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Biomedical subjects

K Guthrie

Publications and source records attributed to K Guthrie.

At least 19 recordsLinked to original sources

Interpreting the findings of the IMPROVE study.

Various findings of the Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers (IMPROVE) study are reviewed. Suggestions for future methodologies that will enhance this study are discussed. The IMPROVE study is one of the largest pharmaceutical care studies conducted. Although it was an intervention study that examined global outcomes following management by pharmacists, it was designed as an effectiveness study. Several new practice and research methods were developed, including a method to identify patients at high risk for drug-related problems utilizing pharmacy databases, a method to identify chronic diseases using pharmacy databases, a method to evaluate the structure and process for delivering pharmaceutical care in Veterans Affairs medical centers (VAMCs), and guidelines for providing care to patients in the IMPROVE study. Nine VAMCs participated in the study, and 1054 patients were randomized to either an intervention group (n = 523) or a control group (n = 531). Pharmacists documented a total of 1855 contacts with the intervention group patients and made 3048 therapy-specific interventions over the 12-month study period. There was no meaningful difference in patient satisfaction or quality of life in the two groups. Selected disease-specific indicators found an improved rate of measurement of hemoglobin A1c tests and better control of total and low-density-lipoprotein (LDL) cholesterol levels in the intervention group compared with the control group. Total health care costs increased in both groups over the 12-month period. The mean increase in costs in the intervention group was $1020, which was lower than the control group's value of $1313. The lessons learned from the IMPROVE study suggest to future investigators how to study and measure the effects of clinical pharmacy services on patient outcome.

Data Interpretation, Statistical↗

Can clinical pharmacists affect SF-36 scores in veterans at high risk for medication-related problems?

BACKGROUND: An objective of pharmaceutical care is for pharmacists to improve patients' health-related quality of life (HRQOL) by optimizing medication therapy. OBJECTIVES: The objective of this study was to determine whether ambulatory care clinical pharmacists could affect HRQOL in veterans who were likely to experience a drug-related problem. RESEARCH DESIGN: This was a 9-site, randomized, controlled trial involving Veterans Affairs Medical Centers (VAMCs). Patients were eligible if they met > or = 3 criteria for being at high risk for drug-related problems. Enrolled patients were randomized to either usual medical care or usual medical care plus clinical pharmacist interventions. HRQOL was measured with the SF-36 questionnaire administered at baseline and at 6 and 12 months. RESULTS: In total, 1,054 patients were enrolled; 523 were randomized to intervention, and 531 to control. After patient age, site, and chronic disease score were controlled for, the only domain that was significantly different between groups over time was the bodily pain scale, which converged to similar values at the end of the study. Patients' rating of the change in health status in the past 12 months was statistically different between groups, intervention patients declining less (-2.4 units) than control subjects (-6.3 units) (P < 0.004). This difference was not considered clinically meaningful. However, a dose-response relationship was observed for general health perceptions (P = 0.004), vitality (P = 0.006), and change in health over the past year (P = 0.007). CONCLUSIONS: These results suggest that clinical pharmacists had no significant impact on HRQOL as measured by the SF-36 for veterans at high risk for medication-related problems.

Aged↗

Reduced quality of life in veterans at risk for drug-related problems.

The relationships between drug therapy and health-related quality of life in 1054 patients who received care from Department of Veterans Affairs medical centers (VAMCs) were assessed. Patients at high risk for drug-related problems were enrolled into a pharmaceutical care study at nine VAMCs. On enrollment, the short form (SF)-36 was completed and medical records were examined for evidence of coexisting illness. Drug therapy in the year before enrollment was analyzed in relation to SF-36 scores. Mean +/- SD SF-36 scores ranged from 37.99+/-41.70 for role physical to 70.78+/-18.97 for mental health domains, with all domain scores significantly below age-adjusted national norms (p<0.05). Patients taking a drug that required therapeutic monitoring had significantly lower SF-36 scores (p=0.0001 to p=0.0033) across all domains except for bodily pain and mental health, compared with patients not taking these agents.

Adult↗

Odors regulate Arc expression in neuronal ensembles engaged in odor processing.

