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Biomedical subjects

David M Patrick

Publications and source records attributed to David M Patrick.

At least 19 recordsLinked to original sources
PubMed2006

Antibiotic use among children in British Columbia, Canada.

BACKGROUND: In North America use of second-generation macrolides such as clarithromycin and azithromycin is popular due to favourable dosing and adverse event profiles. However, studies have also shown that use of second-generation macrolides promotes carriage of macrolide-resistant nasopharyngeal and oral streptococci. The present study was undertaken to characterize overall antibiotic use including macrolide antibiotics among children in British Columbia. METHODS: Population-based data from British Columbia were analysed to determine antibiotic prescribing patterns for outpatient prescriptions from 1996 to 2003. Antibiotic prescription rates per 1000 children per year were evaluated by age (0-4, 5-9, 10-14, <15 years old), sex and physician diagnosis. RESULTS: From 1996 to 2003, the overall BC prescription rate in children <15 years old decreased by one-third from 720 to 488 per 1000 children. The decrease in the rate of antibiotic consumption over time was seen across all age strata; however, the largest decrease (33%) was seen in children between the ages of 0-4 years. From 1996 to 2003, use of penicillins and cephalosporins decreased by 40% and 30%, respectively. This trend of decreasing antibiotic use with beta-lactams was seen in all age groups but the greatest decline was in the age group of 0-4 years (P value <0.05). During this time, macrolide use increased significantly (24%) from 102 to 126 per 1000 children (P value <0.001). This increase was seen in all age groups but again the greatest increase was seen in children of age between 0 and 4 years. Within the macrolides, use of erythromycin decreased by 72% (from 83 to 23 per 1000 children) while clarithromycin use increased by almost 3-fold (18-67 per 1000 children) and azithromycin use increased 81-fold (0.4-35 per 1000 children). In 2003, antibiotics were primarily being used for the treatment of upper respiratory tract infections, acute otitis media and bronchitis. CONCLUSIONS: Overall antibiotic use has declined in children; however, there is increased use of macrolides which may have ramifications on macrolide-resistant streptococci, including Streptococcus pneumoniae and group A streptococci. A large proportion of antibiotic use in children is for upper respiratory tract infections and bronchitis, indications where there is a high likelihood that the aetiology is viral rather than bacterial.

Adolescent↗
PubMed2006

Proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma modulate epithelial barrier function in Madin-Darby canine kidney cells through mitogen activated protein kinase signaling.

BACKGROUND: The tight junction is a dynamic structure that is regulated by a number of cellular signaling processes. Occludin, claudin-1, claudin-2 and claudin-3 are integral membrane proteins found in the tight junction of MDCK cells. These proteins are restricted to this region of the membrane by a complex array of intracellular proteins which are tethered to the cytoskeleton. Alteration of these tight junction protein complexes during pathological events leads to impaired epithelial barrier function that perturbs water and electrolyte homeostasis. We examined MDCK cell barrier function in response to challenge by the proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma). RESULTS: Exposure of MDCK cells to TNFalpha/IFNgamma resulted in a marked sustained elevation of transepithelial electrical resistance (TER) as well as elevated paracellular permeability. We demonstrate that the combination of TNFalpha/IFNgamma at doses used in this study do not significantly induce MDCK cell apoptosis. We observed significant alterations in occludin, claudin-1 and claudin-2 protein expression, junctional localization and substantial cytoskeletal reorganization. Pharmacological inhibition of ERK1/2 and p38 signaling blocked the deleterious effects of the proinflammatory cytokines on barrier function. CONCLUSION: These data strongly suggest that downstream effectors of MAP kinase signaling pathways mediate the TNFalpha/IFNgamma-induced junctional reorganization that modulates MDCK cell barrier function.

Animals↗
PubMed2006

Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus.

Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated by beta-propiolactone) SARS-CoV vaccine and a combination of two adenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike (S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizing antibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoV replication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv mice was more effective than the Ad S/N vaccine administered either intranasally or intramuscularly in inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of the WKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not with cellular immune responses as measured by gamma interferon secretion by mouse splenocytes. Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasally or intramuscularly were significantly lower than those induced by the WKV vaccine. However, Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoV replication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in the sera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play a role in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection.

Administration, Intranasal↗
PubMed2006

Coordinated response to SARS, Vancouver, Canada.

