Appropriateness of proton pump inhibitors prescription in patient admitted to hospital: An observational study.

OBJECTIVES: The objective of this study was to assess the relevance of proton pump inhibitors prescribing in patients entering a ward with a clinical pharmacist and therefore identifying inappropriate prescribing. METHODS: A prospective study was conducted for 4 months. Patients admitted to the hospital for elective or emergency surgery, who had medication reconciliation performed by the clinical pharmacy team and who were prescribed proton pump inhibitors before admission were included. The indication for the proton pump inhibitors was collected from the patient or inferred from the medical history. The compliance of the prescriptions with the marketing authorization indications and the duration of treatment and dose was analyzed. The indications were classified into 3 groups: compliant with marketing authorization, off label but relevant use, and strictly off label use. RESULTS: During the study period, 100 patients were included among whom only 29% had a PPI prescription that did fully comply with the recommendations. Among the twenty-three prescriptions that did not comply with the recommendations in terms of indication, 15 were not relevant at all. Among the 65 prescriptions relevant for indication, 36 were not compliant with dose or duration recommendations. 59% of the total number of patients reported that they had never tried to stop treatment. CONCLUSIONS: Our study highlights the need for regular reassessment of proton pump inhibitors prescriptions. Multi-disciplinary collaboration on the appropriate use of this class of medication as well as increased awareness among general practitioners and hospital doctors is essential.

[Misuse and adverse effects of new direct oral anticoagulants: A prospective observational study in patients admitted to an emergency unit of a French university hospital]. / Mésusage et iatrogénie des anticoagulants oraux directs (AOD) : étude observationnelle dans le service des urgences du CHU de Limoges.

INTRODUCTION: The use of direct oral anticoagulants (NOAC) is complex: indications, dosage adjustments and precautions. Emergency departments (ED) are increasingly faced with patients receiving NOAC. The aim of this study was to evaluate the misuse and the adverse effects (AE) of NOAC. METHODS: All subjects with NOAC admitted to the Limoges University Hospital ED from 1/8/2013 to 1/4/2014 were included in a prospective observational study. Misuse was identified from the NOAC summary of product characteristics and from the 2014 ANSM guideline (indication, dose, co-medications, age, hepatic and renal function); adverse effects were recorded. RESULTS: A total of 198 subjects were included receiving rivaroxaban (68.7 %), dabigatran (30.8 %) or apixaban (0.5 %). Main indications were embolic prevention in patients with non-valvular atrial fibrillation (78.7 %) and curative treatment of venous thromboembolism (17.2 %). In 16.2 % of the cases, the treatment was not in according to the guidelines: 78 % for prescribing errors (incorrect dosage according to age, renal function, co-medications) and 22 % for wrong initial indication. AE related to NOAC were encountered in 25.8 % patients. Hemorrhagic events were diagnosed in 36 patients with no according to the guidelines in 11.1 % of them. Hemorrhagic events resulted in 3 deaths (8.3 %). Thrombotic events occurred in 15 patients, all these patients were issued with appropriate guidelines. CONCLUSION: Through the view of an ED, this study confirms a part of misuse and highlights the risk of spontaneous bleeding of NOAC despite appropriate use.

[Acute psychiatric symptoms during methylphenidate intravenous injections: A case report]. / Symptômes psychiatriques aigus lors d'injections intraveineuses de méthylphénidate : à propos d'un cas.

We report the case of a 32-year-old man who developed acute psychiatric disorders after repeated intravenous injections of methylphenidate. The behavioural disorders with extreme psychomotor restlessness and delirious syndrome have resolved within 24hours. The available data highlight the fact that the prescriptions of methylphenidate, an amphetamine-like substance, are constantly increasing in Europe and Northern America. The potential of abuse and addiction to this drug, which is growingly misused, is now clearly established. The medical professionals should be cautious and attentive to the risk of misuse of this drug.

[Evaluation of the prescription of proton pump inhibitors in persons aged 75years and older in a geriatric acute-care unit]. / Évaluation de la prescription des inhibiteurs de la pompe à protons chez la personne âgée de 75 ans et plus dans un service de gériatrie aiguë.

