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THE PAST DECADE has witnessed an unprecedented upturn in tuberculosis morbidity and outbreaks of difficult-to treat and highly lethal multidrug-resistant tuberculosis. In the early 1990s, a national consensus developed among public health officials to define more comprehensively the problem, and in January 1993 expanded tuberculosis surveillance was implemented nationwide. Carefully selected epidemiologic and case management variables were added to the Report of Verified Case of Tuberculosis form. Information is collected on the health status and treatment of patients, including human immunodeficiency virus status, drug susceptibility test results, and the initial drug regimen. Completion of therapy and use of directly observed therapy are also monitored. The new surveillance system allows a comparison of the quality of care of patients in the public and private sectors. Additional epidemiologic variables include membership in high-risk groups (the homeless, residents of correctional or long-term care facilities, migrant workers, health care workers, and correctional employees) and substance abuse (injecting drug use, non-injecting drug use, and excess alcohol use). The additional information derived from expanded tuberculosis surveillance is crucial to optimal patient management, policy development, resource allocation, as well as program planning, implementation, and evaluation at Federal, State, and local levels. [ABSTRACT FROM AUTHOR]

The authors assessed drug susceptibility patterns among tuberculosis patients reported to the New York City Department of Health in the first quarters of 1991 and 1992. Resistance to one or more drugs was seen in 26 percent (137 divided into 520) in 1991 and 24 percent (122 divided into 517) in 1992. Resistance to isoniazid was seen in 22 percent and 19 percent of patients in 1991 and 1992, respectively; resistance to rifampin in 15 percent and 14 percent; and to both isoniazid and rifampin in 15 percent and 14 percent. Combined resistance to four first line drugs (isoniazid, rifampin, streptomycin, and ethambutol) was seen in 6 percent (1991) and 8 percent (1992). Patients with organisms resistant to both isoniazid and rifampin were as likely among U.S. born as among foreign born, and younger patients were more likely than older patients to have isoniazid and rifampin resistant organisms. These findings underscore the importance of obtaining susceptibility testing in all patients who have cultures positive for Mycobacterium tuberculosis. [ABSTRACT FROM AUTHOR]

Nine secondary cases of tuberculosis and 59 tuberculin skin test conversions occurred after exposure to a hospitalized patient with a large tuberculous abscess of the hip and thigh. Among 442 tuberculin-negative hospital employees, the relative risk of skin test conversion associated with recalled exposure to the patient was 14.0 (95% confidence limits, 6.8, 28.7). Four of 5 surgical suite employees who assisted with incision and debridement of the abscess had skin test conversions, as did 85% of 33 employees on a general medical floor who recalled exposure to the patient and 30% of 20 intensive care unit employees who recalled exposure. The prevalence of tuberculin reactivity in visitors and other patients on two floors also showed a strong association with exposure to the patient. A high concentration of Mycobacterium tuberculosis in the abscessed tissue, disturbance of the surface of liquid drainage from the abscess by irrigations and by the agitated behavior of the patient, and positive air pressure in the patient's room are factors that appear to have contributed to the high risk of tuberculosis transmission. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of obesity continues to rise. People with obesity are at increased risk of several diseases. We tested an algorithm-based screening program for people with a BMI above 30 kg/m 2 and present data on the prevalence of previously undiagnosed obesity-related diseases., Patients and Methods: Seven hundred and sixty-nine persons with BMI > 30 kg/m 2 and age 18-60 years were screened for diabetes (assessed by glycosylated hemoglobin and oral glucose tolerance test at HbA1c 43-48 mmol/mol), sleep apnea (screened by questionnaires and assessed by cardiorespiratory monitoring at indication of sleep disorder), liver steatosis or liver fibrosis (assessed by biochemistry and fibroscan) and arterial hypertension (assessed by both office and 24-hour blood pressure measurement). A reference group of people with a BMI of 18.5-29.9 kg/m 2 was established., Results: Of those referred, 73.0% were women. We identified new diabetes in 4.2%, prediabetes in 9.1%, moderate-to-severe sleep apnea in 25.1%, increased liver fat and increased liver stiffness in 68.1% and 17.4%, respectively, and hypertension or masked hypertension in 19.0%. The prevalence of diseases was much higher among men and increased with BMI. Except for hypertension, we found few participants with undiagnosed disease in the reference group., Conclusion: An algorithm-based screening program is feasible and reveals undiagnosed obesity-related disease in a large proportion of the participants. The disproportional referral pattern calls for a tailored approach aiming to include more men with obesity., Trial Registration: Inclusion of the non-obese group was approved by the Scientific Ethics Committee of The Region of Southern Denmark (project identification number: S-20210091), and the study was reported at clinicaltrials.gov (NCT05176132)., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Juhl et al.)

