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Biomedical subjects

Peter Harper

Publications and source records attributed to Peter Harper.

At least 19 recordsLinked to original sources
PubMed2006

The safety of trivalent influenza vaccine among healthy children 6 to 24 months of age.

OBJECTIVE: The objective of this study was to assess the safety of routine trivalent influenza vaccine (TIV) administration among healthy children 6 through 23 months of age, after the Advisory Committee on Immunization Practices recommendation. METHODS: The study was a retrospective case-control study of children receiving TIV in the first 2 seasons after the Advisory Committee on Immunization Practices recommendation. We assessed outcomes in the 42 days after vaccination in a population of 13,383 children. Each case subject was matched, according to age and gender, with 3 control subjects. Hazard ratios were calculated with conditional logistic regression analysis. RESULTS: We found no statistically significantly elevated hazard ratios for the first TIV dose. An elevated risk of pharyngitis was found for children receiving a second TIV dose. No elevated risk of seizure was found. CONCLUSION: These results, for a population of healthy children, showed no medically significant adverse events related to TIV among children 6 to 23 months of age.

Case-Control Studies↗
PubMed2005

Anaemia of cancer: impact on patient fatigue and long-term outcome.

Anaemia is the most common haematological abnormality encountered by cancer patients. A large European survey of cancer patients (n = 15,367) reported that 67% had anaemia at some point during the survey, and that over 60% of these patients did not receive any treatment for their anaemia. Two other surveys (the FATIGUE surveys) showed that over 75% of cancer patients experienced fatigue at least monthly, with over 30% reporting this symptom on a daily basis. Significantly, patients regarded fatigue as having a greater negative impact on their daily lives than many other cancer- or treatment-related complications, with important emotional and mental consequences including lack of self-motivation, sadness, frustration, and mental exhaustion. Indeed, fatigue was considered so debilitating, 12% of patients felt their quality of life (QoL) was so reduced that they did not wish to continue living. Anaemia is also recognised as an independent predictor of poor prognosis in cancer patients. A systematic review evaluating survival showed a 65% overall increase in the risk of mortality in cancer patients with anaemia. Increasing physicians' awareness of the importance of effectively treating anaemia in cancer patients therefore has the potential to improve prognosis as well as QoL.

Activities of Daily Living↗
PubMed2005

Health-related quality of life in patients undergoing drug therapy for advanced non-small-cell lung cancer.

Health-related quality of life (HRQoL) is increasingly recognized as an important outcome in the treatment of advanced non-small-cell lung cancer (NSCLC). This article reviews HRQoL data from a literature search that identified 32 randomized trials of conventional chemotherapy in patients with advanced NSCLC. In common with much of the research in this area, interpretation of the data from some trials was limited by weaknesses in data collection and reporting of HRQoL results. Nevertheless, the trials comparing chemotherapy with best supportive care consistently identified that some components of HRQoL improved with chemotherapy, despite the associated toxicity of many of the regimens used. Novel targeted therapies promise efficacy without the toxicity typically observed with conventional chemotherapy, and this article also reviews HRQoL data from trials of gefitinib (IRESSA), the first epidermal growth factor receptor tyrosine kinase inhibitor to have demonstrated prospectively defined, clinically meaningful improvements in disease-related symptoms and HRQoL in patients with advanced NSCLC. In all trials reviewed, HRQoL findings to date support the incorporation of well-validated measures of HRQoL and symptom improvement in all future trials of drug therapy in advanced NSCLC patients. Ideally, the trials should have a prospectively defined HRQoL hypothesis, include measures to improve compliance with HRQoL assessments, and address the clinical meaning of the HRQoL findings.

Antineoplastic Agents↗
PubMed2005

(Mis)alignments in counseling for Huntington's Disease predictive testing: clients' responses to reflective frames.

