Impact of polypharmacy and comorbidity on survival and systemic parenteral treatment administration in a cohort of hospitalized lung-cancer patients.

BACKGROUND: Although polypharmacy has been described among cancer patients, very few studies have focused on those with lung cancer. We aimed to assess whether polypharmacy and comorbidity have an impact on systemic parenteral treatment administration and survival among lung-cancer patients. METHODS: In this retrospective monocenter cohort study, we included patients hospitalized in thoracic oncology for the first time between 2011 and 2015. The Elixhauser score was used to assess comorbidity and polypharmacy was estimated with a threshold of at least five prescribed medications. The Fine and Gray competitive risk model was used to estimate the impact of polypharmacy and comorbidity on systemic parenteral treatment administration within the first two months of hospitalization. The effect of comorbidity and polypharmacy on overall survival was evaluated by Cox proportional hazards analysis. RESULTS: In total, 633 patients were included (71% men), with a median age of 66 years. The median Elixhauser score was 6 and median overall survival was four months. Among the patients, 24.3% were considered to be receiving polypharmacy, with a median number of medications of 3, and 49.9% received systemic parenteral treatment within two months after hospitalization. Severe comorbidity (Elixhauser score > 11), but not polypharmacy, was independently associated with a lower rate of systemic parenteral treatment prescription (SdHR = 0.4 [0.3;0.6], p < 0.01) and polypharmacy, but not a high comorbidity score, was independently associated with poorer four-month survival (HR = 1.4 [1.1;1.9], p < 0.01) CONCLUSIONS: This first study to evaluate the consequences of comorbidity and polypharmacy on the care of lung-cancer patients shows that a high comorbidity burden can delay systemic parenteral treatment administration, whereas polypharmacy has a negative impact on four-month survival.

Comparison of seven comorbidity scores on four-month survival of lung cancer patients.

BACKGROUND: The comorbidity burden has a negative impact on lung-cancer survival. Several comorbidity scores have been described and are currently used. The current challenge is to select the comorbidity score that best reflects their impact on survival. Here, we compared seven usable comorbidity scores (Charlson Comorbidity Index, Age adjusted Charlson Comorbidity Index, Charlson Comorbidity Index adapted to lung cancer, National Cancer Institute combined index, National Cancer Institute combined index adapted to lung cancer, Elixhauser score, and Elixhauser adapted to lung cancer) with coded administrative data according to the tenth revision of the International Statistical Classification of Diseases and Related Health Problems to select the best prognostic index for predicting four-month survival. MATERIALS AND METHODS: This cohort included every patient with a diagnosis of lung cancer hospitalized for the first time in the thoracic oncology unit of our institution between 2011 and 2015. The seven scores were calculated and used in a Cox regression method to model their association with four-month survival. Then, parameters to compare the relative goodness-of-fit among different models (Akaike Information Criteria, Bayesian Information Criteria), and discrimination parameters (the C-statistic and Harrell's c-statistic) were calculated. A sensitivity analysis of these parameters was finally performed using a bootstrap method based on 1,000 samples. RESULTS: In total, 633 patients were included. Male sex, histological type, metastatic status, CCI, CCI-lung, Elixhauser score, and Elixhauser-lung were associated with poorer four-month survival. The Elixhauser score had the lowest AIC and BIC and the highest c-statistic and Harrell's c-statistic. These results were confirmed in the sensitivity analysis, in which these discrimination parameters for the Elixhauser score were significantly different from the other scores. CONCLUSIONS: Based on this cohort, the Elixhauser score is the best prognostic comorbidity score for predicting four-month survival for hospitalized lung cancer patients.

Dalbavancin in clinical practice: a particular place for the elderly?

We investigate dalbavancin efficiency and tolerance among elderly in Grenoble-Alpes 32 university hospital. Among the 65 patients who received dalbavancin, 51% (33) were considered as old. Patients presented mainly bones and joint infections (52%), surgical site infection 34 (31%), and infective endocarditis (IE) (8%). Clinical cure was confirmed for 79% of old 35 patients at 1, 3, and 6 months. Six adverse events (9%) were reported after 36 dalbavancin's administration, but each time in combination with other antibiotics. 37 Dalbavancin had a significant effectiveness and safety profile and represents a real 38 therapeutic option in the management of deep and complex infections of elderly patients.

Tablets or oral suspension for posaconazole in lung transplant recipients? Consequences for trough concentrations of tacrolimus and everolimus.

