The Quality and Utility of Surgical and Anesthetic Data at a Ugandan Regional Referral Hospital.

BACKGROUND: There are little primary data available on the delivery or quality of surgical treatment in rural sub-Saharan African hospitals. To initiate a quality improvement system, we characterized the existing data capture at a Ugandan Regional Referral Hospital. METHODS: We examined the surgical ward admission (January 2008-December/2011) and operating theater logbooks (January 2010-July 2011) at Mbarara Regional Referral Hospital. RESULTS: There were 6346 admissions recorded over three years. The mean patient age was 31.4 ± 22.3 years; 29.8 % (n = 1888) of admissions were children. Leading causes of admission were general surgical problems (n = 3050, 48.1 %), trauma (n = 2041, 32.2 %), oncology (n = 718, 11.3 %) and congenital condition (n = 193, 3.0 %). Laparotomy (n = 468, 35.3 %), incision and drainage (n = 188, 14.2 %) and hernia repair (n = 90, 6.8 %) were the most common surgical procedures. Of 1325 operative patients, 994 (75 %) had an ASA I-II score. Of patients undergoing 810 procedures booked as non-elective, 583 (72 %) had an ASA "E" rating. Records of 41.3 % (n-403/975) of patients age 5 years or older undergoing non-obstetric operations were missing from the ward logbook. Missing patients were younger (25 [13,40] versus 30 [18,46] years, p = 0.002) and had higher ASA scores (ASA III-V 29.0 % versus 18.9 %, p < 0.001) than patients recorded in the logbbook; there was no diffence in gender (male 62.8 % versus 67.0 %, p = 0.20). CONCLUSIONS: The hospital records system measures surgical care, but improved data capture is needed to determine outcomes with sufficient accuracy to guide and record expansion of surgical capacity.

An economic analysis comparing health care resource use and cost of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin versus gemcitabine and cisplatin as neoadjuvant therapy for muscle invasive bladder cancer.

PURPOSE: To compare healthcare resource utilization (HRU) and costs associated with dose-dense methotrexate, vinblastine, doxorubicin, cisplatin (ddMVAC) and gemcitabine, cisplatin (GC) as neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). METHODS: Patient treated at Dana-Farber Cancer Institute from 2010 to 2019 were identified. HRU data on chemotherapy administered, supportive medications, patient monitoring, clinic, infusion, emergency department (ED) visits and hospitalization were collected retrospectively. Unit costs for HRU components were obtained from the Centers for Medicare and Medicaid Website and HRU was compared between groups using quantile regression analysis. RESULTS: 137 patients were included; 51 received ddMVAC and 86 GC. Baseline characteristics were similar, except lower mean age (P < 0.001) and higher proportion of ECOG-PS = 0 (P < 0.001) for ddMVAC. ddMVAC required more granulocyte-colony stimulating factor support (P < 0.001), central line placement (P = 0.017), cardiac imaging (P < 0.001), and infusion visits (P < 0.001), whereas GC required more clinic visits. ED visits were higher for ddMVAC (P = 0.048), while chemotherapy cycle delays and hospitalization days were higher for GC (P = 0.008). After adjusting for ECOG-PS and age, the cost per patient was approximately 41% lower (95%CI: 28% to 52%; P < 0.001) for GC vs. ddMVAC, which translated to a median adjusted cost savings of $7,410 (95%CI: $5,474-$9,347) per patient. CONCLUSIONS: Although excess HRU did not clearly favor one regimen, adjusting for PS and age indicated lower costs with GC vs. ddMVAC. Given the similar cumulative cisplatin delivery with both regimens, the associated values and costs supports the preferential selection of GC in the neoadjuvant setting of MIBC.

The P50 midlatency auditory evoked potential in patients with chronic low back pain (CLBP).

