The Khorana score for prediction of venous thromboembolism in cancer patients: An individual patient data meta-analysis.

BACKGROUND: Oncology guidelines suggest using the Khorana score to select ambulatory cancer patients receiving chemotherapy for primary venous thromboembolism (VTE) prevention, but its performance in different cancers remains uncertain. OBJECTIVE: To examine the performance of the Khorana score in assessing 6-month VTE risk, and the efficacy and safety of low-molecular-weight heparin (LMWH) among high-risk Khorana score patients. METHODS: This individual patient data meta-analysis evaluated (ultra)-LMWH in patients with solid cancer using data from seven randomized controlled trials. RESULTS: A total of 3293 patients from the control groups with an available Khorana score had lung (n = 1913; 58%), colorectal (n = 452; 14%), pancreatic (n = 264; 8%), gastric (n = 201; 6%), ovarian (n = 184; 56%), breast (n = 164; 5%), brain (n = 84; 3%), or bladder cancer (n = 31; 1%). The 6-month VTE incidence was 9.8% among high-risk Khorana score patients and 6.4% among low-to-intermediate-risk patients (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). The dichotomous Khorana score performed differently in lung cancer patients (OR 1.1; 95% CI, 0.72-1.7) than in the group with other cancer types (OR 3.2; 95% CI, 1.8-5.6; Pinteraction  = .002). Among high-risk patients, LMWH decreased the risk of VTE by 64% compared with controls (OR 0.36; 95% CI, 0.22-0.58), without increasing the risk of major bleeding (OR 1.1; 95% CI, 0.59-2.1). CONCLUSION: The Khorana score was unable to stratify patients with lung cancer based on their VTE risk. Among those with other cancer types, a high-risk score was associated with a three-fold increased risk of VTE compared with a low-to-intermediate risk score. Thromboprophylaxis was effective and safe in patients with a high-risk Khorana score.

Management of Prostate Cancer in Elderly Patients: Recommendations of a Task Force of the International Society of Geriatric Oncology.

CONTEXT: Prostate cancer is the most frequent male cancer. Since the median age of diagnosis is 66 yr, many patients require both geriatric and urologic evaluation if treatment is to be tailored to individual circumstances including comorbidities and frailty. OBJECTIVE: To update the 2014 International Society of Geriatric Oncology (SIOG) guidelines on prostate cancer in men aged >70 yr. The update includes new material on health status evaluation and the treatment of localised, advanced, and castrate-resistant disease. DATA ACQUISITION: A multidisciplinary SIOG task force reviewed pertinent articles published during 2013-2016 using search terms relevant to prostate cancer, the elderly, geriatric evaluation, local treatments, and castration-refractory/resistant disease. Each member of the group proposed modifications to the previous guidelines. These were collated and circulated. The final manuscript reflects the expert consensus. DATA SYNTHESIS: Elderly patients should be managed according to their individual health status and not according to age. Fit elderly patients should receive the same treatment as younger patients on the basis of international recommendations. At the initial evaluation, screening for cognitive impairment is mandatory to establish patient competence in making decisions. Initial evaluation of health status should use the validated G8 screening tool. Abnormal scores on the G8 should lead to a simplified geriatric assessment that evaluates comorbid conditions (using the Cumulative Illness Score Rating-Geriatrics scale), dependence (Activities of Daily Living) and nutritional status (via estimation of weight loss). When patients are frail or disabled or have severe comorbidities, a comprehensive geriatric assessment is needed. This may suggest additional geriatric interventions. CONCLUSIONS: Advances in geriatric evaluation and treatments for localised and advanced disease are contributing to more appropriate management of elderly patients with prostate cancer. A better understanding of the role of active surveillance for less aggressive disease is also contributing to the individualisation of care. PATIENT SUMMARY: Many men with prostate cancer are elderly. In the physically fit, treatment should be the same as in younger patients. However, some elderly prostate cancer patients are frail and have other medical problems. Treatment in the individual patient should be based on health status and patient preference.