Two Canadian urban areas received travelers with severe acute respiratory syndrome (SARS) before the World Health Organization issued its alert. By July 2003, Vancouver had identified 5 cases (4 imported); Toronto reported 247 cases (3 imported) and 43 deaths. Baseline preparedness for pandemic threats may account for the absence of sustained transmission and fewer cases of SARS in Vancouver.

Adult↗
PubMed2005

Modeling control strategies of respiratory pathogens.

Effectively controlling infectious diseases requires quantitative comparisons of quarantine, infection control precautions, case identification and isolation, and immunization interventions. We used contact network epidemiology to predict the effect of various control policies for a mildly contagious disease, such as severe acute respiratory syndrome, and a moderately contagious disease, such as smallpox. The success of an intervention depends on the transmissibility of the disease and the contact pattern between persons within a community. The model predicts that use of face masks and general vaccination will only moderately affect the spread of mildly contagious diseases. In contrast, quarantine and ring vaccination can prevent the spread of a wide spectrum of diseases. Contact network epidemiology can provide valuable quantitative input to public health decisionmaking, even before a pathogen is well characterized.

British Columbia↗
PubMed2004

Effect of formulary policy decisions on antimicrobial drug utilization in British Columbia.

BACKGROUND: Formularies are used routinely for management of drug expenditures yet evaluations of their impact remain rare. The objective of this study was to analyse the impact of addition or deletion of antimicrobials from the provincial formulary on drug utilization. METHODS: We obtained data from the British Columbia PharmaNet database on all outpatient oral antimicrobial prescriptions from 1996 to 2000 and converted them to their defined daily dose (DDD) equivalents according to the ATC system. Trends in utilization associated with a changing formulary status of new antimicrobial agents were analysed. Maximum likelihood estimation was used to determine the rate of increase in utilization resulting from addition to the formulary. Models were adjusted for seasonal and temporal trends as well as serial correlation. RESULTS: During this time period, clarithromycin was on formulary, later delisted, and then relisted again. Valaciclovir and famciclovir were also added to the formulary. During the time clarithromycin was off the formulary, the rate of change in its monthly consumption was 0.0061 DDD/1000 population/day; following its relisting, the rate of change increased by 818% to 0.0560 DDD/1000 population/day (P=0.002). After the listing of valaciclovir on the formulary, the rate of change in its monthly consumption increased 57% from a baseline of 0.0014 to 0.0022 DDD/1000 population/day (P=0.07). A similar effect was seen with the addition of famciclovir to the formulary whereby the rate of change in monthly consumption increased from 0.0008 (before addition to the formulary) to 0.0018 (after addition to the formulary) (P </= 0.001). CONCLUSIONS: Listing of antimicrobials on provincial or countrywide formularies is followed temporally with increased utilization. However, before governmental agencies can institute reference-based pricing or co-payment programmes, the effect of such a programme on the emergence of antimicrobial resistance and on patient outcomes needs further study.

Anti-Bacterial Agents↗
PubMed2004

Adult tetanus, diphtheria and pertussis immunization: knowledge, beliefs, behavior and anticipated uptake.

BACKGROUND: Lifetime protection against pertussis has been adopted as a goal of immunization programs in Canada. To anticipate adult coverage with a combined product containing tetanus (T) and diphtheria (d) toxoids and acellular pertussis (aP) vaccine as a booster dose, we conducted a survey of households in British Columbia, Canada. METHODS: In a random telephone survey involving 800 adults, 25 years of age and older, we assessed current behaviors related to adult Td immunization and beliefs regarding pertussis vaccine under various scenarios relevant to adult decision-making. RESULTS: Forty-five percent of participants reported having received tetanus vaccine within the previous 10 years; this rate was lowest amongst elderly persons 65 years of age or more (28%). On multi-variate analysis, being up-to-date with tetanus immunization was independently associated with belief that an adult should be immunized against tetanus and perception that tetanus is life-threatening and inversely associated with being elderly. At baseline, 59% of respondents indicated willingness to receive pertussis immunization if provided free; this increased to 76% following sequential information about communicability and severity of pertussis illness and safety, efficacy and convenience of vaccine and up to 87% if accompanied by physician or nurse recommendation. Sixty-three percent of adults indicated they would receive the vaccine if required to pay $40.00 (Cdn) for it. CONCLUSIONS: Personal risk perception, public funding and physician recommendation are important to adults when considering tetanus and pertussis immunization. These factors may be relevant as immunization programs are expanded to include more adults generally.

