Assessing the application of continuity of care indices in the last year of life: a retrospective population-based study.

Context: Most people spend the majority of their last year of life at home or in a home-like setting, receiving outpatient healthcare. Increasing numbers of physicians and teams, including palliative care providers, may become involved in care in addition to a usual provider such as a family physician. Continuity of care (CoC) near the end of life, although considered a marker of quality of care, may be interrupted despite the provision of high-quality care. Objective: To describe continuity of outpatient physician care in the last 12 months of life and determine patient and illness-related factors associated with high continuity. Study Design: Retrospective cohort study. Datasets: Linked population-based health administrative databases for Ontario, Canada, held at ICES. Population: Decedents aged 19 years or older, who died between January 1, 2013, and December 31, 2017. Outcome Measures: Continuity of care scores for the last 12 months of life, using the Usual Provider continuity (UPC), Bice-Boxerman continuity (CoC), and Sequential Continuity (SECON) indices. Multivariate models were used to determine factors associated with higher continuity scores (>= 0.75). Results: Decedents (n=322,445) were on average 76.3 years of age, 47.8% were female, and 13.2% resided in rural regions. Decedents had a mean of 16.2 outpatient physician encounters in the last year of life, from a mean of 3.8 different physician specialties. Mean continuity indices' scores (1 being perfect) were low: UPC= 0.36, CoC= 0.31, and SECON= 0.37. Proportions of decedents with high continuity were: UPC= 12.6%, CoC= 9.6%, and SECON= 12.9%. Decedents who experienced a terminal illness (i.e., cancer) end-of-life trajectory were least likely to experience high UPC (OR= 0.32; 95% CI= 0.30, 0.34). Having six or more comorbidities (OR= 0.65; 95% CI= 0.63, 0.66), and being in the highest quintile of outpatient physician encounters (i.e., >22 visits) (OR= 0.28; 95% CI= 0.27, 0.29) were also negatively associated with high UPC. Results were similar for other indices. Conclusions: Decedents experience low continuity of outpatient physician care in the last year of life, especially those with cancer, comorbidities, and frequent physician visits. Modifications to existing indices may be needed to serve as end-of-life care quality indicators.

Pharmacokinetic interaction between taxanes and amiodarone leading to severe toxicity.

ADVERSE EVENT: A drug interaction leading to severe skin and mucosal toxicity. DRUGS IMPLICATED: Paclitaxel, docetaxel and amiodarone. THE PATIENT: A 77-year-old woman with a history of hypertension, hyperlipidemia, and palpitations, managed with amiodarone, was treated for HER2-positive invasive ductal breast cancer with paclitaxel and trastuzumab as an adjunct to surgery. EVIDENCE THAT LINKS THE DRUG TO THE EVENT: There was a strong temporal relationship between the taxane therapy and the development of severe skin and mucosal toxicity due to an unexpected reduction in taxane clearance. MANAGEMENT: Initially, conversion of paclitaxel to docetaxel, then cessation of docetaxel, symptomatic treatment, rehydration and placement of a nasogastric tube. MECHANISM: Increased exposure to paclitaxel and subsequently docetaxel due to interaction with amiodarone was suspected and confirmed on pharmacokinetic sampling. Analysis of two blood samples taken 9 and 10 days after docetaxel revealed plasma levels of 4.73 and 4.09 ng ml-1 , respectively, leading to a 79% decreased individual (Bayesian maximum a posteriori) clearance estimate of 9.15 l h-1 , corresponding to an estimated fivefold increase in AUC. Paclitaxel was also present in these samples (20 and 21 days after the last administration). IMPLICATIONS FOR THERAPY: Amiodarone inhibits cytochrome P450 (CYP) isoforms 2C8 and 3A4 as well as P-glycoprotein (P-gp) for which taxanes are substrates. However, interactions with amiodarone are not specified in the prescribing information. Clinicians should be aware of this interaction, particularly in an ageing population, where more patients requiring taxanes may already be receiving amiodarone for a comorbid cardiac condition.

Vemurafenib-induced radiation recall dermatitis: case report and review of the literature.