OBJECTIVE: Patients with Chronic Low Back Pain (CLBP) show arousal, attentional and cognitive disturbances. The sleep state-dependent P50 midlatency auditory evoked potential was used to determine if patients with CLBP [with and without co-morbid depression (DEP)] show quantitative disturbances in the manifestation of the P50 potential. METHODS: P50 potential latency, amplitude and habituation to repetitive stimuli at 250, 500 and 1000ms interstimulus intervals (ISIs) was recorded, along with the McGill Pain Questionnaire-Short Form (MPQ-SF). CLBP subjects (n=42) were compared with Controls (n=43), and with subjects with DEP only (n=6). Of the CLBP subjects, 20/42 had clinical depression (CLBP+DEP); 8/20 were taking anti-depressant medication (CLBP+DEP+med), the others were not (CLBP+DEP-med). RESULTS: There were no differences (ANOVA) in age, sex or P50 potential latency, although there was a trend towards increased latencies in CLBP groups. P50 potential amplitude was lower in CLBP groups, but not in sub-groups, again indicating a trend. P50 potential habituation was decreased in the DEP only subjects at the 250m ISI, and decreased in CLBP+DEP-med subjects at the 500ms ISI. This difference was not present in CLBP+DEP+med subjects. The MPQ-SF revealed that patients with CLBP and CLBP+DEP-med showed lower pain scores than CLBP+DEP+med patients. CONCLUSIONS: There is decreased habituation of the P50 potential habituation in unmedicated patients with CLBP+DEP compared to Controls. SIGNIFICANCE: Patients with CLBP+DEP-med may be less able to disregard incoming sensory information, including painful sensations, but anti-depressant medications help correct this deficit. However, their perception of pain may be increased by medication.

Pulmonary disposition of moxalactam.

Moxalactam is a new synthetic oxa-beta-lactam antibiotic with a broad spectrum of activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. It has proven clinical efficacy in pneumonia caused by a variety of infecting organisms. Therapeutic concentrations of moxalactam are achieved in most body tissues and fluids, including pleural fluid and sputum. However, assessment of the adequacy of lung tissue levels in pneumonia requires the sampling of material at an alveolar level. We performed bronchoalveolar lavage (BAL) in 13 patients one hour after they had been given moxalactam intravenously in doses ranging from 250 mg to 2 g. Absolute alveolar drug levels ranged from less than 1 to 6 micrograms/ml, and serum levels from 8 to 50 micrograms/ml. When expressed per micromole of creatinine, there was a significant relationship (r = 0.85; p less than 0.01) between serum and alveolar moxalactam levels in those patients in whom the drug concentration could be quantified accurately in BAL fluid.

Newborn phenylketonuria (PKU) Guthrie (BIA) screening and early hospital discharge.

Recent policies of early discharge of postpartum mothers and their infants has raised concerns of possible decreased sensitivity in Guthrie bacterial inhibition assay (BIA) phenylketonuria (PKU) screening resulting in missed cases. In order to assess the potential impact of early discharge from hospital on neonatal screening for PKU and its variants, we performed 18 standard BIA screening tests on 11 newborn infants with the disease. Blood spot samples were collected from 1 to 24 h after birth and were analyzed at the Ontario Ministry of Health newborn screening laboratory according to the routine screening protocol. Except for one 4-hour postnatal sample from an infant with 'non-PKU mild hyperphenylalaninemia' (MHP) all blood samples showed phenylalanine levels > or = 240 mumol/l, irrespective of the age of the baby. During our 29 year experience with neonatal PKU screening (3.9 million infants tested), employing a cutoff blood phenylalanine of 240 mumol/l in blood spots obtained at > or = 24 h of age, only two biological false negative (one confirmed) tests were discovered in infants subsequently shown to have classical PKU: another three false negative tests were discovered in sibs of infants with MHP. The sensitivity of the screening test was 99.2% for infants with classical and mild PKU. Ascertainment of patients with MHP is unknown and is very likely incomplete. Over a 3-year period (1992-4) the specificity of the test was 99.9% for those screened after 24 h. The positive predictive value was 12.8%. Although early discharge may have an impact on other screened diseases, we conclude, from our studies, that early discharge may not affect the detection of infants with classical and mild (atypical) PKU, but would probably increase the number of infants with MHP missed using the BIA and a cutoff level of 240 mumol/l. Because of our experience and that of others, we recommend that neonates be at least 12 h of age before initial BIA PKU screening be carried out. To confirm this recommendation further prospective studies should be initiated.

