Uppsala Health Care Region Research Articles

Reduction of Rod and Cone Function in 6.5-Year-Old Children Born Extremely Preterm

ImportanceThe function of rods and cones in children born extremely preterm has not yet been fully investigated.ObjectiveTo compare retinal function via full-field electroretinographic (ffERG) recordings in 6.5-year-old children born extremely preterm with children born at term.Design, Setting, and ParticipantsA subcohort study was conducted from July 1, 2010, to January 15, 2014, of the national Extremely Preterm Infants in Sweden Study, including preterm children (<27 weeks’ gestational age) and children born at term, at 6.5 years of age and living in the Uppsala health care region in Sweden. Full-field electroretinography was performed binocularly, using DTL electrodes and electroretinographic (ERG) protocols with flash strengths of 0.009, 0.17, 3.0, and 12.0 candelas (cd)/s/m2, together with 30-Hz flicker and 3.0 cd/s/m2 single-cone flash.Main Outcomes and MeasuresThe ffERG recordings were analyzed, and their associations with gestational age and retinopathy of prematurity were examined.ResultsAdequate ffERG recordings were obtained from 52 preterm children (19 girls and 33 boys; mean [SD] age at examination, 6.6 [0.1] years) and 45 children born at term (22 girls and 23 boys; mean [SD] age at examination, 6.6 [0.1] years). Lower amplitudes of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 3.0 cd/s/m2: mean difference, –48.9 μV [95% CI, –80.0 to –17.9 μV]; P=.003; the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2: mean difference, –55.7 μV [95% CI, –92.5 to –18.8 μV]; P = .004), as well as of the isolated cone response (30-Hz flicker ERG: mean difference, –12.1 μV [95% CI, –22.5 to –1.6 μV]; P = .03), were found in the preterm group in comparison with the group born at term. The implicit time of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2) was longer (mean difference, 1.2 milliseconds [95% CI, 0.3-2.0 milliseconds]; P = .01) in the preterm group, as were the isolated cone responses (30-Hz flicker ERG: mean difference, 1.2 milliseconds [95% CI, 0.5-1.8 milliseconds]; P < .001), than in the group born at term. No association was found between the ffERG recordings and gestational age or retinopathy of prematurity in the preterm group.Conclusions and RelevanceBoth rod function and cone function were reduced in children born extremely preterm when compared with children born at term. There was no association with retinopathy of prematurity in the preterm group, which suggests that being born extremely preterm may be one of the main reasons for a general retinal dysfunction.

Clinical course of Crohn’s disease during the first 5 years. Results from a population-based cohort in Sweden (ICURE) diagnosed 2005–2009

Objective: The aim of the study was to describe the medical treatment, change in phenotype, need for surgery and IBD-associated mortality during the first 5 years after diagnosis.Material and Methods: Patients diagnosed with Crohn’s disease including all age groups in the Uppsala healthcare region in the middle of Sweden 2005–2009 were included in the study. Medical notes were scrutinised and patients contacted. Out of 269 patients, 260 (96.3%) could be followed for 5 full years or until death.Results: The following drugs were used: 5-ASA 66.7%, systemic steroids 76.4%, antimetabolites 56.7% and anti-TNF 20.3%. Described with the Montreal classification, the proportion with inflammatory behaviour decreased from 78.1% to 74.0% from diagnosis to end of the observation, patients with stricturing behaviour increased from 13.0% to 15.4% and patients with penetrating behaviour increased from 8.9% to 10.6%. After the first year, 12.4% had been treated with intestinal resection or colectomy, a figure that increased to 14.8 after 5 years. Two patients suffered an IBD-related death.Conclusions: Compared to similar patient cohorts, the present study demonstrates that although the course of Crohn’s disease seems difficult to change during the first year after diagnosis, the following years up to 5 years shows a more benign course than has usually been described earlier.