The cutaneous effects of BRAF (serine/threonine protein kinase B-raf) inhibitors such as vemurafenib remain poorly defined. Rash, squamous cell carcinoma, keratoacanthoma and photosensitivity are the most common grade 2 or 3 adverse events observed in clinical trials. We here report the case of a patient with a BRAF V600E mutated metastatic melanoma who developed severe radiation recall dermatitis 6 weeks after completing radiotherapy. Vemurafenib treatment had been initiated 1 week before the development of dermatitis because of rapidly progressing disease. Upon topical treatment of the affected skin areas, clinical symptoms regressed over a period of 2 months, although vemurafenib was continuously administered. As our case goes in line with other reports, we believe that physicians should be aware of this additional cutaneous side effect of vemurafenib and that continuation of the treatment is safe when close clinical control and interdisciplinary management can be provided.

Cetuximab in metastatic squamous cell cancer of the skin: a Swiss case series.

BACKGROUND: There is current evidence that non-melanoma skin cancers can be successfully treated with cetuximab. OBJECTIVE: To evaluate the use and efficacy of cetuximab (with or without radiotherapy) in a series of previously treated patients with metastatic squamous cell cancer of the skin (SCCS) in Switzerland. METHODS: We performed a retrospective analysis of six patients from four centers. Endpoints were disease control rates (DCRs) at 4-8 weeks, 12-14 weeks and 20-36 weeks of treatment. Treatment-related toxicity was evaluated additionally. RESULTS: A median of 14 cycles of cetuximab were applied. DCR was 67% at 4-8 weeks, 50% at 12-14 weeks and 33% at 20-36 weeks. In 4-8 weeks responders, mean relapse-free time was 12 ± 6.2 months and mean overall survival was 25 ± 16.2 months. Grade I-III acne-like rash developed around week 3 of treatment in 83%. CONCLUSIONS: Cetuximab treatment in patients with metastatic SCCS achieved an overall DCR of 67% at 4-8 weeks of treatment. This study underlines the current evidence that SCCS can be successfully treated with cetuximab.

[Fever with chemotherapy induced neutropenia]. / Fieber bei chemotherapie-assoziierter Neutropenie.

Cancer patients under chemotherapy are at high risk for neutropenia. If fever occurs in this situation an oncologic emergency is underway. Patient should receive immediate basic diagnostic procedures and broad-spectrum antibiotics have to be initiated. Definition of febrile neutropenia (FN) encloses oral temperature of > 38.3 °C or two consecutive readings of > 38.0 °C one hour apart and an absolute neutrophil count of < 0.5 × 109/l. FN management requires immediate action and therefore needs patient education and standard operating procedures in the clinical setting. Treatment strategies depend on risk factors and symptoms of the patient. Instruments, mainly the Multinational Association for Supportive Care (MASCC), can predict low and high risk situations and are useful tools in clinical practice. Low-risk patients can either be treated by oral or short term intravenous antibacterial therapy with an early change to an oral protocol (oral treatment recommendation: Quinolone with amoxicillin/clavulanic acid). Hospital admission is recommended in low-risk patients but outpatient management has become increasingly appealing in selected cases due to costs, reduction in nosocomial infections and patient's convenience. High-risk patients should always be admitted to the hospital and broad-spectrum intravenous antibiotics should be commenced promptly (intravenous treatment recommendation: anti-pseudomonas cephalosporin. Local epidemiologic bacterial isolate and resistance patterns are important since MRSA or other resistances should be covered). Duration of treatment depends on neutrophil count, patient's symptoms and fever. Evaluation should be done on a daily basis. If fever continues after 48 - 72 hours, antibiotic rotation and/or antifungal therapy may be needed.

End-of-life interventions in patients with cancer.