INTRODUCTION AND OBJECTIVES: Proton pump inhibitors (PPI) are widely prescribed in France and could be responsible for adverse drug reactions especially in elderly persons (EP). In order to reduce the misuse of PPI and the excess cost to the Social Security Agency, the French health authorities (Haute Autorité de santé [HAS]) have published strict guidelines for their prescription. We conducted a study in EP to determine the proportion of PPI prescriptions outside HAS guidelines. METHOD: This was a prospective, single-centre observational study in persons aged≥75 years admitted to a geriatric acute-care unit over a period of 6months. The prevalence of prescriptions for PPI and the proportion of prescriptions outside the guidelines were calculated. The sociodemographic and medical characteristics of EP treated with PPI were studied as were the reasons for the prescription of PPI. RESULTS: Among the 818 patients hospitalized during the study period, 270 were taking PPI on admission (33%). Among these prescriptions, 60% were outside the HAS guidelines. Gastro-oesophageal reflux was the leading indication for PPI (30%), followed by dyspepsia (19%). CONCLUSION: This study confirms the high prevalence of prescriptions for PPI and their misuse. As these drugs are apparently well tolerated, prescriptions are often renewed with no medical re-evaluation.

[Retrospective study of the assessment and management of benzodiazepine withdrawal syndrome in hospital between 2000 and 2015]. / Étude rétrospective de l'évaluation et de la prise en charge du syndrome de sevrage brutal en benzodiazépine en milieu hospitalier entre 2000 et 2015.

INTRODUCTION: Benzodiazepines are prescribed in many indications and are provider of adverse effects in case of abrupt withdrawal or poorly framed. Withdrawal rules are established by the High Authority for Health. METHODS: To evaluate the diagnostic and therapeutic modalities of the benzodiazepine withdrawal syndrome, we performed a retrospective single-center study at the University Hospital of Reims, between January 2000 and May 2015, in patients with a withdrawal syndrome following hospital coding. A collection of clinical and laboratory data was performed for each patient, as well as how to obtain the diagnosis, their care and their future. RESULTS: Sixty-eight cases were initially collected, but 16 cases were included. In benzodiazepine withdrawal took place outside the hospital in 68% of cases. The causes were varied: lack of renewal, not issued by the pharmacist, pill errors. Disorders found during the withdrawal symptoms were variable, there were particular digestive, neurological and psychiatric disorders. The use of biological assessments did not provide diagnostic support, however, in 68% of cases a toxicological assay has helped to support. The management of the withdrawal syndrome has been done primarily by reintroducing the same treatment (60%), while in 27% of alprazolam is introduced relay benzodiazepines. It is noted one death possibly linked to the withdrawal syndrome. CONCLUSION: Despite recommendations and information about the terms of stops, some clinical situations result in withdrawal symptoms, a patient died in our study, death appears in connection with the withdrawal situation. Note that the human factor is the main factor related to the circumstances of occurrence of withdrawal.

[Medicines and elderly patients: abuse, dependency or attraction?] / Médicaments et sujets âgés : abus, dépendance ou attirance ?

Psychotropic medicines represent, after alcohol, the second class of substances most susceptible to abuse by elderly people. It can be particularly difficult for caregivers to understand such behaviour as these are prescription-only medicines. This misuse is partly a result of older people tending to trivialise and overrate pharmaceutical drugs, ignoring the potential of non-medicinal methods and psychotherapeutic treatments. The boundaries between prescribed use, overuse, self-medication, excessive use, dependency or addiction to prescription drugs are blurred in older people. Alongside withdrawal methods, prevention must be prioritised by respecting the recommendations of medicine prescriptions in geriatrics and deprescription.

[Representation of psychotropic medicines and alcohol use disorder]. / Représentation des psychotropes et maladie alcoolique.

An elderly person's use of alcohol can conceal undernutrition, cognitive decline due to dementia or depression. Caregivers have an important role to play with these patients in distress. It is necessary to help them regain their self-esteem and to support their will to live to restore the relationship with others.

[Alcohol intoxication in old age]. / L'ivresse alcoolique dans la vieillesse.

Acute alcohol intoxication occurs in elderly subjects. Drunkenness appears in banal clinical forms in geriatrics: falls, dizziness or confusion. Elderly people are more vulnerable to alcohol and need less alcohol to become intoxicated. Age does not exclude the possibility of receiving alcohol addiction treatment. Broaching the subject with an elderly person, the day after a drunken episode, is useful and recommended.

[Benzodiazepine or non-benzodiazepine hypnotics withdrawal syndrome during hospitalization: A series of 22 cases]. / Syndrome de sevrage aux benzodiazépines ou apparentés au cours d'une hospitalisation, à propos de 22 cas.

