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Biomedical subjects

E Miller

Publications and source records attributed to E Miller.

At least 109 records · Page 6Linked to original sources
PubMed1999

Effects of perceived patient demand on prescribing anti-infective drugs.

BACKGROUND: Although patient demand is frequently cited by physicians as a reason for inappropriate prescribing, the phenomenon has not been adequately studied. The objectives of this study were to determine the prevalence of perceived patient demand in physician-patient encounters; to identify characteristics of the patient, physician and prescribing situation that are associated with perceived demand; and to determine the influence of perceived demand on physicians' prescribing behaviour. METHODS: An observational study using 2 survey approaches was conducted in February and March 1996. Over a 2-day period 20 family physicians in the Toronto area completed a brief questionnaire for each patient encounter related to suspected infectious disease. Physicians were later asked in an interview to select and describe 1 or 2 incidents from these encounters during which perceived patient demand influenced their prescribing (critical incident technique). RESULTS: Perceived patient demand was reported in 124 (48%) of the 260 physician-patient encounters; however, in almost 80% of these encounters physicians did not think that the demand had much influence on their decision to prescribe an anti-infective. When clinical need was uncertain, 28 (82%) of 34 patients seeking an anti-infective were prescribed one, and physicians reported that they were influenced either "moderately" or "quite a bit" by perceived patient demand in over 50% of these cases. Of the 35 critical prescribing incidents identified during the interviews, anti-infectives were prescribed in 17 (49%); the reasons for prescribing in these situations were categorized. INTERPRETATION: This study provides preliminary data on the prevalence and influence of perceived patient demand in prescribing anti-infectives. Patient demand had more influence on prescribing when physicians were uncertain of the need for an anti-infective.

Adolescent↗
PubMed1999

Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association.

BACKGROUND: We undertook an epidemiological study to investigate whether measles, mumps, and rubella (MMR) vaccine may be causally associated with autism. METHODS: Children with autism born since 1979 were identified from special needs/disability registers and special schools in eight North Thames health districts, UK. Information from clinical records was linked to immunisation data held on the child health computing system. We looked for evidence of a change in trend in incidence or age at diagnosis associated with the introduction of MMR vaccination to the UK in 1988. Clustering of onsets within defined postvaccination periods was investigated by the case-series method. FINDINGS: We identified 498 cases of autism (261 of core autism, 166 of atypical autism, and 71 of Asperger's syndrome). In 293 cases the diagnosis could be confirmed by the criteria of the International Classification of Diseases, tenth revision (ICD10: 214 [82%] core autism, 52 [31%] atypical autism, 27 [38%] Asperger's syndrome). There was a steady increase in cases by year of birth with no sudden "step-up" or change in the trend line after the introduction of MMR vaccination. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated. There was no temporal association between onset of autism within 1 or 2 years after vaccination with MMR (relative incidence compared with control period 0.94 [95% CI 0.60-1.47] and 1.09 [0.79-1.52]). Developmental regression was not clustered in the months after vaccination (relative incidence within 2 months and 4 months after MMR vaccination 0.92 [0.38-2.21] and 1.00 [0.52-1.95]). No significant temporal clustering for age at onset of parental concern was seen for cases of core autism or atypical autism with the exception of a single interval within 6 months of MMR vaccination. This appeared to be an artifact related to the difficulty of defining precisely the onset of symptoms in this disorder. INTERPRETATION: Our analyses do not support a causal association between MMR vaccine and autism. If such an association occurs, it is so rare that it could not be identified in this large regional sample.

Autistic Disorder↗
PubMed1999

Overview of recent clinical trials of acellular pertussis vaccines.