Low colectomy rate five years after diagnosis of ulcerative colitis. Results from a prospective population-based cohort in Sweden (ICURE) diagnosed during 2005–2009*

Objective: The medical treatment of ulcerative colitis (UC) has seen a change towards a more active attitude during recent years, including both the use of more traditional drugs as well as new biological substances. In this epidemiological study we have evaluated the results of modern treatment of UC in a population-based cohort of patients including all age groups, with regard to relapse rate, colectomy and IBD-associated mortality.Material and methods: Patients diagnosed with UC in the Uppsala health care region in the middle of Sweden during 2005–2009 were included in the study. Out of 524 patients, 491 (93%) could be followed for five full years or until death.Results: Nineteen patients (3.9%) had died and two of these deaths could be attributed to UC (one postoperative death and one colonic carcinoma). The following drugs were used by the patients during the study period: 5-ASA (91%), systemic steroids (66%), immunomodulators (IMM), mainly thiopurines (26%) and anti-TNF (11%). During the observation period, 74% experienced at least one relapse and 5.3% were subjected to colectomy. Among patients <17 years at diagnosis, colectomy was performed in two (4.8%).Conclusions: Five years after diagnosis of ulcerative colitis, 5.3% had been subjected to colectomy and two patients (0.38%) had died because of the disease.

A prospective study of oral contraceptive use and risk of myocardial infarction among Swedish women

To determine the risk for incident myocardial infarction (MI) in women exposed to modern formulations of oral contraceptives (OCs). Population-based, prospective cohort study begun in 1991 with follow-up through 2002 for an average of 11 years. A total of 48,321 Swedish women aged 30-49 randomly selected from the population residing in the Uppsala Health Care Region of Sweden in 1990-91. Fatal and nonfatal MI ascertained through linkages with nationwide health registries for death, hospitalization, and emigration. There were 214 incident cases of MI. Compared with never users, neither former (relative risk, 1.0; 95% confidence interval, 0.7-1.4) nor current (relative risk, 0.7; 95% confidence interval, 0.4-1.4) OC users at study enrollment had an elevated risk of future MI in models adjusted for coronary heart disease risk factors. Risk of MI was not elevated by prolonged use or in subgroups defined by characteristics of the women or types of OC. Use of OC was not associated with an increased risk of MI in this prospective study, in which most current users of OC were taking low-dose estrogen and second- or third-generation progestins.

Low carbohydrate–high protein diet and mortality in a cohort of Swedish women

The long-term health consequences of diets used for weight control are not established. We have evaluated the association of the frequently recommended low carbohydrate diets - usually characterized by concomitant increase in protein intake - with long-term mortality. The Women's Lifestyle and Health cohort study initiated in Sweden during 1991-1992, with a 12-year almost complete follow up. The Uppsala Health Care Region. 42,237 women, 30-49 years old at baseline, volunteers from a random sample, who completed an extensive questionnaire and were traced through linkages to national registries until 2003. We evaluated the association of mortality with: decreasing carbohydrate intake (in deciles); increasing protein intake (in deciles) and an additive combination of these variables (low carbohydrate-high protein score from 2 to 20), in Cox models controlling for energy intake, saturated fat intake and several nondietary covariates. Decreasing carbohydrate or increasing protein intake by one decile were associated with increase in total mortality by 6% (95% CI: 0-12%) and 2% (95% CI: -1 to 5%), respectively. For cardiovascular mortality, amongst women 40-49 years old at enrolment, the corresponding increases were, respectively, 13% (95% CI: -4 to 32%) and 16% (95% CI: 5-29%), with the additive score being even more predictive. A diet characterized by low carbohydrate and high protein intake was associated with increased total and particularly cardiovascular mortality amongst women. Vigilance with respect to long-term adherence to such weight control regimes is advisable.

Mediterranean dietary pattern and mortality among young women: a cohort study in Sweden

Studies of diet and health focus increasingly on dietary patterns. Although the traditional Mediterranean diet is perceived as being healthy, there is little information on its possible benefit to young people. We studied whether closer adherence to the traditional Mediterranean dietary pattern was associated with overall and cancer mortality in a cohort of 42,237 young women, aged 30-49 years at enrollment, who were recruited in 1991-2 from the general population in the Uppsala Health Care Region, Sweden, and followed up, almost completely, for about 12 years. Adherence to the Mediterranean diet was assessed by a 10-point score incorporating the characteristics of this diet. Among women less than 40 years old at enrollment--whose causes of death are mainly cancer with probable genetic influences, injuries or suicide--there was no association of the Mediterranean diet score with total or cancer mortality. Among women 40-49 years old at enrollment, a 2-point increase in the score was associated with considerable reductions in overall mortality (13%; 95% CI 1%, 23%; P approximately 0.05) and cancer mortality (16%; 95% CI -1%, 29%; P approximately 0.06). Few cardiovascular deaths occurred in this cohort of young women. The findings of the present study in a northern European population of young women indicate that closer adherence to a Mediterranean dietary pattern reduces mortality even among young persons.