OBJECTIVES: To describe variations in the receipt of potentially inappropriate interventions in the last 100 days of life of patients with cancer according to patient characteristics and cancer site. METHODS: We conducted a population-based retrospective cohort study of cancer decedents in Ontario, Canada who died between 1 January 2013 and 31 December 2018. Potentially inappropriate interventions, including chemotherapy, major surgery, intensive care unit admission, cardiopulmonary resuscitation, defibrillation, dialysis, percutaneous coronary intervention, mechanical ventilation, feeding tube placement, blood transfusion and bronchoscopy, were captured via hospital discharge records. We used Poisson regression to examine associations between interventions and decedent age, sex, rurality, income and cancer site. RESULTS: Among 151 618 decedents, 81.3% received at least one intervention, and 21.4% received 3+ different interventions. Older patients (age 95-105 years vs 19-44 years, rate ratio (RR) 0.36, 95% CI 0.34 to 0.38) and women (RR 0.94, 95% CI 0.93 to 0.94) had lower intervention rates. Rural patients (RR 1.09, 95% CI 1.08 to 1.10), individuals in the highest area-level income quintile (vs lowest income quintile RR 1.02, 95% CI 1.01 to 1.04), and patients with pancreatic cancer (vs colorectal cancer RR 1.10, 95% CI 1.07 to 1.12) had higher intervention rates. CONCLUSIONS: Potentially inappropriate interventions were common in the last 100 days of life of cancer decedents. Variations in interventions may reflect differences in prognostic awareness, healthcare access, and care preferences and quality. Earlier identification of patients' palliative care needs and involvement of palliative care specialists may help reduce the use of these interventions at the end of life.

Physician home visits to rostered patients during their last year of life: a retrospective cohort study.

BACKGROUND: Physician home visits are associated with better health outcomes, yet most patients near the end of life never receive such a visit. Our objectives were to describe the receipt of physician home visits during the last year of life after a referral to home care - an indication that the patient can no longer live independently - and to measure associations between patient characteristics and receipt of a home visit. METHODS: We conducted a retrospective cohort study using linked population-based health administrative databases housed at ICES. We identified adult (aged ≥ 18 yr) decedents in Ontario who died between Mar. 31, 2013, and Mar. 31, 2018, who were receiving primary care and were referred to publicly funded home care services. We described the provision of physician home visits, office visits and telephone management. We used multinomial logistic regression to calculate the odds of receiving home visits from a rostered primary care physician, controlling for referral during the last year of life, age, sex, income quintile, rurality, recent immigrant status, referral by rostered physician, referral during hospital stay, number of chronic conditions and disease trajectory based on the cause of death. RESULTS: Of the 58 753 decedents referred in their last year of life, 3125 (5.3%) received a home visit from their family physician. Patient characteristics associated with higher odds of receiving home visits compared to office-based or telephone-based care were being female (adjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 1.21-1.35), being 85 years of age or older (adjusted OR 2.42, 95% CI 1.80-3.26) and living in a rural area (adjusted OR 1.09, 95% CI 1.00-1.18). Increased odds were associated with home care referrals by the patient's primary care physician (adjusted OR 1.49, 95% CI 1.39-1.58) and referrals occurring during a hospital stay (adjusted OR 1.20, 95% CI 1.13-1.28). INTERPRETATION: A small proportion of patients near the end of life received home-based physician care, and patient characteristics did not explain the low visit rates. Future work on system- and provider-level factors may be critical to improve access to home-based end-of-life primary care.

Physician continuity of care in the last year of life in community-dwelling adults: retrospective population-based study.

OBJECTIVE: To describe the timing of involvement of various physician specialties over the last year of life across different levels of primary care physician continuity for differing causes of death. METHODS: We conducted a retrospective cohort study of adults who died in Ontario, Canada, between 1 January 2013 and 31 December 2018, using linked population level health administrative data. Outcomes were median days between death and first and last outpatient palliative care specialist encounter, last outpatient encounter with other specialists and with the usual primary care physician. These were calculated by tertile of score on the Usual Provider Continuity Index, defined as the proportion of outpatient physician encounters with the patient's primary care physician. RESULTS: Patients' (n=395 839) mean age at death was 76 years. With increasing category of usual primary care physician continuity, a larger proportion were palliative care generalists, palliative care specialist involvement decreased in duration and was concentrated closer to death, the primary care physician was involved closer to death, and other specialist physicians ceased involvement earlier. For patients with cancer, palliative care specialist involvement was longer than for other patients. CONCLUSIONS: Compared with patients with lower continuity, those with higher usual provider continuity were more likely to have a primary care physician involved closer to death providing generalist palliative care.

