Women's colposcopy experience and preferences: a mixed methods study

<p>Abstract</p> <p>Background</p> <p>The colposcopy service is a key component in the UK Cervical Screening Programme. Over 120,000 women are referred to the service annually, however up to 25% of women fail to attend their appointment. Little is known about patients' preferences for colposcopic investigation and treatment. This study aims to investigate women's experience of colposcopy, to identify patients' preferences for aspects of appointments within the colposcopy service, and to make suggestions for service improvement.</p> <p>Methods/Design</p> <p>This study has been designed as a two stage, mixed method project. Stage one will involve in-depth interviews with new colposcopy patients to ascertain their experience of colposcopy services. This qualitative stage will generate factors thought to be important by service users in their experience. Stage two will utilise a choice based quantitative technique to identify women's preferences and determine the representativeness of factors generated through the interviews.</p> <p>The initial stage of in-depth interviews will be conducted with patients who are newly referred to colposcopy clinics to investigate the experience that they have of the referral process and appointment attendance. The outcome of these interviews will be analysed qualitatively using Framework analysis. Factors found to be important in women's experience will be extracted and used to construct a choice based questionnaire.</p> <p>The discrete choice experiment (questionnaire) will apply a best-worst technique through scenario-based questions to find women's relative preferences for different aspects of the service. It will be offered to women attending follow-up appointments at two colposcopy clinics in the West Midlands. Women will complete the questionnaire whilst they wait for their appointment, or, if they prefer, will take it home to complete in private. Women who do not attend their appointment will be posted the research information and questionnaire. The questionnaire analysis will use a weighted least squares regression technique for each best/worst pair. The accept/reject 'would you attend this appointment' question will be analysed using a random effects logit model.</p> <p>Discussion</p> <p>Colposcopy is a common procedure and one that is associated with raised anxiety among women experiencing the service. Little is known about women's experience of the service or their preferences for service delivery. The outcomes of the study will comprise a description of women's experience of colposcopy and establishing their preferences for how aspects of the service should be provided. Women's preferences will be fed back to service providers to enable improvements to the service to be made.</p

Dose escalation and pharmacokinetic study of a humanized anti-HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer

We conducted a phase I pharmacokinetic dose escalation study of a recombinant humanized anti-p185HER2 monoclonal antibody (MKC-454) in 18 patients with metastatic breast cancer refractory to chemotherapy. Three or six patients at each dose level received 1, 2, 4 and 8 mg kg–1 of MKC-454 as 90-min intravenous infusions. The first dose was followed in 3 weeks by nine weekly doses. Target trough serum concentration has been set at 10 μg ml–1 based on in vitro observations. The mean value of minimum trough serum concentrations at each dose level were 3.58 ± 0.63, 6.53 ± 5.26, 40.2 ± 7.12 and 87.9 ± 23.5 μg ml–1 respectively. At 2 mg kg–1, although minimum trough serum concentrations were lower than the target trough concentration with a wide range of variation, trough concentrations increased and exceeded the target concentration, as administrations were repeated weekly. Finally 2 mg kg–1 was considered to be sufficient to achieve the target trough concentration by the weekly dosing regimen. One patient receiving 1 mg kg–1 had grade 3 fever, one at the 1 mg kg–1 level had severe fatigue defined as grade 3, and one at 8 mg kg–1 had severe bone pain of grade 3. No antibodies against MKC-454 were detected in any patients. Objective tumour responses were observed in two patients; one receiving 4 mg kg–1 had a partial response in lung metastases and the other receiving 8 mg kg–1 had a complete response in soft tissue metastases. These results indicate that MKC-454 is well tolerated and effective in patients with refractory metastatic breast cancers overexpressing the HER2 proto-oncogene. Further evaluation of this agent with 2–4 mg kg–1 weekly intravenous infusion is warranted. © 1999 Cancer Research Campaig

