radiographs were compared with medial tibiofemoral cartilage and meniscal morphology using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations between the area of the articular surface with 3-D JSW <2.5 mm on SCT, radiographic minimal 2-D JSW, and the WORMS-CM and meniscal scores were assessed using Spearman's rho. RESULTS: For the 19 participants included (33 knees), mean ± SD age was 66.9 ± 5.4 years, body mass index was 29.5 ± 4.4 kg/m(2) , 42.1% of participants were female, and the Kellgren/Lawrence grades were 0 (21.2%), 1 (36.4%), 2 (18.2%), and 3 (24.2%). The articular surface area with 3-D JSW <2.5 mm on SCT correlated with WORMS-CM scores for the central medial tibia (rs = 0.84, P < 0.001), central medial femur (rs = 0.60, P < 0.007), and posterior medial meniscal tear (rs = 0.39, P < 0.026), as did other cut points for 3-D JSW. Correlations with radiographic minimal 2-D JSW were -0.66, -0.52, and -0.40, respectively, differing from SCT only for tibial cartilage (P = 0.001). CONCLUSION: Greater surface area with a low JSW, measured by SCT, correlates more strongly with the severity of tibial cartilage lesions, while correlating with medial femoral cartilage and meniscal damage to a similar extent as radiographic minimal JSW. SCT may enable valid stratification of participants in clinical trials, through quickly and inexpensively characterizing osteoarthritis features.

Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment.

BACKGROUND: The management of unruptured intracranial aneurysms is controversial. Investigators from the International Study of Unruptured Intracranial Aneurysms aimed to assess the natural history of unruptured intracranial aneurysms and to measure the risk associated with their repair. METHODS: Centres in the USA, Canada, and Europe enrolled patients for prospective assessment of unruptured aneurysms. Investigators recorded the natural history in patients who did not have surgery, and assessed morbidity and mortality associated with repair of unruptured aneurysms by either open surgery or endovascular procedures. FINDINGS: 4060 patients were assessed-1692 did not have aneurysmal repair, 1917 had open surgery, and 451 had endovascular procedures. 5-year cumulative rupture rates for patients who did not have a history of subarachnoid haemorrhage with aneurysms located in internal carotid artery, anterior communicating or anterior cerebral artery, or middle cerebral artery were 0%, 2. 6%, 14 5%, and 40% for aneurysms less than 7 mm, 7-12 mm, 13-24 mm, and 25 mm or greater, respectively, compared with rates of 2 5%, 14 5%, 18 4%, and 50%, respectively, for the same size categories involving posterior circulation and posterior communicating artery aneurysms. These rates were often equalled or exceeded by the risks associated with surgical or endovascular repair of comparable lesions. Patients' age was a strong predictor of surgical outcome, and the size and location of an aneurysm predict both surgical and endovascular outcomes. INTERPRETATION: Many factors are involved in management of patients with unruptured intracranial aneurysms. Site, size, and group specific risks of the natural history should be compared with site, size, and age-specific risks of repair for each patient.

Effects of naloxone on canine cerebral vascular smooth muscle.

The pharmacological effects of naloxone on cerebral arterial smooth muscle in vitro were examined using canine basilar arterial strips. Naloxone exerted two different effects on canine basilar artery: (1) at a high concentration (3 X 10(-4) M) it produced nonspecific vasodilation, and (2) at lower concentrations (3 X 10(-7), 3 X 10(-6), and 3 X 10(-5) M) it inhibited the vasoconstrictor effects of norepinephrine without altering KCl-, serotonin-, or hemoglobin-induced constriction. Morphine (2 X 10(-5) or 2 X 10(-4) M) did not reverse the specific vasodilating effect of naloxone (3 X 10(-5) M) on norepinephrine-induced constriction. Rather, morphine and naloxone together produced a greater vasodilating effect on norepinephrine-induced constriction than either agent alone. Naloxone (3 X 10(-5) M) failed to alter either phenylephrine-induced constriction or clonidine-induced constriction. The vasodilating effect of naloxone (3 X 10(-5) M) on 10(-3) M norepinephrine-induced constriction was not reduced with 10(-6) M propranolol. These results suggest that the vasodilating effect of naloxone on norepinephrine-induced constriction does not result from an antagonistic action on opiate receptors, direct inhibition of alpha-adrenoreceptors, or direct stimulation of beta-adrenoreceptors in canine cerebral arterial smooth muscle. The vasodilating effect of naloxone on norepinephrine-induced constriction may influence the CBF changes following naloxone administration.

