Phase I and pharmacokinetic study of tiazofurin (TCAR,NSC 286193) administered by continuous infusion

Summary Tiazofurin (2--D-ribofuranosylthiazole-4-carboxamide, TCAR) is a synthetic C-nucleoside that demonstrated significant in vivo activity against a variety of animal tumors as well as in vitro activity against human tumor-derived cell lines. Thirteen patients were treated with TCAR administered as a 5-day continuous infusion in this Phase I trial. Seventeen complete cycles were administered in three dose levels ranging from 550 to 1450 mg/M². Dose-limiting toxicities were myelosuppression and neurotoxicity including severe lethargy. Other toxicities including superficial skin peeling, myalgias, and tearing were seen at all doses. One patient had chest pain on day 4 resulting in stopping the drug, however, there was no evidence of cardiac or pericardial disease. Uric acid levels rose within one day in the absence of allopurinol treatment. There were no treatment related deaths. HPLC measurement of drug levels demonstrated steady-state plasma levels during the infusion, and a half-life following the infusion of 7.7 ± 0.6 hours. Minor abnormalities in renal function were associated with dramatic changes in pharmacokinetics and toxicity. No clinical responses were observed in this trial.Abbreviations TCAR Tiazofurin - HPLC High performance liquid chromatography - IMPD Inosine monophosphate dehydrogenase - WBC white blood cell - CPK creatine phosphokinase - C_ss steady-state concentration     

Perioperative transcutaneous oxygen monitoring in thoracic anaesthesia

Transcutaneous oxygen tension (PtcO2) was measured in 30 patients scheduled for elective pulmonary resection requiring one-lung ventilation during anaesthesia. Simultaneous PtcO2 and arterial oxygen tension (PaO2) measurements were taken preoperatively (preop), intraoperatively during two-lung endotracheal (ET) and one-lung endobronchial ventilation (EB), and postoperatively (postop). There was a significant correlation (r) between PtcO2 and PaO2 at all time periods: 0.97 (preop); 0.91 (ET); 0.83 (EB); 0.81 (postop). There were no significant differences among the transcutaneous oxygen indices (tcO2 index = PtcO2/PaO2) in the preop (0.69 +/- 0.09), ET (0.68 +/- 0.10) and postop (0.71 +/- 0.12) time period. The tcO2 index was significantly lower during one-lung anaesthesia (0.61 +/- 0.14). The PtcO2 was consistently lower than the corresponding PaO2 measurement, thus providing a continuous estimation of the "minimum" PaO2 level throughout anaesthesia and recovery. In four patients a marked drop in PtcO2 occurred just after the initiation of one-lung ventilation. In three, this was associated with arterial hypoxaemia and in one, haemodynamic compromise. In all four cases the PtcO2 was the first monitored parameter to change. As there is a substantial risk of developing hypoxaemia during thoracic anaesthesia, PtcO2 monitoring provides valuable early warning of impending hypoxaemia or haemodynamic compromise, thereby facilitating early therapeutic intervention.     

Patients' access to personal health information

Four physicians comment on an issue paper from the Department of Health and Social Security about provisions of the Data Protection Act that would permit patient access to computerized health records in 1987 unless the Secretary of State rules otherwise. S. Jenkins, a general practitioner, fears that patient access would refocus the record on the doctor's best interests rather than the patient's. C.J. Dickinson, a medical professor, welcomes access as fostering trust. M.A. Heasman, a health administrator, opposes unrestricted access but urges physicians to reveal more to patients. B.W. Ellis, a consultant surgeon, holds that patients have a right to see their records, subject to physician discretion in disclosing information to the patient's general practitioner or other third party. An interprofessional working group's "Statement on subject access to personal health information" rejects unrestricted access lest it inhibit health professionals from recording sensitive data.     

