Factors related to mortality of aged patients hospitalized with community-acquired pneumonia

OBJECTIVE: To investigate the proportion of a sample of approximal carious lesions extending up to 1 mm into dentine which progressed over a 3-year period and to examine factors which influenced that progression. DESIGN: Prospective, single centre, clinical study. SETTING: Restorative Clinic at Bristol Dental School, UK. SUBJECTS AND METHODS: Sixty-five adult patients were identified who each had an approximal carious lesion which extended up to 1 mm into the dentine and which were assessed at intervals of up to 36 months. All patients were given appropriate preventive advice. MAIN OUTCOME MEASURES: Progression of the lesions was determined by assessment of sequential bitewing radiographs. RESULTS: 29% of the lesions progressed within 8 months, 56% by 20 months and 69% by 36 months. After 36 months, lesions which extended over 0.5 mm and up to 1 mm into the dentine were significantly more likely to have progressed (92%) compared with shallower lesions which extended up to only 0.5 mm into dentine (50%). CONCLUSIONS: The depth of an approximal dentine lesion was the main clinical marker which related to its progression. It is recommended that operative intervention is considered for approximal lesions which extend deeper than 0.5 mm into the dentine, while preventive treatment and re-assessment may be considered for shallower lesions.     

Time course of symptom resolution in patients with community-acquired pneumonia

The majority of patients with community-acquired pneumonia are at low risk for short-term mortality or serious morbidity and are increasingly managed in the outpatient setting. Efforts to improve the quality of care for these patients will need to measure patient outcomes such as disease-specific symptom resolution. The aims of this study were to (1) develop a self-administered daily version of a symptom questionnaire for patients with pneumonia, (2) measure the reliability of this instrument, and (3) provide estimates for recovery rates based on symptom resolution in a cohort of low-risk patients with community-acquired pneumonia. This study was conducted as part of a prospective study of a new emergency department protocol for pneumonia at the Massachusetts General Hospital. Eligible study subjects included all adult patients with pneumonia presenting to the emergency department with a predicted low risk of short-term mortality. The main outcome measures were based on a new five item symptom questionnaire which rates the severity of cough, fatigue, dyspnea, myalgia, and fever. The questionnaires were self-administered on days 0-7, 14, 21 and 28 from the time of diagnosis of pneumonia. The symptom questions were also administered during patient interviews on days 0, 7, 14 and 28 in order to assess the questionnaire's reliability. Of the 166 eligible patients, 134 (81%) consented to participate in this study. The mean intra-class reliability coefficient of the symptom questionnaire was 0.75. The median times to resolution of individual symptoms ranged from 3 days for fever to 14 days for cough and fatigue. Thirty-five percent of patients had at least one symptom still present at the end of the 28-day study period. We found that a daily self-report questionnaire is a reliable measure of symptom resolution for patients with pneumonia. Full resolution of symptoms takes more than 28 days for a significant proportion of patients with pneumonia.     

Early recognition of Streptococcus pneumoniae in patients with community-acquired pneumonia

In order to elucidate the cause of osteonecrosis of the femoral head in spontaneously hypertensive rats (SHRs), which resembles the osteonecrosis of Perthes' disease, we observed the three-dimensional structure of vascular casts of the blood vessels feeding the femoral head using both optical and scanning electron microscopes. During the period of 9-15 weeks after birth, when osteonecrosis of the femoral heads in SHRs occurred frequently, the lateral epiphyseal vessels (LEVs), which were the main feeding vessels, entered from the lateral of the femoral heads. Anastomosing branches of LEVs between the epiphysis and the femoral neck were scarce even in the femoral heads showing normal ossification. It seemed that the development of LEVs in SHRs did not proceed normally in this period. Furthermore, remarkable segmental stenosis and the obstruction of LEVs were often recognized near the lateral of the femoral heads. These results suggest that LEVs in growing SHRs have the vascular structure that could cause an interruption of the blood supply to the femoral heads.     