Synaptic activity is critical to developmental and plastic processes that produce long-term changes in neuronal connectivity and function. Genes expressed by neurons in an activity-dependent fashion are of particular interest since the proteins they encode may mediate neuronal plasticity. One such gene encodes the activity-regulated cytoskeleton-associated protein, Arc. The present study evaluated the effects of odor stimulation on Arc expression in rat olfactory bulb. Arc mRNA was rapidly increased in functionally linked cohorts of neurons topographically activated by odor stimuli. These included neurons surrounding individual glomeruli, mitral cells and transynaptically activated granule cells. Dendritic Arc immunoreactivity was also increased in odor-activated glomeruli. Our results suggest that odor regulation of Arc expression may contribute to activity-dependent structural changes associated with olfactory experience.

Animals↗

Characteristics and outcome of children with Beckwith-Wiedemann syndrome and Wilms' tumor: a report from the National Wilms Tumor Study Group.

PURPOSE: Children with Beckwith-Wiedemann syndrome (BWS) are at increased risk for developing Wilms' tumor (WT). We reviewed the National Wilms Tumor Study Group (NWTSG) records to assess clinical characteristics and outcome of patients with WT and BWS. METHODS: In the NWTSG, treating clinicians were asked to report, for each enrolled patient, whether the patient had BWS. Between 1980 and 1995, 4,669 patients were treated on two consecutive NWTSG protocols (NWTS 3 and NWTS 4). We retrospectively reviewed the clinical characteristics and treatment outcomes of BWS patients compared with patients with WT without BWS. RESULTS: Fifty-three children enrolled onto NWTS 3 and 4 were reported to have BWS. BWS patients were more likely to present with lower-stage tumors (P =.0001), with more than half (27 of 53) presenting with stage I disease. The overall treatment outcomes for the BWS patients were nearly identical to those without BWS, with overall survival at 4 years from diagnosis at 89% and 90%, respectively. Overall, 21% of the patients with BWS had bilateral disease, either at diagnosis (nine of 53) or as metachronous contralateral recurrence (two of 53). BWS patients enrolled onto NWTS 4 had smaller tumors than those enrolled onto NWTS 3 (P =.02), a trend not seen in the non-BWS patients. CONCLUSION: Like children without BWS, children with BWS and WT have an excellent prognosis with modern treatment regimens. There is a high risk of bilateral disease, and increasingly smaller tumors are being detected. This suggests that a national trial assessing the role of ultrasound screening followed by nephron-sparing surgery for some patients may be appropriate.

Beckwith-Wiedemann Syndrome↗

An economic analysis of a randomized, controlled, multicenter study of clinical pharmacist interventions for high-risk veterans: the IMPROVE study. Impact of Managed Pharmaceutical Care Resource Utilization and Outcomes in Veterans Affairs Medical Centers.

STUDY OBJECTIVE: To determine if clinical pharmacists could affect economic resource use and humanistic outcomes in an ambulatory, high-risk population. DESIGN: Prospective, randomized, controlled study. SETTING: Nine Veterans Affairs medical centers. PATIENTS: Patients who were at high risk for medication-related problems. INTERVENTION: Patients were randomized to usual medical care with input from a clinical pharmacist (intervention group) or just usual medical care (control group). MEASUREMENTS AND MAIN RESULTS: Of 1,054 patients enrolled, 523 were randomized to the intervention group and 531 to the control group. The number of clinic visits increased in the intervention group (p=0.003), but there was no difference in clinic costs. Mean increases in total health care costs were $1,020 for the intervention group and $1,313 for the control group (p=0.06). CONCLUSION: Including the cost of pharmacist interventions, overall health care expenditures were similar for patients randomized to see a clinical pharmacist versus usual medical care.

Aged↗

Clinical and economic impact of ambulatory care clinical pharmacists in management of dyslipidemia in older adults: the IMPROVE study. Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers.

We examined the impact of ambulatory care clinical pharmacist interventions on clinical and economic outcomes of 208 patients with dyslipidemia and 229 controls treated at nine Veterans Affairs medical centers. This was a randomized, controlled trial involving patients at high risk of drug-related problems. Only those with dyslipidemia are reported here. In addition to usual medical care, clinical pharmacists were responsible for providing pharmaceutical care for patients in the intervention group. The control group did not receive pharmaceutical care. Seventy-two percent of the intervention group and 70% of controls required secondary prevention according to the National Cholesterol Education Program guidelines. Significantly more patients in the intervention group had a fasting lipid profile compared with controls (p=0.021). The absolute change in total cholesterol (17.7 vs 7.4 mg/dl, p=0.028) and low-density lipoprotein (23.4 vs 12.8 mg/dl, p=0.042) was greater in the intervention than in the control group. There were no differences in patients achieving goal lipid values or in overall costs despite increased visits to pharmacists. Ambulatory care clinical pharmacists can significantly improve dyslipidemia in a practice setting designed to manage many medical and drug-related problems.

