Assessment of postoperative pain after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in the treatment of peritoneal metastasis.

PURPOSE: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new surgical technique, for the treatment of initially unresectable peritoneal metastasis (PM). Our objective was to assess postoperative pain and morbidity. METHODS: Between July 2016 and September 2020, data from 100 consecutive PIPAC procedures with oxaliplatin (PIPAC Ox) or doxorubicin-cisplatin (PIPAC C/D) in 49 patients with PM (all etiologies) were analyzed. Pain was self-assessed using a visual analog scale (VAS) of 0-10. RESULTS: The median PIPAC procedures per patient were 2 [1-3]. Patients indicated greatest pain at 4 pm on the day of the procedure (D0) and on postoperative D1 at 8 am and 4 pm. Postprocedural moderate-to-severe pain (VAS 4-10) was more frequent with PIPAC Ox than with PIPAC C/D, respectively 14 (36.8%) vs 7 (13.5%); p = 0.010. Hospitalization was longer for patients with moderate-to-severe pain than for others (median 4 days [3-7] vs 3 days [2-4], p = 0.004). Multivariate analysis identified oxaliplatin as a factor associated with greater pain (OR [95% CI], 2.95 [1.10-7.89]. Opiate administration was similar after PIPAC Ox and PIPAC C/D procedures, p = 0.477. CONCLUSION: PIPAC was well-tolerated, and pain was well-controlled in the majority of patients. Pain was greatest at 4 pm on D0 and 8 am and 4 pm on D1. PIPAC Ox is associated with greater pain than PIPAC C/D, independently of opiate treatment. Moderate-to-severe pain was associated with longer hospital stays.

Unexpected overdose blood concentration of tacrolimus: Keep in mind the role of inflammation.

Tacrolimus is the cornerstone of the therapeutic immunosuppressive strategy in liver transplantation. The inter-individual and intra-individual variability of its trough blood concentrations is a surrogated biomarker of allograft rejection. Here we described two cases of patients with liver transplant who exhibited increases of tacrolimus blood trough concentration adjusted on the dose while experiencing acute inflammatory episodes. These case reports highlight the inhibitory effect of acute inflammation on tacrolimus metabolism and show that it accounts for the longitudinal intra-individual variability of tacrolimus blood concentrations, beyond drug-drug interaction and observance.

Effect of Pressurized Intraperitoneal Aerosol Chemotherapy on the Survival Rate of Patients with Peritoneal Carcinomatosis of Gastric Origin.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new surgical technique for the treatment of initially unresectable peritoneal carcinomatosis (PC). Our objective was to compare the results of PIPAC associated with systemic chemotherapy (PIPAC_CHEM) with those of systemic chemotherapy alone (ONLY_CHEM) in patients with gastric PC without metastasis other than peritoneal, and the WHO performance status < 3. METHODS: This was a retrospective, single center, comparative non-randomized study. Seventeen PIPAC_CHEM patients were compared to 29 ONLY_CHEM patients. The primary endpoint was overall survival at 6 months from diagnosis of PC. RESULTS: Ninety-eight patients were screened and 46 were included (PIPAC_CHEM, n = 17; ONLY_CHEM, n = 29). The PIPAC_ CHEM population was significantly younger (median 64 years [56; 68] vs 74 years [61; 79]; p = 0.0054). Median PIPAC session per patient is 2 [1-3]. Six-month survival was significantly higher in the PIPAC_CHEM group than in the ONLY_CHEM group 16/17 (94.1% [65-99.2]) vs 19/29 (65.5% [45.4-79.7]), respectively; p = 0.029. Over the entire follow-up, median survival [95% CI] was 12.8 months [7.2-34.3] with PIPAC vs 9.1 months [5.4-11.5] without, p = 0.056. At 6 months, median length of additional hospitalization was significantly less for PIPAC_CHEM (median 2 days [2-7]) than without PIPAC (median 11 days [3-21]) (p = 0.045). CONCLUSION: The overall survival at 6 months after the diagnosis of carcinomatosis was significantly better for PIPAC_CHEM patients. This difference appears to continue until at least 18 months. At 6 months, days of additional hospitalization was significantly less in the PIPAC_CHEM group. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT 04,879,953.

Tolerance of Fentanyl Pectin Nasal Spray for Procedural Pain in Geriatric Patients.