Introduction and Objectives: Studies on the societal burden of patients with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) are sparse. This study examined this question, comparing NAFLD with matched reference groups., Materials and Methods: Nationwide Danish healthcare registers were used to include all patients (≥18 years) diagnosed with biopsy-verified NAFLD (1997-2021). Patients were classified as having simple steatosis or non-alcoholic steatohepatitis (NASH) with or without cirrhosis, and all matched with liver-disease free reference groups. Healthcare costs and labour market outcomes were compared from 5 years before to 11 years after diagnosis. Patients were followed for 25 years to analyse risk of disability insurance and death., Results: 3,712 patients with biopsy-verified NASH (n = 1,030), simple steatosis (n = 1,540) or cirrhosis (n = 1,142) were identified. The average total costs in the year leading up to diagnosis was 4.1-fold higher for NASH patients than the reference group (EUR 6,318), 6.2-fold higher for cirrhosis patients and 3.1-fold higher for simple steatosis patients. In NASH, outpatient hospital contacts were responsible for 49 % of the excess costs (EUR 3,121). NASH patients had statistically significantly lower income than their reference group as early as five years before diagnosis until nine years after diagnosis, and markedly higher risk of becoming disability insurance recipients (HR: 4.37; 95 % CI: 3.17-6.02) and of death (HR: 2.42; 95 % CI: 1.80-3.25)., Conclusions: NASH, simple steatosis and cirrhosis are all associated with substantial costs for the individual and the society with excess healthcare costs and poorer labour market outcomes., Competing Interests: Conflicts of interest Jan Håkon Rudolfsen and Jens Olsen are employees at EY, which is a paid vendor of Pfizer Denmark Aps. Lise Lotte Gluud, Henning Grønbæk, Majken K. Jensen, Mogens Vyberg and Peter Jepsen were paid by Pfizer Denmark Aps. for their work as members of the Study Steering Committee. Peter Bo Poulsen, Nanna Hovelsø, Nikolaj Ture Gregersen and Anne Bloch Thomsen are employees of Pfizer Denmark Aps. Peter Bo Poulsen, Nanna Hovelsø, and Anne Bloch Thomsen owns shares from Pfizer Inc. The authors report no other conflicts of interest in this work. Full ICMJE Disclosure forms are submitted for each co-author., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Aims  In this systematic review, we assessed the literature on the association between fibrinogen levels and stroke in patients with type 2 diabetes (T2D). Methods  MEDLINE and Ovid searches of English reports were performed on the relation between fibrinogen, stroke, and T2D in humans. The search was completed on May 4, 2023. Studies were eligible when T2D patients ≥18 years had stroke confirmed by computed tomography or magnetic resonance imaging, plasma fibrinogen was measured, and a relation between fibrinogen and stroke in T2D patients was reported. Screening of reports and extraction of data were done independently by two authors, and study quality was assessed by predefined issues. Results  Five studies of different designs were included. Three studies reported on significantly increased fibrinogen levels in T2D patients with stroke compared with T2D patients without stroke. Two studies did not observe a significant association between fibrinogen levels and stroke risk. Conclusion  No consistent association was observed between fibrinogen levels and risk of stroke in T2D patients. Due to differences in study design, low sample size, and poorly defined study participants, larger and better-defined studies are needed to elucidate the role of fibrinogen as a stroke risk marker in T2D patients., Competing Interests: Conflict of Interest N.D. received financial support from Steno Diabetes Center Odense., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: Vaginal dysbiosis covers imbalances in the vaginal microbiota, defined by altered composition of bacteria, viruses, and fungi and is associated with euploid pregnancy losses, premature birth, infertility, or bacterial vaginosis. A large proportion of women who have vaginal dysbiosis do not experience any symptoms. Antibiotics are the traditional treatment, recently combined with local probiotics in some cases. Vaginal Microbiota Transplantation (VMT) with eubiotic vaginal bacterial microbiota after antibiotic eradication of pathogens has successfully been performed in a case study with five patients, but no VMT has been performed without the use of antibiotics., Methods: This is a proof of concept case study. The patient was found to have vaginal dysbiosis at the RPL clinic at Copenhagen University Hospital Hvidovre, Denmark on the 23rd of June 2021. She was offered and accepted to receive experimental treatment in the form of a VMT as a compassionate use case. VMT is the transfer of cervicovaginal secretions (CVS) from a healthy donor with a Lactobacillus -dominant vaginal microbiome to a recipient with a dysbiotic vaginal microbiome. CVS is a mixture of e.g., mucus, bacteria, metabolites present in the vaginal canal. Potential donors were thoroughly screened for the absence of STIs, and the most suitable donor sample for the specific patient in this study was determined via an in vitro microbiome competition assay., Findings: A 30-year-old patient with one livebirth and a complicated pregnancy history of two stillbirths and 1 s trimester pregnancy loss in gestational weeks 27 (2019), 17 (2020) and 23 (2020) respectively with complaints of vaginal irritation and discharge that had aggravated in all her pregnancies. Her vaginal microbiome composition showed a 90% dominance of Gardnerella spp. After one VMT there was a complete shift in microbiome composition to 81.2% L. crispatus and 9% L. jensenii with a concurrent resolvement of vaginal symptoms. Single nucleotide polymorphism-analysis confirmed her microbiome to be of donor origin and it remain stable now 1.5 years after the VMT. Five months after the VMT she became pregnant and has successfully delivered a healthy baby at term., Interpretation: Here we report a successful VMT with confirmed donor strain engraftment followed by a successful pregnancy and delivery after a series of late pregnancy losses/stillbirths. Findings suggest that VMT is a potential treatment for severe vaginal dysbiosis. Further, larger studies are required., Funding: The study was partially funded (i.e., analysis costs) by Freya Biosciences Aps, Fruebjergvej, 2100 Copenhagen, Denmark., Competing Interests: Elleke F. Bosma, Brynjulf Mortensen, Kevin DeLong and Johan van Hylckama Vlieg are employees of Freya Biosciences. Johan van Hylckama Vlieg, Anne Bloch Thomsen and Laura Ensign are shareholders of Freya Biosciences. Elleke F. Bosma and Brynjulf Mortensen are listed as inventors on a patent application filed on the use of VMT for RPL. Laura Ensign is the Chair of the Scientific Advisory Board for Freya Biosciences, receives consulting payments from Freya Biosciences, and is an inventor on patent applications related to VMT that are owned by Johns Hopkins University. Anne Bloch Thomsen is a full-time employee of Pfizer as Country Medical Director, CMO of Pfizer Denmark and Iceland and is on the Board of Pfizer Denmark, and is a board member of EMPROS Pharma Sweden. Henriette Svarre Nielsen has received scientific grants from Freya Biosciences, Ferring Pharmaceuticals, BioInnovation Institute, Ministry of Education, Novo Nordisk Foundation, Augustinus Fonden, Oda og Hans Svenningsens Fond, Demant Fonden, and Ole Kirks Fond. HSN received personal payment or honoraria for lectures and presentations from Ferring Pharmaceuticals, Merck, Astra Zeneca, Cook Medical, and IBSA Nordic. Henrik Westh, Andreas Munk Petersen Sarah Mollerup received materials for the study funded by Freya Biosciences and paid to institution. Tine Wrønding, Kilian Vomstein and Julie Elm Heinz do not have any conflicts of interest regarding this publication., (© 2023 The Author(s).)