The evidence from pre-licensure studies does not suggest that there are clinically important differences in reactogenicity between acellular vaccines. The merits of different acellular products will therefore have to be compared on efficacy criteria. Ideally, acellular vaccines with the minimum antigen content necessary to ensure optimum protection should be used in order to avoid administration of superfluous antigens to children and to simplify licensing and batch release procedures. On the basis of the evidence so far available it seems unlikely that monocomponent pertussis toxin (PT) vaccines provide optimal protection and that multicomponent vaccines are needed to achieve a level of disease control that approaches that of a good whole-cell vaccine. It is unclear whether all two component vaccines containing PT and filamentous haemagglutinin (FHA) have similar efficacy but on the available evidence the safest option for policy makers would seem to be to use a vaccine with at least three components, PT+FHA+pertactin. There is now good evidence that the five component vaccine which contains agglutinogens 2 and 3 in addition to PT/FHA and pertactin provides the best protection and is the only acellular vaccine whose efficacy matches that of a good whole cell vaccine. However, the public health advantage of the five component vaccine over other acellular vaccines may not become apparent until they have been in routine use for some decades and their ability to protect against transmission as well as clinical pertussis has emerged. The decision to replace an effective whole-cell vaccine by an acellular vaccine for primary immunisation needs careful consideration. Apart from the probable sacrifice of efficacy for reduced reactogenicity (at least for vaccines which do not contain agglutinogens 2 and 3) there is the question of value for money and the ease with which acellular DTP vaccines can be combined with conjugate polysaccharide vaccines such as Haemophilus influenzae type b. Whatever the decision of policy makers, the need for continued follow up of trial cohorts and active surveillance of the efficacy and safety of those acellular vaccines that are introduced into routine use must be accorded a high priority.

Antigens, Bacterial↗
PubMed1999

Autosomal dominant osteosclerosis: report of a kindred.

Autosomal dominant osteosclerosis (ADO), a rare inherited craniotubular bone disorder, is a generalized hyperostosis that manifests itself as increased cortical thickening of the skull, mandible, metacarpals, metatarsals, long bones, vertebral bodies, ribs, and clavicles. Jaw abnormalities, which clinically resemble the widening and deepening of the mandible seen in cherubism, begin in childhood and have been reported to stabilize after puberty. Teeth and alveolar bone are normal. ADO must be distinguished from Van Buchem's disease, which is characterized by elevated serum alkaline phosphatase, neurologic complications, exopthalmos, periosteal excrescences, and an autosomal recessive pattern of inheritance, as well as from other craniotubular bone disorders such as osteopetrosis. We present clinical and radiographic documentation of members of a kindred representing 4 generations affected with ADO. At initial examination of the proband, a differential diagnosis included cherubism, fibrous dysplasia, osteopetrosis, and Paget's disease. Radiographic examination revealed extensive radiopacity of the inferior border and basal bone of the mandible. The proband's clavicles and humerus were also affected. All family members examined were similarly affected and had mandibular and palatal tori. Authors of a previously published report on the dental and dentoalveolar management of patients with craniotubular bone disorders have recommended prophylactic antibiotics to minimize risk of osteomyelitis in all such cases. The members of our kindred received extensive dental treatment before diagnosis, including extractions of severely carious teeth, preprosthetic dentoalveolar surgery, and endodontic therapy; there was no incidence of osteomyelitis or postsurgical complications. Therefore, the use of prophylactic antibiotics may not be warranted in patients with ADO who have otherwise normal medical histories.

Adult↗
PubMed1999

The prevalence of hepatitis B infection in adults in England and Wales.

Cost effectiveness analyses of alternative hepatitis B vaccination programmes in England and Wales require a robust estimate of the lifetime risk of carriage. To this end, we report the prevalence of infection in 3781 anonymized individuals aged 15-44 years whose sera were submitted in 1996 to 16 microbiology laboratories in England and Wales. One hundred and forty-six individuals (3.9%) were confirmed as anti HBc positive, including 14 chronic carriers (0.37%). The prevalence of infection and carriage was higher in samples collected in London and increased with age. No increased risk of infection was seen in sera from genito-urinary (GUM) clinics. Only 15 sera positive for hepatitis B were also positive for hepatitis C. Our results confirm the low prevalence of hepatitis B in England and Wales, are consistent with previous estimates of carriage and suggest that many infections were acquired while resident outside the UK. Future prevalence studies should determine the country of birth and other risk factors for each individual in order to confirm these findings.

Adolescent↗
PubMed1999

Bordetella pertussis surveillance in England and Wales: 1995-7.