OBJECTIVES: We aimed to assess the tolerance of fentanyl pectin nasal spray (FPNS) when used to treat procedural pain caused by wound dressing or physiotherapy in patients older than 75 years with or without opioid background treatment. DESIGN: This is a prospective monocentric, noncontrolled, nonrandomized study conducted from December 2014 to October 2017 in 2 geriatric wards (rehabilitation and acute medicine). SETTING AND PARTICIPANTS: Fifty-seven patients were included and 314 procedures were monitored. METHODS: For each patient, 6 procedures were monitored: the first 2 without specific treatment, then fentanyl was started at 100 µg with a titration over a few procedures up to 800 µg in non-opioid-naïve patients and 400 µg in opioid-naïve. Sedation and respiratory scale were monitored during the procedures. All adverse drug events occurring from inclusion to 5 days after the intervention were collected and their imputability was assessed separately by 2 pharmacovigilance experts. RESULTS: Overall, 14.4% of the sessions with FPNS administration resulted in adverse drug events. Main adverse drug events were nausea and vomiting, somnolence, and confusion. Most of them were of mild to moderate severity. Four severe adverse events were due to accidental overdoses. No unexpected adverse event occurred. Tolerance was similar for opioid-naïve and non-opioid-naïve patients (P value = .93). CONCLUSION AND IMPLICATIONS: FPNS was overall well tolerated in geriatric patients. Given its interesting pharmacokinetics, fentanyl is a promising lead for procedural pain treatment in geriatric patients, even those who are opioid naïve.

[Analysis of antiretroviral drugs-induced adverse effects]. / Analyse des effets indésirables des médicaments du VIH.

In 1999, The Regional Center of Pharmacogilance and the Department of Infectious Disease of the Toulouse University Hospital set up a system to improve the data collection about antiretroviral-induced adverse reactionss (ADRs). From November 1999 to April 2003, a resident of pharmacovigilance collected ADRs reported with antiretroviral drugs during 2 weekly medical consultations. A total of 613 ADRs corresponding to 428 patients were reported, classified as "non serious" in 88.6% of cases and required the withdrawal of suspected drugs in 57% of cases. Our data show an improvement of antiretroviral drug-induced ADRs reporting.

Why Do Patients with Chronic Inflammatory Rheumatic Diseases Discontinue Their Biologics? An Assessment of Patients' Adherence Using a Self-report Questionnaire.

OBJECTIVE: Concerns have been raised about nonadherence behavior among patients with chronic inflammatory rheumatic diseases (CIRD) receiving biologics. This nonadherence may be caused by various factors. The main objective was to explain why patients discontinue their biologics of their own accord. METHODS: A quantitative and descriptive study was performed using a self-report questionnaire that was sent through the Internet to members of different patient associations. Sociodemographic data, medical and therapeutic history, management of biologic administration, previous experiences, and patients' beliefs and perceptions about treatment efficacy and side effects were studied to explain self-discontinuation (SD). RESULTS: A total of 581 patients answered the questionnaire between June 16, 2012, and July 4, 2012, including patients with ankylosing spondylitis (351/581, 60.4%), rheumatoid arthritis (196/581, 33.7%), psoriatic arthritis (30/581, 5.2%), and other CIRD (4/581, 0.7%). More than 1000 different biologics were described by the 581 patients, with a median of 2 lines per patient. Eighty-six patients discontinued their biologics of their own accord (14.8%). In a multivariate analysis, factors that were significantly related to SD were low level of pain, more than 1 line of biologics tried, self-administration of biologics, negative beliefs about the treatment, and a lack of medical and social support. CONCLUSION: Five predictive factors of this SD were identified, which should be assessed in routine with patients with CIRD receiving biologic treatment: pain, treatment history, self-administration of injections, negative beliefs about treatment, and a lack of perceived medical and social support.

Comparison between two generic questionnaires to assess satisfaction with medication in chronic diseases.

OBJECTIVE: The objective of this work was to compare two generic questionnaires assessing patients' satisfaction with medication. In addition we tested whether satisfaction can predict adherence to medication regimens in patients with chronic diseases, and which dimensions of satisfaction are most involved. METHODS: This prospective, observational study was conducted over one year in a heterogeneous population of patients with various chronic diseases. Satisfaction with medication was assessed by using the TSQM® vII and the SatMed-Q® questionnaires, and adherence to treatment was assessed with the Morisky-Green questionnaire. Clinical pharmacists interviewed patients to collect clinical, demographic and therapeutic data. RESULTS: 190 patients were enrolled. Both questionnaires showed excellent reliability and correlation was high (R=0.70; p<0.001). Adherence was correlated with satisfaction with medication whether assessed with the SatMed-Q® (R=0.23; p=0.002) or the TSQM® (R=0.17; p=0.02). Among different dimensions of satisfaction, convenience of use and side effects are prominent predictors of adherence. CONCLUSION: Adherence is related to the patient's satisfaction with medication whether assessed with the TSQM® vII or the SatMed-Q®. Therefore, these simple questionnaires could be used as predictive tools to identify patients whos' adherence needs to be improved.

Computerized physician order entry system combined with on-ward pharmacist: analysis of pharmacists' interventions.