As a sequel to an earlier paper (Sarangi et al., 2004. J Genet Couns, 13(2), 135-155) examining genetic counselors' initiation of reflective frames, in this paper we analyze the variable ways in which clients respond to such reflective frames in the clinical setting. Of the six types of reflective questions identified, we focus on two types, which recur throughout the counseling protocol: (i) questions about clients' decisions to have genetic testing and (ii) questions exploring the potential impact of a positive or negative test result. The analytic focus here is on the mismatches surrounding clients' apparent readiness to discuss coping with the onset of disease (risk of disease) when they have been asked to discuss coping with genetic test results (risk of knowing). Our theoretical discussion is centered around the notion of alignment as a framework for locating the convergence and divergence of counselors' and clients' agendas in interaction. Drawing on detailed transcripts of 24 Huntington's Disease counseling consultations in South Wales, we analyze 119 counselor-client question-response sequences using the methodology of discourse analysis. Preliminary coding of clients' responses led us to identify three recurrent themes: (a) gaining knowledge as a basis for future action; (b) needing to know as a subjective necessity; and (c) downplaying what can be known. In a further analysis of extended data extracts, we draw attention to how clients display varying degrees of engagement with regard to the testing process and outcomes along the temporal and social axes. At one extreme, clients may take up the opportunity to engage in self-reflection, and thus endorse the legitimacy of the reflective frame. At the other extreme, clients may implicitly or explicitly challenge the relevance of self-reflection, and hence the usefulness of this counselor-initiated routine. We suggest that clients' varied response behaviors result from the perceived need of some clients to display their 'readiness' for predictive testing-an overarching 'meta-question' posed by the very existence of the counseling protocol.

Attitude to Health↗
PubMed2005

Combination therapy versus single agent chemotherapy in non-small cell lung cancer.

There is proven evidence of improved symptom control with platinum-based chemotherapy in the palliation of non-small cell lung cancer, and small but definite improvements in progression-free and overall survival when compared with best supportive care. The newer chemotherapy agents vinorelbine, gemcitabine, docetaxel and paclitaxel all have single agent activity, and in combination with cisplatin these provide superior quality of life and/or survival compared with the single agents, albeit with some increase in haematological toxicity. Doublet chemotherapy consisting of a new agent combined with platinum, cisplatin by preference where tolerated, has become the standard of care for advanced disease. The use of a functional assessment of fitness, rather than chronological age alone, is appropriate in the treatment of elderly patients. Although in this group there is evidence that doublets are superior to single agents, treatment should be undertaken with caution. In the second line setting where patients are unlikely to tolerate combination therapy, single agents have proven superiority over best supportive care. Patients with poor performance status (PS2) without comorbidity may tolerate combination therapy, but currently available evidence is insufficient to allow a definitive recommendation for combination or single-agent chemotherapy.

Antineoplastic Agents↗
PubMed2004

Syndromic surveillance for measleslike illnesses in a managed care setting.

Surveillance for measles must be enhanced to support the objective of measles elimination in the United States. Many conditions produce febrile rash illnesses that are clinically similar to measles; investigations of measleslike illnesses (MLIs) should occur regardless of the incidence of measles. Few data exist regarding the incidence of MLI in the United States, and it is unknown how providers evaluate patients with such conditions. We searched databases at a large managed care organization to obtain complete ascertainment of MLI during 1994-1998. Among 6000000 patient encounters, 68 records were identified that met the study case definition. The incidence of MLI was 4.5 cases/100000 persons/year. Measles diagnoses were considered by physicians for 9 patients (13.2%); 2 were laboratory-tested and reported to the state health department and the other 7 were given alternative diagnoses. It was not possible to determine for the remaining MLI patients whether measles was ruled out on clinical grounds or whether the possibility was not considered. Provider education regarding evaluation and reporting of measles is warranted. Databases at health care plans can be used to address public health issues and to establish syndromic surveillance for communicable diseases.

Databases, Factual↗
PubMed2004

A multicenter Phase I gene therapy clinical trial involving intraperitoneal administration of E1A-lipid complex in patients with recurrent epithelial ovarian cancer overexpressing HER-2/neu oncogene.

PURPOSE: HER-2/neu oncogene is overexpressed in 10-30% of epithelial ovarian cancers and is associated with a poor prognosis. The E1A gene product of adenovirus type 5 down-regulates HER-2/neu and causes tumor regression in animal models. In the current study, we sought to determine the toxicity and biological activity of E1A-lipid complex in ovarian cancer patients. EXPERIMENTAL DESIGN: A Phase I trial involving intraperitoneal (i.p.) administration of E1A-lipid complex was initiated in ovarian cancer patients to assess biological activity (E1A gene transfer/transcription/translation and HER-2/neu expression) and to determine the maximum tolerated dose. Successive cohorts received E1A-lipid complex at doses of 1.8, 3.6, and 7.2 mg DNA/m(2), given as weekly i.p. infusions for 3 of 4 weeks (each cycle) up to a maximum of six cycles. Peritoneal fluid was sampled at baseline and twice monthly for cellularity, cytology, CA-125, and biological activity RESULTS: Fifteen patients, with a median age of 57 years (range, 43-81) were recruited. Three (1.8 mg DNA/m(2)), 4 (3.6 mg DNA/m(2)), and 8 patients (7.2 mg DNA/m(2)) received i.p. E1A. A total of 91 infusions (range, 1-18) was administered. Abdominal pain was the dose-limiting toxicity, and the maximum-tolerated dose was 3.6 mg DNA/m(2). E1A gene transfer and expression was observed in all of the patients and at all of the dose levels. HER-2/neu down-regulation could be demonstrated in the tumor cells of 2 patients (18%). There was no correlation between dose and biological activity. CONCLUSIONS: I.P. EIA-lipid complex gene therapy is feasible and safe. Future studies, either alone or in combination with chemotherapy, particularly in patients with minimal residual disease, should be evaluated.