Psycho-Behavioural Segmentation in Food and Nutrition: A Systematic Scoping Review of the Literature

Inadequate dietary intakes are a key modifiable risk factor to reduce the risk of developing non-communicable diseases. To encourage healthy eating and behaviour change, innovative public health interventions are required. Social marketing, in particular segmentation, can be used to understand and target specific population groups. However, segmentation often uses demographic factors, ignoring the reasons behind why people behave the way they do. This review aims to explore the food and nutrition related research that has utilised psycho-behavioural segmentation. Six databases from were searched in June 2020. Inclusion criteria were: published 2010 onwards, segmentation by psycho-behavioural variables, outcome related to food or nutrition, and healthy adult population over 18 years. 30 studies were included; most were quantitative (n = 28) and all studies used post-hoc segmentation methods, with the tools used to segment the population varying. None of the segments generated were targeted in future research. Psycho-behavioural factors are key in understanding people’s behaviour. However, when used in post-hoc segmentation, do not allow for effective targeting as there is no prior understanding of behaviours that need to change within each segment. In future, we should move towards hybrid segmentation to assist with the design of interventions that target behaviours such as healthy eating.     

Malignant hyperthermia 2020

Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.     

Understanding the Link Between Adolescent Same-Gender Contact and Unintended Pregnancy: The Role of Early Adversity and Sexual Risk Behavior

Past research suggests an apparent paradox: Women who engage in same-gender sexual behavior show higher rates of unintended pregnancy than women with exclusive other-gender sexual behavior. Such women also have disproportionate rates of early adversity (both harshness, such as abuse or neglect, and unpredictability, such as father absence). We used the Add Health data (N?=?5,617 cisgender women) to examine the relative contributions of early adversity, adolescent same-gender sexual behavior, and general sexual risk behavior to women’s risks for adult unintended pregnancy. Women who engaged in adolescent same-gender sexual behavior were more likely to report childhood adversity, and both childhood adversity and adolescent same-gender behavior made independent contributions to subsequent rates of unintended pregnancy. The association between adolescent same-gender sexual behavior and adult unintended pregnancy was partially attributable to the fact that women with adolescent same-gender sexual behavior engaged in greater sexual risk behavior more broadly. These findings suggest that same-gender sexual behavior in adolescence may relate to a broader set of sexual risk behaviors that augment future risk for unintended pregnancy, independent of sexual identity. We draw on life history theory to explain this pattern of results and suggest directions for future research.

     

Cytological screening and management of abnormalities in prevention of cervical cancer: an overview with stochastic modelling.

AIMS--To develop a mathematical model of the histological changes of precancer and the development of invasive cancer and how these are related to cytological findings. To use this to investigate the effects on incidence of cervical cancer, number of smear tests and colposcopies, of different schedules for cervical screening, and the clinical management policies for dyskaryosis. METHODS--A stochastic model was developed relating the available data on tissue progression to the cytological findings. Two strategies, A and B, were compared: under A, women with any abnormal smear receive immediate colposcopy and treatment; under B, women with mild or borderline dyskaryosis have repeated smears at six monthly intervals with colposcopy only for persistent abnormalities. RESULTS--The model predicted an incidence of invasive cervical cancer in an unscreened population of women aged over 18 years of 5.9 per 10,000 per year. With 70% coverage and three yearly screening under strategy A, the incidence fell to 2.00 and under B to 2.10. The number of smears required was similar but A required two to three times as many colposcopies as B. Raising the coverage to 90% reduced the incidence to around 1 per 10,000 per year but changing the screening interval, the specificity or sensitivity of cytology had much less effect. CONCLUSION--The model has been tested under a wide range of possible variations in natural history, specificity and sensitivity of cytology. For low grade smear abnormalities, open colposcopic referral is predicted to reduce invasive cancer only slightly more than repeat cytology, at the expense of much additional colposcopy. Improving cytological coverage is suggested as more effective in reducing invasive cancer than increased use of colposcopy or more frequent screening.