Kaiser Permanente Oakland Medical Center

BACKGROUND: The proportion of screening colonoscopic examinations performed by a physician that detect one or more adenomas (the adenoma detection rate) is a recommended quality measure. However, little is known about the association between this rate and patients' risks of a subsequent colorectal cancer (interval cancer) and death. METHODS: Using data from an integrated health care delivery organization, we evaluated the associations between the adenoma detection rate and the risks of colorectal cancer diagnosed 6 months to 10 years after colonoscopy and of cancer-related death. With the use of Cox regression, our estimates of attributable risk were adjusted for the demographic characteristics of the patients, indications for colonoscopy, and coexisting conditions. RESULTS: We evaluated 314,872 colonoscopies performed by 136 gastroenterologists; the adenoma detection rates ranged from 7.4 to 52.5%. During the follow-up period, we identified 712 interval colorectal adenocarcinomas, including 255 advanced-stage cancers, and 147 deaths from interval colorectal cancer. The unadjusted risks of interval cancer according to quintiles of adenoma detection rates, from lowest to highest, were 9.8, 8.6, 8.0, 7.0, and 4.8 cases per 10,000 person-years of follow-up, respectively. Among patients of physicians with adenoma detection rates in the highest quintile, as compared with patients of physicians with detection rates in the lowest quintile, the adjusted hazard ratio for any interval cancer was 0.52 (95% confidence interval [CI], 0.39 to 0.69), for advanced-stage interval cancer, 0.43 (95% CI, 0.29 to 0.64), and for fatal interval cancer, 0.38 (95% CI, 0.22 to 0.65). Each 1.0% increase in the adenoma detection rate was associated with a 3.0% decrease in the risk of cancer (hazard ratio, 0.97; 95% CI, 0.96 to 0.98). CONCLUSIONS: The adenoma detection rate was inversely associated with the risks of interval colorectal cancer, advanced-stage interval cancer, and fatal interval cancer. (Funded by the Kaiser Permanente Community Benefit program and the National Cancer Institute.).

BACKGROUND: Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. METHODS: We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events. RESULTS: The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent). CONCLUSIONS: This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)

BACKGROUND: Helicobacter pylori infection is a risk factor for gastric adenocarcinoma. We examined whether this infection is also a risk factor for primary gastric non-Hodgkin's lymphoma. METHODS: This nested case-control study involved two large cohorts (230,593 participants). Serum had been collected from cohort members and stored, and all subjects were followed for cancer. Thirty-three patients with gastric non-Hodgkin's lymphoma were identified, and each was matched to four controls according to cohort, age, sex, and date of serum collection. For comparison, 31 patients with nongastric non-Hodgkin's lymphoma from one of the cohorts were evaluated, each of whom had been previously matched to 2 controls. Pathological reports and specimens were reviewed to confirm the histologic type of the tumor. Serum samples from all subjects were tested for H. pylori IgG by an enzyme-linked immunosorbent assay. RESULTS: Thirty-three cases of gastric non-Hodgkin's lymphoma occurred a median of 14 years after serum collection. Patients with gastric lymphoma were significantly more likely than matched controls to have evidence of previous H. pylori infection (matched odds ratio, 6.3; 95 percent confidence interval, 2.0 to 19.9). The results were similar in both cohorts. Among the 31 patients with nongastric lymphoma, a median of six years had elapsed between serum collection and the development of disease. No association was found between nongastric non-Hodgkin's lymphoma and previous H. pylori infection (matched odds ratio, 1.2; 95 percent confidence interval, 0.5 to 3.0). CONCLUSIONS: Non-Hodgkin's lymphoma affecting the stomach, but not other sites, is associated with previous H. pylori infection. A causative role for the organism is plausible, but remains unproved.