Use of heparins in patients with cancer: individual participant data meta-analysis of randomised trials study protocol.

INTRODUCTION: Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits. METHODS AND ANALYSIS: First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to-treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials. ETHICS AND DISSEMINATION: Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline recommendations. Several knowledge users will disseminate results through presentations at clinical rounds as well as national and international conferences. We will prepare an evidence brief and facilitate dialogue to engage policymakers and stakeholders in acting on findings. TRIAL REGISTRATION NUMBER: PROSPERO CRD42013003526.

Palliative sedation for status epilepticus in a patient with progressive multifocal leukoencephalopathy.

Palliative sedation is defined as the use of sedative drugs in order to reduce the patient's consciousness in case of refractory symptoms. The most used drug is midazolam, a benzodiazepine with a short half-life administered either intravenously or subcutaneously. We discuss on a clinical case requiring an exceptionally high dosage of midazolam-up to 160 mg iv daily-to achieve palliative sedation. The patient was an HIV positive 29-year-old male who was suffering from progressive multifocal leukoencephalopathy complicated by a refractory status epilepticus and who was suspected of previous benzodiazepines and opioid abuse. In such situations of a suffering brain doses of midazolam to achieve symptom control may be much higher than expected.

Breakthrough pain in elderly patients with cancer: treatment options.

The prevalence of pain is high in the elderly and increases with the occurrence of cancer. Pain treatment is challenging because of age-related factors such as co-morbidities, and over half of the patients with cancer pain experience transient exacerbation of pain that is known as breakthrough pain (BTP). As with background pain, BTP should be properly assessed before being treated. The first step to be taken is optimizing around-the-clock analgesia with expert titration of the painkiller. Rescue medication should then be provided as per the requested need, while at the same time preventing identified potential precipitating factors. In the elderly, starting treatment with a lower dose of analgesics may be justified because of age-related physiological changes such as decreased hepatic and renal function. Whenever possible, oral medication should be provided prior to a painful maneuver. In the case of unpredictable BTP, immediate rescue medication is mandatory and the subcutaneous route is preferred unless patient-controlled analgesia via continuous drug infusion is available. Recently, transmucosal preparations have appeared in the medical armamentarium but it is not yet known whether they represent a truly efficient alternative, although their rapid onset of activity is already well recognized. Adjuvant analgesics, topical analgesics, anesthetic techniques and interventional techniques are all valid methods to help in the difficult management of pain and BTP in elderly patients with cancer. However, none has reached a satisfying scientific level of evidence as to nowadays make the development of undisputed best practice guidelines possible. Further research is therefore on the agenda.

[Interdisciplinarity in the hospital setting: between daily challenge and group stakes]. / Interdisciplinarité en milieu hospitalier: entre défi hebdomadaire et enjeux de groupe.

Group functioning may limit interdisciplinarity. Four scenarios of health professionals' meetings are described. A) If priority is timing, the group isn't interdisciplinary any longer; decisions are endorsed without questioning or criticism. B) When positions' stakes aren't clarified, speaking helps active persons to take power and passive ones to strengthen their criticisms. C) If caregivers are turned to their duties and territory, recourse to interdisciplinary process is only made in case of difficulties. D) When the group is moved by implicit standards, resources are underutilized. In conclusion, added value of interdisciplinary work is superior when divergent options are brought without influence of recurring problems or protocols.

Do brain T2/FLAIR white matter hyperintensities correspond to myelin loss in normal aging? A radiologic-neuropathologic correlation study.