AIMS: A new formulation of posaconazole (PCZ), delayed-release tablets (PCZ-tab), increases PCZ bioavailability and plasma trough concentrations (Cmin ) over those achieved with an oral suspension (PCZ-susp). PCZ is an inhibitor of cytochrome P450 3A4 and P-glycoprotein. We therefore investigated the impact of PCZ-tab treatment on blood Cmin and doses of tacrolimus (TAC) and everolimus (EVR). METHODS: Eighteen lung transplant patients receiving TAC (n = 13) or TAC + EVR (n = 5) between June 2015 and March 2016 were retrospectively included. Ten of these patients received both PCZ-tab and PCZ-susp (i.e. switched patients); the other 8 received only PCZ-tab. Plasma Cmin of PCZ (n = 64), blood Cmin of TAC (n = 299) and EVR (n = 80) were determined during routine therapeutic drug monitoring by liquid chromatography-tandem mass spectrometry. RESULTS: PCZ Cmin on PCZ-tab treatment (n = 48) was 2.5 times higher than that on PCZ-susp therapy (n = 16), for both PCZ patients (P < .0001) and for switched patients (P = .003). PCZ initiation, regardless of galenic form, increased TAC and EVR Cmin adjusted for dose (D), 3-fold and 3.5-fold, respectively (P < .0001 for both). PCZ-tab treatment was associated with a higher TAC Cmin /D (PCZ-tab vs PCZ-susp: 0.004 ± 0.004 L-1 vs 0.009 ± 0.006 L-1 , P < .0001) and lower TAC daily dose than PCZ-susp (PCZ-tab vs PCZ-susp: 1.08 ± 0.92 vs 2.32 ± 1.62 mg d-1 , P < .0001). EVR Cmin /D was higher and EVR dose tended to be lower on PCZ-tab than on PCZ-susp. CONCLUSION: The greater PCZ exposure achieved during PCZ-tab treatment increased drug-drug interactions with TAC and EVR, resulting in greater exposure, potentially exposing patients to higher risks of adverse effects.

Pharmacokinetic herb-drug interaction between ginger and crizotinib.

The use of complementary and alternative medicine at least once during or after cancer treatment has increased over the past years from an estimated 25% in the 1970s and 1980s to more than 32% in the 1990s and to 49% after 2000. The risk of herb-drug interaction is therefore increasingly recognized as a public health problem. To the best of our knowledge, we report here the first case of interaction between ginger and anticancer drug, with serious consequences for the patient. There is an urgent need regarding complementary and alternative medicine: Both clinicians and patients should be aware of the potential interactions between herbs and prescribed drugs.

Integrating anatomo-physiological changes and pharmacogenomics in anti-infective therapy management: is it a major concern?

Success of anti-infective therapy is a major challenge in some patients given anatomo-physiological changes and genetic variations. In this case anecdote, we report the management strategy of a patient suffering from chronic pulmonary aspergillosis in a context of anorexia nervosa and genetic polymorphism.

Using national data to describe characteristics and determine acceptance factors of pharmacists' interventions: a six-year longitudinal study.

BACKGROUND: In France, hospital pharmacists perform medication order reviews during patients' hospital stays. This activity can be centralized in the pharmacy or carried out directly in the ward, in collaboration with the healthcare team. During this review, pharmacists can make recommendations to optimize therapeutics. Since 2006, they can document their interventions, via the national Act-IP© observatory. AIM: To determine the characteristics of pharmacists' interventions and their acceptance by physicians in French hospitals. METHOD: A 6-year observational study of pharmacists' interventions documented on the Act-IP© French observatory between 2009 and 2014 was performed. Multiple logistic regression was undertaken to determine the predictors of physicians' acceptance of interventions. RESULTS: A total of 194,684 pharmacists' interventions were documented and concerned mainly "dosage adjustment" (25.6%). These interventions were mostly related to drugs from the central nervous system (23.7%). Seventy percent of pharmacists' interventions were accepted by physicians. Acceptance rate was higher when conducted by a pharmacist regularly practicing in the ward (ORa = 1.60, CI 95 [1.57-1.64]). Physicians' acceptance was significantly associated with (1) ward specialty: emergency (ORa = 1.24, CI 95 [1.14-1.35]); (2) type of intervention: "drug discontinuation", "drug switch" (ORa = 1.15, CI 95 [1.12-1.19]) and "addition of a new drug" (ORa = 1.15, CI 95 [1.12-1.19]); (3) drug group: antineoplastic and immunomodulators (ORa = 3.67, CI 95 [3.44-3.92]). CONCLUSION: This 6-year longitudinal study highlights the role of clinical pharmacists, and particularly the impact of those integrated into wards. This was found to improve intervention acceptance, potentially through collaboration with physicians in pursuit of patient care and drug safety.

