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Biomedical subjects

G Richardson

Publications and source records attributed to G Richardson.

At least 55 records · Page 3Linked to original sources

Evaluation of the role of the Parkinson's disease nurse specialist.

A one year follow up study of 108 randomised patients with Parkinson's disease at three centres was performed to investigate differences between care provided by the hospital based Parkinson's disease nurse specialist (PDNS) compared with the Consultant Neurologist (control). Only two (out of 22) differences were found where physical functioning and general health improved more in the control group. Provision of PDNS' for patients with Parkinson's disease cannot therefore be recommended solely on cost-effectiveness grounds because of similar outcomes but increased costs associated with the PDNS providing additional care. However medical and nursing specialists valued their complimentary expertise, and patient and carers responses to consultations also reflect that PDNS's have particular contributions. Aspects of care most valued by patients and carers and consultation interactions are discussed.

Activities of Daily Living↗

The effectiveness of intermediate care in a nursing-led in-patient unit.

In order to assess the potential for a nursing-led in-patient unit (NLIU) to substitute for a period of care in the acute hospital environment and promote recovery before discharge, a randomised controlled trial was conducted. The setting was an acute inner London hospital trust, part of the UK's national health service. Of patients referred to a NLIU from acute wards, 80 were randomly assigned to usual care (remain in normal hospital system) and 97 to the NLIU (nursing-led care with no routine medical involvement). Patients were identified as medically stable but in need of additional nursing intervention by referring medical staff prior to full nursing assessment of suitability. Outcomes compared included functional dependence (Barthel Index), discharge destination and length of hospital stay. Inputs from nursing, paramedical and medical staff were measured. There was no significant difference in functional independence at discharge (p0.05). Patients undergoing usual care stayed in hospital for less time (mean difference 18 days, p<0.01) but the same number of patients were in hospital 90 days after recruitment (23% NLIU, 24% usual care p0.05) due to re-admissions. The model of care implemented differed considerably from that described in the literature with the NLIU having significantly fewer qualified nurses (RNs). Although the anticipated benefits of the NLIU were not demonstrated, the study does not conclude that the model should be rejected. Factors driving length of stay need to be further investigated, as does the possibility of post-discharge benefits. The NLIU does offer some potential to substitute for acute care but also appears to substitute for a period of primary care.

Activities of Daily Living↗

Docetaxel effectively mobilizes peripheral blood CD34+ cells.

We prospectively evaluated docetaxel (100 mg/m2) with G-CSF (10 microg/kg S.C., daily) for mobilization efficiency in 26 patients with breast cancer. The minimum target yield was >4.5 x 10(6) CD34+ cells/kg (optimum = 9 x 10(6)/kg), sufficient to support the subsequent three cycles of high-dose therapy (HDT). The peak days for peripheral blood (PB) CD34+ cells were day 8 and day 9. Seven collections began on day 7, 16 on day 8 and three on day 9. The median peripheral blood progenitor cell (PBPC) CD34+ cell content ranged from 1.2 to 5.9 x 10(6)/kg per day during days 7 to 11 with a median CD34+ content of the total 72 PBPC collections of 3.4 x 10(6)/kg (0.07-15.6). Fifteen patients obtained a PBPC collection exceeding 5 x 10(6)/kg on a single day of collection. Following a median 3 days collection for each patient (range 2-4), the median total CD34+ for all individual sets of collections was 9.7 x 10(6)/kg (range 1.0-28.4). We were able to achieve the minimum CD34+ cell target yield in 22 of 26 patients with one cycle of mobilisation chemotherapy and in two of these patients a second collection yielded sufficient cells. Twenty-two patients have subsequently received repetitive HDT and PBPC transplantation with 57 cycles of HDT having been delivered. For all 57 cycles, the median time to absolute neutrophil count (ANC) >0.5 x 10(9)/l and 1.0 x 10(9)/l was 10 days (range 8-22) and 11 days (range 8-23), respectively. The median time to platelets greater than 20 x 10(9)/l, 50 x 10(9)/l and 100 x 10(9)/l was 13 days (range 11-23), 17 days (range 12-53) and 23 days (range 18-70), respectively. We conclude that docetaxel with G-CSF effectively mobilises PBPCs with apheresis needing to be commenced approximately 8 days after docetaxel administration.

Adult↗

Recurrent penicillin-resistant pneumococcal sepsis after matched unrelated donor (MUD) transplantation for refractory T cell lymphoma.