Twenty-two cases related to benzodiazepine (BZD) withdrawal syndrome were identified and reported to Amiens's regional pharmacovigilance center between January 1st, 1995 and March 25th, 2014, all with a favourable outcome after reintroduction of a BZD. Despite being a very classical well-known side effect, physicians may underestimate this risk. Our series also confirms that the patient is misinformed about the consequences of an abrupt BZD discontinuation especially when the BZD has been consumed for many years. Interviewing patient and his family on the nature of the current medical treatments should be systematic and an early diagnostic step taken by physicians faced with a recent behavioral disorder. Moreover, this would prevent unnecessary, sometimes invasive, expensive investigations and a prolonged hospitalization.

[Characteristics of subjects under opiate maintenance treatment in primary care using the OPEMA data 2013]. / Caractéristiques des sujets sous traitement de substitution vus en médecine générale d'après l'enquête nationale OPEMA 2013.

AIM: The objective of the study is to describe the characteristics of subjects under opiate maintenance treatment by general practionners (GPs). METHOD: Data analysis from observatory for pharmacodependency in ambulatory medicine survey (observation des pharmacodépendances en médecine ambulatoire [OPEMA]) program in 2013 of the subjects under high dosage buprenorphine (HDB) and methadone prescribed or obtained illegally reported by GPs in France. RESULTS: Survey concerned consumers with 862, 433 and 429 of high dosage buprenorphine and respectively methadone. The average age is 39±9 years respectively, and 36±8 years; over 70% are male; 55% have paid employment and over 30% report social benefits; 9% are in temporary housing. In both groups, more than 50% have anxiety and depression; over 25% have associated somatic disorders and digestive diseases, respiratory, pain is the most common. Almost 99% use oral route; nearly 100% have a daily consumption and about 20% of the alcohol concomitantly; 24% of HDB use benzodiazepines and 18% of the methadone group (P=0.06); 33% of the population using methadone consume illicit psychoactive substances and 21% for HDB population (P<0.0001), in particular cannabis (P<0.0001). Heroin and cocaine are also consumed. CONCLUSION: The population consuming opiate maintenance treatments shows social, somatic and psychiatric vulnerability. Misuse associated forms and consumption of other psychoactive substances and illegal drugs are observed. Despite the complexity of management of these patients, general practitioners have a major role to play.

[Misuse of paracetamol in primary care: Cross-sectional study in a French rural context]. / Mésusage du paracétamol en soins primaires : étude transversale dans un contexte rural français.

OBJECTIVE: To estimate the prevalence of the paracetamol use for a reason other than pain (qualitative misuse) during the last 12 months in patients consulting their general practitioner, as well as the reasons for this misuse. METHODS: Descriptive cross-sectional analysis, with gender weighting to estimate the prevalence of paracetamol misuse. RESULTS: In total, data from 209 patients were included in the analysis. Among them, 11 patients declared having taken paracetamol for a reason other than pain, i.e., a gender-weighted prevalence of 5.7% (95% CI: 3.0 to 10.4). Nearly two-thirds of these patients said they had done it to feel better. CONCLUSIONS: The paracetamol misuse is rare but real in general practice. Further studies are needed to better understand it, especially qualitative studies.

[Acute and chronic toxicities associated with the use and misuse of nitrous oxide: An update]. / Toxicités aiguës et chroniques associées à l'usage et au mésusage du protoxyde d'azote : mise au point.

Nitrous oxide (N2O) is used since the eighteenth century as an anesthetic and analgesic but also for recreational use. If the labelled uses of N2O and their modalities are nowadays perfectly framed, the misuse of N2O takes very alarming proportions among teenagers and young adults. This misuse is the cause of acute (hypoxia, barotrauma, burns, neuropsychiatric disorders) and chronic complications if repeated (myeloneuropathy, anemia, thrombosis, inhalant use disorder). The main mechanism of the latter is mainly related to a functional deficit in vitamin B12 induced by N2O. The management of acute complications is symptomatic. The management of chronic complications is based on vitamin B12 supplementation. The best biomarker of chronic N2O exposure is the elevation of the plasmatic level of methylmalonic acid. In all cases of recreational misuses, addiction treatment is necessary to prevent complications or their worsening by providing information in order to stop consumption.

[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.

[Thirty years of nefopam abuse in France]. / Trente ans d'abus de néfopam en France.