BACKGROUND: White matter hyperintensities (WMH) lesions on T2/FLAIR brain MRI are frequently seen in healthy elderly people. Whether these radiological lesions correspond to irreversible histological changes is still a matter of debate. We report the radiologic-histopathologic concordance between T2/FLAIR WMHs and neuropathologically confirmed demyelination in the periventricular, perivascular and deep white matter (WM) areas. RESULTS: Inter-rater reliability was substantial-almost perfect between neuropathologists (kappa 0.71 - 0.79) and fair-moderate between radiologists (kappa 0.34 - 0.42). Discriminating low versus high lesion scores, radiologic compared to neuropathologic evaluation had sensitivity / specificity of 0.83 / 0.47 for periventricular and 0.44 / 0.88 for deep white matter lesions. T2/FLAIR WMHs overestimate neuropathologically confirmed demyelination in the periventricular (p < 0.001) areas but underestimates it in the deep WM (0 < 0.05). In a subset of 14 cases with prominent perivascular WMH, no corresponding demyelination was found in 12 cases. CONCLUSIONS: MRI T2/FLAIR overestimates periventricular and perivascular lesions compared to histopathologically confirmed demyelination. The relatively high concentration of interstitial water in the periventricular / perivascular regions due to increasing blood-brain-barrier permeability and plasma leakage in brain aging may evoke T2/FLAIR WMH despite relatively mild demyelination.

Primary pulmonary malignant meningioma with lymph node and liver metastasis in a centenary woman, an autopsy case.

Primary meningiomas arising outside the central nervous system are very rare. They have been reported in the head and neck region, in the thorax, the retroperitoneum, and the pelvis. Usually, they behave as slow-growing tumors with a good prognosis. Herein, we report an autopsy case of a 108-year-old woman, known for a right-sided slowly growing lung nodule for 39 years. Death was attributed to cachexia. At post-mortem, a 15-cm mass was present in the right inferior lobe of the lung, associated with an ipsilateral hilar lymphadenopathy, and another 10-cm mass in the liver. Histology revealed a WHO grade III meningioma. No tumor was observed in the cranial cavity. This case illustrates a rare location of meningioma and highlights its biological behavior, with a very slow progression from a most probably benign tumor to a malignant lesion with metastasis over four decades.

Palliative sedation: from the family perspective.

UNLABELLED: Palliative sedation (PS) is a treatment option in case of refractory symptoms at the end of life. The emotional impact on nurses and doctors has been widely studied. We explore the experience of family members during a PS procedure. METHOD: An anonymous questionnaire was sent to the closest family members (n = 17) of patients who died while receiving palliative sedation. RESULTS: The response rate was 59% (10 of 17). Nine relatives were sufficiently informed about PS. In all, 70% evaluated the chosen moment for initiation of PS as adequate. All the relatives noticed a significant improvement in the refractory symptom with a mean reduction in the estimated suffering of 6.25 points on a visual analog scale. CONCLUSIONS: Palliative sedation should be performed in the best possible way for the patient and his family in order to efficiently reduce a refractory symptom.

[Demands for death (suicide assistance and euthanasia) in palliative medicine]. / Demandes d'aide au décès (assistance au suicide et euthanasie) en médecine palliative.

During a prospective open survey over 12 months of hospitalized patients, 44 death demands were registered for 39 patients (25 cancer, 6 cardiovascular disorder, 2 Parkinson's disease, 3 arthritis, 1 COPD, 1 dementia and 1 severe depression). 14 patients were also depressed. 28 requested euthanasia, 16 suicide assistance. At 1 month, 3 persisted, 16 had abandoned, 16 had died and 4 were not questioned. At 6 months, 7 were alive but had abandoned and 2 had committed suicide at their home. The majority of death demands correspond to euthanasia which is a murder according to the penal code. In front of such demand, realistic short-term objectives must be established. Many patients give up their project. This indicates great uncertainty in front of care and greatest ambivalence in front of life.

Preferences of elderly cancer patients in their advance directives.

Efforts to improve the quality of end-of-life decision-making have emphasized the principle of individual autonomy to better ensure that patients receive care consistent with their preferences. Advance directives (ADs) can be vehicles for in-depth and ongoing discussions among health care professionals, patients, and families. The aim of our study was to identify preferences and values expressed in ADs of 50 elderly patients with cancer. Main concerns of the patients were resuscitation and introduction of artificial nutrition. Very few patients had unrealistic expectation. Preferences about patient's symptom management were quite different from one to another. Content of ADs not only involved life-sustaining technology, but also psychosocial items and religious beliefs and values. All patients designated at least one surrogate. In conclusion, ADs should not be considered simply as another questionnaire, but more as a process to improve communication.