Patients who undergo splenectomy and recipients of allogeneic marrow (alloBMT) or peripheral stem cell transplantation are at increased risk of overwhelming infection from encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. As prophylaxis against these pathogens splenectomised patients are immunised and may also receive antibiotics for life. We report relapsing overwhelming sepsis caused by penicillin-resistant pneumococcus in a patient who was immunised and received prophylactic phenoxymethylpenicillin for 8 months following splenectomy and matched unrelated donor (MUD) marrow transplantation for refractory T cell lymphoma. No obvious focus of sepsis was found during any of the three episodes and S. pneumoniae serogroup 6, subtype 6B was isolated from blood cultures on each occasion. He was treated with i.v. cephalosporins, as the organisms were resistant to penicillin with a minimum inhibitory concentration (MIC) of 2.0, and there was complete resolution of symptoms each time. In the light of recurrent sepsis with this penicillin-resistant organism the decision was made to give prophylactic levofloxacin for the next 12 months. This case illustrates that the choice of prophylactic regimen and the treatment of sepsis in immunocompromised patients remain difficult and challenging issues.

Adult↗

Repetitive high-dose therapy with cyclophosphamide, thiotepa and docetaxel with peripheral blood progenitor cell and filgrastim support for metastatic and locally advanced breast cancer: results of a phase I study.

This phase I study was designed to determine the optimal dosages of a novel repetitive high-dose therapy regimen for patients with metastatic breast cancer (MBC). The planned treatment was three cycles of high-dose cyclophosphamide, thiotepa and docetaxel delivered every 35 days with progressive dose-escalation in successive cohorts. Each cycle was supported by peripheral blood progenitor cells (PBPC) and filgrastim. Eighteen patients were entered into this trial. Of the planned 54 treatment cycles, 44 were delivered and 11 patients completed all three cycles. The dose-limiting toxicities were interstitial pneumonitis and mucositis with moderately severe diarrhea (n = 3) and rash (n = 3). There were no treatment-related deaths. Of the 17 patients with evaluable disease, 16 patients responded with six patients achieving a complete remission and an additional four patients achieving no detectable disease (negative restaging including PET scan) but a persistently abnormal bone scan. At a median follow-up of 12 months, median progression-free survival was 11 months with the median overall survival not reached. The recommended doses for phase II/III studies are cyclophosphamide (4 g/m2), thiotepa (300 mg/m2) and docetaxel (100 mg/m2).

Adult↗

A phase II trial of paclitaxel and epirubicin in advanced breast cancer.

Initial trials of paclitaxel and doxorubicin in advanced breast cancer yielded high response rates but significant cardiac toxicity was observed. In this phase II trial we investigated the efficacy and safety of paclitaxel combined with epirubicin. Patients with advanced breast cancer, performance status 0-2, measurable disease, and a normal left ventricular ejection fraction, who may have received adjuvant chemotherapy were treated with epirubicin 75 mg m(-2) followed by a 3-h infusion of paclitaxel 175 mg m(-2) repeated every 3 weeks. Forty-three eligible patients were treated at six centres. 67% patients received the maximum of six cycles. The response rate was 54% (95% CI 38-69%), 12% CR and 42% PR. Estimated median progression-free survival was 6.9 months (95% CI 5.4-10.0) and estimated median overall survival was 17.9 months (95% CI 14.2-25.7). Four patients had a decrease in the left ventricular ejection fraction (LVEF) of > or =20% of baseline value, and in two patients the LVEF decreased to below the lower limit of normal, but no patient developed clinical evidence of cardiac failure. Grade 4 neutropenia occurred in 56% cycles, but only 4% of cycles were complicated by febrile neutropenia. Grade 3 or 4 non-haematologic toxicity was uncommon. In conclusion, paclitaxel 175 mg m(-2) and epirubicin 75 mg m(-2) is a well tolerated, promising regimen for the treatment of advanced breast cancer.

Adult↗

Doctors on tribunals. A confusion of roles.

BACKGROUND: Mental health review tribunals are required to apply legal criteria within a clinical context. This can create tensions within both law and psychiatry. AIMS: To examine the role of the medical member of the tribunal as a possible mediator between the two disciplines. METHOD: Observation of tribunal hearings and panel deliberations and interviews with tribunal members were used to describe the role of the medical member. RESULTS: The dual roles imposed on the medical member as witness and decision-maker and as doctor and legal actor create formal demands and ethical conflicts that are hard, in practice, either to meet or to resolve. CONCLUSIONS: The structure for providing tribunals with access to expert psychiatric input and advice requires reconsideration.

Commitment of Persons with Psychiatric Disorders↗

Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group. Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors.