Switch therapy with beta-lactam/beta-lactamase inhibitors in patients with community-acquired pneumonia

BACKGROUND: Antimicrobial drugs are prescribed inappropriately nearly 50% of the time. To address this problem, a hospital antimicrobial team was formed integrating the talents of infectious disease physicians, pharmacists, microbiologists, infectious control practitioners, and nurses. The primary goal of the team is to provide optimal, cost-effective antimicrobial therapy. OBJECTIVE: To review the principles of streamlining antimicrobial therapy, with an emphasis on antibiotic switch therapy. DISCUSSION: With appropriate guidelines, switch therapy appears to be an important means to provide optimal antimicrobial therapy complementing the many social pressures placed on patients, while positively impacting on the overall cost of treatment. The use of beta-lactam/beta-lactamase inhibitor combinations as the antibiotics for initial intravenous medication to oral combination switch therapy is a viable approach to the treatment of hospitalized patients with community-acquired pneumonia. Preliminary data from our institution were obtained with such a therapeutic approach to assess the clinical efficacy, patient satisfaction with their care, and calculated dollar savings in the overall cost of care. The results of this evaluation strongly support the validity and desirability of such an approach. CONCLUSIONS: The prospective use of a program that incorporates the use of beta-lactam/beta-lactamase inhibitor combinations for intravenous and switch-to-oral drug administration is a cost-effective means of providing optimal antimicrobial therapy for patients with community-acquired pneumonia.     

Prognosis and outcomes of patients with community-acquired pneumonia. A meta-analysis

OBJECTIVE: To systematically review the medical literature on the prognosis and outcomes of patients with community-acquired pneumonia (CAP). DATA SOURCES: A MEDLINE literature search of English-language articles involving human subjects and manual reviews of article bibliographies were used to identify studies of prognosis in CAP. STUDY SELECTION: Review of 4573 citations revealed 122 articles (127 unique study cohorts) that reported medical outcomes in adults with CAP. DATA EXTRACTION: Qualitative assessments of studies' patient populations, designs, and patient outcomes were performed. Summary univariate odds ratios (ORs) and rate differences (RDs) and their associated 95% confidence intervals (CIs) were computed to estimate a summary effect size for the association of prognostic factors and mortality. DATA SYNTHESIS: The overall mortality for the 33,148 patients in all 127 study cohorts was 13.7%, ranging from 5.1% for the 2097 hospitalized and ambulatory patients (in six study cohorts) to 36.5% for the 788 intensive care unit patients (in 13 cohorts). Mortality varied by pneumonia etiology, ranging from less than 2% to greater than 30%. Eleven prognostic factors were significantly associated with mortality using both summary ORs and RDs: male sex (OR = 1.3; 95% CI, 1.2 to 1.4), pleuritic chest pain (OR = 0.5; 95% CI, 0.3 to 0.8), hypothermia (OR = 5.0; 95% CI, 2.4 to 10.4), systolic hypotension (OR = 4.8; 95% CI, 2.8 to 8.3), tachypnea (OR = 2.9; 95% CI, 1.7 to 4.9), diabetes mellitus (OR = 1.3; 95% CI, 1.1 to 1.5), neoplastic disease (OR = 2.8; 95% CI, 2.4 to 3.1), neurologic disease (OR = 4.6; 95% CI, 2.3 to 8.9), bacteremia (OR = 2.8; 95% CI, 2.3 to 3.6), leukopenia (OR = 2.5, 95% CI, 1.6 to 3.7), and multilobar radiographic pulmonary infiltrate (OR = 3.1; 95% CI, 1.9 to 5.1). Assessments of other clinically relevant medical outcomes such as morbid complications (41 cohorts), symptoms resolution (seven cohorts), return to work or usual activities (five cohorts), or functional status (one cohort) were infrequently performed. CONCLUSIONS: Mortality for patients hospitalized with CAP was high and was associated with characteristics of the study cohort, pneumonia etiology, and a variety of prognostic factors. Generalization of these findings to all patients with CAP should be made with caution because of insufficient published information on medical outcomes other than mortality in ambulatory patients.     

Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines

CONTEXT: Many groups have developed guidelines to shorten hospital length of stay in pneumonia in order to decrease costs, but the length of time until a patient hospitalized with pneumonia becomes clinically stable has not been established. OBJECTIVE: To describe the time to resolution of abnormalities in vital signs, ability to eat, and mental status in patients with community-acquired pneumonia and assess clinical outcomes after achieving stability. DESIGN: Prospective, multicenter, observational cohort study. SETTING: Three university and 1 community teaching hospital in Boston, Mass, Pittsburgh, Pa, and Halifax, Nova Scotia. PATIENTS: Six hundred eighty-six adults hospitalized with community-acquired pneumonia. MAIN OUTCOME MEASURES: Time to resolution of vital signs, ability to eat, mental status, hospital length of stay, and admission to an intensive care, coronary care, or telemetry unit. RESULTS: The median time to stability was 2 days for heart rate (< or =100 beats/min) and systolic blood pressure (> or =90 mm Hg), and 3 days for respiratory rate (< or =24 breaths/min), oxygen saturation (> or =90%), and temperature (< or =37.2 degrees C [99 degrees F]). The median time to overall clinical stability was 3 days for the most lenient definition of stability and 7 days for the most conservative definition. Patients with more severe cases of pneumonia at presentation took longer to reach stability. Once stability was achieved, clinical deterioration requiring intensive care, coronary care, or telemetry monitoring occurred in 1% of cases or fewer. Between 65% to 86% of patients stayed in the hospital more than 1 day after reaching stability, and fewer than 29% to 46% were converted to oral antibiotics within 1 day of stability, depending on the definition of stability. CONCLUSIONS: Our estimates of time to stability in pneumonia and explicit criteria for defining stability can provide an evidence-based estimate of optimal length of stay, and outline a clinically sensible approach to improving the efficiency of inpatient management.     

Doxycycline is a cost-effective therapy for hospitalized patients with community-acquired pneumonia

BACKGROUND: Doxycycline has a high degree of activity against many common respiratory pathogens and has been used in the outpatient management of lower respiratory tract infections, including pneumonia. OBJECTIVE: To evaluate the efficacy of intravenous doxycycline as empirical treatment in hospitalized patients with mild to moderately severe community-acquired pneumonia. PATIENTS AND METHODS: We conducted a randomized prospective trial to compare the efficacy of intravenous doxycycline with other routinely used antibiotic regimens in 87 patients admitted with the diagnosis of community-acquired pneumonia. Forty-three patients were randomized to receive 100 mg of doxycycline intravenously every 12 hours while 44 patients received other antibiotic(s) (control group). The 2 patient groups were comparable in their clinical and laboratory profiles. RESULTS: The mean+/-SD interval between starting an antibiotic and the clinical response was 2.21+/-2.61 days in the doxycycline group compared with 3.84+/-6.39 days in the control group (P = .001). The mean+/-SD length of hospitalization was 4.14+/-3.08 days in the doxycycline group compared with 6.14+/-6.65 days in the control group (P = .04). The median cost of hospitalization was $5126 in the doxycycline group compared with $6528 in the control group (P = .04). The median cost of antibiotic therapy in the doxycycline-treated patients ($33) was significantly lower than in the control group ($170.90) (P<.001). Doxycycline was as efficacious as the other regimens chosen for the treatment of community-acquired pneumonia. CONCLUSION: Doxycycline is an effective and inexpensive therapy for the empirical treatment of hospitalized patients with mild to moderately severe community-acquired pneumonia.     

Antibody response to pneumococcal polysaccharide vaccine in young, adult and old mice

The anti-pneumococcal antibody response was studied in young (5-week-old) and adult (10-week-old) BALB/c and CBA/J mice and in adult (9-10-week-old) and old (12-, 18- and 24-month-old) AB6F1 and B6D2F1 mice after s.c. immunization with a 23-valent pneumococcal polysaccharide vaccine. Both young and adult mice showed a significant IgM antibody response to the vaccine 6 days after immunization with 1-11 micrograms antigen. There were significant immune responses to serotypes 1, 2, 4 and 7F in contrast to small responses to serotypes 14, 19F and 23F after immunization with the vaccine. One month after immunization, there were only marginal differences in IgM anti-pneumococcal antibody levels to the vaccine (anti-PPS) between immunized and unimmunized BALB/c mice, whereas in CBA/J mice the anti-PPS remained higher in immunized than in unimmunized mice. Immunization of old mice induced a significant IgM antibody response 6 days after immunization, but the anti-PPS thereafter decreased rapidly towards preimmunization values in AB6F1 mice. A significant IgG anti-PPS was not detected in any of the mice studied. The IgA anti-PPS tended to vary over time with no consistent pattern. It is important to carefully consider age and strain of the mice used when studying the immune response to pneumococcal polysaccharide antigens.     