Association between sigmoid diverticulitis and left‐sided colon cancer: a nested, population‐based, case control study

Background: An increased risk of left‐sided colon cancer in patients with diverticular disease of the sigmoid colon has been reported. The aim of this study was to investigate to what extent patients with diverticulitis of the sigmoid colon differ in long‐term risk of colon cancer compared to patients with diverticulosis of the colon without any clinical signs of diverticulitis. Methods: A total of 7159 patients (2478 M, 4681 F) discharged with a diagnosis of diverticulosis or diverticulitis in 1965–83 in the Uppsala Health Care Region were followed‐up with the Swedish Cancer Registry. Sixty‐four cases with colon cancer were identified and compared with 123 controls without cancer matched for sex, age and year of first discharge. Based on information from the patients' charts, an independent observer blinded to the outcome assigned a clinical diagnosis of diverticulitis or not diverticulitis to cases and controls. Results: In patients classified as having sigmoid diverticulitis there was an increased risk of left‐sided colon cancer compared with patients with diverticulosis without any clinical signs of diverticulitis (odds ratio = 4.2, 95% CI 1.3–13.0) which remained after mutually adjusting for several clinical parameters in a multivariate conditional logistic regression analysis. Conclusion: The results of the study indicate a causal association between sigmoid diverticulitis and a long‐term increased risk of left‐sided colon cancer.

Lymphoma subtypes in patients with rheumatoid arthritis: increased proportion of diffuse large B cell lymphoma.

Patients with rheumatoid arthritis (RA) have an increased risk of developing malignant lymphoma. It is not clear whether the increase is confined to certain subtypes of lymphomas. Immunosuppressive therapy and Epstein-Barr virus (EBV) have been linked to the development of these lymphomas. To gain information about the baseline pattern of lymphoma subtypes in RA before the current widespread use of immunosuppressive drugs, we examined the distribution of lymphoma subtypes and the presence of EBV in a cohort of RA patients with a low frequency and duration of treatment with immunosuppressive drugs. By linking data from the Swedish Hospital Discharge Register and the Swedish Cancer Register, 42 cases of lymphoma were identified among 11683 patients with RA in the Uppsala Health Care Region between 1964 and 1984. The medical records and paraffin-embedded lymphoma tissues were collected, and the lymphomas were reclassified using the World Health Organization classification. In situ hybridization was used to detect EBV. Tissues from 35 patients were reviewed. Non-Hodgkin's lymphoma (NHL) was found in 33 patients and Hodgkin's lymphoma in 2 patients. There was an increased frequency of diffuse large B cell lymphoma (DLBCL) (22 of 33 NHL patients, 67%) compared with that in the general population (30-40%). EBV was detected in 5 of 30 examined lymphomas from patients (17%). Twenty of the 22 DLBCL patients had RA with medium or high inflammatory activity, and 6 had been treated with a disease-modifying antirheumatic drug for >or=1 year. The findings of this study suggest an increased incidence of one specific lymphoma subtype, DLBCL, in RA patients, as well as a possible association with RA disease activity.