Aged↗

Types of interventions made by clinical pharmacists in the IMPROVE study. Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers.

The purpose of this study was to describe and evaluate the activities and interventions provided by ambulatory care clinical pharmacists during the IMPROVE (Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers) study. A total of 523 patients were randomized into the intervention arm at nine Veterans Affairs medical centers if they were considered to be at high risk for drug-related problems. Patients randomized to the control group had no interventions and they are not reported. Using a standard form, pharmacists were asked to document the length of visit, method of contact, medical conditions addressed, and drug-related problems addressed and resolved during each contact. Seventy-eight ambulatory care clinical pharmacists documented 1855 contacts over 12 months, an average of 3.54 +/- 2.31/patient. The length of visits was 15 minutes or more for 73% of contacts. In-person contacts accounted for 1421 visits (76.6%), with the remainder being telephone contacts. During each contact the average number of drug-related problems addressed and resolved were 1.64 +/- 1.16 and 1.14 +/- 0.98, respectively. More drug-related problems were addressed and resolved when visits were 15 minutes or longer (p=0.001) and when the contact was in person (p=0.001). These data may provide information to clinical pharmacists developing pharmacy-managed clinics for patients at high risk for drug-related problems. The information may be a benchmark for types of interventions that can be made, as well as the time commitments required to make them.

Aged↗

Randomised trial comparing a policy of early with selective amniotomy in uncomplicated labour at term.

OBJECTIVE: To compare two management policies: rupture of the fetal membranes when women are in normal labour or leave them intact as long as feasible. SETTING: The labour ward of a city university hospital. DESIGN: Automated randomised clinical trial. PARTICIPANTS: 1540 women in uncomplicated term labour. Data on labour duration, blood loss, oxytocin use and fetal condition were collected from 1132 women. Some data from nulliparous women has been presented earlier by the UK Amniotomy Group. MAIN OUTCOME MEASURES: Duration of labour, Apgar score, fetal morbidity and maternal morbidity including perineal injury, mode of delivery, epidural rates and the total number of vaginal examinations in the first stage of labour after amniotomy. INTERVENTIONS: Amniotomy at the next vaginal examination or amniotomy only if indicated. The median cervical dilatation at membrane rupture was 2 cm greater in the first group. RESULTS: A policy of routine amniotomy in labour had no measurable advantage over selective amniotomy for parous women (difference = 4 min) but shortened labour in nulliparous women by 1 h (Mann-Whitney U test: P < 0.05). There was a suggestion of a higher caesarean section rate (OR 1.9; 95% CI 0.9-3.5), and there were more vaginal examinations after membrane rupture in the group allocated routine amniotomy. There were no measurable differences in oxytocin use, fetal condition at birth, retained placenta rates, blood loss, pain or analgesia requirements. CONCLUSION: Routine amniotomy may shorten the first labour but not subsequent ones. There is a suggestion that routine surgical interference may be harmful by increasing the risk of caesarean section, and this agrees with data from other trials (common odds ratio 1.2; 95% CI 0.92-1.6).

Adult↗

Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion.

The synthetic peptides DP-107 and DP-178 (T-20), derived from separate domains within the human immunodeficiency virus type 1 (HIV-1) transmembrane (TM) protein, gp4l, are stable and potent inhibitors of HIV-1 infection and fusion. Using a computer searching strategy (computerized antiviral searching technology, C.A.S.T.) based on the predicted secondary structure of DP-107 and DP-178 (T-20), we have identified conserved heptad repeat domains analogous to the DP-107 and DP-178 regions of HIV-1 gp41 within the glycoproteins of other fusogenic viruses. Here we report on antiviral peptides derived from three representative paramyxoviruses, respiratory syncytial virus (RSV), human parainfluenza virus type 3 (HPIV-3), and measles virus (MV). We screened crude preparations of synthetic 35-residue peptides, scanning the DP-178-like domains, in antiviral assays. Peptide preparations demonstrating antiviral activity were purified and tested for their ability to block syncytium formation. Representative DP-178-like peptides from each paramyxovirus blocked homologous virus-mediated syncytium formation and exhibited EC50 values in the range 0.015-0.250 microM. Moreover, these peptides were highly selective for the virus of origin. Identification of biologically active peptides derived from domains within paramyxovirus F1 proteins analogous to the DP-178 domain of HIV-1 gp4l is compelling evidence for equivalent structural and functional features between retroviral and paramyxoviral fusion proteins. These antiviral peptides provide a novel approach to the development of targeted therapies for paramyxovirus infections.