Background: Men with Klinefelter syndrome (KS) are routinely offered testosterone replacement therapy (TRT) suggested to potentially promote platelet aggregation and increase cardiovascular risk., Objective: We investigated platelet aggregation in men with KS before and during TRT., Materials and Methods: Forty-one adult men with KS participated, of which 20 had no history of TRT at baseline, with 15 completing follow-up after 18 months TRT. Further, we included 21 adult men with KS on long-term TRT (>10 years) and a male reference population. We assessed platelet impedance aggregometry using adenosine diphosphate (6.5 μM), thrombin-receptor-activating-peptide-6 (TRAP 32 μM), and arachidonic acid (ASPI 0.5 mM) as agonists in KS compared to a male reference population and stratified by route of TRT administration., Results: Platelet aggregation among men with KS at baseline or during TRT was not increased compared with the male reference population. For all three agonist, no change was seen in platelet aggregation in KS at follow-up compared with baseline (p ≥ 0.2). Platelet aggregation was not associated with total testosterone and furthermore, platelet count was not affected by treatment with testosterone. Men with KS treated with testosterone gel showed slightly increased TRAP- and ASPI-induced platelet aggregation compared with those treated with testosterone injection (p = 0.02 and p = 0.04, respectively)., Discussion and Conclusions: We observed normal platelet aggregation in men with KS before TRT and following both short and long term treatment. Our findings do not support an independent role of platelets in driving the cardiovascular risk in KS., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Waste in research has been well documented, but initiatives to reduce it are scarce. Here, we share our initial experiences of implementing Lean thinking and visual management into hospital research units in the Region of Southern Denmark. A Transformation Guiding Team (TGT) anchored in the top management was established with participation from leaders, researchers and patient representatives. The role of the TGT was to implement Lean methods, considering patients as primary end-users of the research results. This is in line with an explicit decision on setting patient values first in clinical settings at participating hospitals. The leaders of the research units were instructed in Lean thinking and Lean methods during a five-module course focusing on increasing value and reducing waste in research production. Initial experiences were that Lean tools could create a patient-centred vision that through visual management could identify waste in work processes. Concerns were lack of evidence for using Lean methods in research leadership and that the model itself could be a time consumer. Some lessons learnt were that adding Lean tools in research leadership should not just provide increased research productivity, but also improve other important key performance indicators such as quality of research and patient-relevant results. We intend to evaluate the value of the initiative by follow-up research and publish the outcome of key behavioural and key performance indicators., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Gastrointestinal bleeding (GI-bleeding) is frequent in patients with atrial fibrillation (AF) treated with oral anticoagulation (OAC) therapy. We sought to investigate to what extent lower GI-bleeding represents the unmasking of an occult colorectal cancer., Methods and Results: A total of 125 418 Danish AF patients initiating OAC therapy were identified using Danish administrative registers. Non-parametric estimation and semi-parametric absolute risk regression were used to estimate the absolute risks of colorectal cancer in patients with and without lower GI-bleeding. During a maximum of 3 years of follow-up, we identified 2576 patients with lower GI-bleeding of whom 140 patients were subsequently diagnosed with colorectal cancer within the first year of lower GI-bleeding. In all age groups, we observed high risks of colorectal cancer after lower GI-bleeding. The absolute 1-year risk ranged from 3.7% [95% confidence interval (CI) 2.2-6.2] to 8.1% (95% CI 6.1-10.6) in the age groups ≤65 and 76-80 years of age, respectively. When comparing patients with and without lower GI-bleeding, we found increased risk ratios of colorectal cancer across all age groups with a risk ratio of 24.2 (95% CI 14.5-40.4) and 12.3 (95% CI 7.9-19.0) for the youngest and oldest age group of ≤65 and >85 years, respectively., Conclusion: In anticoagulated AF patients, lower GI-bleeding conferred high absolute risks of incident colorectal cancer. Lower GI-bleeding should not be dismissed as a benign consequence of OAC therapy but always examined for a potential underlying malignant cause., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs) have an increased risk of bleeding including haematuria. In the general population, gross haematuria is associated with urinary tract cancer. Consequently, we aimed to investigate the potential association between gross haematuria and urinary tract cancer in anticoagulated patients with AF., Methods and Results: Using Danish nationwide registers, we included Danish AF patients treated with OACs between 2001 and 2015. Non-parametric estimation and semi-parametric absolute risk regression were used to estimate the absolute risk of urinary tract cancer in patients with and without gross haematuria. We included 125 063 AF patients with a median age of 74 years (interquartile range 65-80) and a majority of males (57%). The absolute risk of gross haematuria 12 months after treatment initiation increased with age ranging from 0.37% [95% confidence interval (CI) 0.31-0.42] to 0.85% (95% CI 0.75-0.96) in the youngest and oldest age groups of ≤70 and >80 years of age, respectively. The 1-year risk of urinary tract cancer after haematuria ranged from 4.2% (95% CI 2.6-6.6) to 6.5% (95% CI 4.6-9.0) for patients in age group >80 and 71-80 years, respectively. Gross haematuria conferred large risk ratios of urinary tract cancer when comparing patients with and without haematuria across all age groups., Conclusion: Gross haematuria was associated with clinically relevant risks of urinary tract cancer in anticoagulated patients with AF. These findings underline the importance of meticulously examining anticoagulated patients with haematuria., (Published on behalf of the European Society of Cardiology. © The Author(s) 2020.)

Background: The biomarker serum S100 calcium-binding protein B (S100B) is used in in-hospital triage of adults with mild traumatic brain injury to rule out intracranial lesions. The biomarker glial fibrillary acidic protein (GFAP) is suggested as a potential diagnostic biomarker for traumatic brain injury. The aim of this study was to investigate the diagnostic accuracy of early prehospital S100B and GFAP measurements to rule out intracranial lesions in adult patients with mild traumatic brain injury., Methods: Prehospital and in-hospital blood samples were drawn from 566 adult patients with mild traumatic brain injury (Glasgow Coma Scale Score 14-15). The index test was S100B and GFAP concentrations. The reference standard was endpoint adjudication of the traumatic intracranial lesion based on medical records. The primary outcome was prehospital sensitivity of S100B in relation to the traumatic intracranial lesion., Results: Traumatic intracranial lesions were found in 32/566 (5.6%) patients. The sensitivity of S100B > 0.10 μg/L was 100% (95%CI: 89.1;100.0) in prehospital samples and 100% (95% CI 89.1;100.0) in in-hospital samples. The specificity was 15.4% (95%CI: 12.4;18.7) in prehospital samples and 31.5% (27.5;35.6) in in-hospital samples. GFAP was only detected in less than 2% of cases with the assay used., Conclusion: Early prehospital and in-hospital S100B levels < 0.10 μg/L safely rules out traumatic intracranial lesions in adult patients with mild traumatic brain injury, but specificity is lower with early prehospital sampling than with in-hospital sampling. The very limited cases with values detectable with our assay do not allow conclusions to be draw regarding the diagnostic accuracy of GFAP., Trial Registration: ClinicalTrials.gov identifier: NCT02867137 .

According to in-hospital guidelines, the biomarker, S100 calcium-binding protein B (S100B), is used to rule out intracranial lesions in mild-moderate traumatic brain injury (TBI). It is currently investigated whether S100B is applicable in a pre-hospital setting. The aim was to compare S100B values and hemolysis index in blood samples drawn and stored under simulated pre-hospital conditions to standardized blood samples. Thirty patients undergoing craniotomy at Department of Neurosurgery, Aarhus University Hospital (Aarhus, Denmark) each had six blood samples drawn. Two samples, drawn in in-hospital standardized Beckton Dickinson tubes and pre-hospital Monovette tubes, respectively, were stored as references at 21°C for 30 min. Two samples were stored at 15°C and 29°C, respectively, one sample was stored at prolonged time (60 min), and one sample was transported for 30 min before centrifugation. S100B values were compared by equivalence test with a pre-defined equivalence margin of ±8.5%. There was no clinically relevant difference between samples stored in different tubes, at various temperatures, or time to analysis compared to reference samples. Transported samples had an 11.5% (90% confidence interval [CI], 6.55; 16.61) higher median S100B value and a 430% (95% CI, 279.6; 661.4) higher median hemolysis index compared to reference samples. Three of 30 (10%) patients had an S100B value above guideline cutoff in the transported sample, which was not found in reference samples (false positive). There were no false negatives. In conclusion, S100B values were not influenced by different tubes, temperatures, and time to analysis. Transported samples had higher median S100B values and hemolysis, icterus, and lipemia index compared to reference samples.