Lung cancer, comorbidities, and medication: the infernal trio.

Most patients with lung cancer are smokers and are of advanced age. They are therefore at high risk of having age- and lifestyle-related comorbidities. These comorbidities are subject to treatment or even polypharmacy. There is growing evidence of a link between lung cancer, comorbidities and medications. The relationships between these entities are complex. The presence of comorbidities and their treatments influence the time of cancer diagnosis, as well as the diagnostic and treatment strategy. On the other hand, cancer treatment may have an impact on the patient's comorbidities such as renal failure, pneumonitis or endocrinopathies. This review highlights how some comorbidities may have an impact on lung cancer presentation and may require treatment adjustments. Reciprocal influences between the treatment of comorbidities and anticancer therapy will also be discussed.

Continuous assessment of volunteers' satisfaction in clinical research through simplified questionnaires.

OBJECTIVES: In our clinical research center, a 27 multiple-choice and 3 verbatim questions satisfaction questionnaire has been used since 2008 in order to assess the satisfaction of the volunteers participating in our studies. In this work, we aimed at reducing the number of questions of this cumbersome questionnaire while exploring the same dimensions. MATERIALS AND METHODS: We used k-mean and hierarchical clustering to determine which questions provided the same information or, on the contrary, which questions were able to discriminate a satisfied volunteer from an unsatisfied volunteer. RESULTS: We were able to reduce our satisfaction questionnaire from 30 questions to 6 closed-ended and 2 open-ended questions, which will allow to save volunteers time while increasing their participation rate. CONCLUSION: This questionnaire could be used in other structures practicing clinical research, as part of their quality process.

Study protocol to assess polypharmacy and comorbidities in lung cancer.

BACKGROUND: At least half of patients with lung cancer have comorbidities, which can affect treatment decisions and survival. Associated with comorbidity, polypharmacy can also have consequences on patient care. This study will evaluate both polypharmacy and comorbidities in a cohort of hospitalized patients on the administration of chemotherapy and survival. METHODS: In this monocentric retrospective study, patients diagnosed with lung cancer during their first hospitalization in thoracic oncology were included between 2011 and 2015. Four datasets were obtained containing the variables of interest. Deterministic data linkage will be performed. The main objective will be to assess the impact of polypharmacy and comorbidities on chemotherapy administration within two months after the first hospitalization in thoracic oncology. The probability of chemotherapy administration will be estimated using the Kaplan Meier method. Prognostic factors will be identified using a Cox model. The Fine and Gray method will be used to analyze the competitive risk of death. EXPECTED RESULTS: We first aim to demonstrate the feasibility of working with real-life data and aggregate different databases. Then our goal is to assess impact of polypharmacy and comorbidities on chemotherapy administration and on the survival of lung cancer patients. This would help to understand the possibilities to aggregate several database for a protocol in view to help clinicians to rationalize treatment and define inappropriate medications for this population.

Restrictive allograft dysfunction after lung transplantation: is there a place for nintedanib?-a case report.

One of the posttransplantation complications is represented by chronic lung allograft dysfunction, which has two main clinical presentations: bronchiolitis obliterans syndrome and restrictive allograft syndrome. The latter being challenging because of poor prognosis and only symptomatic treatment, and characterized by fibrotic process. A 63-year-old man was right lung-transplanted in 2009 due to idiopathic pulmonary fibrosis. In 2011, bronchiolitis obliterans syndrome was diagnosed evolving to restrictive allograft syndrome in 2016. An off-label treatment by nintedanib (150 mg twice a day) was introduced. Unfortunately, it was stopped 4 months later because of digestive intolerance, without any clinical improvement. Contrary to a previous case reported, our patient did not have any benefit of nintedanib. Antifibrotic agents' effects such as nintedanib on restrictive allograft syndrome should be assessed in further randomized double-blind placebo-controlled studies.

Clinical evaluation of pharmacists' interventions on multidisciplinary lung transplant outpatients' management: results of a 7-year observational study.