Bacterial 16S rRNA/rDNA Profiling in the Liquid Phase of Human Saliva

Human saliva can be separated by centrifugation into cell pellet and cell-free supernatant, which are called cellular phase and liquid phase in this study. While it is well documented that the cellular phase of saliva contains hundreds of oral bacteria species, little is known whether the liquid phase of saliva contains any information related to oral microbiota. In this study, we analyzed the bacterial nucleic acid contents of the liquid phase of saliva. Using primers universal to most eubacterial 16S rDNA, we detected large amounts of bacterial 16S rRNA and rDNA in the cell-free phase of saliva. Random sequencing analysis of forty PCR amplicons from the cell-free phase of saliva led to 15 operational taxonomic unit (OTU) groups. Furthermore, using denaturing gradient gel electrophoresis (DGGE), we compared 16S rRNA/rDNA profiles derived from liquid phases and cellular phases of saliva samples, and found positive correlations (Pearson Correlation=0.822, P<0.001) between these sample groups. These findings indicate that the liquid phase of saliva contains numerous bacterial 16S rRNA/rDNA molecules that have correlations with bacteria existing in the cellular phase

A systematic review of physiological methods in rodent pharmacological MRI studies

Rationale: Pharmacological magnetic resonance imaging (phMRI) provides an approach to study effects of drug challenges on brain processes. Elucidating mechanisms of drug action helps us to better understand the workings of neurotransmitter systems, map brain function or facilitate drug development. phMRI is increasingly used in preclinical research employing rodent models; however, data interpretation and integration are complicated by the use of different experimental approaches between laboratories. In particular, the effects of different anaesthetic regimes upon neuronal and haemodynamic processes and baseline physiology could be problematic. Objectives: This paper investigates how differences in phMRI research methodologies are manifested and considers associated implications, placing particular emphasis on choice of anaesthetic regimes. Methods: A systematic review of rodent phMRI studies was conducted. Factors such as those describing anaesthetic regimes (e.g. agent, dosage) and parameters relating to physiological maintenance (e.g. ventilatory gases) and MRI method were recorded. Results: We identified 126 eligible studies and found that the volatile agents isoflurane (43.7 %) and halothane (33.3 %) were most commonly used for anaesthesia, but dosage and mixture of ventilatory gases varied substantially between laboratories. Relevant physiological parameters were usually recorded, although 32 % of studies did not provide cardiovascular measures. Conclusions: Anaesthesia and animal preparation can influence phMRI data profoundly. The variation of anaesthetic type, dosage regime and ventilatory gases makes consolidation of research findings (e.g. within a specific neurotransmitter system) difficult. Standardisation of a small(er) number of preclinical phMRI research methodologies and/or increased consideration of approaches that do not require anaesthesia is necessary to address these challenges

Potential of Optimal Preloading in Anti-CD20 Antibody Radioimmunotherapy: An Investigation Based on Pharmacokinetic Modeling

Recently, it has been suggested that the concept of preloading is limited by using a standard amount of unlabeled antibody. To identify the potential of optimal preloading, a pharmacokinetic model that describes the biodistribution of anti-CD20 antibody was developed. Simulations were conducted for different tumor burdens, spleen sizes, and tumor permeabilities. The optimal amount of unlabeled antibody was determined for each scenario. These simulations show that the currently administered standard amount is not optimal. A preload of 150 mg or lower would result in equal or higher tumor uptake in all cases. For tumors with high permeability, the uptake of labeled antibody could be increased by a factor of 8.5 using the considerably reduced optimal preload. The most sensitive parameter for the choice of the optimal amount of unlabeled antibody is the tumor uptake index. The results indicate that a personalized approach for radioimmunotherapy (RIT) with anti-CD20 antibody is required to account for the interpatient variability. The optimal amount of unlabeled antibody, which has to be determined by using a pharmacokinetic model, could substantially improve tumor uptake and thus RIT with anti-CD20 antibody