Ambulatory health care use by patients in a public hospital emergency department

OBJECTIVE: To describe primary care clinic use and emergency department (ED) use for a cohort of public hospital patients seen in the ED, identify predictors of frequent ED use, and ascertain the clinical diagnoses of those with high rates of ED use. DESIGN: Cohort observational study. SETTING: A public hospital in Atlanta, Georgia. PATIENTS: Random sample of 351 adults initially surveyed in the ED in May 1992 and followed for 2 years. MEASUREMENTS AND MAIN RESULTS: Of the 351 patients from the initial survey, 319 (91%) had at least one ambulatory visit in the public hospital system during the following 2 years and one third of the cohort was hospitalized. The median number of subsequent ED visits was 2 (mean 6.4), while the median number of visits to a primary care appointment clinic was O (mean 1.1) with only 90 (26%) of the patients having any primary care clinic visits. The 58 patients (16.6%) who had more than 10 subsequent ED visits accounted for 65.6% of all subsequent ED visits. Overall, patients received 55% of their subsequent ambulatory care in the ED, with only 7.5% in a primary care clinic. In multivariate regression, only access to a telephone (odds ratio [OR] 0.48; 95% confidence interval [CI] 0.39, 0.60), hospital admission (OR 5.90; 95% CI 4.01, 8.76), and primary care visits (OR 1.68; 95% CI 1.34, 2.12) were associated with higher ED visit rates. Regular source of care, insurance coverage, and health status were not associated with ED use. From clinical record review, 74.1% of those with high rates of use had multiple chronic medical conditions, or a chronic medical condition complicated by a psychiatric diagnosis, or substance abuse. CONCLUSIONS: All subgroups of patients in this study relied heavily on the ED for ambulatory care, and high ED use was positively correlated with appointment clinic visits and inpatient hospitalization rates, suggesting that high resource utilization was related to a higher burden of illness among those patients. The prevalence of chronic medical conditions and substance abuse among these most frequent emergency department users points to a need for comprehensive primary care. Multidisciplinary case management strategies to identify frequent ED users and facilitate their use of alternative care sites will be particularly important as managed care strategies are applied to indigent populations who have traditionally received care in public hospital EDs.     

Manual and computer-aided space analysis: a comparative study

Separate injections of Haemophilus influenzae type b capsular polysaccharide-tetanus conjugate (PRP-T) vaccine and diphtheria-tetanus-pertussis (DTP) reconstitution of freeze-dried PRP-T vaccine with liquid DTP vaccine have been shown to be safe and immunogenic in infants. The present study was conducted to test the safety and immunogenicity of the liquid combination vaccine administered to young infants in the dual-chamber syringe. The study was a monocenter, open clinical trial of 3 month-old infants receiving PRP-T and DTP vaccines in the dual-chamber syringe reconstituted prior to injection. Healthy infants were immunized according to a 3, 4 and 5 months-of-age schedule. The vaccine was administered in a dual-chamber syringe, ready to use with two chambers. The proximal chamber contained freeze-dried PRP-T and the distal chamber contained liquid combination-vaccine DTP. The freeze-dried PRP-T vaccine was reconstituted with the liquid DTP vaccine in the same unidose dual-chamber syringe (0.5 mL) and was injected intramuscularly into the deltoid region. Blood sampling was performed prior to vaccination at 3 months of age and after the third vaccination at 6 months. The primary end-point was the serological response to PRP-T vaccine as expressed by the percentage of infants with an antibody titer greater than or equal to 1 microgram/mL. The reactogenicity was expressed as the percentage of reported local and systemic reactions. A total of 108 infants were included in the study and received the dual-chamber syringe vaccine. After the third injection, all the infants had a PRP antibody titer greater than or equal to 0.15 microgram/mL and 94.4% of infants had a PRP antibody titer greater than or equal to 1 microgram/mL; the pertussis agglutinin titers were over the threshold 40 and 80 in all infants and 98.1% were over the threshold 320. After the third injection, all the infants had diphtheria antibody titers greater than 0.1 IU/mL and 83.3% had titers greater than 1 IU/mL; all the infants had tetanus antibody titers greater than 0.1 IU/mL and 97.2% had results over 1 IU/mL. Thirty-seven infants (34.6%) had local reactions and 64.5% had systemic reactions. The dual-chamber syringe may reduce the cost of vaccine delivery, as well as the workload, and increase the vaccine acceptability and coverage rate of vaccines.     