Malignant irreversible intestinal obstruction: the powerful association of octreotide to corticosteroids, antiemetics, and analgesics.

In the case of malignant intestinal obstruction, surgery often carries important mortality and morbidity risks, and feasibility is neither realistic nor reasonable. A total of 4 clinical cases of intestinal obstruction caused by advanced gastrointestinal cancers in their terminal phase are described. The association of analgesics, corticosteroids, antiemetics, and octreotide was effective to relieve symptoms of intestinal obstruction for the remaining lifetime. The insertion of a nasogastric tube was avoided in 3 of 4 cases. Death occurred 51, 56, and 64 days after clinical and radiological diagnosis of irreversible intestinal obstruction. This combination of drugs appears very powerful and well tolerated. The relatively long survival that was observed should encourage future studies of longer half-life somatostatin analogues with no need of continuous infusion or multiple daily injections.

Factors associated with falls in patients with cancer hospitalized for palliative care.

INTRODUCTION: In geriatrics, most risk factors associated with falls have been identified and management strategies developed accordingly. This is not the case in palliative care. The incidence rate of falls, the consequences related to falls, and other related factors were determined in elderly cancer patients hospitalized for palliative care in an exploratory study. METHODS: All consecutive patients hospitalized with advanced cancer were included over a 1-year period. Each fall was identified and detailed by a routinely collected incident report. Associations between variables and falls were assessed. RESULTS: Mean age of the 198 patients (116 F) was 71.0 +/- 12.1 years. Of these, 36 had a fall at least once. Delirium occurred significantly more often in fallers (p = 0.029). There was a nonsignificant trend for a higher number of prescribed drugs in fallers (n = 8.5 +/- 3.7 versus 7.5 +/- 3.2; p = 0.4) who received significantly more neuroleptics (47.2% versus 29%; p = 0.035). Environmental hazards made little contribution to patients' falls. DISCUSSION: Characteristics of falls in palliative care appear different from those evidenced in geriatric wards. To prevent delirium while prescribing neuroleptic drugs with the greatest caution should help decrease the number of falls in this highly vulnerable group of patients.

Utilisation of dental services in a university hospital palliative and long-term care unit in Geneva.

OBJECTIVES: Dental care plays an important role in the multidisciplinary approach, which is used in palliative and long-term care to address the complex needs of terminally ill patients. The aim of this study was to assess the utilisation of dental services in a University Hospital Palliative and Long-term Care Unit. MATERIAL AND METHOD: Over an observation period of 13 months, structured questionnaires were filled in after each dental appointment. The survey covered three main topics: the initiation and incentive from the dental consultation, particular difficulties because of the patient's health or the hospital's organisation as well as the accomplished treatment. RESULTS: Two hundred and seventy-five questionnaires from a total of 102 patients were available for analysis. The patients' median age was 83 years (SD 10.3, range 49-101 years), 63 were female, 39 male. A majority of first appointments were initiated by a physician (n = 49 of 102), mainly because of pain (n = 62 of 275). 10.5% of the appointments were cancelled on the same day. Only one-fifth of the patients were able to reach the practice on foot. Six used a walking stick and 54 relied on a wheelchair. Eighteen patients needed to be seen in their bed. The most frequently performed procedures were extractions and removal of denture sore spots (n = 67 of 275) followed by the manufacturing of new dentures (n = 38 of 275). In more than 17% of the appointments, no particular treatment was performed. CONCLUSION: The utilisation of dental services in terminally ill and severely compromised elderly patients shown justifies a dental service in a palliative care or geriatric hospital setting. The particular dental work profile requires a practitioner with empathy and professional experience.