Abdominal Pain↗
PubMed2004

Initiation of reflective frames in counseling for Huntingtons Disease predictive testing.

Genetic professionals and clients are likely to assign different meanings to the extended format of the counseling protocols for predictive testing. In order to facilitate informed, client-centered decisions about the possibility of predictive testing, counselors routinely use the question format to initiate what we call "reflective frames" that invite clients to discuss their feelings and encourage them to adopt introspective and self-reflective stances toward their own experience--spanning the past, the present, and the hypothetical future. We suggest that such initiations of reflective frames constitute a key element of counselors' nondirective stance, although the exact nature of their formulations can be complex and varied. Examining 24 Huntington's Disease (HD) clinic sessions involving 12 families in South Wales with the tools of discourse analysis, our focus in this paper is twofold: (i) to propose a classification of six types of reflective questions (e.g. nonspecific invites, awareness and anxiety, decision about testing, impact of result, dissemination, and other) and to examine their distribution across the various clinic appointments, and (ii) to investigate the scope of these questions in terms of temporal and social axes. We link our analysis to the current debate within the genetic counseling profession about the merits of reflection- versus information-focused counseling styles and the need to abide by professionally warranted and institutionally embedded counseling protocols.

Adaptation, Psychological↗
PubMed2004

Chemotherapy of small cell lung cancer: state of the art.

PURPOSE OF REVIEW: Small cell lung cancer was termed chemosensitive with the introduction of combination chemotherapy in the 1970s. However, two decades of trials have seen little significant progress in achieving its "curable" potential. This paper presents an update of data recently published from phase 2 and phase 3 trials. RECENT FINDINGS: Platinum and etoposide combination chemotherapy remains the standard of care in small cell lung cancer. New agents, including irinotecan, may improve outcomes, but confirmatory trials are awaited. Triplet therapy, dose intensification, and maintenance therapy have not demonstrated meaningful survival improvements given the increased associated toxicity. Outcomes in limited-stage disease are optimized with the use of concurrent and early chemoradiation. New agents offering an improved toxicity profile for second-line therapy are emerging. SUMMARY: Small cell lung cancer remains an aggressive disease. Recent advances have yielded, at best, only modest gains. New strategies are required, including incorporation of novel targeted agents.

Antineoplastic Agents↗
PubMed2003

Surgical margins in cutaneous melanoma (2 cm versus 5 cm for lesions measuring less than 2.1-mm thick).

BACKGROUND: This study addressed the question of whether limited surgery for primary malignant melanoma with a 2-cm margin is as good as a 5-cm margin. An update of a 16-year follow-up is provided. METHODS: Nine European Centers, over a period of 5 years, prospectively randomized 337 patients with melanoma measuring less than 2.1 mm in thickness to undergo a local excision with either a 2-cm or a 5-cm margin. Three hundred twenty-six patients were eligible for statistical analysis. Excluded from the trial were patients older than 70 years; those with melanomas from the toe, nail, or finger; and those with acral-lentiginous melanoma. A separate randomization was performed to independently test an adjuvant treatment with a nonspecific immunostimulant, isoprinosine, compared with observation. The median follow-up time was 192 months (16 years) for the estimation of survival and disease recurrences. RESULTS: There were 22 tumor recurrences in the 2-cm arm and 33 in the 5-cm arm. The median time to disease recurrence was 43 months and 37.6 months, respectively. The 10-year disease-free survival rates were 85% for the group with a 2-cm margin and 83% for the group with a 5-cm margin. There was no difference in the 10-year overall survival rates (87% vs. 86%). Isoprinosine did not demonstrate any activity in this setting. CONCLUSIONS: The authors concluded that for melanoma less than 2.1-mm thick, a margin of excision of 2 cm is sufficient. A larger margin of 5 cm does not appear to have any impact on either the rate or the time to disease recurrence or on survival.