Parental knowledge and choice regarding live and inactivated poliovirus vaccines

BACKGROUND: Concern about the 8 to 10 cases per year of vaccine-associated paralytic poliomyelitis caused by the live oral poliovirus vaccine (OPV) has led to revised guidelines for immunization of children in the United States. The use of inactivated poliovirus vaccine (IPV) at 2 and 4 months of age could require administration of 3 injections per visit until combination products are available. OBJECTIVE: To determine parents' knowledge of poliovirus vaccines and the choices they would make between IPV and OPV. METHODS: Parents of 240 children aged 2 weeks to 18 months under the care of 10 private pediatricians in the Baltimore, Md, metropolitan area were interviewed prior to the announcement of revised advisory committee guidelines. RESULTS: The majority (62.5%) of respondents were not aware that 2 poliovirus vaccines are available. After reviewing standardized information about the vaccines and 2 alternate schedules, most (75%) parents would consult someone (primarily their physician) before making a final choice of a vaccine schedule. If parents made the choice without consulting anyone else, 61.3% would choose to have their child receive IPV and 3 injections per visit as compared with an all-OPV schedule and 2 injections per visit. Inactivated poliovirus vaccine was preferred by most parents because it would reduce the risk for vaccine-associated paralytic poliomyelitis. Oral poliovirus vaccine was preferred by 37.9% of parents primarily because it was given orally. If the number of injections at each visit was the same for both vaccines, 76.3% of parents would choose the IPV schedule, and if the number of injections was reduced to 2 by combining IPV with another vaccine, 87.9% of parents would choose IPV. CONCLUSION: The number of injections per visit is an important issue, but a majority of parents would choose to have their children receive extra injections to prevent the low risk for vaccine-associated paralytic poliomyelitis.     

Meta-analysis of DRD3 gene and schizophrenia: ethnic heterogeneity and significant association in Caucasians

BACKGROUND: Children with asthma may be at increased risk for low immunization rates given that they have recurrent illnesses that often result in acute care visits to their pediatrician, visits to the emergency room, admissions to the hospital, and visits to subspecialists, where immunizations are not routinely administered. OBJECTIVES: To assess immunization rates for routine and influenza vaccines in children with asthma and assess factors that may contribute to delay. METHODS: We conducted a cross-sectional survey of 117 children aged 6 to 48 months with onset of asthma within the first 15 months of life. Subjects were recruited from an allergy and immunology clinic at an urban, tertiary care center. Those judged to have immunization delay did not have the required 4 DTP, 3 OPV, and 1 MMR vaccine by age 24 months (4:3:1 series). Receipt of influenza vaccine was determined for eligible children with moderate to severe asthma. RESULTS: Seventy-four (80%) children had up-to-date immunizations at age 24 months. Those with delay had fewer visits to a subspecialist than those who were up-to-date (1 versus 2 visits P = .010). Twenty-two (25%) of 87 eligible subjects received influenza vaccine. Recipients were more likely to have been hospitalized than nonrecipients (77% versus 49%, P = .022). CONCLUSIONS: Though the majority of young children with asthma were up-to-date for routine immunizations, only 25% of children with moderate to severe asthma received influenza vaccine. Greater efforts must be made by pediatricians and asthma subspecialists to ensure that children with moderate to severe asthma are immunized against influenza virus.     

Retinopathy in African Americans and whites with insulin-dependent diabetes mellitus

BACKGROUND: The development and progression of diabetic retinopathy in African Americans with insulin-dependent diabetes mellitus is not known. METHODS: Two hundred subjects with insulin-dependent diabetes mellitus with duration of diabetes 16 years or less at first visit were studied; 58 were African Americans and 142 were whites. All had gradable stereoscopic color fundus photographs (seven standard fields) from at least two visits (mean time between first and second visit was 4.1 years). Subjects with hemoglobinopathy or proliferative retinopathy or subjects who had evidence of treatment for proliferative retinopathy at first visit were excluded. Masked grading of photographs was conducted using the modified Airlie House classification scheme. RESULTS: African Americans were older, heavier, had higher systolic blood pressure (all P < .05), and marginally higher hemoglobin A1 (HbA1) values (P = .06) than the whites at first visit. African Americans had a lower rate of two steps or more progression from preexistent retinopathy (19%) than whites (43%). Progression to proliferative retinopathy or treatment was similar by race. Multivariate analysis predicting development oe progression of retinopathy, while controlling for length of follow-up, found higher HbA1 (odds ratio [OR] = 2.15), longer duration of insulin-dependent diabetes mellitus (OR = 1.69), higher serum creatinine concentration (OR = 1.59), and white race (OR = 2.62) to be independent risk factors. CONCLUSIONS: These data suggest a previously unsuspected reduction in the adjusted risk for development and progression of retinopathy in African Americans. The reason for this apparently reduced risk are not known.     

