Safety of zoster vaccine in adults from a large managed-care cohort: a Vaccine Safety Datalink study.

OBJECTIVES: The aim of this study was to examine a large cohort of adults who received the zoster vaccine for evidence of an increased risk of prespecified adverse events requiring medical attention. DESIGN: Two self-comparison approaches, including a case-centred approach and a self-controlled case series (SCCS) analysis were used. SETTING: Eight managed-care organizations participating in the Vaccine Safety Datalink project in the United States. SUBJECTS: A total of 193 083 adults aged 50 and older receiving a zoster vaccine from 1 January 2007 to 31 December 2008 were included. MAIN OUTCOME MEASURES: Prespecified adverse events were identified by aggregated International Classification of Diseases, Ninth Revision (ICD-9) codes in automated health plan datasets. RESULTS: The risk of allergic reaction was significantly increased within 1-7 days of vaccination [relative risk = 2.13, 95% confidence interval (CI): 1.87-2.40 by case-centred method and relative rate = 2.32, 95% CI: 1.85-2.91 by SCCS]. No increased risk was found for the following adverse event groupings: cerebrovascular events; cardiovascular events; meningitis; encephalitis; and encephalopathy; and Ramsay-Hunt syndrome and Bell's palsy. CONCLUSIONS: The results of this study support the findings from the prelicensure clinical trials, providing reassurance that the zoster vaccine is generally safe and well-tolerated with a small increased risk of allergic reactions in 1-7 days after vaccination.

Predictive value of ICD-9-CM codes used in vaccine safety research.

OBJECTIVES: To assess how well selected ICD-9-CM diagnosis codes predict adverse events; to model bias and power loss when vaccine safety analyses rely on unverified codes. METHODS: We extracted chart verification data for ICD-9-CM diagnosis codes from six Vaccine Safety Datalink (VSD) publications and modeled biases and power losses using positive predictive value (PPV) estimates and ranges of code sensitivity. RESULTS: Positive predictive values were high for type 1 diabetes (80%) in children, relative to WHO criteria, and intussusception (81%) in young children, relative to a standard published case definition. PPVs were moderate (65%) for inpatient and emergency department childhood seizures and low (21%) for outpatient childhood seizures, both relative to physician investigator judgment. Codes for incident central nervous system demyelinating disease in adults had high PPV for inpatient codes (80%) and low PPV for outpatient codes (42%) relative to physicians' diagnoses. Modeled biases were modest, but large increases in frequencies of adverse events are required to achieve adequate power if unverified ICD-9-CM codes are used, especially when vaccine associations are weak. CONCLUSIONS: ICD-9-CM codes for type 1 diabetes in children, intussusception in young children, childhood seizures in inpatient and emergency care settings, and inpatient demyelinating disease in adults were sufficiently predictive for vaccine safety analyses to rely on unverified diagnosis codes. Adverse event misclassification should be accounted for in statistical power calculations.

Predominance of HIV-1 subtype A and D infections in Uganda.

To better characterize the virus isolates associated with the HIV-1 epidemic in Uganda, 100 specimens from HIV-1-infected persons were randomly selected from each of two periods from late 1994 to late 1997. The 200 specimens were classified into HIV-1 subtypes by sequence- based phylogenetic analysis of the envelope (env) gp41 region; 98 (49%) were classified as env subtype A, 96 (48%) as D, 5 (2.5%) as C, and 1 was not classified as a known env subtype. Demographic characteristics of persons infected with the two principal HIV-1 subtypes, A and D, were very similar, and the proportion of either subtype did not differ significantly between early and later periods. Our systematic characterization of the HIV-1 epidemic in Uganda over an almost 3-year period documented that the distribution and degree of genetic diversity of the HIV subtypes A and D are very similar and did not change appreciably over that time.

Evidence of a high frequency of HIV-1 subtype F infections in a heterosexual population in Buenos Aires, Argentina.

We analyzed HIV-1 genetic variability, phylogenetic relationships, and association with transmission modes among 58 HIV-1-infected patients from Buenos Aires City, Argentina. The 58 strains were classified as env(gp41) HIV-1 group M subtype B (n = 34) and subgroup F1 of subtype F (n = 24). Potential recombinants combining parts of viral regions from different subtypes, B(prot)/F(env) and F(prot)/B(env), were found in two patients, and a dual infection with HIV-1 prot subtypes B and F was identified in one individual. Epidemiologic analysis of behavioral risks revealed that the frequency of infection with subtype F viruses was significantly higher (p < 0.0001) among heterosexual patients (71%) compared with homosexual patients (11%). The spread of non-B subtypes into heterosexual populations may be more common than previously thought. Our findings provide important information for monitoring the transmission of HIV-1 strains among different risk groups in Argentina as well as for vaccine development.

Association between nurse-physician collaboration and patient outcomes in three intensive care units.