Adult↗
PubMed2003

Update on gemcitabine/carboplatin in patients with advanced non-small cell lung cancer.

Platinum-based chemotherapy regimens comprise a standard treatment approach for patients with advanced and metastatic non-small cell lung cancer (NSCLC). Based on results from randomized studies and meta-analyses, it has been established that such therapy significantly improves survival and maintains or improves quality of life relative to best supportive care. Combinations of cisplatin or carboplatin with gemcitabine, a newer-generation nucleoside antimetabolite with single-agent activity of 20% to 26% in advanced NSCLC, have shown antitumor activity and are well tolerated. In many studies in the advanced-disease setting, carboplatin has replaced cisplatin because of its improved nonhematologic toxicity profile and greater ease of administration. Encouraging results in the phase II setting have led to the design and implementation of several phase III studies of gemcitabine/carboplatin in the treatment of patients with advanced NSCLC. Results of three phase III trials involving more than 900 patients not previously treated with chemotherapy are discussed herein. These studies compared gemcitabine/carboplatin versus gemcitabine alone, gemcitabine/carboplatin versus gemcitabine/cisplatin, and gemcitabine/carboplatin versus mitomycin/ifosfamide/cisplatin (MIP), a regimen commonly used in Europe. Results show that gemcitabine/carboplatin efficacy was equivalent or superior to that achieved with single-agent gemcitabine or other platinum-based treatments. The regimen was well tolerated overall, and available data from one study show a significant improvement in quality of life. Thus, gemcitabine/carboplatin appears to be a viable option in the first-line treatment of advanced NSCLC. The results of one study reviewed suggest that gemcitabine/carboplatin can be considered for the treatment of patients over 70 years old.

Aged↗
PubMed2002

Multicenter phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer.

PURPOSE: This phase III study was designed to demonstrate equivalence in survival of oral uracil/tegafur (UFT) and oral leucovorin (LV) to conventional intravenous (IV) fluorouracil (5-FU) and LV in previously untreated metastatic colorectal carcinoma. Safety was also compared. PATIENTS AND METHODS: Eight hundred sixteen patients were randomized to receive either UFT (300 mg/m(2)/d) and LV (75 or 90 mg/d) for 28 days every 35 days or IV bolus 5-FU (425 mg/m(2)/d) and LV (20 mg/m(2)/d) for 5 days every 28 days. RESULTS: UFT/LV produced survival comparable to the IV 5-FU/LV regimen. Median survival was 12.4 months (95% confidence interval [CI], 11.2 to 13.6 months) with UFT/LV and 13.4 months (95% CI, 11.6 to 15.4 months) with 5-FU/LV (P =.630). The hazard ratio for survival was 0.964 (95.6% CI, 0.826 to 1.125), supporting equivalent survival. The overall response rate did not differ between treatment arms (UFT/LV, 11.7%; 5-FU/LV, 14.5%; P =.232). Median time to progression favored 5-FU/LV (UFT/LV, 3.5 months; 5-FU/LV, 3.8 months; P =.011), but tumor assessment schedules differed between arms. UFT/LV significantly improved safety compared with 5-FU/LV. Diarrhea, nausea and vomiting, and stomatitis and mucositis were significantly less frequent with UFT/LV, as was myelosuppression. Patients treated with UFT/LV had fewer episodes of febrile neutropenia (P <.001) and documented infections (P <.05). Increased bilirubin, without other liver function abnormalities, was observed more often with UFT/LV (P <.001). Concomitant medications were more frequent with 5-FU/LV, including use of antibiotics, growth factors, and antiemetics. CONCLUSION: UFT/LV provided a safer, more convenient oral alternative to a standard bolus IV 5-FU/LV regimen for metastatic colorectal cancer while producing equivalent survival.

Administration, Oral↗
PubMed2002

Mutations in TITF-1 are associated with benign hereditary chorea.

Benign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement disorder. The early onset of symptoms (usually before the age of 5 years) and the observation that in some BHC families the symptoms tend to decrease in adulthood suggests that the disorder results from a developmental disturbance of the brain. In contrast to Huntington disease (MIM 143100), BHC is non-progressive and patients have normal or slightly below normal intelligence. There is considerable inter- and intrafamilial variability, including dysarthria, axial dystonia and gait disturbances. Previously, we identified a locus for BHC on chromosome 14 and subsequently identified additional independent families linked to the same locus. Recombination analysis of all chromosome 14-linked families resulted initially in a reduction of the critical interval for the BHC gene to 8.4 cM between markers D14S49 and D14S278. More detailed analysis of the critical region in a small BHC family revealed a de novo deletion of 1.2 Mb harboring the TITF-1 gene, a homeodomain-containing transcription factor essential for the organogenesis of the lung, thyroid and the basal ganglia. Here we report evidence that mutations in TITF-1 are associated with BHC.