Comparative reactogenicity and immunogenicity of booster doses of diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine and diphtheria-tetanus-inactivated poliovirus vaccine in preadolescents

BACKGROUND: The changing epidemiology of pertussis in France has emphasized the need for booster vaccinations in adolescents. Although not previously recommended because of the high reactogenicity of whole cell pertussis in children older than 2 years old, the development of less reactogenic acellular pertussis vaccines means that this recommendation may be reconsidered. OBJECTIVES: Assessment of the reactogenicity and immunogenicity of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus (DTPa-IPV=Group 1) vaccine administered as the fifth dose in preadolescents in comparison with a commercial diphtheria-tetanus-inactivated poliovirus (DT-IPV) (Group 2) vaccine currently recommended for this age group. MATERIALS AND METHODS: An open, randomized study involving 115 healthy subjects ages 10 to 13 years previously vaccinated with 4 doses of diphtheria-tetanus-whole cell pertussis-IPV vaccines. Reactogenicity was assessed for 4 days postvaccination using diary cards. Immunogenicity based on antibody assays in sera taken before and 1 month postvaccination was evaluated for all vaccine antigen components. RESULTS: Both vaccines showed good tolerability, local and general reactogenicity being similar. For local reactions Group 1=88.1% and Group 2=86.8%, and for general reactions Group 1=40.7% and Group 2=47.2%. Headache was the most frequent general symptom with 27.1% for DTPa-IPV and 39.6% for DT-IPV. The incidence of fever was 5.1% with DTPa-IPV and 9.4% for DT-IPV. Good immune responses were obtained against all vaccine components. CONCLUSIONS: The inclusion of acellular pertussis did not significantly increase the reactogenicity of DTPa-IPV in comparison with the currently recommended DT-IPV vaccine when given as a fifth dose in preadolescents. To prevent recent resurgence of pertussis in France, this vaccine should be preferred as the booster dose of DTPa-IPV at 11 to 13 years of age as recently approved by the National Council of Hygiene of France.     

Deaths caused by venomous snakes in the State of S?o Paulo: evaluation of 43 cases from 1988 to 1993]

PURPOSE: To examine rheumatology subspecialty practice patterns, determinants of referral to rheumatologists, and utilization of aspiration and injection procedures in a population-based sample of elderly individuals. SUBJECTS AND METHODS: We obtained Medicare physician claims for all visits to rheumatologists among beneficiaries aged 65 years and older in Colorado, Massachusetts, and Virginia in 1993, and for visits to all providers by patients with coded diagnoses of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We examined variations in visit frequency and aspiration/injection procedures, and we analyzed determinants of referral to a rheumatologist for RA or SLE. RESULTS: In 1 year, 144,797 visits were made to rheumatologists by 38,443 patients in the three states. An inflammatory disorder was coded in 45% of visits and a noninflammatory disorder in 50%. Half of patients with RA were seen three or fewer times in the year. For RA and SLE, African Americans were about 60% as likely to be seen by a rheumatologist as whites. Utilization of rheumatologist services for rheumatoid arthritis and systemic lupus erythematosus was highest in the state (Virginia) with the lowest per capita supply of rheumatologists. Among patients with bursitis, tendinitis, and osteoarthritis, African-American women were more likely to receive an injection or aspiration procedure than whites or African-American men. CONCLUSION: Elderly patients with rheumatologic disorders were seen by specialists less frequently than recommended by a recent rheumatology manpower survey. African-Americans with RA and SLE had fewer rheumatology visits than whites.     