OBJECTIVE: To investigate the association of collaboration between intensive care unit (ICU) physicians and nurses and patient outcome. DESIGN: Prospective, descriptive, correlational study using self-report instruments. SETTINGS: A community teaching hospital medical ICU, a university teaching hospital surgical ICU, and a community non-teaching hospital mixed ICU, all in upstate New York. SUBJECTS: Ninety-seven attending physicians, 63 resident physicians, and 162 staff nurses. PROCEDURE: When patients were ready for transfer from the ICU to an area of less intensive care, questionnaires were used to assess care providers' reports of collaboration in making the transfer decision. After controlling for severity of illness, the association between interprofessional collaboration and patient outcome was assessed. Unit-level organizational collaboration and patient outcomes were ranked. MEASURES: Healthcare providers' reported levels of collaboration, patient severity of illness and individual risk, patient outcomes of death or readmission to the ICU, unit-level collaboration, and unit patient risk of negative outcome. MAIN RESULTS: Medical ICU nurses' reports of collaboration were associated positively with patient outcomes. No other associations between individual reports of collaboration and patient outcome were found. There was a perfect rank order correlation between unit-level organizational collaboration and patient outcomes across the three units. CONCLUSIONS: The study offered some support for the importance of physician-nurse collaboration in ICU care delivery, a variable susceptible to intervention and further study.

Dual and recombinant infections: an integral part of the HIV-1 epidemic in Brazil.

We systematically evaluated multiple and recombinant infections in an HIV-infected population selected for vaccine trials. Seventy-nine HIV-1 infected persons in a clinical cohort study in Rio de Janeiro, Brazil, were evaluated for 1 year. A combination of molecular screening assays and DNA sequencing showed 3 dual infections (3.8%), 6 recombinant infections (7.6%), and 70 (88.6%) infections involving single viral subtypes. In the three dual infections, we identified HIV-1 subtypes F and B, F and D, and B and D; in contrast, the single and recombinant infections involved only HIV-1 subtypes B and F. The recombinants had five distinct B/F mosaic patterns: Bgag-p17/Bgag-p24/Fpol/Benv, Fgag-p17/Bgag-p24/Fpol/Fenv, Bgag-p17/B-Fgag-p24/Fpol/Fenv, Bgag-p17/B-Fgag-p24/Fpol/Benv, and Fgag-p17/B-Fgag-p24/Fpol/Fenv. No association was found between dual or recombinant infections and demographic or clinical variables. These findings indicate that dual and recombinant infections are emerging as an integral part of the HIV/AIDS epidemic in Brazil and emphasize the heterogenous character of epidemics emerging in countries where multiple viral subtypes coexist.

Impact of HIV type 1 subtype variation on viral RNA quantitation.

We evaluated the performance of three HIV-1 RNA quantitation methods (Amplicor HIV-1 MONITOR-1.0, NASBA, and Quantiplex HIV RNA 2.0 [branched DNA (bDNA)]) using plasma specimens (N = 60) from individuals from Asia and Africa infected with one of three HIV-1 subtypes (A, Thai B [B'] or E; N = 20 each). Our results demonstrate that of the 20 subtype A specimens, 19 were quantifiable by the bDNA assay compared with 15 by the MONITOR-1.0 and 13 by NASBA. Of those quantifiable, the mean log10 difference was 0.93 between bDNA and MONITOR-1.0 and 0.46 between bDNA and NASBA. For subtype B' specimens, the correlation among methods was better with only 2 specimens missed by NASBA and 3 by the bDNA assay. However the missed specimens had viral burden near the lower limit (1000 copies/ml) for these assays. For the 20 subtype E specimens, MONITOR-1.0 and NASBA quantified RNA in 17 and 14 specimens, respectively, as compared with 19 specimens quantified by the bDNA assay. The correlation among different assays, especially between bDNA/NASBA and MONITOR-1.0/NASBA, was poor, although the mean log10 difference for subtype E specimens was 0.4 between bDNA and MONITOR-1.0 and only 0.08 between bDNA and NASBA. The addition of a new primer set, designed for non-B HIV-1 subtypes, to the existing MONITOR assay (MONITOR-1.0+) resulted in RNA detection in all 60 specimens and significantly improved the efficiency of quantitation for subtypes A and E. Our data indicate that HIV-1 subtype variation can have a major influence on viral load quantitation by different methods. Periodic evaluation and modification of these quantitative methods may be necessary to ensure reliable quantification of divergent viruses.

Introduction of HIV-2 and multiple HIV-1 subtypes to Lebanon.

HIV genetic variability, phylogenetic relationships, and transmission dynamics were analyzed in 26 HIV-infected patients from Lebanon. Twenty-five specimens were identified as HIV-1 and one as HIV-2 subtype B. The 25 strains were classified into six env-C2-V3 HIV-1 subtypes: B (n = 10), A (n = 11), C (n = 1), D (n = 1), G (n = 1), and unclassifiable. Potential recombinants combining parts of viral regions from different subtypes Aenv/Dpol/Agag, Genv/Apol, and the unclassifiable-subtype(env)/unclassifiable-subtype(pol)/Agag were found in three patients. Epidemiologic analysis of travel histories and behavioral risks indicated that HIV-1 and HIV-2 subtypes reflected HIV strains prevalent in countries visited by patients or their sex partners. Spread of complex HIV-subtype distribution patterns to regions where HIV is not endemic may be more common than previously thought. Blood screening for both HIV-1 and HIV-2 in Lebanon is recommended to protect the blood supply. HIV subtype data provide information for vaccine development.