Adult↗
PubMed2004

Per capita antibiotic consumption: how does a North American jurisdiction compare with Europe?

Antibiotic consumption in populations affects the emergence of resistant organisms. We compared 1996-2000 trends in consumption in British Columbia, Canada, with those in Europe. Prescription data from the British Columbia PharmaNet database were converted into SAS files and classified using the Anatomical Therapeutic Chemical system, and weights of antibiotics were converted into defined daily doses (DDDs) using the 2001 definitions from the World Health Organization Collaborating Center for Drug Statistics Methodology. During 1996-2000, consumption in British Columbia decreased from 19.5 to 17.9 DDDs/1000 inhabitant-days. Although antibiotic consumption in British Columbia was less than the European median in 2000, it exceeded that in northern European countries with established antibiotic surveillance and control programs. The consumption rates for fluoroquinolones, newer macrolides, and cephalosporins in British Columbia exceeded those in Denmark (1.44 vs. 0.15, 1.59 vs. 0.92, and 1.86 vs. 0.02 DDDs/1000 inhabitant-days, respectively). The observed increase in and pattern of consumption associated with newer antimicrobials may increase the risk for emergence of antimicrobial-resistant organisms in British Columbia.

Anti-Bacterial Agents↗
PubMed2004

Prevalence and correlates of Chlamydia infection in Canadian street youth.

PURPOSE: To determine the prevalence and correlates of Chlamydia trachomatis in Canadian street youth. METHODS: A cross-sectional study of street youth between the ages of 15-24 years was conducted over a 9-month period in seven large urban centers across Canada. Youth were recruited through "drop-in" centers, outreach work, and mobile vans in each city. Information was collected through a nurse-administered questionnaire. Youth were asked to provide urine to test for chlamydia trachomatis by polymerase chain reaction. Separate logistic regression models were run for males and females controlling for age. RESULTS: The prevalence rate of chlamydia was 8.6% in 1355 youth (95% CI = (7.1%, 10.1%)). Higher prevalence rates were found in females than in males (10.9% vs. 7.3%, respectively) and in Aboriginal youth than in non-Aboriginal youth (13.7% vs. 6.6%, respectively). Four variables were associated with increased risk of chlamydia infection in females: Aboriginal status; self-perceived risk; having no permanent home; and having been in foster care. One predictor of chlamydia for males was having had a social worker. CONCLUSIONS: A high prevalence of chlamydia was found in this vulnerable population in comparison to other Canadian youth. Having been in foster care and having had a social worker were found to have a strong association with chlamydia.

Adolescent↗
PubMed2003

Neisseria meningitidis carriage during an outbreak of serogroup C disease.

During 2001, an outbreak of serogroup C meningococcal disease led to immunization of individuals aged 13-29 years in Abbotsford, British Columbia, Canada. This study addresses the distribution of Neisseria meningitidis carriage in this population and the implications of that distribution for the targeting of the immunization campaign. Pharyngeal swabs were obtained at immunization from 2004 people. Colonies were identified and serogrouped using standard agglutination methods and by PCR. Isolates were characterized using pulsed-field gel electrophoresis (PFGE). The prevalence of N. meningitidis carriage was 153 carriers per 2004 subjects (7.6%; 95% confidence interval, 6.5%-8.9%). Only 6 (4%) of the isolates from these carriers were found to be serogroup C by agglutination or PCR testing, and all of these were from individuals within the age group targeted for immunization. Only 1 of these 6 isolates was found to be identical to the outbreak strain by PFGE. The observation that a virulent strain is not circulating widely suggests the possibility of low background immunity in the population at risk and emphasizes the importance of vaccination in controlling epidemic group C meningococcal disease.

Adolescent↗
PubMed2003

Impact of universal preadolescent vaccination against hepatitis B on antenatal seroprevalence of hepatitis B markers in British Columbia women.

Countries with a low risk of hepatitis B (HB) lack data on the effectiveness of universal HB vaccination programs for children. British Columbia began a program in 1992, offering HB vaccination to 11 year olds. We conducted an anonymous, unlinked serologic survey 7 years later, analyzing a random sample of specimens (n = 1215) from women aged 15-44 years who had undergone antenatal rubella testing. Among those aged 15-19 years inclusive there was no evidence of chronic HB (HB surface antigen), the proportion with evidence of acute HB (anti-HB core antibody) was only 0.6% (compared with 6.5% for the entire sample), and evidence of protective immunity was strong: the prevalence of anti-HB surface antibody (anti-HBs) was 79.1% (compared with 41.4% for the entire sample) and the geometric mean titre was 34.9 IU/mL (compared with 0.6-0.8 IU/mL for the older groups [p < 0.001]).