Describing settings of care in the last 100 days of life for cancer decedents: a population-based descriptive study.

BACKGROUND: Few studies have described the settings cancer decedents spend their end-of-life stage, with none considering homecare specifically. We describe the different settings of care experienced in the last 100 days of life by individuals with cancer and how settings of care change as they approached death. METHODS: A retrospective cohort study from January 2013 to December 2017, of decedents whose primary cause of death was cancer, using linked population-level health administrative datasets in Ontario, Canada. RESULTS: Decedents 125,755 were included in our cohort. The average age at death was 73, 46% were female, and 14% resided in rural regions. And 24% died of lung cancer, 7% breast, 7% colorectal, 7% pancreatic, 5% prostate, and 50% other cancers. In the last 100 days of life, decedents spent 25.9 days in institutions, 25.8 days receiving care in the community, and 48.3 days at home without any care. Individuals who died of lung and pancreatic cancers spent the most days at home without any care (52.1 and 52.6 days), while individuals who died of prostate and breast cancer spent the least days at home without any care (41.6 and 45.1 days). Regardless of cancer type, decedents spent fewer days at home and more days in institutions as they approached death, despite established patient preferences for an end-of-life experience at home. CONCLUSIONS: In the last 100 days of life, cancer decedents spent most of their time in either institutions or at home without any care. Improving homecare services during the end-of-life may provide people dying of cancer with a preferred dying experience.

Inpatient Palliative Care Is Associated with the Receipt of Palliative Care in the Community after Hospital Discharge: A Retrospective Cohort Study.

Background: For hospitalized patients with palliative care needs, there is little evidence on whether postdischarge outcomes differ if inpatient palliative care was delivered by a palliative care specialist or nonspecialist/generalist. Objective: To evaluate relationships between inpatient palliative care involvement and physician-delivered palliative care in the community after hospital discharge among individuals with limited life expectancy. Design: Population-based retrospective cohort study using administrative health data. Settings/Subjects: Adults with a predicted median survival of six months or less admitted to acute care hospitals in Ontario, Canada, between April 1, 2013, and March 31, 2017, and discharged to the community. Measurements: Inpatient palliative care involvement was classified as high (e.g., palliative care unit), medium (e.g., palliative care specialist consult), low (e.g., generalist-delivered palliative care), or none. Community palliative care included outpatient and home and clinic visits three weeks postdischarge. Results: Among 3660 hospitalized adults, 82 (2.2%) received inpatient palliative care with high level of involvement, 462 (12.6%) with medium level of involvement, 525 (14.3%) with low level of involvement, and 2591 (70.8%) had no inpatient palliative care. Patients who received inpatient palliative care were more likely to receive community palliative care after discharge than those who received no inpatient palliative care. These associations were stronger among patients who received high/medium palliative care involvement than patients who received low palliative care involvement. Conclusions: Inpatient palliative care, including that delivered by generalists, is associated with an increased likelihood of community palliative care after discharge. Increased inpatient generalist palliative care may help support patients' palliative care needs.

Continuity of physician care over the last year of life for different cause-of-death categories: a retrospective population-based study.

BACKGROUND: The mix of care provided by family physicians, specialists and palliative care physicians can vary by the illnesses leading to death, which may result in disruptions of continuity of care at the end of life. We measured continuity of outpatient physician care in the last year of life across differing causes of death and assessed factors associated with higher continuity. METHODS: We conducted a retrospective descriptive study of adults who died in Ontario between 2013 and 2018, using linked provincial health administrative data. We calculated 3 measures of continuity (usual provider, Bice-Boxerman and sequential continuity), which range from 0 to 1, from outpatient physician visits over the last year of life for terminal illness, organ failure, frailty, sudden death and other causes of death. We used multivariable logistic regression models to evaluate associations between characteristics and a continuity score of 0.5 or greater. RESULTS: Among the 417 628 decedents, we found that mean usual provider, Bice-Boxerman and sequential continuity indices were 0.37, 0.30 and 0.37, respectively, with continuity being the lowest for those with terminal illness (0.27, 0.23 and 0.33, respectively). Higher number of comorbidities, higher neighbourhood income quintile and all non-sudden death categories were associated with lower continuity. INTERPRETATION: We found that continuity of physician care in the last year of life was low, especially in those with cancer. Further research is needed to validate measures of continuity against end-of-life health care outcomes.