PURPOSE: A phase III trial, Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors (CATAPULT I), was designed to determine the efficacy and safety of tirapazamine plus cisplatin for the treatment of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with previously untreated NSCLC were randomized to receive either tirapazamine (390 mg/m(2) infused over 2 hours) followed 1 hour later by cisplatin (75 mg/m(2) over 1 hour) or 75 mg/m(2) of cisplatin alone, every 3 weeks for a maximum of eight cycles. RESULTS: A total of 446 patients with NSCLC (17% with stage IIIB disease and pleural effusions; 83% with stage IV disease) were entered onto the study. Karnofsky performance status (KPS) was >/= 60 for all patients (for 10%, KPS = 60; for 90%, KPS = 70 to 100). Sixty patients (14%) had clinically stable brain metastases. The median survival was significantly longer (34.6 v 27. 7 weeks; P =.0078) and the response rate was significantly greater (27.5% v 13.7%; P <.001) for patients who received tirapazamine plus cisplatin (n = 218) than for those who received cisplatin alone (n = 219). The tirapazamine-plus-cisplatin regimen was associated with mild to moderate adverse events, including acute, reversible hearing loss, reversible, intermittent muscle cramping, diarrhea, skin rash, nausea, and vomiting. There were no incremental increases in myelosuppression, peripheral neuropathy, or renal, hepatic, or cardiac toxicity and no deaths related to tirapazamine. CONCLUSION: The CATAPULT I study shows that tirapazamine enhances the activity of cisplatin in patients with advanced NSCLC and confirms that hypoxia is an exploitable therapeutic target in human malignancies.

Adult↗

A review of impacted permanent maxillary cuspids--diagnosis and prevention.

As impacted permanent maxillary cuspids occur in 1-2% of the population, the general dentist should know the signs and symptoms of this condition and the interceptive treatment. Features of buccal or palatal cuspid impaction include lack of canine bulges in the buccal sulcus indicating a lingual eruption path and possible impaction; lack of symmetry between the exfoliation and eruption of cuspids that may indicate palatal or lingual impaction; and abnormal mesiodistal location and angulation of the developing maxillary permanent cuspids on radiographs. Diagnosis of impacted cuspid teeth at age 8-10 years can significantly reduce serious ramifications, including surgical exposure and orthodontic alignment as well as root resorption of the lateral incisors. In specific cases, extraction of the primary maxillary cuspids can prevent impaction of the permanent maxillary cuspids and additional sequelae.

Child↗

Would removing indoor air particulates in children's environments reduce rate of absenteeism--a hypothesis.

To conduct a controlled trial to test the ability of a newly developed electrostatic air cleaning technology (EAC) to improve Indoor Air Quality (IAQ) as defined by levels of airborne particles and to investigate the potential to reduce non-attendance rates due to illness among children in two Swedish day care centres. The EAC technology was shown to significantly reduce the indoor particulate load for very fine particles caused by outdoor air pollution by 78% and to reduce the number of fine particles produced indoors by 45%. To test the hypothesis, non-attendance was followed in two centres during 3 years. The EAC technology was in operation during year 2. Non-attendance rates among children in the larger day-care centre decreased by 55%, equalling those levels noted in family-based day care. It is speculated that the air cleaning effect may be due to alterations in electrostatic forces operating within the room enabling fine particulate matter to more easily become and stay airborne. The EAC technology is cost-efficient and might be a way forward to improve IAQ.

Absenteeism↗

Behavioural management in nursing and residential homes: a randomised controlled trial.

BACKGROUND: As more and more elderly people are being cared for in residential and nursing homes, how best can their psychiatric needs be met? We report on evaluation of a behavioural intervention by an old-age psychiatry hospital outreach team. METHODS: This randomised controlled trial of a training and education intervention over 6 months was done in south Manchester, UK. 12 matched nursing and residential homes were randomised to the control or intervention group and within each, the staff selected 10 residents whose behavioural problems made them difficult to care for. Care staff in the intervention homes attended seminars from the hospital outreach team and received weekly visits from a psychiatric nurse to assist in developing care planning skills. The main outcome measures were cognitive impairment and depression, behavioural disturbance, and functional ability, assessed by the geriatric mental state schedule, Crichton Royal behaviour rating scale, and Barthel index, respectively. FINDINGS: Residents in the intervention group had significantly improved scores for depression (before-and-after change difference -0.5 [95% CI -0.8 to -0.1]) and for cognitive impairment (-0.7 [-1.1 to -0.2]) but not for behaviour rating or Barthel index. INTERPRETATION: Elderly residents can benefit from improved quality of care achieved by training from a hospital outreach team.

Aged↗

Chemiluminescent detection of oxidants in vascular tissue. Lucigenin but not coelenterazine enhances superoxide formation.