Safety, tolerability and immunogenicity of concomitant injections in separate locations of M-M-R II, VARIVAX and TETRAMUNE in healthy children vs. concomitant injections of M-M-R II and TETRAMUNE followed six weeks later by VARIVAX

OBJECTIVES AND STUDY DESIGN: The primary objectives of this study were to compare immunologic responses, antibody persistence, safety and varicella breakthrough rates when VARIVAX (varicella vaccine) is given at the same time as M-M-R II (measles, mumps, rubella vaccine) and TETRAMUNE (conjugate Haemophilus influenzae type b, diphtheria, tetanus and whole cell pertussis vaccine) at separate injection sites (Group A) vs. VARIVAX given 6 weeks after M-M-R II and TETRAMUNE (Group B). Six hundred nine healthy children, 12 to 23 months of age, were randomized to one of two treatment (immunization) groups (Group A and Group B). Blood for antibody titers was drawn on the day of immunization, 6 weeks after each injection and 1 year later. Local and systemic adverse reactions were recorded. Exposure and cases of varicella were documented through a 1-year follow-up period. RESULTS: Measles, mumps and rubella seroconversion rates and geometric mean titers (GMTs) were similar for both treatment groups. Varicella seroconversion rates were also similar between groups. However, varicella GMTs and percent with a varicella-protective level [> or =5.0 glycoprotein (gp) enzyme-linked immunosorbent assay (ELISA) units] did not meet the prespecified criteria for similarity were lower for Group A (GMT 10.5; 82.8% > or =5.0 gp ELISA units) than for Group B (GMT 14.5; 91.2% > or =5.0 gp ELISA units). The GMTs between groups for other antibodies were similar. At the 1-year follow-up antibody titers were comparable in both groups and breakthrough varicella cases appeared generally similar. There were fewer local adverse events (AEs) at the VARIVAX injection sites (9.8% and 2.9%, Group A and B, respectively) than at the TETRAMUNE sites (27.9% and 24.0%). Systemic AEs were not statistically different when M-M-R II was administered alone (8.6%) or concomitantly with VARIVAX (8.9%). When VARIVAX was given alone AEs were 1.8%. The rate of fever > or =102 degrees F after M-M-R II and TETRAMUNE administered together was 10.7% on Days 0 to 3 and 23.7% on Days 7 to 21. When VARIVAX was administered alone, the rate of fever was 5.4% on Days 0 to 3 (P = 0.018) and 10.8% on Days 7 to 21 (P<0.001). CONCLUSION: Because the varicella titers were comparable and varicella breakthrough rates generally similar at 1 year in both groups, we expect that the concomitant administration of VARIVAX with M-M-R II and TETRAMUNE has clinical effectiveness similar to that with VARIVAX 6 weeks after the administration of these other two vaccines. VARIVAX appears to be less reactogenic than M-M-R II and TETRAMUNE.     

Substance P- and calcitonin gene-related peptide-containing nerve fibers in the nasal mucosa of chronically hypoxic rats

Changes made in 1997 and 1998 in the U.S. childhood immunization schedule are discussed, with a focus on the use of poliovirus, pertussis, and combination vaccines. Oral poliovirus vaccine (OPV), the vaccine of choice for all four doses in the polio immunization series since 1962, can cause vaccine-associated paralytic poliomyelitis (VAPP). The inactivated poliovirus vaccine (IPV) has not been associated with VAPP but must be administered by injection and provides inferior intestinal immunity. With the reduced threat of poliovirus importation into the United States, the risk of VAPP, although low, has become less acceptable. The Centers for Disease Control and Prevention accordingly recommended a shift from OPV to IPV in the childhood immunization schedule for the United States, effective January 1997. A sequential OPV and IPV series is recommended, but the schedule includes an OPV-only option, which may be preferred in order to avoid the required injections, and an IPV-only option, which is recommended for immunocompromised persons and their contacts. Concern over local and systemic reactions associated with whole-cell pertussis vaccines, in addition to controversy over a possible relationship between the whole-cell vaccine and neurologic damage, has led to the development of new diphtheria and tetanus toxoids and acellular pertussis vaccine products for use in the diphtheria and tetanus toxoids and pertussis immunization series. Several combination products were licensed in 1997, and more are on the way. This will mean fewer inoculations for children. Increased use of IPV and acellular pertussis products could reduce the frequency of VAPP due to OPV and the local and systemic reactions associated with whole-cell pertussis vaccine.     