Symptom trajectories of non-cancer patients in the last six months of life: Identifying needs in a population-based home care cohort.

INTRODUCTION: The end-of-life symptom prevalence of non-cancer patients have been described mostly in hospital and institutional settings. This study aims to describe the average symptom trajectories among non-cancer patients who are community-dwelling and used home care services at the end of life. MATERIALS AND METHODS: This is a retrospective, population-based cohort study of non-cancer patients who used home care services in the last 6 months of life in Ontario, Canada, between 2007 and 2014. We linked the Resident Assessment Instrument for Home Care (RAI-HC) (standardized home care assessment tool) and the Discharge Abstract Databases (for hospital deaths). Patients were grouped into four non-cancer disease groups: cardiovascular, neurological, respiratory, and renal (not mutually exclusive). Our outcomes were the average prevalence of these outcomes, each week, across the last 6 months of life: uncontrolled moderate-severe pain as per the Pain Scale, presence of shortness of breath, mild-severe cognitive impairment as per the Cognitive Performance Scale, and presence of caregiver distress. We conducted a multivariate logistic regression to identify factors associated with having each outcome respectively, in the last 6 months. RESULTS: A total of 20,773 non-cancer patient were included in our study, which were analyzed by disease groups: cardiovascular (n = 12,923); neurological (n = 6,935); respiratory (n = 6,357); and renal (n = 3,062). Roughly 80% of patients were > 75 years and half were female. In the last 6 months of life, moderate to severe pain was frequent in the cardiovascular (57.2%), neurological (42.7%), renal (61.0%) and respiratory (58.3%) patients. Patients with renal disease had significantly higher odds for reporting uncontrolled moderate to severe pain (odds ratio [OR] = 1.21; 95% CI: 1.08 to 1.34) than those who did not. Patients with respiratory disease reported significantly higher odds for shortness of breath (5.37; 95% CI, 5.00 to 5.80) versus those who did not. Patients with neurological disease compared to those without were 9.65 times more likely to experience impaired cognitive performance and had 56% higher odds of caregiver distress (OR = 1.56; 95% CI: 1.43 to 1.71). DISCUSSION: In our cohort of non-cancer patients dying in the community, pain, shortness of breath, impaired cognitive function and caregiver distress are important symptoms to manage near the end of life even in non-institutional settings.

Intensity of outpatient physician care in the last year of life: a population-based retrospective descriptive study.

BACKGROUND: For many patients, health care needs increase toward the end of life, but little is known about the extent of outpatient physician care during that time. The objective of this study was to describe the volume and mix of outpatient physician care over the last 12 months of life among patients dying with different end-of-life trajectories. METHODS: We conducted a retrospective descriptive study involving adults (aged ≥ 18 yr) who died in Ontario between 2013 and 2017, using linked provincial health administrative databases. Decedents were grouped into 5 mutually exclusive end-of-life trajectories (terminal illness, organ failure, frailty, sudden death and other). Over the last 12 months and 3 months of life, we examined the number of physician encounters, the number of unique physician specialties involved per patient and specialty of physician, the number of unique physicians involved per patient, the 5 most frequent types of specialties involved and the number of encounters that took place in the home; these patterns were examined by trajectory. RESULTS: Decedents (n = 359 559) had a median age of 78 (interquartile range 66-86) years. The mean number of outpatient physician encounters over the last year of life was 16.8 (standard deviation [SD] 13.7), of which 9.0 (SD 9.2) encounters were with family physicians. The mean number of encounters ranged from 11.6 (SD 10.4) in the frailty trajectory to 24.2 (SD 15.0) in the terminal illness trajectory across 3.1 (SD 2.0) to 4.9 (SD 2.1) unique specialties, respectively. In the last 3 months of life, the mean number of physician encounters was 6.8 (SD 6.4); a mean of 4.1 (SD 5.4) of these were with family physicians. INTERPRETATION: Multiple physicians are involved in outpatient care in the last 12 months of life for all end-of-life trajectories, with family physicians as the predominant specialty. Those who plan health care models of the end of life should consider support for family physicians as coordinators of patient care.