Peripheral cell-mediated immune response to mycobacterial antigens in inflammatory bowel disease

A mycobacterial etiology has been proposed in Crohn's disease (CD). We have sought evidence of increased or modified T lymphocyte immune responses to Mycobacterium tuberculosis and Myco, paratuberculosis in patients with CD (n = 13), compared with ulcerative colitis (UC; n = 17) and controls (n = 17). Peripheral blood cells were cultured with phytohaemagglutinin (positive mitogen control), mycobacterial purified protein derivative (PPD) preparations, lysates, column fractions and whole, heat-killed bacteria. Responses of T cells and T cell subsets were assessed by expression of activation markers (CD25, CD69), coupled with blastogenesis assays (3H-thymidine uptake) and estimates of proliferation. Virtually all patients responded to Myco. paratuberculosis and Myco. tuberculosis antigens. There were no significant differences between patient groups, although there was a very high overall correlation (r = 0.95; P < 0.0001) between responses to the two mycobacterial species. Most of the activation and proliferative responses resided in the CD4+ (T helper) subset. Although up to 15% of CD8+ (suppressor/cytotoxic) cells also became activated, the CD8+ cells did not proliferate subsequently. Cells expressing the alternate gamma delta form of the T cell receptor (TCR gamma delta+) did not activate or proliferate in response to mycobacterial antigens. There were no differences in any of these parameters between patient groups. We conclude that there is no specific increase or alteration in cell-mediated anti-mycobacterial immunity in inflammatory bowel disease (IBD). Thus our data do not support a mycobacterial etiopathology of Crohn's disease.     

Early switch from intravenous to oral cephalosporins in the treatment of hospitalized patients with community-acquired pneumonia

BACKGROUND: Switch therapy is defined as the early transition from intravenous to oral antibiotics during treatment of infection. This study was designed to evaluate the clinical outcome and length of stay of hospitalized patients with community-acquired pneumonia treated with an early switch from intravenous to oral third-generation cephalosporins. METHODS: Patients with a new roentgenographic pulmonary infiltrate and at least two symptoms (cough, fever, or leukocytosis) were enrolled in this study and treated with intravenous ceftizoxime sodium (1 g every 12 hours) or ceftriaxone sodium (1 g every 24 hours). Patients were switched to oral cefixime (400 mg every 24 hours) as soon as they met the following criteria: (1) resolution of fever; (2) improvement of cough and respiratory distress; (3) improvement of leukocytosis; and (4) presence of normal gastrointestinal tract absorption. RESULTS: Of the 120 patients enrolled, 75 (62%) had clinical data evaluated. Long-term follow-up showed that 74 patients (99%) were cured; one patient required readmission for further intravenous therapy. Mean duration of hospital stay was 4 days. CONCLUSIONS: This investigation demonstrated that an early switch to oral cefixime may be reasonable in hospitalized patients with community-acquired pneumonia who have already shown a good clinical and laboratory response to therapy with intravenous third-generation cephalosporins. This approach is clinically effective and minimizes hospital stay.     

Distribution of histocompatibility antigens in patients with pulmonary tuberculosis depending on disease course and immune response pattern

In mature male rabbits and outbred male rats (body weight 180-280 g) the implantation of the different tissues (adenohypophysis, ventricular myocardium, pharyngeal and bronchial epithelium) with hypothalamic nonapeptidergic nuclei in vivo and in vitro was performed by means of light microscopy, histochemistry, immunocytochemistry, histoautoradiographic (3H Thymidine) and electron microscopy methodics. It is demonstrated that hypothalamic nonapeptides (oxytocin and vasopressin) and monoamines are the interlevel regulatory factors of the proliferation, growth and cytodifferentiation of the different genesis tissues. Their role in realization by tissues of histo- and organotypic potentiality adaptive properties and adequate intercellular correlations in appropriate histotypes is indicated.     

Immunoglobulin A response in murine schistosomiasis: stimulatory role of egg antigens

The immunoglobulin G (IgG) and IgA antibody responses to different Schistosoma mansoni antigens have been determined in chronically infected mice as well as in unisexually infected animals. With a panel of enzyme-linked immunosorbent assays (ELISAs), soluble antigens from furcocercariae, adult worms, and eggs were probed with sera collected at 3-week intervals. Bisexually infected animals developed significant IgG and IgA antibody responses to the antigens tested, which increased after egg deposition. In unisexual infections no significant differences were recorded in the IgG antibody profile for furocercaria and adult worm antigens, whereas the IgA antibody response was impaired. Both the IgA and IgG antibody responses toward egg antigens were reduced compared with those in a bisexual infection. Furthermore, a specific mucosal IgA antibody response was observed only in the bisexually infected animals. Histological analysis performed on bisexually infected mice led to the observation of eggs and granulomatous lesions within the Peyer's patch follicles, which are essential sites for the induction of mucosal immunity in the intestine. These data suggest a relationship between egg deposition and the induction of the IgA antibody response toward schistosomes.     