Available data sources on disease due to Bordetella pertussis, including notifications, hospital admissions, deaths, and an enhanced laboratory-based surveillance system commenced in January 1994, were reviewed for the period 1995-7. Pertussis notifications continued their approximately 3-year cycle although at historically reduced levels. A slight seasonal increase in late summer/early autumn existed over and above a relatively constant background rate. Over time, the proportion of pertussis cases in younger, unvaccinated children, and to a lesser extent, adolescents and young adults, is increasing. There is a continuing significant and underreported mortality associated with pertussis in the very young age group. Disease due to serotype 1,2 is on the increase despite persistent high vaccination levels and this serotype causes more severe disease. The provision of preventative antibiotics prior to disease onset reduced the severity of the disease but its use remains uncommon in England and Wales. While overall levels of pertussis notifications have declined in recent times, vaccination efficacy wanes with increasing age, and pertussis remains a significant cause of mortality and severe morbidity in the very young. This could be reduced by timely booster vaccination and increased recognition of mild disease in older cases followed by early antibiotic therapy for the very young household contacts.

Adolescent↗
PubMed1999

Distinct endoplasmic reticulum signaling pathways regulate apoptotic and necrotic cell death following iodoacetamide treatment.

Environmental stress induces the synthesis of glucose-regulated proteins (Grps) in the endoplasmic reticulum (ER) and heat shock proteins (Hsps) in the cytoplasm. Iodoacetamide (IDAM), a prototypical alkyating agent, induces both Grp and Hsp synthesis in renal epithelial cells and causes necrosis which is prevented by prior activation of the ER stress response (pre-ER stress) [Liu, H., et al. (1997) J. Biol. Chem. 272, 21751-21759]. In this study, we examined the biochemical pathways leading to IDAM-induced apoptosis and investigated the role of the ER stress response in apoptotic cell death. The antioxidant N,N'-diphenyl-p-phenylenediamine (DPPD) prevented necrosis after IDAM treatment, but the cells went on to die with hallmarks of apoptosis, i.e., cell detachment, caspase-3 activation, cleavage of poly(ADP-ribose)polymerase (PARP), and DNA-ladder formation, all of which were blocked by the general caspase inhibitor zVAD. As with IDAM-induced necrosis, dithiothreitol protected against apoptosis, but cell permeable calcium chelators did not, suggesting that distinct biochemical pathways mediate these two forms of cell death. Pre-ER stress, but not heat shock, prevented IDAM-induced apoptosis. pkASgrp78 cells are deficient in Grp78 induction due to expression of a grp78 antisense RNA and are more sensitive to necrosis. However, these cells were resistant to IDAM-induced apoptosis and had increased basal levels of Grp94 and a KDEL-containing protein of about 50 kDa. Thus, the expression of grp78 antisense perturbs ER functions and activates expression of other ER stress genes accounting for the resistance to apoptosis. Taken together, the data describe functionally distinct signaling pathways through which the ER regulates apoptosis and necrosis caused by chemical toxicants.

Alkylating Agents↗
PubMed1999

The effect of oxygen on propofol-induced inhibition of microsomal cytochrome P450 3A4.

We have shown previously that both hypoxia and propofol may inhibit the metabolism of midazolam. We now wished to see whether there was any additive or synergistic effect when they occurred together. Microsomes were incubated with 20 microns midazolam for 60 min, and propofol 0, 50, 100 or 1000 microM was added. Incubates were further subdivided so that the environment contained 0, 10, 21 or 70% oxygen. The results confirmed our earlier study showing that propofol only had a significant inhibitory effect at a concentration greater than that seen clinically (1000 microM). Anoxia was the only environment in which significant depression of the metabolism of midazolam occurred at all concentrations of propofol. This reduced it to almost zero. Post hoc analysis of the data showed that, with the greatest concentration of propofol (1000 microM), there was increasing inhibition of metabolism of midazolam with increases of oxygen from 10 to 70%.

Anesthetics, Intravenous↗
PubMed1999

Conversion hysteria: is it a viable concept?

The notion of conversion hysteria is built around three assumptions to the effect that symptoms can arise without an adequate pathological base, that the patient experiences these symptoms as ''real'' in that they are not consciously feigned, and that psychological distress can be transformed or ''converted'' into physical symptoms. It is argued that the first of these assumptions is valid and that the truth of the second cannot be judged with adequate reliability to make it acceptable as a criterion for classification. The last assumption is questionable in that it is difficult to conceive of a satisfactory explanation as to how the process of conversion might operate.