Acute Disease↗
PubMed2003

Oculo-respiratory syndrome: a new influenza vaccine-associated adverse event?

During the 2000-2001 influenza immunization campaign in Canada, a new adverse event, oculo-respiratory syndrome (ORS), was noted in association with administration of vaccine supplied by one manufacturer. The original case definition for ORS specified bilateral conjunctivitis, facial edema, or respiratory symptoms beginning 2-24 h after influenza vaccination and resolving within 48 h after onset. To characterize the spectrum, severity, and impact of ORS, we contacted persons who had reported any influenza vaccine-associated adverse event in British Columbia, Canada, during the 2000-2001 vaccination campaign. With use of a standardized telephone interview, we collected information from 609 (79%) of 769 eligible persons. Thirteen percent of ORS-affected persons reported onset 48 h, and 42% considered the symptoms to be severe. The surveillance case definition for ORS for 2001-2002 was revised to include onset <or=24 h after vaccination, with no restriction on duration. ORS should be incorporated into annual influenza vaccine safety monitoring.

Adolescent↗
PubMed2003

Targeted mass treatment for syphilis with oral azithromycin.

From mid 1997 to end of 1999, there was a sexually-transmitted infectious syphilis outbreak mainly in heterosexual people in British Columbia, Canada, that was concentrated in Vancouver. The rate across the province increased from less than 0.5 to 3.4 per 100000, and the rate in Vancouver reached 12.9 per 100000. We aimed to eliminate the syphillis outbreak by treating people at risk of infection. In 2000, a targeted mass treatment programme provided azithromycin (1.8 g orally) to 4384 at-risk residents in this city. After the programme, syphilis frequency fell significantly for 6 months (p=0.016), but rose again in 2001. Results from curve fitting analyses showed that the number of cases in 2001 (177) was higher than expected (0.0001<p<0.0044). This rate rebound and the absence of a sustained effect suggest that targeted mass treatment for syphilis, even though feasible, should not be done routinely.

Adolescent↗
PubMed2003

Elimination of acute hepatitis B among adolescents after one decade of an immunization program targeting Grade 6 students.

BACKGROUND: British Columbia introduced a preadolescent hepatitis B (HB) immunization program in 1992. This study documents trends in the reported rate of acute HB disease since 1992 and examines factors bearing on the rate of infection throughout the period of program implementation. METHODS: All Grade 6 students were eligible for immunization. Vaccine uptake was reported annually for every school. Acute HB infections were reported by physicians and by biomedical laboratories. Year-to-year trends were analyzed overall and by age group using the electronic public health information system and S-plus. Likelihood ratio tests were used to establish whether a variable was associated with the rate of acute HB in a given cohort. Poisson regression was applied to determine which variables were independently associated with the rate of acute HB. RESULTS: Immunization coverage ranged between 90 and 93% for each year between 1993 and 2001. The overall rate of reported acute HB declined from 7 per 100,000 to just more than 2 per 100,000, whereas that in 12- to 21-year-olds declined from 1.7 to 0 per 100,000 over this one decade period. In the final Poisson regression model, the rate of acute HB infection was significantly associated with year, urban region and lower vaccine uptake. There was an interaction between region and vaccine uptake such that higher vaccine uptake appeared more protective in rural than in urban regions. CONCLUSIONS: Acute HB has been eliminated in the immunized adolescent cohort. A higher carrier rate in urban regions most likely explains the apparent difference in program effectiveness between urban and rural regions.

Adolescent↗
PubMed2003

Injection-site reactions to booster doses of acellular pertussis vaccine: rate, severity, and anticipated impact.