Safety and efficacy of purified Vero cell rabies vaccine given intramuscularly and intradermally. (Results of a prospective randomized trial)

OBJECTIVES: To determine adverse reactions as a result of pre- and post-exposure rabies vaccination, using the conventional intramuscular, and reduced dose intradermal regimens and purified Vero cell rabies vaccine. DESIGN: A prospective and randomized study of patients exposed to rabies and of subjects in need of pre-exposure rabies vaccination. SETTING: A metropolitan rabies control center in a canine rabies endemic country. PATIENTS: 1198 subjects were recruited between May, 1994 and March, 1996. They were divided into four groups. Patients with suspected or proven rabies exposures were given the vaccine intramuscularly using the conventional regimen, or intradermally using the World Health Organization approved Thai Red Cross schedule. Human or equine rabies immune globulin was administered where indicated. Pre-exposure and post-exposure vaccine recipients were divided randomly into two groups each and given the vaccine either by the intramuscular or intradermal schedules. MEASUREMENTS: All local and systemic adverse reactions were recorded and statistically analyzed. RESULTS: Pruritus at injection sites was the only significant local reaction. It was more common in the intradermal groups. Low-grade fever, the only significant adverse systemic event, was more common in the intramuscular groups and was noted in 8% of all subjects. Eighty-four patients bitten by proven rabid animals were found to be alive and well 3 years later. Forty-four of these had received the intramuscular and 40 the intradermal postexposure regimens with human or equine immune globulin injected into wounds on the first day of treatment. CONCLUSIONS: Purified Vero cell rabies vaccine is safe, carries a very low adverse reaction rate and is effective in preventing rabies in severely exposed subjects when used with human or equine rabies immune globulin.     

Inadequate management of blood pressure in a hypertensive population

BACKGROUND: Many patients with hypertension have inadequate control of their blood pressure. Improving the treatment of hypertension requires an understanding of the ways in which physicians manage this condition and a means of assessing the efficacy of this care. METHODS: We examined the care of 800 hypertensive men at five Department of Veterans Affairs sites in New England over a two-year period. Their mean (+/-SD) age was 65.5+/-9.1 years, and the average duration of hypertension was 12.6+/-5.3 years. We used recursive partitioning to assess the probability that antihypertensive therapy would be increased at a given clinic visit using several variables. We then used these predictions to define the intensity of treatment for each patient during the study period, and we examined the associations between the intensity of treatment and the degree of control of blood pressure. RESULTS: Approximately 40 percent of the patients had a blood pressure of > or =160/90 mm Hg despite an average of more than six hypertension-related visits per year. Increases in therapy occurred during 6.7 percent of visits. Characteristics associated with an increase in antihypertensive therapy included increased levels of both systolic and diastolic blood pressure at that visit (but not previous visits), a previous change in therapy, the presence of coronary artery disease, and a scheduled visit. Patients who had more intensive therapy had significantly (P<0.01) better control of blood pressure. During the two-year period, systolic blood pressure declined by 6.3 mm Hg among patients with the most intensive treatment, but increased by 4.8 mm Hg among the patients with the least intensive treatment. CONCLUSIONS: In a selected population of older men, blood pressure was poorly controlled in many. Those who received more intensive medical therapy had better control. Many physicians are not aggressive enough in their approach to hypertension.     