Risk of myocardial infarction after oophorectomy and hysterectomy

To determine the risk of developing a first myocardial infarction after a hysterectomy and/or oophorectomy. Case-cohort analysis performed among 17,126 women in the Uppsala Health Care Region of Sweden, who had undergone a hysterectomy and/or oophorectomy in 1965 to 1983. Record linkage was used for follow-up and medical records to ascertain the actual history of oophorectomy. Risk estimates were calculated by relating the observed number of cases in the cohort to that expected on the basis of incidence rates in the population. Overall, 214 cases of myocardial infarction were observed. In premenopausal women a bilateral oophorectomy alone tended to increase the relative risk 1.6; 95% CI 0.8–3.1, but this operation combined with hysterectomy increased the risk only among those aged 50 and over at surgery. Hysterectomy at premenopausal age or unilateral oophorectomy did not alter the risk of myocardial infarction. In naturally menopausal women, hysterectomy—mainly for uterine myoma—was associated with a four-fold increase in relative risk (3.8; 95% CI 1.9–7.8). Hysterectomy for treatment of myoma performed after a natural menopause is linked to an excess risk for myocardial infarction. Bilateral oophorectomy before menopause may increase the risk of myocardial infarction.

Breast cancer risk associated with gynecologic surgery and indications for such surgery.

Risk of breast cancer was assessed in relationship to gynecologic operations using data from a record-linkage study involving 15,844 women in the Uppsala Health Care Region of Sweden, who underwent surgery between 1965 and 1983. Data abstracted from medical records for the breast cancer cases and a random sample of the cohort allowed examination of risk associated with these operations in regard to menopausal status and indications for the operations. Among women who were pre-menopausal at the time of operation, a bilateral oophorectomy before the age of 50 years was associated with a 50% reduction in the risk of breast cancer compared with the background population, a reduction in risk evident within 10 years of the operation. A bilateral oophorectomy after the age of 50 years in pre-menopausal women or after a natural menopause was not associated with any reduction in risk. There were no reductions in risk associated with a unilateral oophorectomy or hysterectomy among women who were pre-menopausal at the time of operation. In fact, hysterectomy alone was associated with a slight increase in breast cancer risk when the operation was due to myomas, abnormal bleeding, and, possibly, severe forms of endometriosis but not to other reasons. Risk did not vary substantially by indications for oophorectomy, including benign ovarian neoplasms and functional ovarian cysts, though endometriosis was associated with a non-significant increase in breast cancer risk.

Long-Term Trends in Incidence of and Mortality from Acute Myocardial Infarction and Stroke in Women

We studied the trends from 1969 to the mid-1980s in the incidence and mortality of acute myocardial infarction and stroke in Swedish women residing in the Uppsala Health Care Region. We used data from the Inpatient Care and Causes of Death registers to obtain total first event incidence and mortality rates. In our population, there were 20,182 acute myocardial infarctions and 30,462 stroke events, and 17,359 and 21,336 deaths, respectively. We found an average overall annual increase of 1.3% in the age-standardized incidence of acute myocardial infarction during the 1970s, followed by decreasing rates during the early 1980s. Mortality was virtually unchanged. Notably, among women 45-49 years of age, we observed a rising trend during the whole period, whereas in the oldest age groups, the increase slowed and reversed in the latter years. Both the incidence and mortality for stroke declined steadily: the age-standardized incidence fell by an average of 2.1% per year for all stroke and 7.8% for intracerebral hemorrhage. The falling rate of stroke was best explained by birth cohort effects, with a 30% reduction in women born in 1920 and later as compared with those born in 1890. We conclude that important changes in Swedish women's cardiovascular health have taken place and that increasing cigarette smoking and hypertensive treatment are major determinants.

Medical diagnostic x rays and thyroid cancer.

Diagnostic x rays are the largest man-made source of exposure to ionizing radiation for the general population. Whether there are meaningful cancer risks associated with such exposures is unclear. Most previous case-control studies have relied on recalled histories of x rays, and there is concern that completeness and accuracy of recall might differ between cancer case and control subjects. The present study used information recorded prospectively in hospital charts to address the relationship between medical diagnostic x rays and risk of thyroid cancer. The Swedish Cancer Registry and the Uppsala-Orebro Regional Cancer Registry were used to identify persons with papillary or follicular thyroid cancer diagnosed from January 1, 1980, through December 31, 1992, among residents of the Uppsala Health Care Region. After histopathologic review, there were 484 such case subjects available for study. An equal number of age-, sex-, and county of residence-matched control subjects from the general population were randomly selected on the basis of the Swedish Registry of the Total Population. Lifetime residential histories were compiled, and radiology records were searched at all Swedish hospital serving regions where study subjects ever maintained an official residence. Approximate radiation doses to the thyroid gland for specific types of x-ray examinations were assigned on the basis of mean values of measurements made in Sweden in 1973-1975 and in the United States in 1970. Odds ratios were used to evaluate the association between diagnostic radiography and risk of thyroid cancer. A total of 3853 medical diagnostic x rays were ascertained among thyroid cancer case subjects and 4039 among the matched control subjects. There were no tendency for case subjects to have had more of the types of x-ray procedure associated with higher radiation dose to the thyroid gland (i.e., those involving the head or neck area). This finding was true even when analysis was restricted to x rays occurring before 1960, when doses likely were higher than in more recent years, and for examinations occurring in childhood and adolescence, when susceptibility to radiation-induced thyroid cancer is greatest. The relative risk of thyroid cancer was not significantly associated with estimated cumulative dose to the thyroid gland from diagnostic x rays (two-sided P for trend = .80). These data indicate that the risk of thyroid cancer due to medical diagnostic x rays, if any, is very small.

