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Biomedical subjects

H D Davies

Publications and source records attributed to H D Davies.

At least 19 recordsLinked to original sources

Bloodstream infection-associated sepsis and septic shock in critically ill adults: a population-based study.

BACKGROUND: Few studies have investigated the epidemiology of sepsis and septic shock in a large population and none have been from Canada. The objective of this study was to define the epidemiology of bloodstream infection (BSI)-associated sepsis and septic shock among all critically ill patients in a large, fully integrated health region in Canada. PATIENTS AND METHODS: All critically ill adults admitted to multidisciplinary intensive care units (ICU) in the Calgary Health Region during May 1, 1999 to April 30, 2000 were included. Clinical, microbiologic and outcome information was obtained from regional databases. RESULTS: We surveyed 1981 patients having at least one ICU admission. Systemic inflammatory response syndrome (SIRS) was diagnosed in 92%, BSI-associated sepsis (BSI with SIRS) in 6% and BSI-associated septic shock (BSI with SIRS and hypotension) in 3%; respective hospital mortality rates were 36%, 40% and 49%. The most common BSI etiologies were Staphylococcus aureus, Escherichia coli and Streptococcus species; only one isolate (1%) was highly antibiotic resistant. Independent risk factors for death among patients with SIRS included age (>or= 65), hypothermia (< 35 degrees C), and higher APACHE II and TISS scores. A surgical diagnosis was associated with decreased mortality risk. Neither a positive blood culture nor hypotension at presentation independently predicted death. CONCLUSION: Knowledge of the epidemiology of these syndromes is important for assessing the burden of disease and providing background information for investigating new therapies.

Adult↗

The pathology of rotavirus-associated deaths, using new molecular diagnostics.

Rotavirus, the most common cause of severe, dehydrating gastroenteritis among children worldwide, annually causes approximately 500,000 deaths among children aged <5 years. The primary site of rotavirus infection is the small intestine. Pathologic investigations of patients who died of rotavirus infection are limited to data from a few reported autopsies, and dehydration with electrolyte imbalance is believed to be the major cause of death. Several recent reports suggest that children who died during a rotavirus illness were viremic before death, because rotavirus was detected at several extraintestinal sites. We report 3 rotavirus-associated deaths among children, 2 of whom had evidence of rotavirus genome in extraintestinal tissues detected by use of novel molecular diagnostic methods. The part played by rotavirus in fatal cases is unclear and requires additional investigation of diarrhea-associated deaths, because a better understanding might alter the approach to treatment and the need for antiviral therapy.

Brain Stem↗

Clinical evaluation of Double Strength Isotrexin versus Benzamycin in the topical treatment of mild to moderate acne vulgaris.

BACKGROUND: Topical retinoid therapy has been shown to be an effective means of treating both the inflammatory and non-inflammatory lesions of acne vulgaris. AIM: To assess the efficacy and safety of the test product, a gel containing isotretinoin 0.1% w/w and erythromycin 4.0% w/w, with a currently used and effective treatment for mild to moderate acne vulgaris, a gel containing benzoyl peroxide 5.0% w/w and erythromycin 3.0% w/w. METHODS: This multi-centre, single-blind (investigator blind), parallel group study compared the efficacy and safety of isotretinoin/erythromycin gel (Double Strength Isotrexin) once daily against benzoyl peroxide/erythromycin gel (Benzamycin twice daily in the topical treatment of mild to moderate acne vulgaris. Patients (n = 188) with a history (mean duration 3.3 years) of facial acne vulgaris and with 15-100 inflammatory lesions and/or 15-100 non-inflammatory lesions, but not more than three nodulocystic lesions, were included. At baseline and weeks 2, 4, 8 and 12, the investigator assessed efficacy (total number and severity of inflammatory and non-inflammatory lesions and acne grade) while subjective global change assessments of facial acne from baseline and symptom-specific skin tolerance were assessed by the patient. The investigator recorded an overall global assessment of skin tolerability at week 12. Adverse events were recorded throughout. RESULTS: The treatments were comparable with regard to their effects on inflammatory and non-inflammatory lesions and acne grade. Few adverse events were considered to be treatment-related. Both the isotretinoin/erythromycin and benzoyl peroxide/erythromycin gels were generally well tolerated. Compliance was better with the isotretinoin/erythromycin gel, which had the advantages of not requiring mixing or storage in a refrigerator, and was applied once rather than twice daily. CONCLUSIONS: Isotretinoin/erythromycin gel given only once daily showed comparable efficacy with benzoyl peroxide/erythromycin given twice daily in the treatment of mild to moderate acne vulgaris of the face.