Amino Acid Sequence↗

Effect of using protocols on medical care: randomised trial of three methods of taking an antenatal history.

OBJECTIVE: To compare the effectiveness of three methods of taking an antenatal history on the quality of obstetric care. DESIGN: Randomised controlled trial. SETTING: Antenatal clinic of St James's University Hospital, Leeds. SUBJECTS: 2424 women attending the hospital for the first (booking) visit. INTERVENTIONS: Histories were taken by midwives using an unstructured paper questionnaire, a structured paper questionnaire (incorporating a checklist), or an interactive computerised questionnaire (incorporating 101 clinical reminders). MAIN OUTCOME MEASURES: The number of clinical responses to factors arising from the antenatal booking history according to method of taking the history. Actions were categorised as medical and surgical, obstetric, personal, current symptoms and treatment, related to maternal age, and related to two common actions (cervical smear testing and dental hygiene) and were weighted for clinical importance by 10 obstetricians. RESULTS: Overall the unstructured questionnaire generated 1063 actions, the structured questionnaire 1146, and the computerised questionnaire 1122. The clinical importance of these actions was lowest for the unstructured questionnaire (overall total value score 1987 v 2182 and 2110 for the structured and computerised questionnaires respectively). The structured questionnaire was better than the computerised questionnaire in the medical and surgical (total value score 191 v 184), obstetric (275 v 241), and personal (430 v 360) categories but inferior in the current symptoms category (179 v 191). CONCLUSION: Structured questionnaires (computerised or paper) provide more and better information, and their use improves clinical response to risk factors. Computerised systems offer no further advantage in antenatal clinics.

Clinical Protocols↗

Use of colistin-polymyxin B-cellobiose agar for isolation of Vibrio vulnificus from the environment.

Colistin-polymyxin B-cellobiose agar was employed for the isolation of Vibrio vulnificus from shellfish. Isolates were examined phenotypically and with a gene probe and monoclonal antibody specific for V. vulnificus. Results indicated that colistin-polymyxin B-cellobiose agar is superior to both sodium dodecyl sulfate-polymyxin B-sucrose agar and thiosulfate-citrate-bile salts-sucrose agar in its ability to select and differentiate this species from background vibrios.

Agar↗

Viral and host cellular transcription in Autographa californica nuclear polyhedrosis virus-infected gypsy moth cell lines.

Infection of two gypsy moth cell lines (IPLB-Ld652Y and IPLB-LdFB) by the Autographa californica multiple-enveloped nuclear polyhedrosis virus (AcMNPV) is characterized by extremely attenuated viral protein synthesis followed by a total arrest of all viral and cellular protein production. In this study, AcMNPV- and host cell-specific transcription were examined. Overall levels of viral RNAs in infected gypsy moth cells were, at most measured times, comparable to RNA levels from an infected cell line (TN-368) permissive for AcMNPV replication. Northern blot (RNA) analyses using viral and host gene-specific probes revealed predominantly normal-length virus- and cell-specific transcripts postinfection. Transport of viral RNAs from the nucleus to the cytoplasm and transcript stability in infected gypsy moth cells also appeared normal compared with similar parameters for AcMNPV-infected TN-368 cells. Host cellular and viral mRNAs extracted from gypsy moth and TN-368 cells at various times postinfection and translated in vitro yielded similar spectra of host and viral proteins. Treatment of infected gypsy moth cells with the DNA synthesis inhibitor aphidicolin eliminated the total protein synthesis shutoff in infected IPLB-LdFB cells but had no effect on protein synthesis inhibition in infected IPLB-Ld652Y cells. The apparent selective block in the translation of viral transcripts early in infection and the absence of normal translation or transcription of host cellular genes at later times is discussed.

Animals↗