AIM OF THE STUDY: The use of nefopam is constantly increasing in France. The objectives of this study were to quantify the intensity of the drug dependence signal, to identify the populations at risk and the risk factors of dependence. METHODS: All serious and non-serious cases of misuse, abuse, drug dependence, overdose and withdrawal syndrome reported to the French Addictovigilance Network since 1988 were reviewed. An analysis of nefopam reimbursement data from the French national EGB (échantillon généraliste des bénéficiaires) database for the period 2006-2017 was also performed. RESULTS: The drug dependence profile of nefopam is close to that of a psychostimulant. Our literature review and the analysis of spontaneous reports confirm the risk of abuse and dependence of nefopam. In addition to a frequent psychiatric history (depression, psychosis, anxiety), nearly half of the patients also present addictive disorders, including more than one-third with opioid-dependence. In almost half of the 120 reported cases, the main adverse reaction was dependence and the frequency of serious effects was greater than 40%. In nearly 70% of the reported cases, the use was associated with chronic pain, which might explain the prolonged use. Moreover, the analysis of data on the reimbursement of nefopam in the general population showed that one French person out of two, having a prescription for nefopam, presented chronic pain. However, nefopam is only indicated in the treatment of acute painful conditions. Although it does not seem to be associated with a greater risk of abuse or dependence, taking the drug orally is another very frequent off-label use that needs to be regulated. CONCLUSION: In France, the prescription of nefopam outside of its marketing authorization is regrettable, because it contributes to the development of abuse and drug dependence.

[Population of people placed in police custody, hidden barometer of diverted medicines]. / La population des personnes placées en garde à vue à Paris, baromètre du détournement invisible des médicaments.

PURPOSE OF THE STUDY: The population of people in police custody is a sentinel niche that is poorly represented in the "usual panels" of public health studies. The aim is to make an overview of their diversion of drugs. PATIENTS AND METHODS: A retrospective study based on cases of misuse in a sample of people in custody examined between 2015 and 2016 at the forensic medicine unit of the hospital Hôtel-Dieu-Paris. RESULTS: Of the 5149 medical examinations, 302 were for substance use disorder or drug misuse. In 2016, the number of notifications for misuse of clonazepam increased (n=65); the user population appears to be getting younger (average age=23.5 years) and to be supplied mainly by deal (63%). Regarding opioid substitution treatments, the indicators of abuse and diversion are confirmed, while morphine sulfate stands out with a strong deal (>75%), IV injection (62%) and polydrug use, including methadone, cocaine (62%). CONCLUSION: From our results, national surveys in general population and studies carried out in the context of deprivation of liberty, people in police custody constitute a real barometer of the parallel market for street drugs. Clinical impacts can be major; a better monitoring is needed. For caregivers, it is also a matter of better identification of misuse, substance use disorder for a future orientation of the patient.

[French trends in the misuse of Fentanyl: From 2010 to 2015]. / Le mésusage du fentanyl en France : 2010 à 2015.

OBJECTIVES: The aim of this study was to evaluate the French use, misuse and abuse/dependence of non-injectable forms of fentanyl (transdermal and transmucosal fentanyl formulations). METHODS: Problematic use of transdermal and transmucosal fentanyl formulations was evaluated using an approach combining multiple sources of information: (1) spontaneous notifications recorded during 6 years (2010-2015) for transdermal fentanyl form and 3 years for transmucosal fentanyl forms and (2) data from annual epidemiological systematic surveys conducted by the French Addictovigilance Network during 6 years (2010-2015). RESULTS: In all, 147 cases were notified for transdermal fentanyl formulation and 109 cases for transmucosal fentanyl formulations. According to the galenic formulation, analysis of these cases emphasizes different profiles: for transdermal fentanyl formulation, two consumption profiles: 1/mainly for analgesic effects (74 %): women (61 %), 47 years, with addictive and/or psychiatric history (46 %), treated for chronic non-cancer related pain (93 %), 2/seeking positive psychic effects other than analgesia (26 %): men (82 %), 32 years, with addictive and/or psychiatric history (87 %) and having obtained the fentanyl patch illegally (60 %) for non-medical use. For transmucosal fentanyl formulations, only one consumption profile was observed: women (52 %), 48 years, with addictive (24 %) and/or psychiatric history (28 %), off label indication (72 %) (indications for non-cancer pain and/or no or insufficient opioid background treatment). The misuse of transmucosal fentanyl formulations implies a high risk of adverse effects: those already known of opioid-based drugs, sometimes lethal (withdrawal syndrome, respiratory and central nervous system depression…) but also serious reactions at the application site (buccal or nasal). For the transdermal fentanyl formulation, 27 cases (18 %) of involuntary intoxication were observed, of which 25 were serious. Nineteen deaths involving both forms of fentanyl have been reported (2 for the transmucosal formulations and 17 for the transdermal formulation). CONCLUSION: Our results report significant and worrying misuse of transmucosal fentanyl formulations with wide off-label use and also primary dependence on fentanyl, regardless of galenic formulation, in patients treated for chronic non cancer pain. Given the significant risks of fentanyl, it is necessary to continue the monitoring of misuse, in particular, thanks to the activities of the French Addictovigilance network allowing a multisource approach and who provides information concerning cases of abuse, misuse and dependence.

