Effects of Proton Pump Inhibitors Intake During Chemoradiotherapy for Rectal Cancer: a Retrospective Cohort Study.

PURPOSE: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine. METHOD: A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher's exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61-2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33-2.76, p = 0.93). CONCLUSION: No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately.

[Oral drugs containing alcohol: Should we be careful?] / Médicaments par voie orale contenant de l'alcool : faut-il être vigilant ?

Ethanol is an excipient with known effect whose presence is regulated because it can cause adverse effects, notably a misuse. In order to raise awareness of this risk, this study searched all oral drugs with ethanol as an excipient from the Theriaque® database. All drugs marketed in France with a unit dose ethanol intake of 0.1g or more were identified and analyzed, according to the maximum unit and daily dosage recommended by the manufacturer. This research revealed 106 pharmaceutical specialties responsible for a unit intake of ethanol of 0.1g or more among the 8532 oral drugs containing ethanol (1.2 %): 2 at a daily dose >13g and the majority (57/106; 54 %) at a daily dose <1g. These are mainly oral solutions (97/106; 91 %) of phytotherapy (45/97; 46 %). The most frequently found therapeutic class was antitussive (12/106; 11 %). The majority of drugs are over-the-counter medication (56/106; 53 %). Overall, 106 drugs on the French market can be associated with a risk of misuse and cause adverse effects in vulnerable populations such as children and pregnant women. Vigilance and appropriate monitoring is required for these drugs (especially those over-the-counter ones), and their substitution should be preferred if possible.

Hypervitaminosis A Following the Ingestion of Fish Liver: Report on 3 Cases from the Poison Control Center in Marseille.

In European countries, vitamin A toxicity is most often the result of an excessive intake of vitamin supplements and rarely the consequence of the ingestion of a large carnivorous fish liver. We report 3 cases of vitamin A poisoning after fish liver ingestion in mainland and overseas France. The patients were a 12-y-old girl, a 36-y-old pregnant woman, and a 62-y-old man. They experienced headache, nausea, emesis, and desquamation. Laboratory examination showed a high serum retinol level in the girl. The woman's pregnancy progressed to a miscarriage. This case series shows that this kind of poisoning is not restricted to the polar regions. In patients presenting with flushing combined with signs of intracranial hypertension, accurate questioning of the patient's diet is crucial to avoid misdiagnosis and unnecessary examinations. Pregnant women or women of child-bearing age should be informed of the risk to pregnancy in the case of excessive fish liver ingestion.

Complementary and alternative medicine use in glioma patients in France.

PURPOSE: Complementary and alternative medicine (CAM) use increases in cancer patients, including adult patients with diffuse gliomas. METHODS: Questionnaires addressing CAM use were distributed to adult patients with gliomas of WHO grades II-IV and ECOG performance score of 0-2 during hospital visits and filled in anonymously. The study was conducted in nine centers in France from May 2017 to May 2018. Descriptive cohort analyses and comparative analyses according to gender, age, WHO grade, and recurrent versus newly diagnosed disease were conducted. RESULTS: Two hundred twenty-seven questionnaires were collected; 135 patients (59%) were male. Median age was 48 years, 105 patients (46%) declared having glioblastoma, 99 patients (43%) declared having recurrent disease. Hundred-three patients (45%) had modified their alimentary habits after the glioma diagnosis. At the time of the questionnaire, 100 patients (44%) were on complementary treatment, mainly vitamins and food supplements, and 73 patients (32%) used alternative medicine approaches, mainly magnetism and acupuncture. In total, 154 patients (68%) declared using at least one of these approaches. Expenditures exceeding 100 € per month were reported by users in 14% for modification of alimentary habits, in 25% for complementary treatment, and in 18% for alternative medicines. All approaches were commonly considered as improving quality of life and experienced as efficient, notably those associated with more expenditures. CONCLUSIONS: CAM are frequently used by glioma patients in France. Underlying needs and expectations, as well as potential interactions with tumor-specific treatments, and financial and quality of life burden, should be discussed with patients and caregivers.

Methylphenidate in Adults with Attention Deficit Hyperactivity Disorder and Substance Use Disorders.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopment disorder occurring during childhood. However, ADHD persists into adulthood in 45.7% of cases. The global prevalence of adult ADHD is estimated to 5.3%, with no difference between Europe and North America. ADHD is often comorbid with substance use disorder (SUD), with Odds Ratio ranges from 1.5 to 7.9, depending on the substance and the dependence level. Conversely, the prevalence of ADHD among patients with SUD is 10.8%, versus 3.8% for patients without SUD. Methylphenidate (MPH) alleviates ADHD symptoms and, as such, is currently considered as a first choice medication. MPH blocks the dopamine and norepinephrine transporters leading to an increase in extracellular dopamine. It should be noted that its subjective effects are highly dependent on the pharmacokinetic and especially on the rate of input, which highlights the importance of choosing a sustained-release formulation. Meanwhile, prescribing MPH to patients with comorbid SUD has always been challenging for clinicians. The aim of this review is to address the benefits and pitfalls of using MPH in adults with ADHD comorbid SUD, depending on each of the following types of SUD: amphetamine, cocaine, nicotine, alcohol, cannabis and opiates. Overall, due to the prevalence of ADHD in SUD and to the benefits of MPH observed in this population, and considering the mild or low side effects observed, the response to MPH treatment should be evaluated individually in adults with comorbid ADHD and SUD. The choice of the formulation should favor sustained- release MPH over immediate release MPH. Cardiovascular parameters also have to be monitored during long-term use.