Background: More data regarding effects of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes (T2D) and heart failure (HF) are required., Objectives: The purpose of this study was to investigate the effects of liraglutide on cardiovascular events and mortality in LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) participants, by HF history., Methods: In the multinational, double-blind, randomized LEADER trial, 9,340 patients with T2D and high cardiovascular risk were assigned 1:1 to liraglutide (1.8 mg daily or maximum tolerated dose up to 1.8 mg daily) or placebo plus standard care, and followed for 3.5 to 5 years. New York Heart Association (NYHA) functional class IV HF was an exclusion criterion. The primary composite major adverse cardiovascular events outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Post hoc Cox regression analyses of outcomes by baseline HF history were conducted., Results: At baseline, 18% of patients had a history of NYHA functional class I to III HF (liraglutide: n = 835 of 4,668; placebo: n = 832 of 4,672). Effects of liraglutide versus placebo on major adverse cardiovascular events were consistent in patients with (hazard ratio [HR]: 0.81 [95% confidence interval (CI): 0.65 to 1.02]) and without (HR: 0.88 [95% CI: 0.78 to 1.00]) a history of HF (p interaction = 0.53). In both subgroups, fewer deaths were observed with liraglutide (HR: 0.89 [95% CI: 0.70 to 1.14] with HF; HR: 0.83 [95% CI: 0.70 to 0.97] without HF; p interaction = 0.63) versus placebo. No increased risk of HF hospitalization was observed with liraglutide, regardless of HF history (HR: 0.98 [95% CI: 0.75 to 1.28] with HF; HR: 0.78 [95% CI: 0.61 to 1.00] without HF; p interaction = 0.22). Effects of liraglutide on the composite of HF hospitalization or cardiovascular death were consistent in patients with (HR: 0.92 [95% CI: 0.74 to 1.15]) and without (HR: 0.77 [95% CI: 0.65 to 0.91]) a history of HF (p interaction = 0.19)., Conclusions: Based on these findings, liraglutide should be considered suitable for patients with T2D with or without a history of NYHA functional class I to III HF. (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER]; NCT01179048)., (Copyright © 2020. Published by Elsevier Inc.)

If anticoagulant therapy is stopped, the risk of recurrence after unprovoked venous thromboembolism is high. After anticoagulant treatment for at least three months, the indication for prolonging therapy should be decided after thorough evaluation of individual risk factors for recurrence and bleeding. Clinical parameters, imaging modalities and D-dimer levels can guide this decision. The lower risk of bleeding on non-vitamin K-antagonist oral anticoagulants compared to warfarin is expected to increase the number of patients on extended treatment, but costs and patients' preferences should be considered.

Background: Agonists of the glucagon-like peptide-1 (GLP-1) receptor provide pharmacological levels of GLP-1 activity, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors increase concentrations of endogenous GLP-1 and glucose-dependent insulinotropic polypeptide. We aimed to assess the efficacy and safety of the human GLP-1 analogue liraglutide versus the DPP-4 inhibitor sitagliptin, as adjunct treatments to metformin, in individuals with type 2 diabetes who did not achieve adequate glycaemic control with metformin alone., Methods: In this parallel-group, open-label trial, participants (aged 18-80 years) with type 2 diabetes mellitus who had inadequate glycaemic control (glycosylated haemoglobin [HbA(1c)] 7.5-10.0%) on metformin (>or=1500 mg daily for >or=3 months) were enrolled and treated at office-based sites in Europe, the USA, and Canada. Participants were randomly allocated to receive 26 weeks' treatment with 1.2 mg (n=225) or 1.8 mg (n=221) subcutaneous liraglutide once daily, or 100 mg oral sitagliptin once daily (n=219). The primary endpoint was change in HbA(1c) from baseline to week 26. The efficacy of liraglutide versus sitagliptin was assessed hierarchically by a non-inferiority comparison, with a margin of 0.4%, followed by a superiority comparison. Analyses were done on the full analysis set with missing values imputed by last observation carried forward; seven patients assigned to liraglutide did not receive treatment and thus did not meet criteria for inclusion in the full analysis set. This trial is registered with ClinicalTrials.gov, number NCT00700817., Findings: Greater lowering of mean HbA(1c) (8.5% at baseline) was achieved with 1.8 mg liraglutide (-1.50%, 95% CI -1.63 to -1.37, n=218) and 1.2 mg liraglutide (-1.24%, -1.37 to -1.11, n=221) than with sitagliptin (-0.90%, -1.03 to -0.77, n=219). Estimated mean treatment differences for liraglutide versus sitagliptin were -0.60% (95% CI -0.77 to -0.43, p<0.0001) for 1.8 mg and -0.34% (-0.51 to -0.16, p<0.0001) for 1.2 mg liraglutide. Nausea was more common with liraglutide (59 [27%] patients on 1.8 mg; 46 [21%] on 1.2 mg) than with sitagliptin (10 [5%]). Minor hypoglycaemia was recorded in about 5% of participants in each treatment group., Interpretation: Liraglutide was superior to sitagliptin for reduction of HbA(1c), and was well tolerated with minimum risk of hypoglycaemia. These findings support the use of liraglutide as an effective GLP-1 agent to add to metformin., Funding: Novo Nordisk., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Objective and Design: A cross-sectional segregation analysis of polymorphisms in the estrogen receptor (ER) genes (Pvull and Xbal in ERalpha, and Alul in ERAbeta with bone mineral density in the lumbar spine and forearm and with lipid profile was performed in 1098 postmenopausal women. Additionally, in a subpopulation of 280 women, who completed 1 year of treatment with estrogen plus progestin, the association between genotypes and the response to treatment in both plasma lipids and bone was investigated. In another untreated subpopulation of 443 women, genotype influence on the prevalence of vertebral fractures and on annual rate of bone loss during a mean follow-up period of 11 years was estimated., Results: Baseline plasma lipids, bone mineral density, annual rate of bone loss and prevalence of spinal fractures were not significantly associated with polymorphisms in the ERbeta gene. The ERA polymorphism was significantly associated with bone loss from the distal forearm (P = 0.04) but not with bone loss from the spine. After 1 year of treatment with hormone therapy there was also a significant association between the ERbeta polymorphism and the response in total cholesterol (P = 0.02); while the ERalpha gene polymorphisms did not significantly influence the response to hormone therapy., Conclusions: In a large white population of postmenopausal women, ERalpha gene polymorphisms were not associated with bone mineral density or lipid profile at baseline or after hormone therapy. Conversely, the ERbeta genotype appeared to segregate with bone loss from the forearm and to modulate the decrease in total cholesterol during hormone therapy.