Intracranial operation within seven days of aneurysmal subarachnoid hemorrhage. Results in 150 patients.

We evaluated the results of intracranial operation in 150 consecutive patients surgically treated within seven calendar days of aneurysmal subarachnoid hemorrhage (SAH). Patients in all clinical grades, except those who were moribund, were treated. Those with either anterior or posterior circulation aneurysms were included. On follow-up assessment, favorable outcomes were noted in 107 patients (71%), 17 had major disabilities (11%), and 26 had died (17%). During hospitalization, vasospasm was diagnosed in 63 patients (42%) and rebleeding occurred in 39 (25%). Operations were performed throughout the first week after SAH; results of operation were similar on each day. A lower rate of good recovery was observed among patients operatively treated four to seven days after SAH than among those operated on earlier. The admitting neurologic condition influenced outcome after early operation, but age did not have a major impact. We find that aneurysm surgery can be performed within one week of SAH with acceptable results, although there is room for improvement.

Prevalence of diabetes mellitus among patients with subarachnoid hemorrhage.

Diabetes mellitus is generally accepted as an important risk factor in cerebrovascular disease. The importance of this condition varies with the type of stroke. Patients with aneurysmal subarachnoid hemorrhages (SAHs) have a lower or equivalent prevalence of diabetes mellitus than the general population. In particular, insulin-dependent diabetes is rarely present prior to aneurysmal rupture. These observations suggest that diabetic patients are not at increased risk for aneurysmal SAH.

Antifibrinolytic therapy in patients with aneurysmal subarachnoid hemorrhage. A report of the cooperative aneurysm study.

Antifibrinolytic therapy was used in 1,114 patients who had aneurysmal subarachnoid hemorrhage (SAH) and who were treated by the 13 institutions of the Cooperative Aneurysm Study. Patients were started on treatment within one week after SAH was diagnosed, and therapy was discontinued 14 days after the ictus. Rebleeding occurred in 10% of the treated patients. Overall mortality among the treated patients during the two weeks following hemorrhage was 10.7%. Though some minor and a few major side effects occurred, serious complications of therapy were infrequent.

Cooperative study of intracranial aneurysms and subarachnoid hemorrhage: a long-term prognostic study. II. Ruptured intracranial aneurysms managed conservatively.

The late natural history of ruptured intracranial aneurysms was studied in 568 cases reported to the Cooperative Study of Intracranial Aneurysms and Subarachnoid Hemorrhage from 1958 to 1965. The patients had been selected for conservative management of their aneurysms at the time of diagnosis. A follow-up search in 1981 and 1982 revealed 378 known deaths; 40% had occurred within six months of hemorrhage. During the next two decades, the patients' survival probabilities were significantly worse than those of a matched US population. Multiple aneurysms did not differ prognostically from single aneurysms, but posterior circle aneurysms carried a better prognosis after ten-year survival. The rate of probable recurrent bleeding after six months was 2.2% per year for the first 9 1/2 years and 0.86% per year for the second decade. Reported rebleeding episodes were fatal in 78%.

Cooperative study of intracranial aneurysms and subarachnoid hemorrhage: a long-term prognostic study. III. Subarachnoid hemorrhage of undetermined etiology.