Acne Vulgaris↗

Antibodies to capsular polysaccharides of group B Streptococcus in pregnant Canadian women: relationship to colonization status and infection in the neonate.

In a cohort study of 1207 pregnant women in Alberta, Canada, the serotype distributions of vaginal-rectal group B Streptococcus (GBS) isolates were compared with all isolates from neonates with invasive GBS disease identified by population-based surveillance. Serum concentrations of Ia, Ib, II, III, and V capsular polysaccharide (CPS)-specific IgG also were determined, according to serotype of the vaginal-rectal colonizing GBS strain. GBS colonization was detected in 19.5% (235 of 1207) of women. Serotype III accounted for 20.6% (48 of 233) of colonizing strains available for typing but for 37% (27 of 73) of invasive isolates from neonates (P<.01). Maternal colonization with type III was least likely to be associated with moderate concentrations of III CPS-specific IgG. Serotype III GBS is more invasive than other serotypes in this population; this may be due, at least in part, to poor maternal type III CPS-specific antibody response.

Adult↗

Physicians' prevention practices and incidence of neonatal group B streptococcal disease in 2 Canadian regions.

BACKGROUND: The impact of expert guidelines on the prevention of neonatal group B streptococcal (GBS) disease has not been studied in Canada. Our aim was to determine physician practices with regard to this condition before and after publication of Canadian guidelines and to monitor concurrent trends in the incidence of neonatal GBS disease. METHODS: We used repeat cross-sectional surveys, distributed by mail to all family practitioners and obstetricians attending deliveries in Alberta and in the Metropolitan Toronto and Peel region, Ontario, in 1994, 1995 and 1997, to document prevention practices. Audits were conducted for a subset of respondents to confirm reported practices. Population-based surveillance involving all microbiology laboratories in both regions for 1995-1998 was used to document rates of neonatal disease. RESULTS: The overall survey response rates were as follows: for 1994, 1128/1458 (77%); for 1995, 1054/1450 (73%); and for 1997, 1030/1421 (72%). During 1995 and 1997, significantly more obstetric care providers were screening at least 75% of pregnant women in their practices than had been the case in 1994 (747/916 [82%] and 693/812 [85%] v. 754/981 [77%]; p < 0.001). The percentage of obstetric care providers who reported practice that conformed completely with any of 3 consensus prevention strategies increased from 10% in 1994 to 29% in 1997 (p < 0.001). There was a concurrent overall significant decrease in incidence of neonatal GBS disease during the same period. INTERPRETATION: The adoption by Canadian obstetric care providers of neonatal GBS prevention practices recommended by expert groups was slow but improved significantly over time. These findings highlight the difficulties associated with achieving compliance with diverse and frequently changing recommendations. However, the associated incidence of neonatal GBS disease, which was low or declining, suggests that efforts to disseminate current GBS prevention guidelines have been moderately successful.

Alberta↗

Population-based active surveillance for neonatal group B streptococcal infections in Alberta, Canada: implications for vaccine formulation.

