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The use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice.

IntroductionPembrolizumab is an established first-line option for patients with advanced non-small-cell lung cancer (NSCLC) expressing programmed death-ligand 1 ≥50%. Durable responses are seen in a subset of patients; however, many derive little clinical benefit. Biomarkers of the systemic inflammatory response predict survival in NSCLC. We evaluated their prognostic significance in patients receiving first-line pembrolizumab for advanced NSCLC.MethodsPatients treated with first-line pembrolizumab for advanced NSCLC with programmed death-ligand 1 expression ≥50% at two regional Scottish cancer centres were identified. Pretreatment inflammatory biomarkers (white cell count, neutrophil count, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, albumin, prognostic nutritional index) were recorded. The relationship between these and progression-free survival (PFS) and overall survival (OS) were examined.ResultsData were available for 219 patients. On multivariate analysis, albumin and neutrophil count were independently associated with PFS (P < 0.001, P = 0.002, respectively) and OS (both P < 0.001). A simple score combining these biomarkers was explored. The Scottish Inflammatory Prognostic Score (SIPS) assigned 1 point each for albumin 7.5 × 109/l to give a three-tier categorical score. SIPS predicted PFS [hazard ratio 2.06, 95% confidence interval (CI) 1.68-2.52 (P < 0.001)] and OS [hazard ratio 2.33, 95% CI 1.86-2.92 (P < 0.001)]. It stratified PFS from 2.5 (SIPS2), to 8.7 (SIPS1) to 17.9 months (SIPS0) (P < 0.001) and OS from 5.1 (SIPS2), to 12.4 (SIPS1) to 28.7 months (SIPS0) (P < 0.001). The relative risk of death before 6 months was 2.96 (95% CI 1.98-4.42) in patients with SIPS2 compared with those with SIPS0-1 (P < 0.001).ConclusionsSIPS, a simple score combining albumin and neutrophil count, predicts survival in patients with NSCLC receiving first-line pembrolizumab. Unlike many proposed prognostic scores, SIPS uses only routinely collected pretreatment test results and provides a categorical score. It stratifies survival across clinically meaningful time periods that may assist clinicians and patients with treatment decisions. We advocate validation of the prognostic utility of SIPS in this and other immune checkpoint inhibitor treatment settings.

Comparative studies were conducted on intertidal algal and faunal communities associated with Sargassum muticum and native algae on the Isle of Cumbrae, Scotland. Significant differences were detected in the structure and composition of the communities. The abundance of the dominant native algae Dictyota dichotoma was found to be reduced in areas dominated by S. muticum and displacement through competition for substrate or light is inferred. Elevated faunal abundances were associated with S. muticum and evidence indicates that increased detrital input may be a possible contributory factor. Differences in faunal community composition were most pronounced in the sessile epifauna below the S. muticum canopy. Faunal communities associated with S. muticum were less heterogeneous in composition than those associated with native algae at equivalent shore positions. Some of the compositional differences may be coincidental and attributable to factors favouring the establishment of S. muticum rather than to the direct influence of the S. muticum canopy.

This study used a geographically diverse sample to estimate the total cost of informal care and formal services for community-residing Alzheimer's disease (AD) care recipients. Baseline data were used for 1200 family caregivers from the Resources for Enhancing Alzheimer's Caregiver Health (REACH) study, a multisite intervention trial. The replacement-wage-rate approach estimated informal cost. Formal services were assigned a cost based on secondary sources. Annual cost per care recipient amounted to $23,436 for informal care and $8,064 for formal services. Variation in informal cost was almost entirely due to instrumental activities of daily living (IADLs) assistance. Cross-site differences in cost persisted after controlling for caregiver and care-recipient characteristics. Geographic variation may suggest regional preferences or ethnic/cultural values. Further study is needed to determine whether this reflects differences in access or availability or how including a control group for care recipients with nondementia diagnoses might have affected these findings.

Following standard treatment, the prognosis remains poor in patients with high-grade glioma and new therapies are urgently required. Herpes simplex virus 1716 (HSV1716) is an ICP34.5 null mutant that is selectively replication competent and shown to be safe and to replicate following injection into high-grade glioma. We demonstrate that following surgical resection, HSV1716 is safe when injected into the brain adjacent to excised tumour. In all, 12 patients with recurrent or newly diagnosed high-grade glioma underwent maximal resection of the tumour. HSV1716 was injected into eight to 10 sites around the resulting tumour cavity with the intent of infecting residual tumour cells. As clinically indicated, patients proceeded to further radiotherapy or chemotherapy. There has been no clinical evidence of toxicity associated with the administration of HSV1716. Longitudinal follow-up has allowed the assessment of overall survival compared to that of similar patients not treated with HSV1716. Three patients remain alive and clinically stable at 15, 18 and 22 months postsurgery and HSV1716 injection. Remarkably, the first patient in the trial, who had extensive recurrent disease preprocedure, is alive at 22 months since injection of HSV1716 and 29 months since first diagnosis. Imaging has demonstrated a reduction of residual tumour over the 22-month period despite no further medical intervention since the surgery and HSV1716 injection. In this study, we demonstrate that on the basis of clinical observations, there has been no toxicity following the administration of HSV1716 into the resection cavity rim in patients with high-grade glioma. The survival and imaging data, in addition to the lack of toxicity, give us confidence to proceed to a clinical trial to demonstrate efficacy of HSV1716 in glioma patients.