Among 6,638 cases reported to the Cooperative Study of Intracranial Aneurysms and Subarachnoid Hemorrhage were 477 cases in which the cause of hemorrhage could not be determined after carotid and vertebral angiography. These patients were followed up for up to 24 years after hemorrhage. Twenty patients were subsequently found to have an aneurysm or arteriovenous malformation missed by the first angiographic survey. After six-month survival, the rate of recurrent hemorrhage was a maximum 0.86% per year. Survival was significantly better than that of patients with verified ruptured aneurysms managed conservatively in this cooperative study. For normotensive patients who survived the first six months, the life expectancy for the next 20 years equaled that of an age- and sex-matched US population. Hypertensive patients had a higher mortality than normotensive patients.

Family history and prostate cancer risk in a population-based cohort of Iowa men.

A family history of prostate cancer has been associated with prostate cancer risk in most prior studies, and more limited data suggest that a family history of breast cancer may also be important; however, there are no data from a population-based cohort study of prostate cancer incidence that adjusts for major confounders. We conducted follow-up through 1995 on 1557 men, ages 40-86 years, who were randomly selected (81% response rate) as cancer-free controls for a population-based case-control study conducted in Iowa from 1987-1989. Family history of cancer in parents and siblings was obtained using a mailed questionnaire. Incident cancers and deaths were ascertained through linkages to state and national databases; 101 incident cases of prostate cancer were identified. At baseline, 4.6% of the cohort reported a family history of prostate cancer in a brother or father, and this was positively associated with prostate cancer risk after adjustment for age [relative risk (RR) = 3.2; 95% confidence interval (CI), 1.8-5.7] or after multivariate adjustment for age, alcohol, and dietary factors (RR = 3.7; 95% CI, 1.9-7.2). Risk was greater if a brother had prostate cancer (RR = 4.5; 95% CI, 2.1-9.7) than if a father had prostate cancer (RR = 2.3; 95% CI, 1.0-5.3). Also at baseline, 9.6% of the cohort had a family history of breast and/or ovarian cancer in a mother or sister, and this was positively associated with prostate cancer risk (age-adjusted RR = 1.7; 95% CI, 1.0-3.0; multivariate RR = 1.7; 95% CI, 0.9-3.2). Men with a family history of both prostate and breast/ovarian cancer were also at increased risk of prostate cancer (RR = 5.8; 95% CI, 2.4-14). There was no association with a family history of colon cancer. Exclusion of well-differentiated, localized tumors did not alter these findings. These data from an incidence study confirm that a family history of prostate cancer is a strong prostate cancer risk factor after adjustment for dietary and other risk factors, and suggest that selection and recall bias have not had an important influence on most case-control study results. These data also support the idea that a family history of breast cancer may also be a prostate cancer risk factor.

Epidemiologic evidence for a changing natural history of myasthenia gravis.

OBJECTIVE: To survey the epidemiologic literature for evidence of an increasing prevalence of myasthenia gravis (MG) over time, and to explore the reasons for the increase. DATA SOURCES: We found population-based reports of the epidemiology of MG by searching bibliographic databases. We used MG, epidemiology, prevalence, incidence, and mortality as search terms. STUDY SELECTION: We included population-based studies that reported the number of cases and the time period from which rates were calculated. STATISTICAL METHODS: We performed a regression analysis of rates versus date of study, comparing the slopes of regression lines for prevalence, incidence, and mortality. We performed a second analysis grouping rates by decade of study and calculating a mean rate weighted by the size of the population studied. We calculated 95% confidence intervals for each rate. RESULTS: We included 33 studies from 1950 through 1995. Prevalence and incidence rates increased over time, but the regression line for prevalence significantly exceeded that for incidence. Mortality rates declined slightly. The weighted means for prevalence rose significantly, but there was no significant change in incidence or mortality. CONCLUSION: The prevalence of MG has increased over the past forty-five years, probably because patients with the disease have longer life spans owing to present-day treatment.