BACKGROUND: The efficacy of sigmoidoscopic screening in reducing mortality from colorectal cancer remains uncertain. A randomized trial would be ideal for clarifying this issue but is very difficult to conduct. Case-control studies provide an alternative method of estimating the efficacy of screening sigmoidoscopy. METHODS: Using data on the 261 members of the Kaiser Permanente Medical Care Program who died of cancer of the rectum or distal colon from 1971 to 1988, we examined the use of screening by rigid sigmoidoscopy during the 10 years before the diagnosis and compared it with the use of screening in 868 control subjects matched with the case subjects for age and sex. RESULTS: Only 8.8 percent of the case subjects had undergone screening by sigmoidoscopy, as compared with 24.2 percent of the controls (matched odds ratio, 0.30; 95 percent confidence interval, 0.19 to 0.48). Adjustment for potential confounding factors increased the odds ratio to 0.41 (95 percent confidence interval, 0.25 to 0.69). The negative association was as strong when the most recent sigmoidoscopy was 9 to 10 years before diagnosis as it was when examinations were more recent. By contrast, for 268 subjects with fatal colon cancer above the reach of the sigmoidoscope and for 268 controls, the adjusted odds ratio was 0.96 (95 percent confidence interval, 0.61 to 1.50). The specificity of the negative association for cancer within the reach of the sigmoidoscope is consistent with a true efficacy of screening rather than a confounding by unmeasured selection factors. CONCLUSIONS: Screening by sigmoidoscopy can reduce mortality from cancer of the rectum and distal colon. A screening once every 10 years may be nearly as efficacious as more frequent screening.

OBJECTIVE: To provide clinicians with evidence-based strategies to optimize the support of the family of critically ill patients in the ICU. METHODS: We used the Council of Medical Specialty Societies principles for the development of clinical guidelines as the framework for guideline development. We assembled an international multidisciplinary team of 29 members with expertise in guideline development, evidence analysis, and family-centered care to revise the 2007 Clinical Practice Guidelines for support of the family in the patient-centered ICU. We conducted a scoping review of qualitative research that explored family-centered care in the ICU. Thematic analyses were conducted to support Population, Intervention, Comparison, Outcome question development. Patients and families validated the importance of interventions and outcomes. We then conducted a systematic review using the Grading of Recommendations, Assessment, Development and Evaluations methodology to make recommendations for practice. Recommendations were subjected to electronic voting with pre-established voting thresholds. No industry funding was associated with the guideline development. RESULTS: The scoping review yielded 683 qualitative studies; 228 were used for thematic analysis and Population, Intervention, Comparison, Outcome question development. The systematic review search yielded 4,158 reports after deduplication and 76 additional studies were added from alerts and hand searches; 238 studies met inclusion criteria. We made 23 recommendations from moderate, low, and very low level of evidence on the topics of: communication with family members, family presence, family support, consultations and ICU team members, and operational and environmental issues. We provide recommendations for future research and work-tools to support translation of the recommendations into practice. CONCLUSIONS: These guidelines identify the evidence base for best practices for family-centered care in the ICU. All recommendations were weak, highlighting the relative nascency of this field of research and the importance of future research to identify the most effective interventions to improve this important aspect of ICU care.

BACKGROUND: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. RESULTS: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).

OBJECTIVE: To evaluate any association between obesity in middle age, measured by body mass index and skinfold thickness, and risk of dementia later in life. DESIGN: Analysis of prospective data from a multiethnic population based cohort. SETTING: Kaiser Permanente Northern California Medical Group, a healthcare delivery organisation. PARTICIPANTS: 10,276 men and women who underwent detailed health evaluations from 1964 to 1973 when they were aged 40-45 and who were still members of the health plan in 1994. MAIN OUTCOME MEASURES: Diagnosis of dementia from January 1994 to April 2003. Time to diagnosis was analysed with Cox proportional hazard models adjusted for age, sex, race, education, smoking, alcohol use, marital status, diabetes, hypertension, hyperlipidaemia, stroke, and ischaemic heart disease. RESULTS: Dementia was diagnosed in 713 (6.9%) participants. Obese people (body mass index > or = 30) had a 74% increased risk of dementia (hazard ratio 1.74, 95% confidence interval 1.34 to 2.26), while overweight people (body mass index 25.0-29.9) had a 35% greater risk of dementia (1.35, 1.14 to 1.60) compared with those of normal weight (body mass index 18.6-24.9). Compared with those in the lowest fifth, men and women in the highest fifth of the distribution of subscapular or tricep skinfold thickness had a 72% and 59% greater risk of dementia, respectively (1.72, 1.36 to 2.18, and 1.59, 1.24 to 2.04). CONCLUSIONS: Obesity in middle age increases the risk of future dementia independently of comorbid conditions.