The value of screening for psychiatric disorders in rheumatology referrals

BACKGROUND: Musculoskeletal complaints are common and often unexplained and often lead to rheumatology referrals. The prevalence of psychiatric disease in patients with musculoskeletal complaints is unknown. OBJECTIVES: To determine the prevalence of common psychiatric disorders among patients referred to a rheumatology clinic and the likelihood of establishing a rheumatic diagnosis if a psychiatric disorder is present. DESIGN: Prospective diagnostic survey. SETTING: Two hospital-based rheumatology clinics and a general medicine clinic. PARTICIPANTS: A consecutive sample of newly referred patients (n = 185) and their rheumatologists (n = 9). INTERVENTION: Before their visit, all patients filled out a self-administered version of PRIME-MD (Primary Care Evaluation of Mental Disorders), a questionnaire that makes Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: Primary Care Version, diagnoses of depressive, anxiety, and somatoform disorders. After the visit, the study rheumatologists, who were unaware of the PRIME-MD results, completed a questionnaire regarding their diagnostic assessment. These patients were compared with 210 patients with musculoskeletal complaints who were cared for in a general medicine clinic. MAIN OUTCOME MEASURES: Psychiatric and rheumatic disorders. RESULTS: Compared with patients with musculoskeletal complaints in a general medicine clinic, patients referred to a rheumatology clinic had a higher prevalence of psychiatric disease (40% vs 29%; P = .008), had an almost 2-fold higher prevalence of anxiety disorders, and were more likely to have multiple psychiatric disorders (odds ratio = 2.70, 95% confidence interval = 1.50-5.00). The likelihood of a psychiatric disorder differed among patients with connective tissue disease, nonsystemic articular or periarticular disorders, and nonarticular disorders (27%, 38%, 55%, respectively; P = .006). In a best-fitting logistic regression model, psychiatric disorders markedly decreased the likelihood of a connective tissue disease (odds ratio = 0.24, 95% confidence interval = 0.09-0.62). CONCLUSIONS: Forty percent of patients referred to a rheumatology clinic in this study had a psychiatric disorder, and its presence predicted a lower likelihood of a connective tissue disease. Prospective studies are needed to determine if screening for psychiatric disease before referring patients with unexplained musculoskeletal complaints would reduce costs or improve recognition of potentially treatable psychiatric disorders.     

Spiral CT with ionic and nonionic contrast material: evaluation of patient motion and scan quality

STUDY OBJECTIVES: To determine if subcutaneous administration of influenza vaccine is as immunogenic as the intramuscular route, and to evaluate the frequency of local adverse events associated with both routes in elderly anticoagulated men. DESIGN: Single-blind, prospective study of consecutively enrolled subjects. SETTING: Ambulatory clinic at a university-affiliated Veterans Affairs medical center. PATIENTS: Twenty-six men age 60 years or older, receiving therapeutic dosages of warfarin. INTERVENTIONS: Subjects were randomized to receive either intramuscular or subcutaneous injection of a standard trivalent influenza vaccine. MEASUREMENTS AND MAIN RESULTS: Serum antibody titers to the vaccine's components were measured at baseline, and 6 weeks and 4 months after vaccination. Both routes of administration induced comparable serum antibody titers. There were no differences in adverse events at administration sites between routes of administration. CONCLUSIONS: Elderly individuals are able to mount an immune response to influenza vaccine and produce antibody concentrations deemed protective. The routes of administration are similarly effective at inducing an immune response. The intramuscular route in anticoagulated elderly men does not commonly result in local bleeding complications.     

Sharing care: the psychiatrist in the family physician's office

OBJECTIVE: One way of strengthening ties between primary care providers and psychiatrists is for a psychiatrist to visit a primary care practice on a regular basis to see and discuss patients and to provide educational input and advice for family physicians. This paper reviews the experiences of a program in Hamilton, Ontario that brings psychiatrists and counsellors into the offices of 88 local family physicians in 36 practices. METHOD: Data are presented based on the activities of psychiatrists working in 13 practices over a 2-year period. Data were gathered from forms routinely completed by family physicians when making a referral and by psychiatrists whenever they saw a new case. An annual satisfaction questionnaire for all providers participating in the program was also used to gather information. RESULTS: Over a 2-year period, 1021 patients were seen in consultation by one full-time equivalent psychiatrist. The average duration of a consultation was 51 minutes, and a family member was present for 12% of the visits. Twenty-one percent of the patients were seen for at least one follow-up visit, 75% of which were prearranged. In addition, 1515 cases were discussed during these visits without the patient being seen. All participants had a high satisfaction rating for their involvement with the project. CONCLUSIONS: Benefits of this approach include increased accessibility to psychiatric consultation, enhanced continuity of care, support for family physicians, and improved communication between psychiatrists and family physicians. This model, which has great potential for innovative approaches to continuing education and resident placements, demands new skills of participating psychiatrists.     