Objective: In postmenopausal women, we investigated if the response in bone mineral density (BMD) was associated with the response in the atherogenic lipid profile during hormone replacement therapy., Methods: We performed an exploratory, post-hoc analysis of data from a prospective double-blind placebo-controlled trial. Healthy postmenopausal women were randomised into five groups, each receiving different combinations of 17 beta-estradiol and gestodene or placebo. A total of 133 women completed the study. The study period was 3 years. The response in bone mass was expressed as the percentage change in BMD from baseline calculated by linear regression from semi-annual measurements. The change in lipid profile was evaluated as the average of three mid-cycle and end-cycle values in percentage from baseline in order to account for cyclic changes during sequential hormone therapy., Results: A significant correlation between the increase in BMD of the spine and hip and forearm with the decrease in serum low density lipoprotein (LDL) and cholesterol was found. Additionally, the decrease in atherogenic lipids correlated significantly with the response in biochemical bone markers for resorption and formation., Conclusion: In conclusion, our study shows that it is the same women who have a favourable response in BMD as in the lipid-profile during hormone replacement therapy (HRT). The association is most likely driven by a common response in FSH to exogenous estradiol therapy. This indicates that common denominators for the response to HRT exist. Further studies are needed to explore and identify such predictors.

IGF2 is known to affect the normal development and pathology of the cardiovascular system. We previously created mutant mice with targeted expression of an Igf2 transgene in the smooth muscle cells and showed that these mice spontaneously develop aortic intimal cushions. In the present work, we provide a general description of the phenotype of two independent lines of heterozygous transgenics. These mice showed organomegaly and a shortened life span. The latter trait was stronger in the line with a relatively more marked organomegaly and more pronounced in males than females in both lines. Postmortem histology revealed gross abnormalities of the cardiac architecture, suggesting that transgenic mice may accumulate lethal cardiovascular defects. Accordingly, apparently normal transgenic mice had mild cardiomegaly, an enlarged left ventricle, bradycardia, and hypotension. These observations are discussed in the light of the proposed therapeutic use of IGF2 in human cardiac diseases.

Objective: On August 31, 1998, the rhesus-human reassortant rotavirus vaccine (RRV-TV) was licensed for use in the U.S. During the next nine months, 15 cases of intussusception were reported among infants who received the vaccine. Case-control and cohort studies showed a significantly increased risk of developing intussusception within one week of receiving the vaccine; subsequent ecologic studies did not. In this study, the authors used data on RRV-TV vaccination rates from the National Immunization Survey (NIS) to estimate state and national RRV-TV uptake rates and factors associated with receiving RRV-TV. These estimates are a key component in evaluating published ecologic studies designed to investigate the relationship between receipt of the vaccine and intussusception., Methods: The authors analyzed NIS data for children ages 19 to 35 months who were eligible to receive RRV-TV between September 1998 and July 1999. The authors estimated vaccine coverage and the number of doses administered by state, NIS sampling quarter, and birth cohort, and analyzed demographic and socioeconomic variables to evaluate their relationship with receiving RRV-TV., Results: It was estimated that approximately 1 million doses of RRV-TV were administered to 504,585 (+/-61,854) children, 13.4% (+/-1.6%) of children who were eligible. The estimated number of doses administered and the vaccination coverage rate varied greatly from state to state. Children living in households with higher socioeconomic conditions were more likely to receive the vaccine., Conclusion: Ecologic studies had a limited ability to detect a significant increase in the population incidence rate of intussusception that could be attributed to RRV-TV because populations in these studies consisted primarily of children who did not receive the vaccine. The example from RRV-TV demonstrates some of the challenges of assessing the magnitude of the association between a vaccine and an uncommon or rare adverse event.

Setting: The highest priority for tuberculosis (TB) control is to ensure patients complete therapy. However, standardized, detailed evaluation of national performance on completion of therapy in the United States has been lacking. Since 1982, the Centers for Disease Control and Prevention (CDC) has had a program objective that at least 90% of TB cases complete therapy. Since 1986, the standard of practice for patients with drug-susceptible TB has been 6 months of therapy., Objective: To determine completion of therapy rates and duration of therapy for US TB patients reported in 1993., Design: Expanded TB surveillance data on all US TB patients reported to the CDC in 1993 with initial therapy of two or more drugs were analyzed with respect to completion and duration of therapy., Results: A disposition (reason therapy stopped) was obtained on 98.7% of 23 489 treated patients. Overall, 91.2% of evaluable patients completed therapy. The overall completion rate at 12 months of therapy was 66.8%, and 90% completion was reached at 23 months. For patients with initially drug-susceptible TB, completion was 7.1% at 6 months, 66.5% at 12 months, and reached 90% at 22 months., Conclusion: While completion rates ultimately exceeded 90% nationwide, there was considerable delay in reaching this objective, especially in patients with drug-susceptible TB. It is critical that health departments and health care providers identify and remedy any deficiencies responsible for prolonged therapy.

Objective: To investigate an outbreak of tuberculosis, determine the number of active cases and infections, and examine efforts to control the spread of disease., Setting: A small town in Maine, in which no cases of tuberculosis had been reported in the previous 3 years., Design: Epidemiologic investigation of an outbreak of tuberculosis infection and disease., Measurements: A patient with an active case of tuberculosis was defined as a resident of the town or the surrounding area or an employee of the local shipyard who had a culture of sputum or tissue that was positive for Mycobacterium tuberculosis between June 1989 and May 1992. A case of tuberculous infection was defined as a positive tuberculin skin test result in a person with no previous positive test result., Results: 21 active cases of tuberculosis occurred among shipyard workers and persons residing in the affected community between 1989 and 1992. One patient was the source of the outbreak; 8 months lapsed between the onset of this patient's illness and appropriate diagnosis and treatment. The M. tuberculosis strains isolated from this patient and from six other patients belonged to phage type I, auxiliary 14. All isolates were susceptible to drug treatment. Of 9898 persons who were tested, 697 (7%) were newly infected. Because isoniazid prophylaxis was not routinely offered to infected persons older than 35 years of age, only 341 (49%) infected persons completed isoniazid prophylaxis., Conclusions: Many secondary cases of tuberculosis occurred throughout this small Maine community because of delayed diagnosis and treatment of the source patient, delayed outbreak investigation, and failure to promote isoniazid prophylaxis to all persons infected during the outbreak. Aggressive efforts to identify persons with new infection are of limited value in controlling tuberculosis unless they are accompanied by an equally aggressive use of isoniazid prophylaxis.