Amino Acid Sequence↗
PubMed2002

Influenza vaccination and chemotherapy: a shot in the dark?

Influenza infection is a potential cause of excess morbidity in patients who are immunosuppressed because of haemato-oncological malignancy or its treatment. Therefore vaccination against influenza is recommended in these patient groups. This systematic review of the literature and vaccine manafacturers' data assesses the current levels of knowledge concerning influenza vaccination in this patient group. There is a paucity of data, and the patient groups in the studies are heterogeneous. Serological responses are generally lower than expected in healthy controls and may be critically dependent on the timing of vaccination relative to chemotherapy. Antibody levels considered protective in healthy individuals may not prevent clinical infection in those with malignant disease. There are no data on protection from clinical infection. The vaccine appears to be well tolerated in this patient group. It is reasonable to offer vaccination to patients receiving treatment for haemato-oncological disorders. However, the degree of clinical protection afforded may be inferior to that experienced by healthy individuals. Further trials are warranted to assess the magnitude of benefit and optimal schedules of vaccination.

Antibodies, Viral↗
PubMed2002

Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patients.

PURPOSE: The primary objective of this study was to investigate the influence of renal impairment on the pharmacokinetics of capecitabine and its metabolites in cancer patients. Capecitabine (Xeloda) is an orally administered precursor of 5'-deoxy-5-fluorouridine (5'-DFUR), which is preferentially activated to 5-fluorouracil (5-FU) in tumors. METHODS: A total of 27 patients were enrolled, of whom 24 were evaluable for pharmacokinetics (6 with normal renal function, 8 with mild, 6 with moderate, and 4 with severe renal impairment at baseline). Patients received capecitabine orally at the standard dosing regimen (1250 mg/m(2) capecitabine twice daily for 2 weeks followed by a 1-week rest period). On study days 1 and 14, blood samples were collected to evaluate the pharmacokinetics of capecitabine and its metabolites. The relationship between the area under the plasma concentration-time curve (AUC) and creatinine clearance (CL(CR)) was assessed by log-linear regression analysis. RESULTS: The primary pharmacokinetic parameter with respect to the effect of renal dysfunction was systemic exposure to 5'-DFUR, 5-FU and FBAL determined on study day 14. Renal impairment led to an increase in the systemic exposure to 5'-DFUR and FBAL (23% and 109% increase in AUC, respectively) for a 50% reduction in CL(CR). By contrast, renal impairment may lead to decreased exposure to 5'-DFCR. There was no evidence for an effect of renal impairment on systemic exposure to 5-FU or capecitabine. Renal impairment did not have a major effect on peak concentration (C(max)) or elimination half-life (t(1/2)) of capecitabine, 5'-DFCR, 5'-DFUR, and 5-FU. However, in the case of FBAL, moderate or severe renal impairment caused up to a twofold increase in C(max) and prolongation of t(1/2). All patients with severe renal impairment (four patients) had drug-related grade 3 or 4 adverse-events (AEs) and serious AEs. Patients with moderate renal impairment experienced a similar number of grade 3 or 4 AEs (six of nine patients) but had a higher incidence of serious AEs (three of nine patients) when compared with those with normal renal function (four of six patients and one of six patients, respectively). A similar effect was seen in patients with mild renal dysfunction (grade 3 or 4 AEs in four of eight patients; serious AEs in three of eight patients). The relationship between systemic exposure to capecitabine or its metabolites and safety was investigated using logistic regression. This exploratory analysis showed a strong positive relationship between AUC of 5'-DFUR and treatment-related grade 3 or 4 AEs, whereas there was no relationship with exposure to capecitabine, 5'-DFCR, 5-FU or FBAL. CONCLUSIONS: Renal impairment has no effect on the pharmacokinetics of capecitabine or 5-FU, but leads to an increase in the systemic exposure to 5'-DFUR and FBAL. However, only the AUC of 5'-DFUR is correlated with safety. Based on the safety results in patients with severe renal impairment, a dose modification cannot be recommended for these patients and they should not be treated with capecitabine. Additional data from the clinical safety database and pharmacokinetic results from the present study support the recommendation that patients with moderate renal impairment should be treated with 75% of the recommended standard starting dose to achieve systemic exposure comparable to that in patients with normal renal function.

Antimetabolites, Antineoplastic↗