BACKGROUND: Knowledge of circulating serotypes of group B Streptococcus (GBS) is important for formulation of vaccines. There are no Canadian data on the serotype distribution of neonatal GBS isolates. METHODS: Using a retrospective laboratory and health record survey between 1993 and 1994 (before introduction of Canadian prevention guidelines) and prospective active laboratory-based surveillance from 1995 to 1999 of all laboratories in Alberta, we identified 168 cases of invasive neonatal GBS infections including stillbirths among 262,398 total births; 118 of 123 (96%) isolates from 1995 to 1999 were serotyped, and the corresponding neonatal health records were reviewed. RESULTS: The average annual incidence was 0.64 of 1000 total births/year. Of these 95 (57%) had early onset disease (EOD), 15 (9%) were still births and 58 (34%) had late onset disease (LOD). Eighty-one percent of EOD cases were caused by serotypes Ia, Ia/c, Ia/c/R, III, III/R and V, V/R, whereas 81% of LOD cases were caused by serotypes III and III/R. GBS serotypes containing the C protein along with serotypes III and V as a group constituted 91% (107 of 118) of all GBS cases in our population. The most common clinical presentation was bacteremia without focus (74%) followed by meningitis (14%) and pneumonia (12%). During 1995 to 1999, in addition to 13 stillbirths, there were 6 of 64 (9%) neonatal deaths among EOD cases and 1 of 46 (2%) neonatal death among LOD cases. CONCLUSIONS: In this population-based study stillbirths account for a proportion of cases that are not routinely counted and represent a group for which intrapartum antibiotics would likely not be effective, but potentially preventable by vaccination. Inclusion of serotypes Ia, III and V in a conjugate vaccine or serotypes III and V conjugated with the C protein in a GBS vaccine could theoretically provide protection against the majority of GBS invasive disease in Alberta neonates.

Alberta↗

Olecranon septic bursitis managed in an ambulatory setting. The Calgary Home Parenteral Therapy Program Study Group.

BACKGROUND: The epidemiology, outcome and management of olecranon septic bursitis (OSB) have not been described in a large cohort of ambulatory patients. METHODS: A retrospective study of all 118 cases of OSB presenting over 21 months to all regional Home Parenteral Therapy Program clinics in Calgary (referral base approximately 1 million). RESULTS: The minimum population annual incidence was 10/100,000. The mean (and standard deviation) age was 44 (13) years, and males predominated (88%). One-third of patients had at least one comorbid illness, with preceding injury in 53% of cases. The most common symptoms were pain (87%), redness (77%) and fever or chills (45%). Common signs included erythema (92%), swelling (85%), edema (75%), tenderness (59%), fluctuance (50%), heat (36%) and reduced range of motion (27%). Fever (body temperature of > or =37.8 degrees C) occurred in 20%. Staphylococcus aureus was identified in 88% of culture-proven cases of OBS. The most common antibiotic regimen was sequential intravenous administration of cefazolin (for a median of 4 d) followed by clindamycin orally (for a median of 8 d). Sixty (51%) patients required a drainage procedure and only 1 patient required admission to hospital. CONCLUSION: OSB is more common than reported and can be treated successfully in ambulatory settings with sequential intravenous therapy followed by oral therapy and drainage in selected cases.

Adult↗

Canadian Acute Respiratory Illness and Flu Scale (CARIFS): development of a valid measure for childhood respiratory infections.

Although acute respiratory infection (ARI) is the most frequent clinical syndrome in childhood, there is no validated measure of its severity. Therefore a parental questionnaire was developed: the Canadian Acute Respiratory Illness Flu Scale (CARIFS). A process of item generation, item reduction, and scale construction resulted in a scale composed of 18 items covering three domains; symptoms (e.g., cough); function (e.g., play), and parental impact (e.g., clinginess). The validity of the scale was evaluated in a study of 220 children with ARI. Construct validity was assessed by comparing the CARIFS score with physician, nurse, and parental assessment of the child's health. Data were available from 206 children (94%). The CARIFS correlated well with measures of the construct (Spearman's correlations between 0.36 and 0.52). Responsiveness was shown, with 90% of children having a CARIFS score less than a quarter of its initial value, by the tenth day.

Acute Disease↗

Invasive group A streptococcal disease in children and association with varicella-zoster virus infection. Ontario Group A Streptococcal Study Group.