Antibiotic misuse: How to evaluate the costs?

OBJECTIVE: Few studies have assessed the costs associated with the misuse of antibiotics in hospitals in France, despite the value of health economic data to inform antibiotic stewardship activities. We aimed to identify the methodological tools used to assess the cost of antibiotic misuse in hospitals. METHODS: We performed a literature review using the major electronic medical databases. An index of relevance was developed to assess the intrinsic quality of selected articles. RESULTS: Four hundred and three articles were retrieved, but 35 were selected for analysis. Most studies investigated the inadequate choice of the antibiotic molecule (n=17), the incorrect treatment duration (n=9), and the administration of an inappropriate dosage (n=7). Only three studies were medical/economic evaluations of specific interventions, such as prescription control by pharmacists or the implementation of a new diagnostic test. Considering our aim, the relevance of the studies was limited: few had defined the economic assessment as the primary objective or had detailed the method for calculating costs. Nevertheless, the misuse evaluation was usually better described. CONCLUSIONS: Despite these limits, key factors for measuring antibiotic misuse (i.e., molecule choice, dosage) in relation to the costs (i.e., over/under prescription, hospital stay, staff remuneration) might serve as the basis for the development of a reference methodology to value the costs of misuse. The application of this methodology on identified situations of antibiotic misuse would help hospital decision-makers to justify resource allocation for implementing antimicrobial stewardship activities.

[Standardized screening of alcohol misuse in emergency wards: The experience of a systematic use of the FACE scale in the European Georges-Pompidou Hospital]. / Repérage standardisé du mésusage de l'alcool au service d'accueil des urgences : l'exemple de la passation systématique du questionnaire FACE à l'hôpital Européen Georges-Pompidou.

INTRODUCTION: By using a standardized and systematic screening with the FACE questionnaire, our aims were : - to determine the prevalence of alcohol misuse (AM) among patients admitted in the emergency department of the European Georges-Pompidou Hospital; - to search for risk factors associated with AM. METHODS: Patients admitted between 9 am and 5 pm were included for 7 consecutive days in June 2017. The variables collected were age, gender, reason for and day of admission, acute alcohol intoxication, benzodiazepines misuse, use of illicit drugs, and the FACE. An AM was defined by a score ≥5 for men and ≥4 for women. Descriptive analyses calculated the prevalence of AM and logistic regressions calculated the risks for AM. RESULTS: A total of 190 men and 221 women were included, with 31% and 19% of them with AM, respectively. The risk of AM was positively associated with male gender, weekend admission and illicit drug use. It was negatively associated with age. The risk of AM was not significantly different according to the reason for admission (trauma versus medical). The risk of AM was not associated with misuse of benzodiazepines. Among the 100 patients with AM, only six had been admitted in acute alcohol intoxication. CONCLUSION: A systematic screening is crucial to identify patients that should benefit from brief intervention or specialized intervention in an addictology unit.

[Evaluation of the prescription of furosemide in persons aged 75years and older in a geriatric acute-care unit]. / Évaluation de la prescription du furosémide chez la personne âgée de 75 ans et plus dans un service de gériatrie aiguë.

INTRODUCTION: Furosemide is very often prescribed in France. It may cause important adverse effects especially in elderly persons. In order to limit its misuse and excessive expenditure for health insurance organizations, the European Society of Cardiology drafted strict guidelines for its prescription. We conducted a study in this population to determine the rate of prescription of furosemide in elderly persons outside the guidelines. METHOD: This was a prospective, single-centre, observational study bearing on elderly persons aged 75years and more admitted to a geriatric acute-care unit over a period of 6months. The prevalence of furosemide prescription and the proportion of prescriptions outside guidelines were calculated. The sociodemographic and medical characteristics of patients treated with furosemide were studied as were the modalities of furosemide prescription. RESULTS: In the 818 patients hospitalized during the period of the study, 267 were taking furosemide at admission (32.6%). Among these prescriptions, 69.2% were outside the guidelines. Arterial hypertension was the leading indication for furosemide (38.2%), followed by chronic heart failure (24.3%). CONCLUSION: This study confirmed the high prevalence of furosemide prescription and its misuse. Furosemide is often re-prescribed with no medical re-evaluation.