Can we understand partnerships in general practice? A pilot study

BACKGROUND: Partnerships have been investigated in different professions,but other than identifying problems, little work has been carriedout on general practice. OBJECTIVE: The aim of this present study was to develop methods for studyingpartnerships in general practice. METHOD: A tripartite methodological approach was used, with questionnairesadapted from other instruments in use in other professions,followed by an individual interview with each partner, and non-participantobservation at a partnership meeting. Results for one case-studypartnership are given. RESULTS: There were no major differences between the partners on alldimensions measured; the minor differences indicated by theresults of the questionnaires were corroborated by the partnerinterviews and observations. CONCLUSIONS: We conclude that the use of such techniques could provide supportto partnerships going through significant periods of change. Keywords. General practice, interview, observation, partnerships, questionnaire.     

Influences on prescribing in non-fundholding general practices.

BACKGROUND: The experience from general practice fundholding suggests that financial incentives may influence prescribing; guidelines and hospital prescribing are two other suggested influences. AIM: A study was undertaken to establish general practitioners' attitudes to a financial prescribing incentive scheme, the presence and use of guidelines, and the influence of prescribing initiated within secondary care. METHOD: A postal questionnaire survey of non-fundholding general practices in the former Northern Region was conducted. RESULTS: Practices' thinking and subsequent decisions about the incentive prescribing scheme were most often influenced by discussions within the practice (45%). Those practices that achieved their savings under the incentive scheme were less likely than those not achieving savings to feel that the target was not achievable, the time scale was unacceptable, and that the philosophy behind the scheme was unacceptable. Forty-five per cent of practices received advice from neither a medical nor a pharmaceutical adviser; 27% of practices received advice from both, 12% from a medical adviser only and 16% from a pharmaceutical adviser only. Of the practices that tried to make their target savings, 91% intended to increase generic prescribing; fewer than one-third of practices mentioned any other measure. Prescribing guidelines were reported by a minority of practices, although reported rates of use were high when these were present. Clinical guidelines for three conditions, asthma, diabetes and hypertension, were present in more than 50% of practices; 25% of practices had no clinical guidelines. Hospital prescribing was reported as 'always' or 'usually' influencing prescribing for diabetes by 57% of respondents, ischaemic heart disease by 55%, peptic ulceration by 49%, asthma by 42% and hypertension by 39%. CONCLUSIONS: General practitioner prescribing is influenced by a complex web of factors, with no single factor pre-eminent. To understand this area further, there is a need to take each of these areas and ascertain the match between doctors' perceptions and actual practice.     

Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.     

Colorectal cancer extracellular acidosis decreases immune cell killing and is partially ameliorated by pH-modulating agents that modify tumor cell cytokine profiles

Tumor cells upregulate myriad proteins that are important for pH regulation, resulting in the acidification of the extracellular tumor microenvironment (TME). Abnormal pH is known to dampen immune function, resulting in a worsened anti-tumor immune response. Understanding how extrinsic alterations in pH modulate the interactions between immune cells and tumors cells will help elucidate opportunities for new therapeutic approaches. We observed that pH impacts the function of immune cells, both natural killer (NK) and T cells, which is relevant in the context of a highly acidic TME. Decreased NK and T cell activity was correlated with decreasing pH in a co-culture immune cell-mediated tumor cell-killing assay. The addition of pH-modulating drugs cariporide, lansoprazole, and acetazolamide to the co-culture assay was able to partially mitigate this dampened immune cell function. Treatment of colorectal cancer (CRC) cells with NHE1 inhibitor cariporide increased CRC cell-secreted cytokines involved in immune cell recruitment and activation and decreased cytokines involved in epithelial-mesenchymal transition (EMT). Cariporide treatment also decreased CRC cell shed TRAIL-R2, TRAIL-R3, and PD-L1 which is relevant in the context of immunotherapy. These experiments can help inform future investigations into how the pH of the tumor microenvironment may be extrinsically modulated to improve anti-tumor immune response in solid tumors such as colorectal cancer.     

Meta-analysis of surgery in advanced ovarian carcinoma: is maximum cytoreductive surgery an independent determinant of prognosis?

OBJECTIVE: If maximum cytoreductive surgery benefits the survival of women with advanced ovarian cancer, the median survival time of groups of such women will improve as the proportion of women undergoing maximum cytoreductive surgery is increased. STUDY DESIGN: Fifty-eight suitable studies that encompass 6962 patients with advanced ovarian cancer were identified. Multiple linear regression was used to analyze the effects on median survival time of the following variables: the proportion of each cohort undergoing maximum cytoreductive surgery, the use of platinum-containing chemotherapy, the dose intensity of chemotherapy, the proportion of each cohort with stage IV disease, and the year of publication of the study. RESULTS: Maximum cytoreductive surgery was associated with only a small improvement in median survival time, but platinum-containing chemotherapy improved median survival time substantially. Increased dose intensity also conferred a useful survival benefit. CONCLUSION: Cytoreductive surgery probably has only a small effect on the survival of women with advanced ovarian cancer. The type of chemotherapy used is more important.     

A comparison of cytology and cervicography in cervical screening

The sensitivity and specificity of cervical cytology and of cervicography in the detection of CIN and invasive cancer of the cervix were determined in a screening programme of an asymptomatic population of 418 women. Because all of the subjects were examined colposcopically and biopsies were taken from any suspicious areas, the presence or absence of disease was determined by the histology of directed cervical biopsies independently of the screening methods being tested. Cervicography correctly identified 24 of the 27 women with CIN or invasive cancer, whereas cytology detected only 14 (sensitivity of 0.89 vs. 0.52; P < 0.01). Cervicography detected CIN in 11 women with negative smears, six having CIN III. Only one case of CIN I was detected by cytology when cervicography was negative. Two cases of CIN II were not detected by either method. Inclusion in the analysis of the results from 23 women with technically defective cervigrams reduced the size of the difference in sensitivity, but it remained significant (0.74 vs. 0.48; P < 0.05). Cervicography was only slightly less specific than cytology (0.92 vs. 0.94; NS). Cervicography appears to be more effective than cytology in screening for cervical premalignancy but may be more demanding of those who perform the test.     

Simultaneous measurement of gallbladder emptying with cholescintigraphy and US during infusion of physiologic doses of cholecystokinin: a comparison

Both ultrasonography (US) and cholescintigraphy are used to study gallbladder dynamics. The present study was undertaken to determine whether the two methods provide the same or different information relating to gallbladder emptying. Emptying was simultaneously studied with both methods during infusion of graded physiologic doses of cholecystokinin (CCK) in six healthy subjects. Infusion of stepwise increasing doses of CCK, ranging from 0.03 to 0.5 Ivy dog units per kilogram of body weight per hour (IDU/kg.h), induced significant dose-related increases in plasma CCK, decreases in gallbladder volume assessed with US, and gallbladder emptying assessed with cholescintigraphy. The threshold dose for inducing significant gallbladder emptying was 0.13 IDU/kg.h, as determined with both techniques, indicating similar detection limits. There was a highly significant correlation between decreases in gallbladder volume and decreases in radioactive counts over the gallbladder region, with a tendency toward greater gallbladder responses at sonography during the early phase of gallbladder contraction and toward greater responses at cholescintigraphy during the later phase of gallbladder contraction. It is concluded that these methods can be used interchangeably for the quantitation of gallbladder emptying.