Characterization of cross-reacting serotypes of Campylobacter jejuni.

Some strains of Campylobacter jejuni react with more than one reference antiserum from the serotyping scheme based on heat-stable lipopolysaccharide antigens. To investigate the molecular basis of these cross-reactions, lipopolysaccharides from the reference strains for serotypes 4, 13, 16, 43, and 50 and isolates recovered during two different outbreaks of C. jejuni enteritis were analyzed by passive haemagglutination and sodium dodecyl sulphate-polyacrylamide gel electrophoresis coupled with silver staining or immunoblotting. The results showed that lipopolysaccharides from the reference strains and the isolates reacted with antisera prepared against heterologous strains in various combinations and that both silver-stainable, low Mr and non-silver-stainable, high Mr lipopolysaccharide components provided the antigenic determinants associated with the cross-reactions. There were strain-to-strain differences in the structural and antigenic properties of these macromolecules and shared antigenic determinants were not always provided by a common structure. Analysis of the silver-stained lipopolysaccharide profiles, outer membrane protein patterns, and chromosomal DNA restriction patterns indicated that strains with the same lipopolysaccharide profile could have the same outer membrane protein pattern and the same DNA restriction pattern. These results provided evidence for the presence of clones within this antigenic complex and implicated antigenic variation in some strains as the phenomenon responsible for the multiplicity of cross-reactions.

Structural and antigenic properties of lipopolysaccharides from serotype reference strains of Campylobacter jejuni.

To investigate the molecular basis for heat-stable antigenic diversity in Campylobacter jejuni, lipopolysaccharides (LPSs) from serotype reference strains and serotyped isolates were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with silver staining and immunoblotting. By silver staining, only low-Mr components, consisting of one major band and as many as three minor bands ranging in Mr from 4,500 to 5,000, were detected. However, by immunoblotting with homologous antisera, 10 of 34 strains were shown to have a series of high-Mr LPS components characteristic of molecules with O side chains of various lengths. Isolates of the same serotype as the reference strain that had high-Mr LPS molecules were also found to have high-Mr LPS and in one case of cross-reacting strains it was found that the cross-reaction was associated with antibodies against high-Mr LPS. The reactions of LPSs with homologous and heterologous antisera indicated that both high- and low-Mr-type LPSs were strain-specific antigens, but in some cases cross-reactions were noted. Evidently, all C. jejuni strains possess low-Mr LPS that is readily detectable by silver staining, but some serotypes also possess high-Mr LPS components that can be visualized by immunoblotting.

Differences among Providencia species in their in vitro susceptibilities to five antibiotics.

Significant differences among the three Providencia species (P. alcalifaciens, P. stuartii, and P. rettgeri) in antimicrobial susceptibilities to five antibiotics were shown. P. stuartii was the most resistant of the three species, and P. alcalifaciens was the most susceptible. P. rettgeri was similar to P. stuartii in susceptibilities to cefoxitin, cephalothin, and cefamandole but differed in showing greater susceptibilities to tobramycin and gentamicin. Cefoxitin (16 micrograms/ml) and cefamandole (16 micrograms/ml) inhibited a greater proportion of P. stuartii isolates than did cephalothin, tobramycin, or gentamicin. The susceptibilities of urea-positive isolates of P. stuartii resembled more closely the susceptibilities of urea-negative isolates of this species than those of P. rettgeri isolates, a finding consistent with the recent recommendation for transferring such urea-positive strains to P. stuartii. Among P. stuartii isolates, marked resistance to cefoxitin accompanied by susceptibility to cefamandole was predominantly restricted to isolates of one serotype (O55). The use of isolates that had been serotyped and classified according to recent proposals for taxonomic changes in the Proteeae provided for clearer demonstration of species differences in susceptibility.