Oral iloprost in Raynaud's phenomenon secondary to systemic sclerosis: a multicentre, placebo-controlled, dose-comparison study

OBJECTIVE: To identify the optimal dose of oral iloprost on the basis of efficacy and tolerability in patients with Raynaud's phenomenon secondary to systemic sclerosis. DESIGN: Multicentre, randomized, parallel-group comparison of two different doses of oral iloprost and placebo. SETTING: European university hospitals. PATIENTS: A total of 103 patients with Raynaud's phenomenon secondary to systemic sclerosis. INTERVENTION: Patients received one of three treatments for 6 weeks: placebo, oral iloprost 50 microg or oral iloprost 100 microg. Each treatment was taken twice daily, giving total daily doses of iloprost of 100 and 200 microg. MEASUREMENTS: The frequency, total daily duration and severity of Raynaud's attacks were recorded in a specially designed patient diary; physician's global assessment and adverse events were recorded at visits to the clinic. Analysis was performed on an intention-to-treat population. RESULTS: A total of 103 patients were recruited, 89 completed the assessments throughout the treatment period and 82 completed an additional 6 weeks of follow-up after treatment. Thirty-five patients received placebo, 33 received iloprost 50 microg and 35 received iloprost 100 microg. The mean percentage reductions in the frequency, total daily duration and severity of Raynaud's attacks were numerically greater in the iloprost groups at the end of treatment and at the end of follow-up. At the end of treatment (6 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.03), but not in the severity (P = 0.07) or the frequency of attacks (P = 0.37). At the end of follow-up (12 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.001) and in the severity of attacks (P = 0.007), but not in the frequency of attacks (P = 0.07). Percentages of patients improved at the end of treatment as assessed by the physician were 44% placebo, 57% iloprost 50 microg and 64% iloprost 100 microg (not significant). Side-effects were reported by 80% of patients on placebo, 85% on oral iloprost 50 microg and 97% on oral iloprost 100 microg. Premature discontinuations of treatment in each group were 9, 30 and 51%, respectively, with 6, 27 and 51% being due to adverse events. CONCLUSION: The results on the daily duration of Raynaud's attacks suggest that both 50 and 100 microg oral iloprost twice daily may be effective in the treatment of Raynaud's phenomenon secondary to systemic sclerosis. The 50 microg iloprost dose was better tolerated in this patient group.     

Access and outcomes of elderly patients enrolled in managed care

OBJECTIVE: To determine differences in access to care and medical outcomes for Medicare patients with an acute or a chronic symptom who were enrolled in health maintenance organizations (HMOs) compared with similar fee-for-service (FFS) nonenrollees. DESIGN: A 1990 household telephone survey of Medicare beneficiaries who reported joint pain or chest pain during the previous 12 months. SAMPLE: Stratified random sample of HMO enrollees (n = 6476) and comparable sample of FFS Medicare beneficiaries (n = 6381). ACCESS AND OUTCOME MEASURES: Care-seeking behavior, physician visits, diagnostic procedures performed, therapeutic interventions prescribed, follow-up recommended by a physician, and symptom response to treatment. RESULTS: After controlling for demographic factors, health and functional status, and health behavior characteristics, HMO enrollees with joint pain (n = 2243) were more likely than nonenrollees (n = 2009) to have a physician visit (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.03 to 1.38) and medication prescribed (OR, 1.35; 95% CI, 1.14 to 1.60). Patients with chest pain who were enrolled in HMOs (n = 556) were less likely than nonenrollees (n = 524) to have a physician visit (OR, 0.50; 95% CI, 0.30 to 0.82). For both joint and chest pain, HMO enrollees were less likely to see a specialist for care, have follow-up recommended, or have their progress monitored. There were no differences in complete elimination of symptoms, but HMO enrollees with continued joint pain reported less symptomatic improvement than nonenrollees (OR, 0.72; 95% CI, 0.59 to 0.86). CONCLUSIONS: Reduced utilization of services for patients with specific ambulatory conditions was observed in HMOs with Medicare risk contracts, with less symptomatic improvement in one of the four outcomes studied.     

Cytotoxicity of synthetic barium hydroxyapatite

Development of an effective immunotherapeutic approach for treatment of CNS tumors must take into account the unique anatomic and immunologic features of the brain. We explored the antitumor immune response in the brain elicited by nonreplicating melanoma cells genetically engineered to produce either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) in a paracrine fashion. Using a new model of intracranial melanoma in C57BL/6 mice, the cytokine-producing cells were given either as a subcutaneous vaccine to induce systemic antitumor immunity or as a direct injection into the brain as local immunotherapy. We found that GM-CSF-transduced cells, as a subcutaneous vaccine but not as an intracranial injection, afforded some protection from intracranial challenge with the wild-type tumor. In contrast, direct intracranial injection of tumor cells secreting IL-2 was protective whereas flank vaccination with IL-2 transductants was not. Combination therapy with both the subcutaneous GM-CSF-transductants as a vaccine and local administration of IL-2-transductants in the brain achieved a synergistic response. These findings provide a basis for the application of paracrine cytokine delivery to brain cancer therapy both as a systemic vaccine and via local administration. The demonstration of synergy between paracrine cytokine therapies holds promise as a novel therapy for brain tumors.     