Cholecystectomy protects against extrahepatic bile duct cancer: is this a result of the removal of gallstones?

The aetiology of cancer of the extrahepatic bile duct is unknown. Gallstones have been proposed to be a risk factor on the basis of ecological and epidemiological evidence. As gallstones are formed in the gallbladder, the occurrence of extrahepatic bileduct cancer in patients after cholecystectomy is of interest. All patients (62 734) who had had a cholecystectomy during 1965-1983 within the Uppsala Health Care Region, Sweden, were followed up to the end of 1987. Excluding the first year of follow-up, 23 cancers of the extrahepatic bileduct occurred vs 26.3 expected for a standardised incidence ratio (SIR) of 0.88 (95% confidence interval [CI] 0.56-1.31). Ten years or more after operation there was a greater reduction of risk (SIR=0.27; 95% CI 0.06-0.80). Similar patterns were observed for men and women, and among patients who had undergone cholecystectomy only compared with those who had had their common bileducts explored. To assess surveillance bias the incidence of primary liver cancer was also analysed: SIR=1.15; 95% CI 0.91-1.44 overall, and 10 years or more after cholecystectomy SIR=0.98; 95% CI 0.66-1.40. This study shows a reduced risk of extrahepatic bileduct cancer 10 or more years after cholecystectomy, indicating that gallstones may be a cause of cancer.

Pancreatitis and pancreatic cancer: a population-based study.

Little is known about the etiology of cancer of the exocrine portion of the pancreas, which produces a variety of digestive enzymes. Smoking, certain dietary factors, and diabetes mellitus are considered to be risk factors, although the risk estimates are modest in most instances. A recent cohort study of patients with chronic pancreatitis indicated a ninefold to 16-fold increased risk for pancreatic cancer. Our purpose was to evaluate the relationship between various clinical types of pancreatitis and pancreatic cancer. Data for this study were collected from all inpatient medical institutions in Sweden from 1965 until 1983 by the Swedish National Board of Health and Welfare. Data were recorded on individual hospital admissions and discharges in the Inpatient Register. All patients with records in the Inpatient Register coded for acute, chronic, or unspecified pancreatitis were considered for inclusion in the study. A population-based cohort of 7956 patients with at least one discharge diagnosis of pancreatitis was monitored (up to 19 years of follow-up) for the occurrence of pancreatic cancer by record linkages to the Swedish Cancer Registry and Registry of Causes of Death. A total of 46 pancreatic cancers were diagnosed during follow-up compared with 21 expected (standardized incidence ratio [SIR] of 2.2; 95% confidence interval [CI] 1.6-2.9) for the Uppsala Health Care Region. The excess risk for women and men was similar--most pronounced during the first period of follow-up (2-4 years) after discharge and close to unity after more than 10 years of follow-up. Patients with chronic pancreatitis and patients with more than one discharge diagnosis of either acute or unspecified pancreatitis were at higher risk (SIR = 3.8; 95% CI 1.4-8.2 and SIR = 4.8; 95% CI 1.9-9.9, respectively) compared with those with only one discharge of acute (SIR = 1.6; 95% CI 0.9-2.7) or unspecified (SIR = 2.1; 95% CI 1.2-3.2) pancreatitis. Our finding of a moderate excess of pancreatic cancer among patients with pancreatitis, especially the chronic or recurrent forms, supports some earlier clinical and case-control studies, but it is not consistent with the ninefold to 16-fold risk reported in a recent cohort study. The absence of an increased risk 10 years or more after first discharge for pancreatitis argues against a straight-forward causal relationship. Because of the relatively short interval between diagnosis of pancreatitis and pancreatic cancer, it is possible that some forms of pancreatitis are a precursor to pancreatic cancer or that shared risk factors for both diseases (e.g., cigarette smoking) may also be involved.