Objective: To ascertain predictors of survival in HIV-infected tuberculosis (TB) patients., Design: Retrospective cohort study., Setting: New York City public hospital., Patients: Fifty-four consecutive HIV-seropositive patients with newly diagnosed TB and no other AIDS-defining illnesses., Main Outcome Measures: CD4+ T-lymphocyte counts, completion of anti-TB therapy, repeat hospitalizations with TB, and survival., Results: Forty-five (84%) of the 54 patients died a median of 15 months after TB diagnosis (range, 1-80 months), five (9%) were alive after a median of 81 months (range, 75-84 months), and four (7%) were lost to follow-up after a median of 42 months (range, 30-66 months). In univariate analyses, disseminated TB, intrathoracic adenopathy, oral candidiasis and CD4 count depletion were each associated with decreased survival. In a multivariate analysis, CD4 count depletion was the only independent predictor of decreased survival. Repeat hospitalization with TB occurred in 10 out of 15 patients who did not complete anti-TB therapy compared with one out of 21 patients who completed anti-TB therapy (P < 0.001)., Conclusion: The clinical presentation of TB and CD4 count at TB diagnosis are each predictive of survival in HIV-seropositive TB patients. The CD4 count is the only independent predictor of survival.

Background: Elucidation of the relationship between tuberculosis (TB) and the acquired immunodeficiency syndrome (AIDS) is needed to help predict the future course of these two epidemics. We examined nationwide trends in TB and AIDS occurring in the same individual., Methods: Health departments in the 50 states, District of Columbia, Puerto Rico, and Guam matched their TB and AIDS case registries to determine the number of persons diagnosed with both TB and AIDS. The number of AIDS cases, TB cases, AIDS cases that matched with a TB case on the TB registry, and TB cases that matched with an AIDS case on the AIDS registry were reported to the Centers for Disease Control and Prevention, Atlanta, Ga. Data were analyzed for the period from 1981 through 1991. The number of matched TB-AIDS cases was compared with a modeled estimate of excess TB cases during the period from 1985 through 1990., Results: From 1981 through 1991 there were 11,299 AIDS cases that matched with a TB case on the TB registry, representing 5.1% (geographic variation, 0% to 9.3%) of AIDS cases. The TB cases that matched with an AIDS case on the AIDS registry represent 4.3% (geographic variation, 0% to 15.1%) of TB cases from 1981 through 1991. Since 1981, matched TB and AIDS cases increased yearly through 1990. When examined by year of AIDS report, the percentage of AIDS cases that matched with a TB case increased from 1981 to 1982 (1.9% to 5.1%), remained fairly constant from 1983 through 1987 (range, 4.0% to 4.7%), increased in 1988 (5.4%) after extrapulmonary TB was added to the AIDS case definition, and increased slightly through 1990 (5.8%). When examined by year of TB report, the percentage of TB cases that matched with an AIDS case increased steadily from 1981 through 1990 (0.1% to 9.5%). The calculated fraction of excess TB cases during the period from 1985 through 1990 that could be accounted for by identified TB-AIDS cases was 30%., Conclusion: The risk of TB or AIDS among persons already diagnosed with one disease is much higher than among the general population. The percentage of persons with TB who are also diagnosed with AIDS has been increasing rapidly. Human immunodeficiency virus-induced immunosuppression is an important contributor to the TB epidemic and probably accounts for a minimum of 30% of excess TB cases during the period from 1985 through 1990.

Objective: To determine antituberculosis drug resistance patterns, geographic distribution, demographic characteristics, and risk factors of reported tuberculosis (TB) patients in the United States., Design: Survey of reported TB cases in the United States. For culture-positive cases reported to the Centers for Disease Control and Prevention, we asked health departments to provide drug susceptibility test results from initial Mycobacterium tuberculosis isolates., Study Population: Culture-positive TB cases in the United States reported during the first quarter of 1991., Main Outcome Measures: Individual TB case reports submitted to the Centers for Disease Control and Prevention and drug susceptibility test results., Results: Resistance to one or more antituberculosis drugs was found in 14.2% of cases. Resistance to isoniazid and/or rifampin was found in 9.5% of cases whose isolates were tested against one or both drugs; such cases were found in 107 counties in 33 states. Resistance to both isoniazid and rifampin (multidrug-resistant [MDR] TB) was found in 3.5% of cases whose isolates were tested against both drugs; such cases were found in 35 counties in 13 states. New York City accounted for 61.4% of the nation's MDR TB cases. The 3-month population-based incidence rate of MDR TB in New York City was 52.4 times (95% confidence interval [CI], 35.5 to 78.3) that of the rest of the nation (9.559 vs 0.182 cases per million population). Compared with the rate in non-Hispanic whites in the rest of the nation (0.032 cases per million), the relative risk of MDR TB in New York City non-Hispanic whites was 39.0 (95% CI, 8.1 to 164.5), 299.3 (95% CI, 112.5 to 927.1) in Hispanics, 420.9 (95% CI, 121.0 to 1515.8) in Asian/Pacific Islanders, and 701.0 (95% CI, 296.4 to 2018.1) in non-Hispanic blacks., Conclusions: With nearly 10% of TB patients resistant to isoniazid and/or rifampin, greater use of four-drug regimens and directly observed therapy is indicated. Aggressive intervention to prevent the further spread of MDR TB is needed to find every TB patient and to provide optimal patient management to ensure completion of chemotherapy.

Recent data have suggested that there are racial differences in the susceptibility to infection by Mycobacterium tuberculosis. An opportunity to test this suggestion was afforded by an outbreak of tuberculosis in a racially mixed elementary school in St. Louis County, Missouri. A physical education teacher was discovered to have cavitary pulmonary tuberculosis. Of 343 students in the school, 176 (51 percent) were found to be tuberculin skin test positive (> or = 5 mm induration by Mantoux method); 32 children had abnormal chest radiographs. More frequent contact with the physical education teacher was associated with infection (p < 0.001). Black children were no more likely to be infected than were white children (relative risk (RR) = 0.98, 95% confidence interval (CI) 0.78-1.22). However, black children who were tuberculin positive had larger skin reactions than did white children (mean, 18.9 vs. 16.6 mm, p < 0.001) and were more likely to have abnormal chest radiographs (RR = 2.76, 95% CI 1.44-5.27). Among tuberculin-positive children, low body mass index (less than 10th percentile) was associated with active disease (RR = 2.90, 95% CI 1.45-5.80). The analysis of race was unchanged after controlling for sex, body build, and level of contact with the physical education teacher. Widespread tuberculous infection resulted from contact with a highly infectious staff person. Thin body build was a risk factor for active disease. Black children were no more susceptible to infection than were white children, although they more commonly developed radiographic evidence of active disease.