OBJECTIVES: To describe the incidence and clinical features of invasive group A streptococcal (GAS) disease in children in Ontario and determine the risk of invasive GAS infection following chickenpox. METHODS: During 1992-1996, we conducted prospective, active, population-based surveillance for pediatric invasive GAS disease in Ontario, Canada (population: 11 million; 2.5 million children) and reviewed clinical and laboratory records. RESULTS: There were 1.9 cases of invasive GAS disease per 100,000 children per year. Streptococcal toxic shock syndrome (STSS) occurred in 7% of cases and necrotizing fasciitis (NF) in 4% for incidences of.08 and.13 per 100,000 per year, respectively. Case-fatality rates were 56% for STSS, 10% for NF, and 4% overall. The presence of chronic underlying illness other than asthma was associated with death (relative risk [RR]: 11; 95% confidence interval [CI]: 2.4-45). Fifteen percent of children identified had preceding chickenpox infection, which significantly increased the risk for acquisition of invasive GAS disease (RR: 58; 95% CI: 40-85). Children with invasive GAS and recent chickenpox were more likely to have NF (RR: 6.3; 95% CI: 1.8-22.3). CONCLUSIONS: Childhood invasive GAS disease occurs at an incidence similar to the adult population but has a lower rate of STSS and case-fatality. Chickenpox dramatically increases the risk for acquiring invasive GAS disease, and universal chickenpox vaccination could potentially prevent up to 15% of all pediatric invasive GAS disease.

Adolescent↗

Disseminated bacille Calmette-Guérin infection in an infant with a novel deletion in the interferon-gamma receptor gene.

Six weeks after receiving BCG vaccination, a Canadian aboriginal infant presented with suspected sepsis, lymphadenopathy and hepatosplenomegaly. Lymph node biopsy revealed macrophages filled with acid-fast bacilli. Mycobacterium bovis was cultured from tissue specimens and there was evidence of concomitant cytomegalovirus disease. The infant died of disseminated BCG infection. A novel deletion at nucleotide 165 in the interferon-gamma receptor (IFN-gammaR1) was identified. The incidence of this mutation in the aboriginal population and the impact on the heterozygous state are unknown.

BCG Vaccine↗

A CD-1 mouse model of infection with Staphylococcus aureus: influence of gender on infection with MRSA and MSSA isolates.

Staphylococcus aureus is an important pathogen of humans and other animals, causing bacteremia, abscessation, toxemia, and other infectious diseases. An animal model using CD-1 mice was developed to study the pathogenesis of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). When inoculated into the CD-1 mouse model, it was shown that both MSSA isolates, (HR 78 and CSA-1) and MRSA isolates (MRSA 456 and MRSA 457) led to chronic infection of the kidney. Female CD-1 mice inoculated with MRSA 456 proved to be more susceptible to infection and mortality than their male counterparts. Castrated mice became more susceptible to infection than intact male mice, suggesting a hormonal involvement in the infection process.

Animals↗

Candida infection in pediatric liver transplant recipients.

A retrospective review of 100 liver transplantations in 98 children was performed to determine the incidence of infection caused by Candida organism in these patients and to identify risk factors that may predispose to serious fungal infection. Thirty-one infections caused by Candida organisms developed during the initial 28 days posttransplantation: 19 were definite invasive infections (one deep site or one positive blood culture), 2 were probable invasive infections (three superficial sites), and 10 were urinary tract infections. Eleven of 19 patients had fungemia or a disseminated infection (two noncontiguous deep organs involved and/or positive blood cultures) and 8 of 19 had peritoneal candidiasis. Infection caused by Candida organisms was a contributing factor to mortality in 7 of 21 patients (case fatality rate of 33%) with invasive infection. Risk factors that were predictive for invasive infection by univariate analysis included the following: pretransplantation antibiotic therapy, length of transplant operation, transfusion requirement, number of days in the intensive care unit, number of days intubated, number of concurrent bacterial infections, number of antibiotics administered, number of laparotomies performed posttransplantation, retransplantation, hepatic artery thrombosis, bile leaks, and renal and respiratory failure. By logistic regression analysis, bile leak, hepatic artery thrombosis, preoperative steroid use, transfusion requirement, and the number of days intubated were identified as independent risk factors for invasive infection caused by Candida organisms. The use of prophylactic antifungal agents in high-risk patients may be important in reducing the serious morbidity and mortality associated with sepsis caused by Candida organisms in pediatric liver transplant recipients.