Journal Article↗
PubMed1999

Meningococcal serogroup C conjugate vaccine is immunogenic in infancy and primes for memory.

The safety, immunogenicity, and immunologic priming of 2 dosages (2 microgram or 10 microgram) of a meningococcal C oligosaccharide-CRM197 conjugate vaccine was evaluated in 114 infants vaccinated at ages 2, 3, and 4 months. Antibody persistence and response to boosting with 10 microgram of meningococcal C polysaccharide were assessed. The meningococcal conjugate vaccine produced fewer local reactions than concurrent routine immunizations. Total serogroup C-specific immunoglobulin geometric mean concentration (GMC) increased from 0.3 microgram/mL before vaccination to 13.1 microgram/mL at age 5 months. Serum bactericidal antibody (SBA) geometric mean titers (GMTs) rose from <1:4 to 1:1057 at 5 months and fell by 14 months to 1:19. Following boosting, anti-C-specific immunoglobulin GMC rose to 15.9 microgram/mL and SBA GMT to 1:495. Antibody responses in the 10-microgram dose cohort were significantly higher at 5 months (P<.01) than in the 2-microgram dose cohort but were lower after polysaccharide boosting (P=.02). This meningococcal conjugate vaccine was well tolerated and immunogenic and induced immunologic memory in infants.

Bacterial Capsules↗
PubMed1999

The induction of immunologic memory after vaccination with Haemophilus influenzae type b conjugate and acellular pertussis-containing diphtheria, tetanus, and pertussis vaccine combination.

The significance of reduced antibody responses to the Haemophilus influenzae type b (Hib) component of acellular pertussis-containing combination vaccines (DTaP-Hib) is unclear. A DTaP-Hib vaccine evaluated in infants vaccinated at ages 2, 3, and 4 months showed reduced anti-Hib polysaccharide IgG (geometric mean concentration [GMC], 1.23 microgram/mL; 57%, >1.0 microgram/mL). Polyribitolribosyl phosphate (PRP) and Hib conjugate (PRP-T) vaccine given as a booster during the second year of life was evaluated for the presence of immunological memory. After boosting, most children achieved anti-PRP IgG >1.0 microgram/mL, although the GMC was higher with PRP-T (88.5 microgram/mL) than with PRP vaccine (7.86 microgram/mL, P<.001). The GMC of the PRP group was higher than anticipated for naive PRP recipients of the same age. PRP-specific IgG avidity was significantly higher after boosting than after priming, providing further evidence for the generation of memory. Despite reduced immunogenicity, DTaP-Hib combination vaccines appear to prime for immunologic memory.

Antibodies, Bacterial↗
PubMed1999

Guidance for control of parvovirus B19 infection in healthcare settings and the community.

Interventions for parvovirus B19 infection need to balance the low risk of infection at a population level with the potential for serious adverse outcome for particular groups, notably the fetus, people with haemoglobinopathies and the immunocompromised. This guidance aims to assist the local decision-making process to be as evidence-based as the available evidence allows.

Adolescent↗
PubMed1999

Improving computer skills to support hospital restructuring.

A vital part of restructuring in hospitals is a continuing effort to find ways to meet the growing demands of caregivers for efficient ways to enter and retrieve patient information. The process of effectively meeting these demands was coordinated through the leadership and efforts of the chief nurse executive and the information manager for nursing at New York Veterans Affairs Medical Center. These efforts resulted in timely support for restructuring, improvement in the development of competency skills among nursing staff, and increase in the use of electronic methods for documentation of patient care. Discussion of the changes implemented include approaches and content of training for computer skills development, a position description for an expanded role of a nurse in the field of informatics, and the facility's structure that fits a patient-centered care model.

Computer User Training↗
PubMed1999

Reengineering the role of a nurse manager in a patient-centered care organization.