The risk of hip fractures in patients with primary hyperparathyroidism: a population-based cohort study with a follow-up of 19 years.

To evaluate primary hyperparathyroidism (HPT) as a risk factor for hip fractures. A population-based, record-linked, prospective study with a mean observation time of 17 years (women) and 16.5 years (men). A cohort obtained from a register of hospital admissions in the Uppsala Health Care Region, Sweden, 1965-1983. All patients (1373 women and 551 men) who were admitted to hospital with the diagnosis of HPT during the period. Comparisons were made with the entire background population. Cohort subjects were followed with regard to a first instance of hip fracture prior to or after the diagnosis of HPT. The observed number of cases was compared with that expected on the basis of person-years of observation and incidence rates in the background population. Analyses were made for cervical and trochanteric fractures, and for patients operated and not operated for HPT. (i) Women. During 23,341 person-years of observation, 67 cases of first hip fractures occurred, yielding a relative risk (RR) of 0.93 (95% confidence interval [CI] 0.72-1.19). The RR for cervical fractures was 0.77 (CI 0.54-1.06), and for trochanteric fractures 1.33 (CI 0.88-1.93). Operation for HPT did not influence the risk of hip fracture. (ii) Men. The total person-years was 9091. Eleven fractures were observed--compared with the expected 7.90 (RR 1.39; CI 0.69-2.50). Men operated for HPT had an increased risk for cervical hip fractures (RR 2.73; CI 1.18-5.39). Owing to the few fractures in this group (n = 8) the relevance of this is uncertain. This study indicates that HPT is not a risk factor for hip fractures in women.

Risk of extrahepatic bileduct cancer after cholecystectomy

The aetiology of cancer of the extrahepatic bile duct is unknown. Gallstones have been proposed to be a risk factor on the basis of ecological and epidemiological evidence. As gallstones are formed in the gallbladder, the occurrence of extrahepatic bileduct cancer in patients after cholecystectomy is of interest. All patients (62 734) who had had a cholecystectomy during 1965-1983 within the Uppsala Health Care Region, Sweden, were followed up to the end of 1987. Excluding the first year of follow-up, 23 cancers of the extrahepatic bileduct occurred vs 26·3 expected for a standardised incidence ratio (SIR) of 0·88 (95% confidence interval [Cl] 0 56-1 31). 10 years or more after operation there was a greater reduction of risk (SIR=0 27; 95% Cl 0·06-0 80). Similar patterns were observed for men and women, and among patients who had undergone cholecystectomy only compared with those who had had their common bileducts explored. To assess surveillance bias the incidence of primary liver cancer was also analysed: SIR = 1·15; 95% Cl 0 91-1·44 overall, and 10 years or more after cholecystectomy SIR = 0·98; 95% Cl 0·66-1 40. This study shows a reduced risk of extrahepatic bileduct cancer 10 or more years after cholecystectomy, indicating that gallstones may be a cause of this cancer.

Hormone Replacement Therapy and the Risk of Stroke

Falkeborn, Margareta; Persson, Ingemar; Terént, Andreas; Adami, Hans-Olov; Lithell, Hans; Bergström, Reinhold Author Information

Scleroderma and malignancy: an epidemiological study.