MRI and 18FET-PET Predict Survival Benefit from Bevacizumab Plus Radiotherapy in Patients with Isocitrate Dehydrogenase Wild-type Glioblastoma: Results from the Randomized ARTE Trial.

PURPOSE: To explore a prognostic or predictive role of MRI and O-(2-18F-fluoroethyl)-L-tyrosine (18FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma. PATIENTS AND METHODS: Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this post hoc analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial 18FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm. RESULTS: Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm3 0.94; 95% confidence interval (CI), 0.89-0.99] and for higher ADC (HR 0.18; CI, 0.05-0.66). Higher 18FET-TBR on pretreatment PET scans was associated with inferior overall survival in both arms. Response assessed by standard MRI-based Response Assessment in Neuro-Oncology criteria was associated with overall survival in the bevacizumab plus radiotherapy arm by trend only (P = 0.09). High 18FET-TBR of noncontrast-enhancing tumor portions during bevacizumab therapy was associated with inferior overall survival on multivariate analysis (HR 5.97; CI, 1.16-30.8). CONCLUSIONS: Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent 18FET-PET signal of no longer contrast-enhancing tumor after concomitant bevacizumab plus radiotherapy suggests pseudoresponse and predicts poor outcome.

Complementary and alternative medicine use by glioma patients in Switzerland.

BACKGROUND: During the course of disease, most glioma patients learn that there is no cure for their tumor. It is therefore not uncommon for patients or caregivers to seek complementary and alternative medicine (CAM) treatments. Patterns of CAM use vary across the globe, but little is known about the type of, and motivation for, CAM use in most countries. METHODS: Here we conducted a cross-sectional survey of CAM use in patients harboring gliomas of World Health Organization (WHO) grades II to IV at 3 specialized neuro-oncology centers in Switzerland. RESULTS: Of 208 patients who returned the survey, approximately half reported having used or using CAM. CAM use was associated with younger age. Patients suffering from WHO grade II gliomas were less likely to indicate CAM use. The leading motivation for CAM use was to contribute actively to the treatment of the disease. CAM use was commonly not counseled or supervised by a health care professional. Cost and issues of reimbursement were not an important factor in the decision against or for CAM use. CONCLUSIONS: Physicians caring for glioma patients should be aware of and explore CAM use to better understand patients' attitudes toward their disease, to provide counseling, and to identify potential interactions of CAM with standard treatments for gliomas.

Incidence and predictors of Bone Metastases (BM) and Skeletal-Related Events (SREs) in Small Cell Lung Cancer (SCLC): A Swiss patient cohort.

Objectives: Bone metastases (BM) and skeletal-related events (SREs) are frequent complications in patients with lung cancer. Whereas in non-small-cell lung cancer (NSCLC) incidence, prognostic impact, and risk factors are well established, there is only little knowledge in patients with small cell lung cancer (SCLC). We retrospectively evaluated the incidence of BM, SRE and their treatment in a SCLC patient cohort treated at our hospital. We further assessed the role of Lactate Dehydrogenase (LDH), a possible predictor of BM development in SCLC patients. Materials and Methods: We retrospectively analyzed patients with the diagnosis of SCLC for BM, SRE, overall treatment patterns, outcome and established prognostic parameters by record review. The prognostic role of LDH was tested using univariate longitudinal regression analysis. Results: We identified 92 consecutive patients with SCLC diagnosed between 2000 and 2010 at our institution. Overall, 36.9% presented with BM at first diagnosis. Median time to BM from first diagnosis was 14.8 months (range) in limited disease (LD) and 0.9 months (range) in extensive disease (ED). The overall incidence of SRE was 18.4%. Only 19.6% of patients with BM were initially treated with bisphosphonates. Conclusions: Elevated LDH, as well as age ≥75 years were independent predictors for BM development in SCLC patients. Although SREs are relevant complications in SCLC, early antiresorptive treatment of BM to reduce the risk of SREs was rare. LDH served as a predictive factor for BM development in our SCLC cohort and therefore should be taken into account in future randomized controlled trials.