OBJECTIVES: Lung transplant (LT) recipients require multidisciplinary care because of the complexity of therapeutic management. Pharmacists are able to detect drug-related problems and provide recommendations to physicians through pharmacists' interventions (PIs). We aimed at assessing the clinical impact of PIs on therapeutic management in LT outpatients. DESIGN: Data were collected prospectively from an LT recipients cohort during 7 years. A multidisciplinary committee assessed retrospectively the clinical impact of accepted PIs. SETTING: French University Hospital. PARTICIPANTS: LT outpatients followed from 2009 to 2015. PRIMARY OUTCOME MEASURES: Clinical impact of PIs performed by pharmacists using the CLEO tool and the Pareto chart. RESULTS: 1449 PIs led to a change in patient therapeutic management and were mainly related to wrong dosage (39.6%) and untreated indication (19.6%). The clinical impact of PIs was 'avoids fatality', 'major' and 'moderate', in 0.1%, 7.0% and 57.9%, respectively. Immunosuppressants, antimycotics for systemic use and antithrombotic agents had the greatest clinical impact according to the Pareto chart. PIs related to drug-drug interactions (10%) mainly had a moderate and major clinical impact (82.3%, p<0.0001). CONCLUSION: Clinical pharmacists play a key role for detecting drug-related problems mostly leading to a change in therapeutic management among LT outpatients. Our study provides a new insight to analyse the clinical impact of PIs in order to target PIs which have most value and contribute to patient care through interdisciplinary approach.

Unusually prolonged pemetrexed cytotoxicity in a patient with a lung adenocarcinoma: a case report.

BACKGROUND: We describe a case of pemetrexed toxicities related to reabsorption by an ileal neobladder, which caused prolonged hematotoxicity and nephrotoxicity. CASE PRESENTATION: A 59-year-old white man was diagnosed with metastatic wild-type adenocarcinoma of the upper lobe of his right lung. After a first cycle of cisplatin and pemetrexed, he had unusually prolonged aplasia and acute kidney injury. The prolonged aplasia was caused by pemetrexed reabsorption by the ileal mucosa of the neobladder as pemetrexed was eliminated renally in an active form and is partly lipophilic. CONCLUSIONS: Pemetrexed may be reabsorbed by the ileal mucosa of the neobladder because of its hydrophobic structure and renal excretion in its active form. Acute urinary retention may maintain this phenomenon. Published data excluded a potential role for cisplatin in this toxicity; furthermore, we could not assess pemetrexed concentrations in the blood or urine as these assay techniques are not validated. Thus, care is needed when giving chemotherapy to patients with a neobladder.

Targeting the Prostacyclin Pathway: Beyond Pulmonary Arterial Hypertension.

Pioneering work demonstrated that an unstable substance isolated from rabbit and pig aortas could relax arterial smooth muscle and inhibit platelet aggregation. Since then, prostacyclin (prostaglandin I2, PGI2) and its analogs have raised much pharmacological interest. In this review we detail how the PGI2 signaling pathway is much more complex than was initially anticipated, involving peroxisome proliferator-activated receptors (PPARs), prostaglandin transporters (PGTs), and PGI2-thromboxane A2 (TXA2) receptor (IP TP) heterodimerization. We discuss the distinct affinities of PGI2 analogs for prostanoid receptors. In addition, we introduce the new direct and indirect pharmacological approaches to targeting the PGI2 pathway within the systemic circulation, including non-prostanoid agonists of the prostacyclin receptor (IP) and PGT inhibitors, as well as transcutaneous pathways using iontophoresis and nanostructured lipid carriers.

Partial response of pulmonary adenocarcinoma with symptomatic brain metastasis to nivolumab plus high-dose oral corticosteroid: a case report.

BACKGROUND: Nivolumab, a monoclonal antibody targeting the programmed death-1 receptor, is indicated in locally advanced or metastatic non-small cell lung cancer, with progression after platinum-based chemotherapy. Up-to-now, few data are available concerning brain activity of this treatment and concomitant use of corticosteroids. CASE PRESENTATION: A 64-year-old caucasian man with a pulmonary adenocarcinoma associated with brain metastases received four courses of nivolumab in concomitance with a high dose of corticosteroids for his neurologic symptoms. He experienced a partial response in his brain and chest with an improvement in his general condition. Nivolumab was effective in shrinking symptomatic brain metastases, and metastases at other sites, in a patient with non-small cell lung cancer and first-line chemotherapy failure. The effect of nivolumab was obtained despite concomitant high-dose corticosteroid therapy. Combined nivolumab and high-dose corticosteroid therapy did not induce unexpected adverse events. CONCLUSION: Nivolumab and concomitant high-dose corticosteroid therapy was found to be efficient and well tolerated.