BACKGROUND: Acellular pertussis (aP)-containing vaccines cause fewer adverse events than whole-cell versions for primary doses. Booster doses, however, may be followed by extensive injection-site reactions. This study compares the frequency, severity, and impact of local reactions among children receiving 5 consecutive doses of an aP combination vaccine (including inactivated polio virus, conjugated Haemophilus influenzae type b antigen, and diphtheria and tetanus toxoids) to children receiving a mixed series of whole-cell and aP combination vaccines. METHODS: Participants were parents or guardians of children 4 to 6 years old immunized at public health clinics across British Columbia, Canada. This included 398 children receiving the fifth consecutive dose of an aP combination vaccine and 402 receiving the fifth dose in a mixed series consisting of at least 1 prior dose of whole-cell pertussis combination vaccine with the remainder as aP combination vaccine. A cross-sectional telephone survey evaluated the extent of local reactions 48 to 96 hours after immunization by asking participants to compare the size of redness and swelling with familiar household items such as Oreo cookies or coins. Associated discomfort and impact on recreational activities, health care utilization, parental time off work, and attitudes toward immunization were also assessed. RESULTS: Children who received the fifth consecutive dose of an aP combination vaccine more often experienced redness (24%) or swelling (16%) the size of an Oreo cookie or larger (>or=46 mm) than children given a mixed series (10% and 9%, respectively) but less often experienced tenderness or limitation of movement at the injection site. Related health care utilization was low. There was no discernible effect on participation in recreational activities or parental attitudes toward vaccine; 90% would recommend the same vaccine to others with children of the same age. CONCLUSIONS: We conclude that injection-site reactions are more extensive after the fifth consecutive dose of an aP combination vaccine compared with the fifth dose in a mixed series of whole-cell and aP combination vaccines. These reactions are unlikely to affect parental acceptance of immunization recommendations or health care utilization.

Attitude↗
PubMed2003

Levels of antibodies against cytomegalovirus and Chlamydophila pneumoniae are increased in early onset pre-eclampsia.

OBJECTIVE: The origins of pre-eclampsia/eclampsia lie in a mismatch between feto-placental demands and utero-placental supply, a situation that also arises in normotensive intrauterine growth restriction (IUGR). Could reactivated chronic infection be both a trigger for these differential maternal responses to the same underlying pathology and a link between pre-eclampsia and its attendant lifelong risks of atherosclerosis? DESIGN: Nested case-control study. SETTING: Tertiary obstetric centre. POPULATION: Cases of pre-eclampsia, normotensive IUGR and controls. METHODS: A nested case-control study of serum from a population-based bank was performed. Seroprevalence and levels of anti-cytomegalovirus (CMV) and Chlamydophila pneumoniae immunoglobulin G (IgG) were compared (non-parametrically) between women with early onset pre-eclampsia (<34 weeks of gestation, n = 9), late onset pre-eclampsia (> or =34 + 0 weeks of gestation, n = 29), normotensive IUGR (birthweight less than third centile, n = 33) and matched normal pregnancy (n = 113, up to 2 per case). RESULTS: There was a significant difference in both anti-CMV and Chl. pneumoniae antibodies between groups (Kruskal-Wallis test, P < 0.05). Women with early onset pre-eclampsia had higher anti-CMV levels (median: 79, 95% confidence interval [95% CI] = 47, 164) than women with late onset pre-eclampsia (26 [95% CI = 22, 82], P < 0.05), normotensive IUGR (40 [95% CI = 31, 72], P < 0.05) and normal pregnancy (49 [95% CI = 45, 70], P < 0.05). Women with normotensive IUGR had significantly lower anti-Chl. pneumoniae antibodies (0.10 [95% CI = 0.08, 0.38]) than did normal pregnancy controls (0.21 [95% CI = 0.20, 0.28], P <0.05). CONCLUSIONS: The anti-CMV and anti-Chl. pneumoniae antibodies were higher in early onset pre-eclampsia than in late onset pre-eclampsia, normotensive IUGR and normal pregnancy. This may provide a pathophysiological link between pre-eclampsia and the known increased risk for subsequent atherosclerosis.

Adult↗
PubMed2002

Skin testing to evaluate oculo-respiratory syndrome (ORS) associated with influenza vaccination during the 2000-2001 season.

A syndrome of red eyes and respiratory symptoms was noted following receipt of influenza vaccine in Canada during the 2000-2001 influenza season. We conducted intra-dermal skin testing to determine if oculo-respiratory syndrome (ORS) was related to failure of the splitting process during vaccine manufacturing, if it was associated with a particular viral strain and to identify individuals at risk for subsequent ORS reaction. Skin testing with minute quantities of vaccine antigen induced ORS symptoms at a higher rate amongst persons previously affected by this syndrome compared to previously unaffected persons. Skin test reaction size or quality could not identify persons at risk of ORS. Skin testing could not identify a specific strain or the stage in the manufacturing process during which the trigger may have been introduced.

Adult↗