Psychiatric diagnosis and intervention in older and younger patients in a primary care clinic: effect of a screening and diagnostic instrument

OBJECTIVES: To determine whether patient age is associated with psychiatric diagnosis or provider intervention in a busy primary care clinic, and, if so, whether a screening and diagnostic tool, the PRIME-MD, modifies age-related differences. DESIGN, SETTING, AND PARTICIPANTS: PRIME-MD use, psychiatric diagnosis, and provider interventions for psychiatric conditions were recorded for eligible patients attending a Veterans Affairs Medical Center primary care clinic. Data from 952 younger (<65 years) and 1135 older patients (> or =65 years) were analyzed to determine whether there were age-related differences in diagnosis/intervention and if use of the PRIME-MD modified these differences. INTERVENTION: Implementation of the PRIME-MD, a two-step instrument consisting of a self-administered patient questionnaire and a provider-administered structured diagnostic interview. MEASUREMENTS: Outcome measures were rates of (1) PRIME-MD use, (2) overall psychiatric diagnosis, (3) new psychiatric diagnosis, and (4) provider intervention for psychiatric conditions. RESULTS: There was no association between patient age and PRIME-MD use. Older patients were less likely to receive a psychiatric diagnosis in analyses that adjusted for "highly positive" screening questionnaires (OR = .45; P<.001). Older patients were also less likely to receive an intervention for a psychiatric condition in analyses that adjusted for whether a psychiatric diagnosis (OR = .62, P = .015) or a new psychiatric diagnosis (OR = .36, P<.001) was made during the study visit. The PRIME-MD increased rates of diagnosis and intervention but did not alter age-related disparities. CONCLUSIONS: Decreased rates of psychiatric diagnosis and intervention in older primary care patients are of concern. Implementing the PRIME-MD will likely increase rates of diagnosis and intervention but will need to be accompanied by additional measures to eliminate age-related disparities.     

The evaluation of action of anesthetic drugs: Xylodont and Mepidont

The aim of the study was to establish the quality of the therapeutical action- of two local anaesthetics Xylodont and Mepidont, produced by MOLTENI pharmaceutical firm. The investigation was performed in 199 patients of our clinic undergoing teeth extractions or other small surgical procedures. The following data were specified in a questionnaire: name of a drug, applied doses, range of anaesthetic effect, kind and duration of a surgical procedure. We also paid the very attention to the systemic side effects of the used drugs. The significant number of surgical procedures (96, 5%) were painless. The application of additional drug was necessary only in few cases. The obtained results show that the tested anaesthetics Xylodont and Mepidont are safe and effectively acting drugs suitable for local anaesthesia.     

International bank for foot-and-mouth disease vaccine: assessment of Montanide ISA 25 and ISA 206, two commercially available oil adjuvants

The International Vaccine Bank at Pirbright has recently installed large-scale vaccine formulation equipment for the preparation of oil-adjuvanted vaccines. Such vaccines are claimed to offer a number of advantages over Al(OH)3, particularly their ability to raise better immunity in pigs. This paper reports on the potency in pigs, cattle and guinea-pigs of foot-and-mouth disease vaccines prepared with two novel oil adjuvants, Montanide ISA 25 and 206 (Seppic, Paris). The results indicate that vaccines adjuvanted with these oils retain potency for a longer period than our conventional aqueous formulation, following storage at +4 degrees C, and elicit good antibody responses in both pigs and cattle regardless of injection route. In addition they gave no evidence of toxicity or prolonged pyrexia following their administration. Local reactions at the site of inoculation were not observed in cattle vaccinated intramuscularly, even following a booster dose. Pigs vaccinated intramuscularly only showed local reactions if the volume administered exceeded the 2.0 ml dose or the animals received a second vaccination. These observations on the efficacy of such oil formulated vaccines suggest that they have potential as an alternative to the current aqueous formulation.