Abstract Objectives : To review the effect of specific types of alcoholic drink on coronary risk. Design : Systematic review of ecological, case-control, and cohort studies in which specific associations were available for consumption of beer, wine, and spirits and risk of coronary heart disease. Subjects : 12 ecological, three case-control, and 10 separate prospective cohort studies. Main outcome measures : Alcohol consumption and relative risk of morbidity and mortality from coronary heart disease. Results : Most ecological studies suggested that wine was more effective in reducing risk of mortality from heart disease than beer or spirits. Taken together, the three case-control studies did not suggest that one type of drink was more cardioprotective than the others. Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found such an association for beer, and four for spirits. Conclusions : Results from observational studies, where alcohol consumption can be linked directly to an individual's risk of coronary heart disease, provide strong evidence that all alcoholic drinks are linked with lower risk. Thus, a substantial portion of the benefit is from alcohol rather than other components of each type of drink. Key messages Key messages We examined the relation between specific alcoholic drinks and reduction of risk of coronary heart disease by summarising published reports from ecological, case-control, and cohort studies Most ecological studies suggested that wine was more effective in reducing risk of mortality than beer or spirits, whereas the three case-control studies together did not suggest that one type of drink was more cardioprotective than others Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found the association for beer, and four found it for spirits. The evidence suggests that all alcoholic drinks are linked with lower risk, so that much of the benefit is from alcohol rather than other components of each type of drink

The etiology, incidence, acute and late prognosis, and treatment of sudden hearing loss (SHL) are described variously in the literature. In an 8-year prospective study of 225 SHL patients, initiated in July 1973, overall, normal, or complete recovery occurred in 45% of patients and late otologic complications in 28%. Important prognostic indicators were severity of initial hearing loss and vertigo, time to initial audiogram, and elevated erythrocyte sedimentation rate; other indicators were age greater than 60 and less than 15 years, midfrequency audiogram configuration, and hearing status of the opposite ear. A common inflammatory cause is suggested for all degrees of severity in SHL, and a prognostic table is provided to aid the practitioner in predicting recovery. There is still no evidence that treatment achieves a result better than expected with spontaneous recovery.

Acute Myocardial Infarction and Covid-19 Data from the Kaiser Permanente Northern California health care system were used to compare rates of hospitalization for acute MI from March 4 through April...

BACKGROUND: Glycemic control is associated with microvascular events, but its effect on the risk of heart failure is not well understood. We examined the association between hemoglobin (Hb) A(Ic) and the risk of heart failure hospitalization and/or death in a population-based sample of adult patients with diabetes and assessed whether this association differed by patient sex, heart failure pathogenesis, and hypertension status. METHODS AND RESULTS: A cohort design was used with baseline between January 1, 1995, and June 30, 1996, and follow-up through December 31, 1997 (median 2.2 years). Participants were 25 958 men and 22 900 women with (predominantly type 2) diabetes, >/=19 years old, with no known history of heart failure. There were a total of 935 events (516 among men; 419 among women). After adjustment for age, sex, race/ethnicity, education level, cigarette smoking, alcohol consumption, hypertension, obesity, use of beta-blockers and ACE inhibitors, type and duration of diabetes, and incidence of interim myocardial infarction, each 1% increase in Hb A(Ic) was associated with an 8% increased risk of heart failure (95% CI 5% to 12%). An Hb A(Ic) >/=10, relative to Hb A(Ic) <7, was associated with 1.56-fold (95% CI 1.26 to 1.93) greater risk of heart failure. Although the association was stronger in men than in women, no differences existed by heart failure pathogenesis or hypertension status. CONCLUSIONS: These results confirm previous evidence that poor glycemic control may be associated with an increased risk of heart failure among adult patients with diabetes.