Poly-cyclodextrin functionalized porous bioceramics for local chemotherapy and anticancer bone reconstruction.

The progress in bone cancer surgery and multimodal treatment concept achieve only modest improvement in the overall survival, due to failure in clearing out residual cancer cells at the surgical margin and extreme side-effects of adjuvant postoperative treatments. Our study aims to propose a new method based on cyclodextrin polymer (polyCD) functionalized hydroxyapatite (HA) for achieving a high local drug concentration with a sustained release profile and a better control of residual malignant cells via local drug delivery and promotion of the reconstruction of bone defects. PolyCD, a versatile carrier for therapeutic molecules, can be incorporated into HA (bone regeneration scaffold) through thermal treatment. The parameters of polyCD treatment on the macroporous HA (porosity 65%) were characterized via thermogravimetric analysis. Good cytocompatibility of polyCD functionalized bioceramics was demonstrated on osteoblast cells by cell vitality assay. An antibiotic (gentamicin) and an anticancer agent (cisplatin) were respectively loaded on polyCD functionalized bioceramics for drug release test. The results show that polyCD functionalization leads to significantly improved drug loading quantity (30% more concerning gentamicin and twice more for cisplatin) and drug release duration (7 days longer concerning gentamicin and 3 days longer for cisplatin). Conclusively, this study offers a safe and reliable drug delivery system for bioceramic matrices, which can load anticancer agents (or/and antibiotics) to reduce local recurrence (or/and infection).

Effects of hyperthermia on pharmacokinetics of ertapenem in rats.

The aim of this study was to document the influence of hyperthermia on the pharmacokinetics of ertapenem. Two groups of Wistar rats, normothermic (n = 6) and hyperthermic (n = 8), were injected a single intravenous bolus of ertapenem (15 mg/kg of body weight). Hyperthermia-induced animals were placed in a water-bath at 47 degrees C and control group animals were kept in a water-bath at 25 degrees C to obtain a stable mean core temperature of 39.8 and 36.9 degrees C respectively. Hyperthermia induced significant higher plasma concentrations and exposure, whereas total apparent clearance and volume of distribution were significantly decreased. If confirmed in humans, these results will be of interest to take into account such modifications in hyperthermic clinical situations.

Chronopharmacokinetics of imipenem in the rat.

There are no studies indicating a possible modification of imipenem pharmacokinetics related to the hour (i.e., circadian time) of its administration. The aim of this study was to evaluate the influence of different times of intramuscular imipenem administration on its disposition in Wistar AF EOPS rats. Four groups of eight animals were given a single intramuscular injection of 140 mg/kg of imipenem either at 10:00, 16:00, 22:00, or 04:00 h. Blood samples were collected 0.5, 1, 2, 3, 4, 6, and 8 h after drug injection, and the main pharmacokinetic parameters determined were C(max), T(max), elimination half-life (t(1/2)), area under the concentration-versus-time curve (AUC), total serum clearance (CL/F), and volume of distribution (V/F). Circadian variation of C(max) (49%), T(max) (92%), and AUC (19%) was observed leading to variability of imipenem exposure. Clearance and volume of distribution were modified according to the circadian time of drug injection but did not reach statistical significance. The results suggest that varying the time of administration induces intra-individual variability.

Biologic rhythms and Parkinson's disease: a chronopharmacologic approach to considering fluctuations in function.

The existence of circadian rhythms and their implication in many pathologic processes have been underlined in several diseases but have not been evaluated in Parkinson's disease. The aim of this paper is to review diurnal variations of clinical, biologic, or experimental factors described with Parkinson's disease. Clinical data often report daily fluctuations of motor activity pattern, but the effect of the stage of the disease and the respective roles of drugs are difficult to evaluate. Sleep disturbances in Parkinson's disease patients also reveal alterations of circadian rhythms. Autonomic dysfunction, described in Parkinson's disease, reveals numerous alterations in circadian regulations including loss of circadian rhythm of blood pressure, increased diurnal blood pressure variability, and postprandial hypotension. Many biologic indices such as cortisol, catecholamines, and melatonin are also altered. Circadian rhythms in dopaminergic systems as well as possible daily fluctuations in kinetics of drug treatments are likely involved in such variations. Few clinical studies have been devoted to circadian patterns of drug response. As for other diseases where biologic rhythms are concerned Parkinson's disease therapy may be influenced by further understanding of circadian influence.