Genetic variability and molecular typing of Shigella sonnei strains isolated in Canada.

Restriction fragment length polymorphisms (RFLPs) of genomic DNAs from 49 clinical isolates of Shigella sonnei were analyzed by using a modified restriction endonuclease analysis procedure to investigate the genetic variability of this species. After cleavage with the restriction enzyme HaeIII or RsaI, DNA samples were electrophoresed in polyacrylamide gels and the RFLP patterns were visualized by silver staining. The results showed that among 20 strains associated with sporadic cases of infection in three Canadian provinces, 15 distinct RFLP patterns were revealed by HaeIII digestion and 12 distinct patterns were revealed by RsaI digestion. In contrast, the RFLP patterns of individual isolates within six groups of epidemiologically related isolates were identical to each other but distinct from those of unrelated isolates, and these patterns could be used to determine the genetic relationships between isolates associated with separate outbreaks of shigellosis. Our results indicate that the modified restriction endonuclease analysis technique represents a rapid, reproducible, and highly discriminatory method for the molecular typing of this species.

Orchestrating the points of community intervention: enhancing the diffusion process.

Recent interest in community-based health education programs has emphasized the need to promote change in social systems, as well as individual behaviors. The problem is where and when to intervene to effect these multiple levels of change. Components of community programs have tended to be implemented simultaneously at only one or two points within a community. A potentially more effective approach would consider both where differing types of people can be reached, and the appropriate time to intervene at each point, to maximize the effective diffusion of information and behavior change across the community. The present article outlines eight points of community intervention including centers, institutions, major media, minor media, special events, formal social networks, informal social networks, and created social networks. A sequencing of intervention efforts at these points is proposed which is predicated on their role in regard to the need for preparation, public awareness, notification about planned events and implementation of the program. The proposed orchestration of the points for community program implementation capitalizes on the diffusion process and on the synergistic effects of multimodal education efforts.

Epidemiologic subtyping of Escherichia coli serogroup O157 strains isolated in Ontario by phage typing and pulsed-field gel electrophoresis.

Phage typing and DNA macrorestriction fragment analysis by pulsed-field gel electrophoresis (PFGE) were evaluated for use in the epidemiological subtyping of Escherichia coli serogroup O157 strains isolated in Ontario, Canada. Among 30 strains isolated from patients with sporadic cases of infection, 22 distinct XbaI macrorestriction patterns were identified and 17 strains exhibited unique PFGE patterns. In contrast, phage typing identified only seven different phage types and 17 strains belonged to the same phage type. A total of 25 phage type-macrorestriction pattern combinations were identified among the strains from patients with sporadic cases of infection. PFGE subtyping differentiated between unrelated strains that exhibited the same phage type, and in one group of strains, phage typing differentiated between strains of the same PFGE subtype. Both typing procedures correctly identified outbreak-related isolates as belonging to the same type in four separate outbreaks. Each outbreak strain was characterized by a distinct macrorestriction pattern, while phage typing subdivided the outbreak strains into only three different types. A small percentage of outbreak-related isolates had PFGE patterns that differed slightly (one or two DNA fragment differences) from that of the outbreak strain. On the other hand, each isolate from the same outbreak belonged to the same phage type as that of the outbreak strain. We conclude that phage typing and PFGE fingerprinting represent complementary procedures for the subtyping of E. coli serogroup O157 and that the combined use of these procedures provides optimal discrimination.

Antimicrobial susceptibility of pathogenic Yersinia enterocolitica isolated in Canada from 1972 to 1990.