Although case reports and some patient series suggest an increased risk of cancer among patients with scleroderma, there are no population based studies to support this association. A population based follow up study was therefore carried out of 233 patients with scleroderma from the six-county Uppsala health care region of Sweden for the time period 1955-84. Using the inpatient registry for the Uppsala health care region, all patients with scleroderma were identified. Their unique identification codes were then used to perform a record linkage with the National Cancer Registry. Expected cancer rates were determined using the age and gender specific rates for the Uppsala health care region. The standardised incidence ratio (SIR) for all cancers among these patients was significantly increased (SIR = 2.4; 95% CI = 1.5 to 3.6). The SIRs for lung cancer (SIR = 7.8; 95% CI = 2.5 to 18.2) and non-Hodgkin's lymphoma (SIR = 9.6; 95% CI = 1.1 to 34.5) were also significantly increased. Excluding patients who were diagnosed with cancer within a year of their scleroderma diagnosis resulted in similar findings, though the SIR for non-Hodgkin's lymphoma was no longer statistically significant. Larger population based investigations of cancer risk among patients with scleroderma are needed to confirm these initial findings and to evaluate in greater detail possible cancer risk among these patients.

Hormone Replacement Therapy and the Risk of Stroke

The protective effect of postmenopausal estrogen replacement therapy on coronary heart disease has been shown in several studies. However, the effect on stroke is more controversial, and data on estrogen-progestin combinations are sparse. A total of 23,088 women living in the Uppsala (Sweden) Health Care Region were identified from pharmacy records as having been prescribed noncontraceptive estrogens during 1977 through 1980. They were followed up from 1977 to 1983 for admissions to the hospital because of a first stroke (International Classification of Diseases, Eighth Revision, codes 430 through 438 and 344). The mean observation time was 5.8 years. The expected number was based on person-years in the cohort and incidence rates in the population of the region. Overall, 361 cases of first stroke were observed in the cohort, as compared with 403.2 expected (relative risk [RR], 0.90; 95% confidence limits, 0.81, 0.99). The RR for acute stroke (International Classification of Diseases, Eighth Revision, codes 431 through 436) was 0.85 (0.75, 0.97). In women younger than 60 years at entry who were prescribed estradiol compounds (1 to 2 mg) or conjugated equine estrogens (0.625 to 1.25 mg), the risk of any stroke was reduced by almost 30% (RR, 0.72; 0.58, 0.88) and the risk of acute stroke was reduced by 40% (RR, 0.61; 0.46, 0.79). Women prescribed a combined estradiol-levonorgestrel brand also had a lowered risk of stroke (RR, 0.61; 0.40, 0.88). Weak compounds (mainly estriol) showed no stroke-protective effect, nor was there any relationship between hormone replacement and risk of subarachnoid hemorrhage. Hormone replacement therapy with potent estrogens alone or cyclically combined with progestins can, particularly when started shortly after menopause, reduce the risk of stroke.

Pernicious anemia and subsequent cancer. A population-based cohort study

Elevated risk of cancers of the stomach, colon, and buccal cavity, as well as of lymphoma and leukemia, have been reported for patients with pernicious anemia in case reports and hospital-based and cross-sectional studies. A cohort of 2021 men and 2496 women living in the Uppsala health care region in Sweden, discharged with a hospital diagnosis of pernicious anemia from 1965 to 1983, was followed for 20 years for subsequent risk of cancer. A total of 553 cancers were diagnosed among these patients, significantly more than expected based on cancer standardized incidence rates (SIRs) in the general population (SIR = 1.4; 95% confidence interval [CI], 1.2-1.5). Most prominent were excesses for cancer of the stomach (SIR = 2.9; 95% CI, 2.4-3.5), esophagus (SIR = 3.2; 95% CI, 1.8-5.2), and pancreas (SIR = 1.7; 95% CI, 1.2-2.4) among men and women; myeloid leukemia among men (SIR = 4.4; 95% CI, 1.8-5.2); and multiple myeloma among women (SIR = 2.5; 95% CI, 1.1-4.9). An excess of gastric carcinoid tumors also was evident in this cohort. The risk of stomach cancer was highest in the first year after diagnosis of pernicious anemia (SIR = 7.4; 95% CI, 5.3-10.1), but an increased risk persisted throughout the follow-up period. The risk of esophageal cancer also remained elevated throughout the study period, although the risk of pancreatic cancer dropped off after 5 years. This study confirms the excess risk of gastric carcinoma and carcinoid tumors associated with pernicious anemia, and suggests that the susceptibility state may extend to esophageal and other cancers.