Adolescent↗

Evaluation of the Strep A OIA assay versus culture methods: ability to detect different quantities of group A Streptococcus.

The Strep A OIA assay by Biostar (Boulder, Co., USA) is a unique optical immunoassay system for the rapid detection of Group A streptococcal carbohydrate. As part of a community-based pediatric cohort study of Group A Streptococcus (GAS) persistence following antibiotic therapy of pharyngitis, the performance of the Strep A OIA assay was compared with the amount of growth from standard throat swab culture methods. A total of 363 throat swabs taken over the course of the study was evaluated from 248 children between 2 and 18 years of age. Two culture methods were performed: an agar plate with the throat swab using Columbia agar base with 5% sheep blood incubated under an anaerobic environment for 48 h and Todd-Hewitt broth (THB) enhancement. The Strep A OIA was then performed. A total of 144 of 363 (39.7%) samples was positive for GAS by one or more of the laboratory tests across study visits: agar culture detected 132 of 144 (91.7%), THB culture detected 128 of 144 (88.9%), and the Strep A OIA assay detected 129 of 144 (89.6%). Complete agreement among all three laboratory tests was found for 333 of 363 (91.7%) of the samples. Agar culture results were comparable to THB cultures with a sensitivity of 96.9%, specificity of 96.6%, a positive predictive value of 93.9%, and a negative predictive value of 98.3%. Although the performance of the Strep A OIA assay had similar specificity (96.5%) and positive predictive value (93.8%) compared with the combined results of the two culture methods, the sensitivity (89.0%) and negative predictive value (93.6%) were lower. A significant difference (p < 0.001) was found in the ability of the Strep A OIA assay to detect agar culture-positive swabs that had a light growth (1+ or 2+) (63.0%) versus a moderate (3+) or heavy (4+) growth (98.1%) of GAS. Although the Strep A OIA assay allows GAS throat swab results to be reported an average of 24 h sooner than either of the cultures, the rapid assay was not as sensitive in detecting light growth GAS-positive cultures.

Adolescent↗

Two-year survey of Alberta laboratories processing of antenatal group B streptococcal (GBS) screening specimens: implications for GBS screening programs.

We evaluated specimen types received and methods used by laboratories to process screening GBS specimens from pregnant women. Surveys during 1995 and 1997 of all laboratories in the province of Alberta, Canada that culture GBS from screening genital specimens were completed. Between surveys, there was dissemination of information about appropriate culture techniques. Survey completion rates were 100% in both years (38/38 in 1995 and 20/20 in 1997). During 1995 as compared to 1997, laboratories were less likely to a) have a specific written protocol for identification of genital GBS screening specimens (1995: 78.2% versus 1997: 100%, p = 0.08) b) be receiving combined vaginal-anorectal swabs (1995: 18% of all swabs received versus 1997: 60.4%, p < 0.001), and c) be using selective GBS culture media (1995: 45.5% versus 1997: 86.7%, p = 0.01). Regions using screening based approaches for GBS prevention need to ensure that their laboratories are using adequate techniques for GBS detection.

Alberta↗

Invasive group A streptococcal infections in children.

Invasive group A streptococcal infections and STSS have increased as causes of morbidity and mortality among children and adults. In children, respiratory foci appear to be the most common, but skin and soft tissue infection, particularly associated with varicella, also are common. Early diagnosis requires awareness of the presenting features and a high index of suspicion. Antimicrobial therapy that includes clindamycin, therapy with IVIG for those with STSS, and surgical intervention for patients with necrotizing fasciitis may improve outcome. Chemoprophylaxis should be considered among household contacts of patients with severe group A streptococcal disease in high-risk settings. Further studies are ongoing to evaluate the hypothesized link of invasive group A streptococcal infection in children with varicella and NSAID use, to better clarify the pathogenesis of STSS and necrotizing fasciitis, and to better document the risk of secondary spread among close contacts of case patients.

Adolescent↗

Predictors and outcome of admission for invasive Streptococcus pneumoniae infections at a Canadian children's hospital.