The development and evaluation of a probe hybridization method for subtyping HIV type 1 infection in Uganda.

We developed a method for large-scale screening of HIV-1 genotypic variation based on DNA probe hybridization. Nested PCR amplifications were performed to generate fragments in the env C2-V3 region and also in the gp41 region, which encompasses the immunodominant domain. The proviral DNA sequences were derived from 68 samples and phylogenetically analyzed. For comparison, the C2-V3 fragment was used in DNA probe hybridization to rapidly determine the infecting HIV subtype. The hybridizing probes were designed on the basis of the two most prevalent subtypes in Uganda, A and D. The results were compared to evaluate the feasibility of using this hybridization method for large-scale genotypic screening. Sequence analysis of the 68 amplified PCR fragments showed that 39 were subtype A and 29 were subtype D. The results of DNA hybridization to the amplified products with A and D subtype-specific probes were more than 90% concordant with the subtypes determined by sequence analysis. Our findings suggest that probe hybridization with subtype-specific probes is effective for large-scale screening of HIV-infected populations. Application of this method will significantly reduce the time needed for large, population-based investigations.

A molecular epidemiologic survey of HIV in Uganda. HIV Variant Working Group.

OBJECTIVE: Previous data, based on a small sampling of convenience, reported subtypes A, B, C, D, and G in Uganda, but neither the extent nor the proportion of these subtypes could be evaluated. To establish correctly the prevalence and distribution of HIV-1 subtypes, we analysed viral clades in 739 HIV-1-seropositive specimens from different areas of Uganda. METHODS: Blood specimens from 1100 patients were collected in five districts of Uganda. Within this collection, 929 HIV-1-seroreactive samples underwent analysis of viral DNA, and 739 were selected for further subtyping in env or pol regions. RESULTS: Using a combination of subtype A- and D-specific probes to C2-V3 region and DNA sequencing, HIV-1 env subtypes were determined in 594 specimens: 341 were of subtype A (57.4%), 250 of subtype D (42.1%), and three of subtype C (0.5%). Sixty-two samples showed reactivity with both probes, suggesting potential mixed infections, cross-reactivity to probes, or possibly other subtypes. Subsequent sequence analysis of 19 randomly selected specimens revealed subtypes A (n = 4), D (n = 12), and C (n = 3). Sequence analysis of the 27 samples chosen from the remaining 83 samples, which could be amplified only with viral gp41 or protease gene primers, classified them as subtypes A (n = 13) and D (n = 14). No significant clinical, demographic, or geographic differences were found between HIV-1 infections with viruses of subtypes A and D, despite considerable genetic diversity within these clades. CONCLUSIONS: This is the first major population-based study of the prevalent HIV-1 strains in an African country selected for vaccine trials. The subtyping methods we describe should be of use to investigators seeking to conduct large-scale screening for HIV variants in other populations.

Nurse-physician collaboration and satisfaction with the decision-making process in three critical care units.

OBJECTIVE: To assess and compare levels of nurse-physician collaboration and satisfaction with the decision-making process as reported by critical care nurses, resident physicians (residents), and attending physicians (attendings) in making decisions to transfer individual patients out of the critical care unit, and to assess if satisfaction predicts nurse retention. DESIGN: Longitudinal descriptive correlational study using self-reporting instruments. SETTINGS: A university hospital's surgical ICU, a community teaching hospital's medical ICU, and a community hospital's mixed ICU. SUBJECTS: Eighty-one nurses, 23 residents, and 37 attendings from the surgical ICU; 44 nurses and 51 residents from the medical ICU; 25 nurses and 45 attendings from the community hospital's ICU, reporting on the transfers of 473, 465, and 494 patients, respectively. MAIN OUTCOME MEASURES: Healthcare providers' reported levels of collaboration and satisfaction with the decision-making process, the correlations between collaboration and satisfaction, and nurse retention. RESULTS: Nurses and physicians within sites (except attendings from the surgical ICU) reported similarly moderate amounts of collaboration, but nurses reported less satisfaction with decision making than did physicians in all sites. Collaboration was related to satisfaction with decision making for all providers, but more strongly for nurses. The strength of the relationship for nurses was similar in all sites. Nurses' satisfaction with decision making did not predict their retention. CONCLUSIONS: Collaboration between nurses and physicians is a more important component of satisfaction with decision making for nurses than for physicians. Any interventions to change the amount of collaboration in practice must take account of this difference.

Rooming-in for elderly surgical patients.

Elderly patients are at risk for developing acute confusion during hospitalization. Rooming-in, an intervention frequently used for pediatric patients, was compared to usual care in a sample of 24 elderly patients hospitalized for orthopedic surgery. Although confusion during hospitalization, complicate rate, and length of stay did not differ between patients who did and did not have rooming-in, the family members and friends who roomed in were very satisfied with the experience. These findings suggest that rooming-in is feasible and highly satisfactory to the patient's family and/or friends.