BACKGROUND AND METHODS: In postmenopausal women, the serum concentrations of endogenous sex hormones and vitamin D might influence the risk of hip and vertebral fractures. In a study of a cohort of women 65 years of age or older, we compared the serum hormone concentrations at base line in 133 women who subsequently had hip fractures and 138 women who subsequently had vertebral fractures with those in randomly selected control women from the same cohort. Women who were taking estrogen were excluded. The results were adjusted for age and weight. RESULTS: The women with undetectable serum estradiol concentrations (<5 pg per milliliter [18 pmol per liter]) had a relative risk of 2.5 for subsequent hip fracture (95 percent confidence interval, 1.4 to 4.6) and subsequent vertebral fracture (95 percent confidence interval, 1.4 to 4.2), as compared with the women with detectable serum estradiol concentrations. Serum concentrations of sex hormone-binding globulin that were 1.0 microg per deciliter (34.7 nmol per liter) or higher were associated with a relative risk of 2.0 for hip fracture (95 percent confidence interval, 1.1 to 3.9) and 2.3 for vertebral fracture (95 percent confidence interval, 1.2 to 4.4). Women with both undetectable serum estradiol concentrations and serum sex hormone-binding globulin concentrations of 1 microg per deciliter or more had a relative risk of 6.9 for hip fracture (95 percent confidence interval, 1.5 to 32.0) and 7.9 for vertebral fracture (95 percent confidence interval, 2.2 to 28.0). For those with low serum 1,25-dihydroxyvitamin D concentrations (< or =23 pg per milliliter [55 pmol per liter]), the risk of hip fracture increased by a factor of 2.1 (95 percent confidence interval, 1.2 to 3.5). CONCLUSIONS: Postmenopausal women with undetectable serum estradiol concentrations and high serum concentrations of sex hormone-binding globulin have an increased risk of hip and vertebral fracture.

CONTEXT: A Papanicolaou (Pap) test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5% to 10% of women with ASCUS harbor serious cervical disease, but more than one third of the high-grade squamous intraepithelial lesions (HSILs) in screening populations are identified from ASCUS Pap test results. OBJECTIVE: To determine whether human papillomavirus (HPV) DNA testing of residual material from liquid-based Pap tests and referral of cases found to be HPV-positive directly to colposcopy could provide sensitive detection of underlying HSILs in women with ASCUS Pap results, compared with repeat Pap testing. DESIGN AND SETTING: Natural history of women with ASCUS Pap smear results, all of whom had liquid-based cytology, HPV testing, and subsequent repeat Pap tests and colposcopy with histologic evaluation, conducted at 12 gynecology clinics in a large managed care organization between October 1995 and June 1996. PARTICIPANTS: From a cohort of 46009 women who had routine cervical examinations, 995 women with Pap test results of ASCUS who consented to participate were identified. MAIN OUTCOME MEASURES: Cervical histology, HPV test results, and repeat Pap smear results, and sensitivity of HPV testing to identify patients found to have HSIL+ histology. RESULTS: Of 995 participants with ASCUS Pap test results, 973 had both a definitive histologic diagnosis and HPV result. Sixty-five (6.7%) had histologic HSIL or cancer. For women with histologic HSIL+, the HPV test was positive in 89.2% (95% confidence interval [CI], 78.4%-95.2%), and the specificity was 64.1 % (95% CI, 60.9%-67.2%). The repeat Pap smear result was abnormal in 76.2% (95% CI, 63.5%-85.7%). Triage based on HPV testing only or on repeat Pap testing only would refer similar proportions (approximately 39%) to colposcopy. The sensitivity of HPV DNA testing for HSIL was equivalent to, if not greater than, that of the repeat Pap test. We further estimated that an HPV-based algorithm including the immediate colposcopy of HPV-positive women, and then repeat Pap testing of all others, would provide an overall sensitivity of 96.9% (95% CI, 88.3%-99.5%). CONCLUSIONS: For women with ASCUS Pap tests, HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying HSIL. By testing the specimen collected at initial screening, the majority of high-risk cases can be identified and referred for colposcopy based on a single screening.