Lucigenin-amplified chemiluminescence has frequently been used to assess the formation of superoxide in vascular tissues. However, the ability of lucigenin to undergo redox cycling in purified enzyme-substrate mixtures has raised questions concerning the use of lucigenin as an appropriate probe for the measurement of superoxide production. Addition of lucigenin to reaction mixtures of xanthine oxidase plus NADH resulted in increased oxygen consumption, as well as superoxide dismutase-inhibitable reduction of cytochrome c, indicative of enhanced rates of superoxide formation. Additionally, it was revealed that lucigenin stimulated oxidant formation by both cultured bovine aortic endothelial cells and isolated rings from rat aorta. Lucigenin treatment resulted in enhanced hydrogen peroxide release from endothelial cells, whereas exposure to lucigenin resulted in inhibition of endothelium-dependent relaxation in isolated aortic rings that was superoxide dismutase inhibitable. In contrast, the chemiluminescent probe coelenterazine had no significant effect on xanthine oxidase-dependent oxygen consumption, endothelial cell hydrogen peroxide release, or endothelium-dependent relaxation. Study of enzyme and vascular systems indicated that coelenterazine chemiluminescence is a sensitive marker for detecting both superoxide and peroxynitrite.

Acetylcholine↗

The ankle-link antigen: an epitope sensitive to calcium chelation associated with the hair-cell surface and the calycal processes of photoreceptors.

A monoclonal antibody, mAb E40, that specifically recognizes hair cells and photoreceptors was derived from a mouse immunized with a membrane fraction prepared from the sensory maculae of the chick inner ear. In the mature chick inner ear, punctate labeling is observed along each stereocilium, but staining is mostly concentrated around the basal end of the sensory hair bundles, where it is closely associated with surface specializations known as ankle links. The epitope recognized by mAb E40 is therefore referred to as the ankle-link antigen (ALA). During early embryogenesis, the ALA is initially distributed evenly over the surface of the hair bundle. As development proceeds, it becomes more restricted to the base of the hair bundle, although a spot of the ALA remains associated with the bundle tip until just before hatching. In the eye, mAb E40 stains the calycal processes of photoreceptors. When maculae and retinae are treated with the calcium chelator BAPTA at room temperature, the ALA disappears. BAPTA-induced loss of the ALA from the hair-bundle surface is substantially reduced by lowering the temperature to 2 degrees C. The ALA and ankle links reappear on the hair-bundle surface when cells are cultured for 20 hr after BAPTA treatment. BAPTA sensitivity and recovery after BAPTA-induced loss are properties similar to those described for the tip link, a surface structure thought to gate the mechanotransducer channel. However, unlike the tip link, the ALA and ankle links are sensitive to subtilisin treatment. The results define a new component of the hair-bundle surface, with properties both common to and distinct from those of the tip link.

Animals↗

Repetitive high-dose therapy with ifosfamide, thiotepa and paclitaxel with peripheral blood progenitor cell and filgrastim support for metastatic and locally advanced breast cancer: results of a phase I study.

BACKGROUND: This phase I study was designed to determine the optimal dosages of a novel repetitive high-dose therapy regimen for patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: The planned treatment was three cycles of high-dose ifosfamide, thiotepa and conventional-dose paclitaxel delivered every 28 days with progressive dose-escalation in successive cohorts. Each cycle was supported by peripheral blood progenitor cells (PBPC) and filgrastim. RESULTS: Twenty-three patients were entered into this trial. Of the planned 69 treatment cycles, 59 were delivered and fifteen patients completed all three cycles. The dose-limiting toxicities were renal tubular acidosis, encephalopathy, mucositis and enterocolitis. There was one treatment-related hemorrhagic death. CONCLUSIONS: The recommended doses for phase II or III studies are ifosfamide (10 g/m2), thiotepa (350 mg/m2) and paclitaxel (175 mg/m2).

Adult↗

Ifosfamide in combination with paclitaxel or doxorubicin: regimens which effectively mobilize peripheral blood progenitor cells while demonstrating anti-tumor activity in patients with metastatic breast cancer.