Rates of admission for invasive Streptococcus pneumoniae infection in children vary considerably between institutions. We performed a retrospective study to investigate factors used in the decision to admit patients with invasive S. pneumoniae infection to Alberta Children's Hospital. Of 254 patients who were initially assessed in the emergency department, 38.2% were admitted to the hospital. Significant risk factors for admission as determined by a logistic regression model included murmur (odds ratio [OR], 18.98; 95% confidence interval [CI], 4.08-88.23), focal infection (OR, 11.41; 95% CI, 5.07-25.67), and older age (OR, 2.72; 95% CI, 1.03-7.17). Higher hemoglobin level (OR, 0.96; 95% CI, 0.93-0.99) and temperature of > 38.5 degrees C (OR, 0.39; 95% CI, 0.18-0.85) were associated with a lower risk of admission. Two patients died (case-fatality rate, 0.7%). Despite the low rate of admission for invasive S. pneumoniae infections at our hospital, the mortality rate was comparable with those at institutions with higher rates of admission, thus suggesting that the factors we identified may be useful in deciding whether to admit patients with (or who are at high risk for) invasive S. pneumoniae infections.

Canada↗

Epidemiology and outcome of osteomyelitis in the era of sequential intravenous-oral therapy.

BACKGROUND: There has been little recent information on the epidemiology and outcome of childhood osteomyelitis since the era of sequential intravenous-oral antibiotic therapy. METHODS: Retrospective chart review. OBJECTIVE: To review the recent experience and outcome of osteomyelitis in children. RESULTS: Between 1984 and 1996 we identified 146 patients with osteomyelitis. Decreased limb use and fever were the most common presenting symptoms, and tenderness was the most common sign. Staphylococcus aureus was the most common causative organism, and Haemophilus influenzae was not identified after 1990. Bone biopsies or aspirates were superior (83%) to blood cultures (32%) in yielding organisms. 99mTc bone scan was the most sensitive imaging test (94%). Lack of use of anti-teichoic acid titers and serum bactericidal titers did not adversely affect outcome. The median duration of intravenous antibiotic therapy was 11 days, with a median duration of total antibiotics of 38 days. Complications occurred in 6.6% of patients. CONCLUSION: S. aureus remains the most important cause of osteomyelitis. Despite inconsistent use of tests for diagnosis and management and use of sequential intravenous-oral therapy, the overall outcome remains excellent.

Administration, Oral↗

Safety and immunogenicity of two inactivated poliovirus vaccines in combination with an acellular pertussis vaccine and diphtheria and tetanus toxoids in seventeen- to nineteen-month-old infants.

OBJECTIVES: To compare the safety and immunity of an acellular pertussis vaccine containing pertussis toxoid, filamentous hemagglutinin, 69 kd protein, fimbriae 2 and 3 combined with diphtheria and tetanus toxoids given as single or separate injection with inactivated poliovirus vaccine (MRC-5-or Vero cell-derived) or live attenuated polio vaccine. METHODS: A total of 425 healthy children between 17 and 19 months of age who were receiving the fourth dose of their routine immunization series were randomly allocated to receive either the acellular pertussis vaccine and oral poliovirus vaccine or one of two inactivated poliovirus vaccines as a combined injection or separate injections. RESULTS: Although minor adverse events were commonly reported, differences between the groups were few. Fever and decreased feeding were less common in recipients of live attenuated poliovirus vaccine than the combination vaccine containing MRC-5 cell-derived inactivated poliovirus vaccine. A significant antibody response was demonstrated in all groups against all the antigens contained in the vaccines. Antibodies against poliovirus were higher in the groups immunized with the inactivated poliovirus vaccine than the live attenuated vaccine. Anti-69 kd protein antibodies were higher in the group given the MRC-5 cell-derived inactivated poliovirus vaccine as a combined injection than in the group given the separate injection or the group immunized with the live attenuated poliovirus vaccine. CONCLUSION: The five-component acellular pertussis vaccine combined with diphtherid and tetanus toxoids is safe and immunogenic when combined with either MRC-5- or Vero cell-derived inactivated poliovirus vaccine. This will facilitate the implementation of acellular pertussis vaccine and the movement to inactivated poliovirus vaccine programs.

Antibody Formation↗