Transfusion therapy for sickle cell anemia is limited by the development of antibodies to foreign red cells. To evaluate the frequency and risk factors associated with such alloimmunization, we determined the transfusion history, red-cell phenotype, and development of alloantibodies in 107 black patients with sickle cell anemia who received transfusions. We compared the results with those from similar studies in 51 black patients with sickle cell disease who had not received transfusions and in 19 nonblack patients who received transfusions for other forms of chronic anemia. We assessed the effect that racial differences might have on the frequency of alloimmunization by comparing the red-cell phenotypes of patients and blood-bank donors (n = 200, 90 percent white). Although they received transfusions less frequently, 30 percent of the patients with sickle cell anemia became alloimmunized, in contrast to 5 percent of the comparison-group patients with other forms of anemia (P less than 0.001). Of the 32 alloimmunized patients with sickle cell anemia, 17 had multiple antibodies and 14 had delayed transfusion reactions. Antibodies against the K, E, C, and Jkb antigens accounted for 82 percent of the alloantibodies. Comparison of red-cell phenotypes in the three study groups (the patients with sickle cell anemia, the patients with other forms of anemia, and the blood donors) revealed statistically significant differences between the patients with sickle cell anemia and the donors but not between the patients with other forms of anemia and the donors. These differences are most likely racial. We conclude that alloimmunization is a common, clinically serious problem in sickle cell anemia and that it is partly due to racial differences between the blood-donor and recipient populations.

OBJECTIVE: To study the relation between alcohol intake and mortality in a large ambulatory population with attention to causes of death and differences related to age, sex, race, and baseline risk. DESIGN: Prospective cohort study. SETTING: Prepaid comprehensive health care program facilities in Oakland and San Francisco, California. PARTICIPANTS: Adults (n = 128,934) who supplied data at health evaluations between 1978 and 1985. MEASUREMENTS: Demographic data and health history were supplied using questionnaires. Death was ascertained by an automated linkage system and was individually validated. Relative risk for death at various levels of drinking was calculated by Cox proportional hazards models using lifelong nondrinkers as the reference and controlling for eight covariables. RESULTS: Heavier drinkers were at greater risk for death from noncardiovascular causes (relative risk at greater than or equal to 6 drinks per day compared with no alcohol = 1.6, 95% Cl, 1.3 to 2.0) especially cirrhosis, unnatural death, and tobacco-related cancers. This alcohol-associated risk was higher in women (relative risk for death from all causes at greater than or equal to 6 drinks per day = 2.2; Cl, 1.4 to 3.8) and younger persons (for persons less than 50 years of age, relative risk for death from all causes at greater than or equal to 6 drinks per day = 1.9; Cl, 1.3 to 2.9). Lighter drinkers were at lower risk for death from cardiovascular disease, especially coronary heart disease (relative risk at 1 to 2 drinks per day = 0.7; Cl, 0.6 to 0.9), independent of baseline risk, with the greatest reduction of risk in older persons. Lighter drinkers over 60 years of age also had a slightly lower risk for noncardiovascular death, but this finding was not independent of baseline coronary heart disease risk. CONCLUSIONS: Women and younger persons appear more susceptible to the increased mortality risk of heavy drinking. The reduced cardiovascular risk of lighter drinkers is more pronounced in older persons. Lower coronary disease prevalence may reduce the noncardiovascular mortality risk of lighter drinkers.