For patients with metastatic breast cancer (MBC) who undergo high-dose therapy with autologous peripheral blood progenitor cell (PBPC) transplantation, an important prerequisite is a mobilization regimen that efficiently mobilizes PBPCs while producing an effective anti-tumor effect. We prospectively evaluated ifosfamide-based chemotherapy for mobilization efficiency, toxicity and disease response in 37 patients. Patients received two cycles of the ifosfamide-based regimen; ifosfamide (5 g/m2 with conventional-dose cycle and 6 g/m2 with mobilization cycle) with either 50 mg/m2 doxorubicin (if limited prior anthracycline and/or progression more than 12 months after an anthracycline-based regimen) or 175 mg/m2 paclitaxel. For the mobilization cycle, all patients received additional G-CSF (10 microg/kg SC, daily) commencing 24 h after completion of chemotherapy. The target yield was >6x10(6) CD34+ cells/kg, sufficient to support the subsequent three cycles of high-dose therapy. The mobilization therapy was well tolerated and the peak days for peripheral blood (PB) CD34+ cells were days 10-13 with no significant differences in the PB CD34+ cells mobilization kinetics between the ifosfamide-doxorubicin vs. ifosfamide-paclitaxel regimens. The median PBPC CD34+ cell content ranged from 2.9 to 4.0x10(6)/kg per day during days 9-14. After a median of 3 (range 1-5) collection days, the median total CD34+ cell, CFU-GM and MNC for all 44 individual sets of collections was 9.2x10(6)/kg (range 0.16-54.9), 37x10(4)/kg (range 5.7-247) and 7.3x10(8)/kg (range 2.1-26.1), respectively. The PBPC target yield was achieved in 35 of the 37 patients. The overall response rate for the 31 evaluable patients was 68% with 10% having progressive disease. Thirty-three patients have subsequently received high-dose therapy consisting of three planned cycles of high-dose ifosfamide, thiotepa and paclitaxel with each cycle supported with PBPCs. Rapid neutrophil and platelet recovery has been observed. Ifosfamide with G-CSF in combination with doxorubicin or paclitaxel achieves effective mobilization of PBPC and anti-tumor activity with minimal toxicity.

Adult↗

Identifying, evaluating and implementing cost-effective skill mix.

BACKGROUND: The British National Health Service (NHS) employs a large number of individuals, at great monetary cost, to provide direct care to patients. Changes in the combinations of staff, including nurses, nurse practitioners and midwives, delivering this care have been shown to be effective in many settings. FINDINGS: The (opportunity) cost implications of such changes in the skill mix are rarely evaluated adequately. The impact of releasing professionals' time has not been estimated and therefore determining whether changes are cost-effective is difficult; these difficulties have often been increased by poor study design. CONCLUSIONS: Economic evaluation has been under-utilized in studies of skill mix. If economic evaluation demonstrates that skill mix changes reduce cost and improve or maintain patient outcomes, this is strong evidence that these changes should be implemented. Incentives may be required to attract the necessary personnel. This in itself may influence the cost of changing the skill mix and therefore the situation should be monitored as both costs and effectiveness can alter over time.

Clinical Competence↗

Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer.

PURPOSE: This phase III study compared docetaxel and doxorubicin in patients with metastatic breast cancer who had received previous alkylating agent-containing chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive an intravenous infusion of docetaxel 100 mg/m(2) or doxorubicin 75 mg/m(2) every 3 weeks for a maximum of seven treatment cycles. RESULTS: A total of 326 patients were randomized, 165 to receive doxorubicin and 161 to receive docetaxel. Overall, docetaxel produced a significantly higher rate of objective response than did doxorubicin (47.8% v 33.3%; P =.008). Docetaxel was also significantly more active than doxorubicin in patients with negative prognostic factors, such as visceral metastases (objective response, 46% v 29%) and resistance to prior chemotherapy (47% v 25%). Median time to progression was longer in the docetaxel group (26 weeks v 21 weeks; difference not significant). Median overall survival was similar in the two groups (docetaxel, 15 months; doxorubicin, 14 months). There was one death due to infection in each group, and an additional four deaths due to cardiotoxicity in the doxorubicin group. Although neutropenia was similar in both groups, febrile neutropenia and severe infection occurred more frequently in the doxorubicin group. For severe nonhematologic toxicity, the incidences of cardiac toxicity, nausea, vomiting, and stomatitis were higher among patients receiving doxorubicin, whereas diarrhea, neuropathy, fluid retention, and skin and nail changes were higher among patients receiving docetaxel. CONCLUSION: The observed differences in activity and toxicity profiles provide a basis for therapy choice and confirms the rationale for combination studies in early breast cancer.

Adult↗

Skill mix changes: substitution or service development?

An extensive review of published studies where doctors were replaced by other health professions demonstrates considerable scope for alterations in skill mix. However, the studies reported are often dated and have design deficiencies. In health services world-wide there is a policy focus which emphasises the substitution of nurses in particular for doctors. However, this substitution may not be real and increased roles for non-physician personnel may result in service development/enhancement rather than labour substitution. Further study of skill mix changes and whether non-physician personnel are being used as substitutes or complements for doctors is required urgently.

Clinical Competence↗