Background: After the identification of five suspected cases of tuberculosis (TB) in a Nassau County (New York) jail during a 3-week period, an epidemiologic investigation was begun to document the number of cases of TB infection and disease associated with the jail, the characteristics of current or former inmates with TB disease, and the factors contributing to TB transmission in the jail., Methods: The county TB register was matched against the inmate files of the jail. Medical records from hospitals, the health department, and the jail were then reviewed. All inmates in the jail were skin tested during a mass screening., Results: From January 1, 1988, through March 16, 1990, of 205 TB cases in the county, 49 (24%) were associated with the jail. Forty of the cases occurred among current or former inmates, one in a corrections officer, and eight among community contacts of inmates. The 40 inmates with TB were predominantly nonwhite (75%), unmarried (80%) men (90%), with a median age of 32 years. Twenty-three (58%) had a history of injecting drug use, and 14 (35%) were known to be seropositive for the human immunodeficiency virus. Thirty (75%) of the inmates had culture-confirmed pulmonary TB. Five (29%) of 17 Mycobacterium tuberculosis isolates had the same phage type and DNA fingerprint, which was consistent with transmission of infection within the jail. The mass screening revealed that 374 (20%) of 1855 inmates were tuberculin positive., Conclusions: Without an effective program of TB control, jails can act as reservoirs of disease for inmates and staff, and for the community into which the inmates are released.

A survey of the 15,379 cases of tuberculosis reported to the Centers for Disease Control and Prevention by 29 State health departments in 1984 and 1985 revealed that 7.7 percent of the victims older than age 64 were living in a nursing home at the time of diagnosis and 1.8 percent between the ages of 15 and 64 were living in a correctional institution at the time of diagnosis. Incidence rates of tuberculosis for residents of nursing homes and for inmates of Federal and State prisons and local jails were estimated using denominators derived from institutional population counts provided by the National Center for Health Statistics and by the Department of Justice, Bureau of Justice Statistics, and Bureau of Prisons. The aggregate tuberculosis incidence rate for nursing home residents in the 29 States was 1.8 times higher than the rate seen in elderly persons who were living in the community (95 percent confidence interval on the relative risk 1.64, 2.02). The aggregate tuberculosis incidence rate for inmates in correctional facilities was 3.9 times higher than the rate for persons of a similar age who were not incarcerated (95 percent confidence interval on the relative risk 3.35, 4.49). Strengths and limitations of the design and implications of the first survey of tuberculosis incidence, in a large number of States, among residents of nursing homes and correctional facilities are discussed.

Objective: To assess nosocomial transmission of tuberculosis (TB)., Design: A historical cohort study of hospitalized patients with the human immunodeficiency virus (HIV) and a purified protein derivative (PPD) tuberculin skin test survey of health care workers (HCWs)., Setting: A large public teaching hospital in San Juan, Puerto Rico., Patients: For the cohort study, a case patient was defined as any patient in the HIV unit at the hospital who developed culture-positive TB from 31 days or more after admission through December 31, 1989. For the PPD survey, of 1420 HCWs from the hospital, 908 agreed to participate and had sufficient data for analysis., Main Outcome Measures: For the cohort study, to compare the risk of developing active TB among patients who were exposed to hospital roommates with infectious TB and the risk among nonexposed patients. For the HCW PPD survey, to determine the prevalence of and risk factors for tuberculous infection., Results: Eight of 48 (9.7/10,000 person-days) exposed case patients vs four of 192 (0.8/10,000 person-days) nonexposed case patients developed active TB (relative risk [RR] = 11; 95% confidence interval [CI], 2.3, 50.3). Positive PPDs (greater than or equal to 10 mm of induration) in HCWs were associated with older age (P = .0001) and with history of community TB exposure (P = .0002). In a multivariable logistic model that adjusted for these variables, HIV unit nurses (nine of 19) and nurses in the internal medicine ward (45 of 90) had a higher proportion of positive PPDs than the reference group (clerical personnel on other floors: 35 of 188, P = .0005)., Conclusions: These data suggest that patient-to-patient transmission of TB in HIV units can occur and that HCWs are at risk of acquiring TB infection.

From 1985 through 1988, 5.1 percent of TB cases reported in the United States were diagnosed at death. Differences in the proportions diagnosed at death by race/ethnicity, sex, and place of birth (United States vs foreign-born) were relatively small. The proportion of cases diagnosed at death increased with age, from 0.7 percent in patients less than 5 years old to 18.6 percent among patients 85 years and older. Only 26.0 percent of cases diagnosed alive were among those 65 years and older, but 60.3 percent of those diagnosed at death were in this age group. Eighteen percent of cases with miliary, meningeal and peritoneal TB were diagnosed at death, compared with 4.8 percent among those with pulmonary TB. These data indicate that TB too often remains unrecognized and that, to prevent continuing deaths from this curable disease, a high index of suspicion of TB remains important, particularly among the elderly and among persons with extrapulmonary sites of disease.

Of 48,712 acquired immunodeficiency syndrome (AIDS) cases reported to the Centers for Disease Control from October 1987 through March 1989, 1239 (2.5%) were diagnosed with extrapulmonary tuberculosis. Extrapulmonary tuberculosis was diagnosed in 1013 (2.3%) of the US-born persons with AIDS, compared with 26 (8%) of the Mexican-born, 82 (13%) of the Haitian-born, and 4 (1%) of the Cuban-born. Patients with AIDS with and without extrapulmonary tuberculosis were similar in age, except that extrapulmonary tuberculosis was relatively rare in patients with AIDS under the age 10. Compared with white homosexual/bisexual men, black race (odds ratio, 2.7), intravenous drug use (odds ratio, 2.0), heterosexual AIDS transmission category (odds ratio, 1.9), and Hispanic ethnicity (odds ratio, 1.6) were independently associated with extrapulmonary tuberculosis. In 1988, extrapulmonary tuberculosis in persons known to be human immunodeficiency virus seropositive represented 21% of national extrapulmonary tuberculosis morbidity.

An outbreak of hepatitis A occurred in a north Georgia trailer park served by a private well. Of 18 residents who were serosusceptible to hepatitis A virus (HAV), 16 (89%) developed hepatitis A. Well water samples were collected 3 months after illness onset in the index case and 28 days after illness onset in the last trailer park resident. Hepatitis A virus antigen (HAVAg) was detected in the samples by enzyme immunoassay from three of the five cell lines following two 30-day passages and from a fourth cell line following a third passage of 21 days.