RATIONALE, AIMS AND OBJECTIVES: To analyse pharmacists' interventions in a setting where a computerized physician order entry system (CPOE) is in use and a pharmacist works on the ward. METHOD: A prospective cohort study was conducted in seven wards of a French teaching hospital using CPOE along with the presence of a full-time on-ward pharmacy resident. We documented the characteristics of pharmacists' interventions communicated to physicians during the medication order validation process whenever a drug-related problem was identified. Independent predictors of the physician's acceptance of the pharmacist's intervention were assessed using multiple logistic regression analysis. RESULTS: The 448 pharmacists' interventions concerned: non-conformity to guidelines or contraindications (22%), too high doses (19%), drug interactions (15%) and improper administration (15%). The interventions consisted of changes in drug choice (41%), dose adjustment (23%), drug monitoring (19%) and optimization of administration (17%). Interventions were communicated via the CPOE in 57% of cases and 43% orally. The rate of physicians' acceptance was 79.2%. In multivariate analysis, acceptance was significantly associated with the physician's status [higher for residents vs. seniors: OR = 7.23, CI 95 (2.37-22.10), P < 0.01], method of communication [higher for oral vs. computer communication: OR = 12.5, CI 95 (4.16-37.57), P < 0.01] and type of recommendation [higher for drug monitoring vs. drug choice recommendations: OR = 10.32, CI 95 (3.20-33.29), P < 0.01]. CONCLUSIONS: When a clinical pharmacist is present on a ward in which a CPOE is in use, the pharmacists' interventions are well accepted by physicians. Specific predictors of the acceptance by physicians emerge, but further research as to the impact of CPOE on pharmacist-physician communication is needed.

Physicians' perception of CPOE implementation.

OBJECTIVE: To identify perceptions held by physicians of the benefits of computerized physician order entry (CPOE) and factors influencing its successful implementation in the context of the increased presence of a clinical pharmacist on ward. SETTING: A 2000-bed University Hospital. METHOD: A cross-section opinion survey was conducted of all permanent physicians of the hospital to determine their perception on the benefits, or otherwise, of CPOE. Questionnaires, built upon the analysis of 10 preliminary semi-structured interviews with physicians, were sent to physicians by electronic and paper mail. It comprised three sections with a 4 level Likert scale: general perception of CPOE benefits (items 1.1-1.8); opinion on the introduction of the CPOE system in the hospital (item 2); opinion on the presence of a pharmacist on ward (item 3). A fourth section recorded the respondent's profile. MAIN OUTCOME MEASURES: Level of agreement on the items describing the general perception of CPOE benefits; opinion on the introduction of a CPOE system in the hospital; and opinion on the pharmacist's presence on ward. A Principal Component Analysis (PCA) was conducted on sections one and two. Analysis of this PCA representation in terms of the respondents' profile was performed. RESULTS: One hundred and one physicians (18%) participated in the survey. Most (83%) physicians favoured the implementation of a CPOE (item 2). Among the advantages of CPOE, the greatest agreement concerned items related to safety and regulatory issues (from 80 to 76% agreement). Other items related to management issues were perceived as less tangible benefits (from 50 to 67% agreement). The increased presence of a pharmacist on the ward was supported by 94% of physicians. The PCA representation using profile items produced a 2-factor solution, accounting for 68% of the variance, with former experience of collaboration with a pharmacist (P = 0.002) and senior physician status (P = 0.013) positively influencing the perception of the CPOE. CONCLUSION: Endorsement by senior physicians and the presence of a clinical pharmacist on ward promote a positive attitude towards CPOE and facilitate its implementation.

Educating diabetic children: integrating representations by children aged 7 to 11 and their parents.

OBJECTIVE: A patient living with a chronic disease develops illness-related knowledge, representations, and specific behaviour leading to attitudes. Our objective was to assess the interaction between representations from diabetic children 7 to 11 years of age and their parents, on the disease and its treatment, in order to improve the therapeutic education process. METHOD: A qualitative approach was developed. Semi-structured interviews and free association technique were used on 10 children 7 to 11 years of age and 10 parents, in the Toulouse Hospital, France. Qualitative and quantitative (Alceste(R) software) discourse analysis relating to representations was performed (distribution, frequency, and meaning of word sequences were compared). RESULTS: Children seemed to cope naturally with their environment in order to manage their disease. Their attitudes were neutral and their behaviour pragmatic. The parents' representations were more conceptual and negative. They expressed their fear of the disease, their difficulty to endorse the responsibilities and overcome everyday constraints. CONCLUSION: The educator must adapt his language level to integrate the child's universe and facilitate assimilation of knowledge. The therapeutic education process for diabetic children should integrate a specific support and training for parents. These results have influenced our choice of a strategy involving continuous group education focusing parents.