Effects of potassium citrate or potassium chloride in patients with combined glucose intolerance: A placebo-controlled pilot study.

BACKGROUND: Experimental K(+) depletion reversibly inhibits insulin secretion, while chronic metabolic acidosis decreases insulin sensitivity. We aimed to investigate the effects of potassium supplementation and alkali supplementation in non-acidotic, normokalemic humans with combined glucose intolerance. STUDY DESIGN AND RESULTS: In this double-blind, placebo-controlled study in 11 subjects (7 male, 4 female, ages 47-63 years), 90meqs of oral KCl or Kcitrate per day for 2weeks each increased insulin production as measured by homeostasis model assessment Beta [KCl=86 (CI 81-91), Kcitrate=88 (82-94), placebo=78 (73-83)%, p<0.04], but only Kcitrate attenuated insulin resistance as assessed by HOMA-IR (insulin resistance, Kcitrate=2.8 (2.5-3.1), placebo=3.2 (2.9-3.5), p<0.03) and only Kcitrate increased quantitative insulin sensitivity check index (Quicki, Kcitrate=0.355 (0.305-0.405), placebo=0.320 (0.265-0.375) p<0.04). These results were confirmed by independent measurements, i.e. HOMA C-peptide and whole body insulin sensitivity index measured during oral glucose tolerance testing. Kcitrate significantly decreased systolic and diastolic 24-hour ambulatory blood pressures (-4.0 (-3 to -5) and -2.7 (-1.9 to -3.5), respectively as compared to placebo, p<0.02) while KCl was without a significant effect. CONCLUSIONS: K(+) supplementation in the absence of overt K(+) depletion improves beta-cell function in subjects with combined glucose intolerance. The insulin-sensitizing and hypotensive effect, however, depend on citrate as the accompanying anion.

[Meningioma: management of the most common brain tumour]. / Das Meningeom: Management des häufigsten hirneigenen Tumors.

Meningiomas are the most common primary brain tumours in adults and are therefore relevant for general practitioners. Most meningiomas are benign and neurosurgical resection offers the best chance of cure. However, complete resection is not achievable in many patients. This accounts for a relevant rate of tumour recurrences within 15 years of follow up. In atypical and anaplastic meningiomas of WHO grade II and III time to recurrence is dramatically shorter and these tumours need multimodal treatment strategies including postoperative radiotherapy. Various systemic treatments have occasionally been used as salvage therapy, but were essentially not effective. Only recently, Sunitinib, a small thyrosine kinase inhibitor as well as bevacizumab, a therapeutic antibody, have shown more promising results in highly pretreated, refractory meningioma patients.

Acute occlusive large vessel disease leading to fatal stroke in a patient with systemic lupus erythematosus: arteritis or atherosclerosis?

A woman with a history of systemic lupus erythematosus presented with extensive bilateral strokes due to acute inflammatory, occlusive large vessel disease affecting several aortic branches including the carotid, subclavian, renal, and iliac arteries. We quantitatively characterized the arterial inflammation in this patient and compared it with the inflammatory infiltrates from 22 patients with conventional atherosclerosis. Profound histomorphologic differences from conventional atherosclerosis (predominance of CD8-positive lymphocytes, relative absence of macrophages, no ectopic neovascularization, no signs of plaque hemorrhage, concentric instead of eccentrical stenosis) suggest that this patient's accelerated arteriopathy was precipitated by pathogenic events other than conventional atherosclerosis.