Symptomatic tuberculosis (TB) can occur as an opportunistic disease in immunosuppressed persons who are infected with human immunodeficiency virus (HIV) and who have been previously infected with Mycobacterium tuberculosis. Increases in TB cases have occurred in areas which have reported large numbers of cases of the acquired immunodeficiency syndrome (AIDS), and a high proportion of these TB cases have been HIV seropositive. Therefore, increasing numbers of HIV-infected persons may be found in TB clinics and hospitals. HIV serologic surveys in TB clinics and hospitals providing clinical services to TB patients are needed to assess the local prevalence of HIV infection in TB patients and the consequent need for public health intervention to prevent further spread of HIV and TB infection. The Centers for Disease Control (CDC), in collaboration with State and local health departments, has initiated HIV surveillance of patients with confirmed and suspected TB in TB clinics and hospitals in the United States. Blinded (serologic test results not linked to identifiable persons) HIV seroprevalence surveys are conducted in sentinel TB clinics and hospitals that provide TB clinical services each year to obtain estimates of the level of HIV infection in TB patients and to follow trends in infection over time. Nonblinded (voluntary) surveys will also be conducted to evaluate behaviors that have placed TB patients at risk for or protected them against HIV infection. Data from these surveys will be used to target education and prevention and control programs for TB and HIV infection and to monitor changes in behavior in response to such programs.

A total of 35 patients diagnosed with tuberculosis in 1976-1984 were identified as part of a sustained outbreak involving five communities located in southern Delaware. The index case, a 25-year-old black female with sputum smear-positive, cavitary pulmonary tuberculosis, was a sexual partner of three other persons with cavitary pulmonary tuberculosis and a close contact of 10 other persons with tuberculosis. The median age of the 35 patients was 23 years (range 15 months to 77 years), and 13 (37%) were less than 15 years of age. Sixteen patients (46%) were male, and 34 (97%) were black. Pulmonary parenchymal disease was noted in 18 cases (51%), including nine (26%) with cavitary lesions; 11 (31%) had lymphatic disease (hilar and/or mediastinal); five (14%) had pleural disease; and one (3%) had a normal chest radiograph. Infection prevalence (per 100 tested) was 44.7 for close contacts of cases and 18.3 for other than close contacts, and disease prevalence (per 100 tested) was 8.9 and 1.4 for those two groups, respectively. This outbreak highlights several points: Outbreaks of tuberculosis may go undetected for several years; aggressive and complete surveillance and containment efforts are needed to control tuberculosis; and tuberculosis in children and minorities is still a problem in the United States.

Two outbreaks of group A streptococcal abscesses following receipt of diphtheria-tetanus toxoid-pertussis (DTP) vaccine from different manufacturers were reported to the Centers for Disease Control (CDC) in 1982. The clustering of the immunization times of cases, the isolation of the same serotype of Streptococcus from all cases in each outbreak, and the absence of reported abscesses associated with receipt of the same lots of vaccine in other regions of the country, suggest that each outbreak was probably caused by contamination of a single 15-dose vial of vaccine. The preservative thimerosal was present within acceptable limits in unopened vials from the same lot of DTP vaccine in each outbreak. Challenge studies indicate that a strain of Streptococcus from one of the patients can survive up to 15 days in DTP vaccine at 4 degrees C. Contamination of vials during manufacturing would have required survival of streptococci for a minimum of 8 months. Preservatives in multidose vaccine vials do not prevent short-term bacterial contamination. Options to prevent further clusters of streptococcal abscesses are discussed. The only feasible and cost-effective preventive measure now available is careful attention to sterile technique when administering vaccine from multidose vials.

Measles has had a severe impact on children in the United States since colonial times. In the early decades of the 20th century, thousands of fatal measles infections were reported each year. During the 1950s an annual average of greater than 500,000 cases of measles and nearly 500 deaths due to measles were reported in the United States. Surveys indicated that 95% of the population had been infected with measles by the age of 15 years. The introduction of measles vaccine and its widespread use, which began in 1963, has had a major impact on the occurrence of measles in the United States. Reported numbers of cases, deaths due to measles, and complications of measles (e.g., encephalitis) have declined dramatically. Accompanying the decline in reported incidence of measles and following it by approximately seven years, has been a decline in the reported incidence of subacute sclerosing panencephalitis (SSPE). In recent years, the incidence of measles has dropped to levels that are less than 1% of those seen in the prevaccine era. In 1981, provisional figures indicated that only 10% of counties in the United States reported any cases of measles. The reported incidence in 1981 was 1.3 cases per 100,000 population, compared with an average incidence of 336.3 cases per 100,000 population in the decade 1950-1959. Thus, the impact of measles in the United States has been markedly reduced, and it is anticipated that indigenous transmission will be eliminated entirely from the country within the year.

In the period 1980-1981, two hundred nine imported measles cases were reported in the United States. These cases represent 1.3% of the total of 16,630 cases of measles reported to the Centers for Disease Control (CDC) during that period. An average of two imported measles cases were reported each week. The travelers with imported measles were United States citizens and foreign nationals who arrived from 47 different countries throughout the world. However, returning United States citizens have accounted for a rising proportion of imported measles cases. Approximately half (49.3%) of the imported cases were reported by four areas: California, New York State exclusive of New York City, New York City, and Florida. Seven measles outbreaks occurring following importations during the two-year period were identified. In addition to 114 imported measles cases reported to the CDC in 1981, 437 measles cases were reported to be caused directly or indirectly by those importations. The actual number of import-associated cases may have been considerably higher. Imported measles and associated cases together accounted for at least 17% (551/3,124) of reported measles cases in 1981.

In February 1981, a measles outbreak occurred in a pediatric practice in DeKalb County, GA. The source case, a 12-year-old boy vaccinated against measles at 11 1/2 months of age, was in the office for one hour on the second day of rash, primarily in a single examining room. On examination, he was noted to be coughing vigorously. Seven secondary cases of measles occurred due to exposure in the office. Four children had transient contact with the source patient as he entered or exited through the waiting room; only one of the four had face-to-face contact within 1 m of the source patient. The three other children who contracted measles were never in the same room with the source patient; one of the three arrived at the office one hour after the source patient had left. The risk of measles for unvaccinated infants (attack rate 80%, 4/5) was 10.8 times the risk for vaccinated children (attack rate 7%, 2/27) (P = .022, Fisher exact test, two-tailed). Airflow studies demonstrated that droplet nuclei generated in the examining room used by the source patient were dispersed throughout the entire office suite. Airborne spread of measles from a vigorously coughing child was the most likely mode of transmission. The outbreak supports the fact that measles virus when it becomes airborne can survive at least one hour. The rarity of reports of similar outbreaks suggests that airborne spread is unusual. Modern office design with tight insulation and a substantial proportion of recirculated ventilation may predispose to airborne transmission.