Objectives: To operationalize the measurement and interpretation of pharmaceutical underutilization using private insurance medical and drug claims data. This study also examined the relationship between underutilization of pharmaceuticals and patient outcomes. Design: Five definitions of pharmaceutical underutilization were used to identify underutilizers of 14 pharmaceuticals in a population of people aged 55 and over. Definitions 1 to 4 required the calculation of the apparent daily dose of the drug versus a standard dose. Definition 5 identified underutilization by the variation in apparent daily dose. Average monthly health services utilization figures were I compared among appropriate utilizers and both moderate and severe pharmaceutical underutilizers for each of the five definitions. Results: The most consistent results were found using Definition 5, variability in dosage. There were statistically significant (p Conclusion: Viewing noncompliance from the perspective of stability of consumption rather than the absolute value of the consumption may be a better predictor of increased health services utilization. Acknowledgments: This research was supported by the American Pharmaceutical Association and Marion Merrell Dow and performed at PharMark Corporation, Arlington, Va. The views and opinions in this paper are those of the authors, and no endorsement by the sponsors is intended or should be inferred. This paper was previously presented at the American Pharmaceutical Association Annual Meeting, March 20, 1994, Seattle, Wash.

Objectives The purpose of our study was to use health-related quality of life data from the Women's Health Initiative to calculate health-related utility weights and examine differences in these health utility weights across different hemoglobin (Hgb) levels. These utility weights could then be used in future cost-effectiveness studies. Methods Health utility weights were measured by the Short Form-6D (SF-6D), a health utility index derived from the Short Form Medical Outcomes questionnaire. Adjusted least square means were calculated for each level of Hgb at baseline and in longitudinal regression analysis the relationship between change in Hgb and change in the SF-6D was examined. Both baseline and longitudinal analyses were performed for all postmenopausal women and separately for those with self-reported heart failure, cancer, and osteoarthritis. Results Women with Hgb in the anemic range had lower health utility weights than those with higher Hgb levels. Longitudinally, a loss of of 2 g/dl Hgb or more was associated with a statistically significant and clinically meaningfully decline in SF-6D in all participants and also in the group of participants with cancer and osteoarthritis, but not in those with heart failure. Conclusions Lower levels of Hgb and a loss of Hgb are associated with a statistically significant and clinically meaningful decrement in health utility in all postmenopausal women we studied and also in those with chronic conditions.

This study compares the 12-month changes in substance use following admission to substance abuse treatment in Massachusetts between adolescents enrolled in Medicaid managed care and other publicly funded adolescents. Two hundred and fifty-five adolescents were interviewed as they entered substance abuse treatment and at 6 and 12 month follow-ups. Medicaid enrollment data were used to determine the managed care enrollment status. One hundred forty two (56%) adolescents were in the managed care group and 113 (44%) comprise the comparison group. Substance use outcomes include a count of negative consequences of substance use, days of alcohol use, days of cannabis use, and days of any substance use in the previous 30 days. Repeated measures analysis of covariance (ANCOVA) was used to assess change with time of measurement and managed care status as main effects and the interaction of time and managed care included to measure differences between the groups over time. Although several changes across time were detected for all four outcomes, we found no evidence of an impact of managed care for any of the outcomes. The results of our study do not support the fears that behavioral managed care, by imposing limits on services provided, would substantially reduce the effectiveness of substance abuse treatment for adolescents. At the same time, the results do not support those who believe that the continuity of care and improved resource utilization claimed for managed care would improve outcomes.

This study examines the influence of six patient characteristics (age, race, socioeconomic status, comorbiditics, mobility and presentational style) and two physician characteristics (medical specialty and years of clinical experience) on physicians' clinical decision making behaviour in the evaluation and treatment of an unknown and known breast cancer. Physicians' variability and certainty associated with diagnostic and treatment behaviour were also examined. Separate analyses explored the influence of these non-medical factors on physicians' cognitive processes. Using a fractional factorial design, 128 practising physicians were shown two videotaped scenarios and asked about possible diagnoses and medical recommendations. Results showed that physicians displayed considerable variability in response to several patient-based factors. Physician characteristics also emerged as important predictors of clinical behaviour, thus confirming the complexity of the medical decision-making process.

This article describes the total cost of care, including both informal caregiving and formal services for a cohort of disabled elderly living in the community. The cost of informal caregiving hours was calculated using a market value approach. The total annual cost of caring was estimated to be $9,600. Increased disability was associated with increased costs. High-cost elders were more likely to be severely disabled, live with their caregiver, and become institutionalized. For most elders, even the cost of a complete substitution of informal care for formal services, plus living expenses, was less costly than nursing home care.

I read with interest the article in the Archives regarding the exposure of internal medicine trainees to gynecology and obstetrics. 1 One question that was not addressed in detail was the reason that the educational process was deficient in these areas. As an internist who is frequently called on to act as a patient's provider of gynecologic care, as well as to consult on medical problems in obstetrics, I can appreciate the problem of teaching our future colleagues the skills that they will need. My experiences in training may shed some light on some of the problems involved. I was fortunate to attend a residency program where stress was placed on acquiring these skills. In our resident's clinic, we were not allowed to refer a patient to the gynecologic clinic for examination unless cleared by an attending physician. This forced us to become adept at gynecologic examination. In addition, a