Yersinia enterocolitica has emerged as an enteropathogen associated with several types of human infections that often require antimicrobial therapy, but little is known about the antimicrobial susceptibilities of pathogenic strains isolated from humans in Canada. To determine the present patterns of antimicrobial susceptibility, to identify changes in these patterns that occurred during the past two decades, and to investigate the relationships between O serotypes and patterns of susceptibility, we tested a total of 1,105 pathogenic Y. enterocolitica strains isolated during 1972 to 1976, 1980, 1985, and 1990 for their susceptibilities to 22 antimicrobial agents. Susceptibility testing was performed by using a single breakpoint concentration in agar procedure. The results showed that all strains were susceptible to ciprofloxacin and piperacillin, and 98% or more of the strains from each period were susceptible to trimethoprim, sulfamethoxazole, cotrimoxazole, tetracycline, chloramphenicol, cefamandole, cefotaxime, aztreonam, and four aminoglycosides. In contrast, all strains were nonsusceptible to erythromycin, furazolidone, and clindamycin and 90% or more of the strains from each period were nonsusceptible to ampicillin, carbenicillin, ticarcillin, and cephalothin. Strains belonging to serotypes O:3, O:5,27, and O:8 had different patterns of susceptibility to ampicillin, carbenicillin, ticarcillin, and amoxicillin-clavulanic acid. No major difference in susceptibility was observed between any of the groups of human or animal strains included in the study, but nonsusceptibility to tetracycline increased from 0.4% in 1985 to 2% in 1990 in human strains isolated in those years. Our results indicate that between 1972 and 1990 there was no marked decrease in susceptibility to agents commonly used for therapy among pathogenic Y. enterocolitica strains isolated in Canada.

Effect of dietary chromium on glucose tolerance and serum cholesterol in guinea pigs.

The effects of feeding three levels of dietary chromium (Cr) to non-pregnant guinea pigs, guinea pigs during pregnancy and lactation and F-1 offspring guinea pigs on weight gain, glucose tolerance, glucose peak time value and serum cholesterol concentration has been investigated. Dietary levels of Cr were: Basal Diet (B) = 0.125 ppm; B supplemented with 0.5 ppm Cr (S1 Diet) and B supplemented with 50 ppm Cr (S2 Diet). All groups had similar weight gain patterns and daily feed intake levels. Parent generation guinea pigs fed the B diet consumed less than 10 mug Cr/kg body weight/day while F-U guinea pigs consumed more than this amount. Mortality rates during pregnancy were greater in guinea pigs fed the B diet than in the Cr supplemented groups suggesting a possible protective effect by Dr. Glucose tolerance, glucose peak time values and serum cholesterol appeared to be more affected by pregnancy and generation of guinea pigs than by the level of dietary Cr. Results suggest that species differences may exist between Cr requirements of guinea pigs and rodents for avoiding glucose tolerance.

Simulated acute hemorrhage through lower body negative pressure as an activator of the hypothalamic-pituitary-adrenal axis.

While insulin induced hypoglycemia is the principle method of producing hypothalamic-pituitary-adrenal stress response, the mechanism by which this occurs may be different from that produced by other stressors. In a pilot study, we explored ways to standardize lower body negative pressure (LBNP), as a simulator of hemorrhage, to determine its utility for future studies of hypothalamic-pituitary-adrenal (HPA) axis function. Reduced atmospheric pressure of -40 mmHg applied at the level of the iliac crests during LBNP rapidly lowers blood pressure in most subjects, simulating acute hemorrhage. In 6 normal subjects, ACTH and cortisol values were measured before, during and after the application LBNP at 0800, 1600 and 2300 hours in the baseline state and at 1600 hours on the day following 1 mg of dexamethasone. Peak ACTH values of 60-250 pg/ml occurred 2 to 10 minutes after the cessation of the stimulus in subjects experiencing presyncope or having a systolic or diastolic blood pressure decrease of greater than 20 mmHg with a rise in pulse of 30 beats per minute or more. There was no significant difference between ACTH responses at different times of day. Peak cortisol values of 25-30 micrograms/dl occurred 15-20 minutes after cessation of the stimulus. In all subjects, administration of dexamethasone greatly attenuated the ACTH response and decreased but did not ablate the cortisol response. In conclusion, these data indicate that LBNP may be used to simulate hemorrhage as a stimulus of the HPA axis. HPA axis changes occur only when physiologic evidence of hypovolemic stress is present. Dexamethasone may be used to modulate the response to this stress paradigm.