The Department of Veterans Affairs Medical Center in New York City expanded the role of a nurse manager to a manager and leader of the interdisciplinary team within a structure reorganized to focus on patients. As the literature noted the critical nature of the role of a middle manager, an interdisciplinary team reached the consensus that a registered nurse with progressive clinical and head nurse experience should be the first-line manager in a patient-centered care organization. The process of reengineering the role of a Patient Care Team Coordinator (PCTC), the support systems designed to develop the new leadership role, and the benefits associated with the changes implemented are discussed. The functional statement for the PCTC's position is included, as well as an organizational structure to show how staff are grouped to promote the continuity and coordination of care provided to patients.

Continuity of Patient Care↗
PubMed1999

Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins.

We recently cloned monoclonal IgM autoantibodies which bind to epitopes of oxidized low-density lipoprotein (OxLDL) from apoE-deficient mice (EO- autoantibodies). We now demonstrate that those EO- autoantibodies that were originally selected for binding to copper-oxidized low-density lipoproteins (CuOx-LDL), also bound both to the oxidized protein and to the oxidized lipid moieties of CuOx-LDL. The same EO- autoantibodies showed specific binding to products of oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine (OxPAPC) and to the specific oxidized phospholipid, 1-palmitoyl-2-(5-oxovaleroyl)-phosphatidyl-choline (POVPC), whereas oxidation of fatty acids (linoleic or arachidonic acid) or cholesteryl esters (cholesteryl-oleate or cholesteryl-linoleate) did not yield any binding activity. Those EO- autoantibodies that bound to oxidized phospholipids (e.g., EO6) inhibited the binding and degradation of CuOx-LDL by mouse peritoneal macrophages up to 91%, whereas other IgM EO- autoantibodies, selected for binding to malondialdehyde (MDA)-LDL, had no influence on binding of either CuOx-LDL or MDA-LDL by macrophages. F(ab')2 fragments of EO6 were equally effective as the intact EO6 in preventing the binding of CuOx-LDL by macrophages. The molar ratios of IgM to LDL needed to maximally inhibit the binding varied from approximately 8 to 25 with different CuOx-LDL preparations. Finally, a POVPC-bovine serum albumin (BSA) adduct also inhibited CuOx-LDL uptake by macrophages. These data suggest that oxidized phospholipid epitopes, present either as lipids or as lipid-protein adducts, represent one class of ligands involved in the recognition of OxLDL by macrophages, and that apoE-deficient mice have IgM autoantibodies that can bind to these neoepitopes and inhibit OxLDL uptake.

Animals↗
PubMed1999

Efficacy of lithium vs. valproate in the treatment of mania in the elderly: a retrospective study.

BACKGROUND: This retrospective study was conducted to assess the efficacy of lithium and valproate and associated serum levels in the treatment of mania in elderly patients. METHOD: Records of 59 patients aged 55 years and older with minimal or no neurologic impairment, hospitalized for mania, and discharged on lithium (N = 30) or valproate (N = 29) therapy were reviewed. Data on mood stabilizer choice, serum levels, and type of mania were recorded. A clinician blinded to medications rated improvement in each case with Clinical Global Impressions (CGI) scores based on abstracted notes. RESULTS: Overall, the percentage of patients improved was significantly greater in the lithium group than in the valproate group (67% vs. 38%, chi2 = 4.88, p = .027). Patients taking lithium with serum levels > or =0.8 mmol/L were more improved at discharge than those outside this range (> or =0.8, CGI 2.0+/-0.6 vs. <0.8, CGI 2.6+/-0.8, t = 2.15, p = .043). Patients taking valproate with serum levels between 65-90 microg/mL were more improved at discharge than those outside this range (65-90, CGI 2.1+/-0.6 vs. <65, >90, CGI 3.3+/-0.8, t = 3.73, p = .002). When response rates among only patients with these "therapeutic" levels were assessed, they were similar for lithium (82%) and valproate (75%). The difference in efficacy between drugs was maintained in classic mania, but the 2 drug groups were similar when only mixed mania was analyzed (lithium 63% vs. valproate 67% improved). CONCLUSION: Results suggest that lithium may be more efficacious than valproate overall, but response rates for the 2 drugs were similar when "therapeutic" serum levels were achieved. For lithium, levels similar to those reported for younger adults were associated with response. For valproate, a "therapeutic window" different from that in younger adults was found. While the retrospective and naturalistic design of this study has limitations, these data may help direct further studies and treatment of mania in the elderly.

Age Factors↗