Anticarrier immunity suppresses the antibody response to polysaccharide antigens after intranasal immunization with the polysaccharide-protein conjugate

We have conjugated cholera toxin (CT) B subunit (CTB) to dextran and studied the effect in mice of previous immunization with CT and CTB on the response to dextran after intranasal immunizations with conjugate. Preexisting immunity to CTB was found to inhibit both the lung mucosal response and serum antibody response to dextran, but this effect could be overcome by using a higher dose of conjugate and delaying the conjugate immunization until the CTB antibody titers had declined. The role of anti-CTB antibodies on the mucosal surface was probably to prevent uptake of the conjugate through a mechanism of immune exclusion. Passively transferred serum antibodies against CTB, on the other hand, suppressed both the serum response and the local antibody response against CTB but did not affect the response to dextran after intranasal immunization with conjugate.     

Secretory immune response to membrane antigens during Giardia lamblia infection in humans

The secretory immune response in humans infected with Giardia lamblia was studied by using saliva samples and a membrane-rich protein fraction. The membrane fraction, studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, showed 24 antigen bands, ranging from 170 to 14 kDa. Saliva samples from giardiasis patients showed a heterogeneous response against the membrane fraction when they were assayed by immunoblotting. Among the antigens recognized by patient saliva samples, those of 170, 105, 92, 66, 32, 29, and 14 kDa stood out. These antigens were not recognized by saliva samples from healthy individuals. They may be of importance in future studies of protection from or diagnosis of G. lamblia infections.     

Humoral and cellular immune response to elastin in patients with systemic sclerosis

Fifty-six patients (age range, 15-79 yr, average, 37.0+/-18.5 yr), with a clinical and/or radiological diagnosis of acute maxillary sinusitis, were prospectively studied with ultrasound (US) and computed tomography (CT). The imaging finding which supported the diagnosis of acute sinusitis with US was the identification of the hyperechoic posterior antral wall through the hypoechoic inflammation. The findings were compared to CT (3 mm axial sections). The sensitivity of US for maxillary sinus disease was found to be 66.7% and the specificity was 94.9%, which were similar to the plain film ones (65.2 and 96.8%, respectively). The results of the present study suggest US as the method of first choice for acute sinusitis of the maxillary antra, particularly for children and pregnant women.     

A survey of the humoral immune response of cancer patients to a panel of human tumor antigens

Evidence is growing for both humoral and cellular immune recognition of human tumor antigens. Antibodies with specificity for antigens initially recognized by cytotoxic T lymphocytes (CTLs), e.g., MAGE and tyrosinase, have been detected in melanoma patient sera, and CTLs with specificity for NY-ESO-1, a cancer-testis (CT) antigen initially identified by autologous antibody, have recently been identified. To establish a screening system for the humoral response to autoimmunogenic tumor antigens, an enzyme-linked immunosorbent assay (ELISA) was developed using recombinant NY-ESO-1, MAGE-1, MAGE-3, SSX2, Melan-A, and tyrosinase proteins. A survey of sera from 234 cancer patients showed antibodies to NY-ESO-1 in 19 patients, to MAGE-1 in 3, to MAGE-3 in 2, and to SSX2 in 1 patient. No reactivity to these antigens was found in sera from 70 normal individuals. The frequency of NY-ESO-1 antibody was 9.4% in melanoma patients and 12.5% in ovarian cancer patients. Comparison of tumor NY-ESO-1 phenotype and NY-ESO-1 antibody response in 62 stage IV melanoma patients showed that all patients with NY-ESO-1(+) antibody had NY-ESO-1(+) tumors, and no patients with NY-ESO-1(-) tumors had NY-ESO-1 antibody. As the proportion of melanomas expressing NY-ESO-1 is 20-40% and only patients with NY-ESO-1(+) tumors have antibody, this would suggest that a high percentage of patients with NY-ESO-1(+) tumors develop an antibody response to NY-ESO-1.