Detection of lipopolysaccharides in polyacrylamide gels by transfer to nitrocellulose followed by immunoautoradiography with antibody and 125I-protein A: "LPS blotting".

Lipopolysaccharides (LPS), which constitute the somatic (O) antigen of gram-negative bacteria, were used to demonstrate the procedure of LPS blotting involving the electrophoretic transfer of electrophoretically resolved LPS from sodium dodecyl sulfate-polyacrylamide gels to nitrocellulose filters. Immobilized LPS could then be immunoautoradiographically visualized in situ by reaction with specific anti-LPS antibody and subsequent binding of radioiodinated Staphylococcus protein A. LPS blotting is expected to provide an efficient and specific means of investigating the LPS (O) antigens of gram-negative bacteria.

Species differences in susceptibilities of Proteeae spp. to six cephalosporins and three aminoglycosides.

Six cephalosporins and three aminoglycosides were examined for activity against 1,693 isolates belonging to six species of Proteeae. The most notable species-specific differences included the marked susceptibility of Providencia alcalifaciens and Proteus mirabilis to cephalothin, the resistance of Proteus vulgaris to cefamandole, and the resistance of Providencia stuartii to gentamicin and tobramycin. The third-generation cephalosporins cefotaxime and moxalactam were substantially more inhibitory than were cefoperazone, cefamandole, and cefoxitin. P. stuartii, generally the most resistant species, was, however, markedly susceptible to moxalactam and cefotaxime.

In vitro susceptibility of "Campylobacter upsaliensis" to twenty-four antimicrobial agents.

The in vitro susceptibility of 41 strains of "Campylobacter upsaliensis" to 24 antimicrobial agents was determined using a broth microdilution procedure. Most isolates were susceptible to the fluoroquinolones and beta-lactam antibiotics tested, but all strains were resistant to trimethoprim (MBCs greater than or equal to 128 micrograms/ml) and teicoplanin (MBCs greater than or equal to 32 micrograms/ml). These agents may be useful in a selective isolation medium for "Campylobacter upsaliensis".

Human Escherichia coli O157:H7 infection associated with the consumption of unpasteurized goat's milk.

A cluster of four cases of haemolytic uraemic syndrome in children occurred in Northern Bohemia, Czech Republic, between 15 June and 7 July, 1995. All the cases had significantly elevated titres of anti-O157 lipopolysaccharide (LPS) antibodies as detected by the indirect haemagglutination assay. All but one of them had drunk unpasteurized goat's milk from the same farm within the week before the disease. Evidence of E. coli O157 infection was subsequently found in 5 of 15 regular drinkers of the farm's raw goat's milk; four of them were asymptomatic, 1 had mild diarrhoea at the end of June. Verocytotoxin 2-producing E. coli O157:H7 strains of phage type 2 and of identical pulsed-field gel electrophoresis patterns were isolated from 1 of 2 farm goats and from 1 of the asymptomatic goat's milk drinkers. The frequency of anti-O157 LPS antibodies found among regular drinkers of the farm's raw goat's milk (33%; 5 of 15) was significantly higher than that found in control population (0%; none of 45) (P = 0.0005; Fisher's exact test). Our findings indicate that goats may be a reservoir of E. coli O157:H7 and a source of the infection for humans; raw goat's milk may serve as a vehicle of the pathogen transmission.