IMPORTANCE: Hypertension control for large populations remains a major challenge. OBJECTIVE: To describe a large-scale hypertension program in Northern California and to compare rates of hypertension control in that program with statewide and national estimates. DESIGN, SETTING, AND PATIENTS: The Kaiser Permanente Northern California (KPNC) hypertension program included a multifaceted approach to blood pressure control. Patients identified as having hypertension within an integrated health care delivery system in Northern California from 2001-2009 were included. The comparison group comprised insured patients in California between 2006-2009 who were included in the Healthcare Effectiveness Data and Information Set (HEDIS) commercial measurement by California health insurance plans participating in the National Committee for Quality Assurance (NCQA) quality measure reporting process. A secondary comparison group was included to obtain the reported national mean NCQA HEDIS commercial rates of hypertension control between 2001-2009 from health plans that participated in the NCQA HEDIS quality measure reporting process. MAIN OUTCOMES AND MEASURES: Hypertension control as defined by NCQA HEDIS. RESULTS: The KPNC hypertension registry included 349,937 patients when established in 2001 and increased to 652,763 by 2009. The NCQA HEDIS commercial measurement for hypertension control within KPNC increased from 43.6% (95% CI, 39.4%-48.6%) to 80.4% (95% CI, 75.6%-84.4%) during the study period (P < .001 for trend). In contrast, the national mean NCQA HEDIS commercial measurement increased from 55.4% to 64.1%. California mean NCQA HEDIS commercial rates of hypertension were similar to those reported nationally from 2006-2009 (63.4% to 69.4%). CONCLUSIONS AND RELEVANCE: Among adults diagnosed with hypertension, implementation of a large-scale hypertension program was associated with a significant increase in hypertension control compared with state and national control rates. Key elements of the program included a comprehensive hypertension registry, development and sharing of performance metrics, evidence-based guidelines, medical assistant visits for blood pressure measurement, and single-pill combination pharmacotherapy.

The multiphasic-examination findings of 464 persons in whom a first myocardial infarction later developed were compared with those of two control groups, one matched for age, sex and race (ordinary controls), and the other matched in addition for standard coronary risk factors (risk controls). The total leukocyte count, measured, on the average, 16.8 months before the myocardial infarction, was strikingly related to development of infarction. The mean leukocyte count in cases was significantly higher (p<0.001) than in either control group. Ascending from lowest to highest quartile in the cases and ordinary controls the increase in risk of myocardial infarction associated with the leukocyte count was similar to that found for cholesterol and blood pressure. Cigarette smoking, which was strongly related to the leukocyte count, may account for about two thirds of the relation of the count to infarction. The leukocyte count may prove valuable in the routine assessment of risk of myocardial infarction. (N Engl J Med 290:1275–1278, 1974)

BACKGROUND: In patients with decreased resistance to infection, Staphylococcus aureus is a major cause of bacteremia and its complications. The capsular polysaccharides are essential for the pathogenesis of and immunity to S. aureus infection and are targets for vaccines. METHODS: In a double-blind trial involving patients with end-stage renal disease who were receiving hemodialysis, we evaluated the safety, immunogenicity, and efficacy of a vaccine with S. aureus type 5 and 8 capsular polysaccharides conjugated to nontoxic recombinant Pseudomonas aeruginosa exotoxin A. Between April 1998 and August 1999, 1804 adult patients at 73 hemodialysis centers were randomly assigned to receive a single intramuscular injection of either vaccine or saline. IgG antibodies to S. aureus type 5 and 8 capsular polysaccharides were measured for up to two years, and episodes of S. aureus bacteremia were recorded. Efficacy was estimated by comparing the incidence of S. aureus bacteremia in the patients who received the vaccine with the incidence in the control patients. RESULTS: Reactions to the vaccine were generally mild to moderate, and most resolved within two days. The capsular polysaccharides elicited an antibody response of at least 80 microg per milliliter (the estimated minimal level conferring protection) in 80 percent of patients for type 5 and in 75 percent of patients for type 8. The efficacy during weeks 3 to 54 was only 26 percent (P=0.23). However, between weeks 3 and 40 after vaccination, S. aureus bacteremia developed in 11 of 892 patients in the vaccine group who could be evaluated for bacteremia, as compared with 26 of 906 patients in the control group (estimate of efficacy, 57 percent; 95 percent confidence interval, 10 to 81 percent; nominal P=0.02). CONCLUSIONS: In patients receiving hemodialysis, a conjugate vaccine can confer partial immunity against S. aureus bacteremia for approximately 40 weeks, after which protection wanes as antibody levels decrease.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness and acute illness who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest. The panel included 3 patient representatives. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 2 recommendations. The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness or acute illness who do not have confirmed or suspected VTE. CONCLUSIONS: These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation. They will be updated using a living recommendation approach as new evidence becomes available.

MCGAHAN, JOHN P. MD; BROWNING, PATRICK D. MD; BROCK, JOHN M. BS; TESLUK, HENRY MD Author Information