Actigraphy assessment of motor activity and sleep in patients with alcohol withdrawal syndrome and the effects of intranasal oxytocin.

BACKGROUND AND AIMS: The alcohol withdrawal syndrome increases autonomic activation and stress in patients during detoxification, leading to alterations in motor activity and sleep irregularities. Intranasal oxytocin has been proposed as a possible treatment of acute alcohol withdrawal. The aim of the present study was to explore whether actigraphy could be used as a tool to register symptoms during alcohol detoxification, whether oxytocin affected actigraphy variables related to motor activity and sleep compared to placebo during detoxification, and whether actigraphy-recorded motor function during detoxification was different from that in healthy controls. METHODS: This study was a part of a randomized, double blind, placebo-controlled trial in which 40 patients with alcohol use disorder admitted for acute detoxification were included. Of these, 20 received insufflations with intranasal oxytocin and 20 received placebo. Outcomes were actigraphy-recorded motor activity during 5-hour sequences following the insufflations and a full 24-hour period, as well as actigraphy-recorded sleep. Results were related to clinical variables of alcohol intake and withdrawal, including self-reported sleep. Finally, the actigraphy results were compared to those in a group of 34 healthy individuals. RESULTS: There were no significant differences between the oxytocin group and the placebo group for any of actigraphy variables registered. Neither were there any correlations between actigraphy-recorded motor function and clinical symptoms of alcohol withdrawal, but there was a significant association between self-reported and actigraphy-recorded sleep. Compared to healthy controls, motor activity during alcohol withdrawal was lower in the evenings and showed increased variability. CONCLUSION: Intranasal oxytocin did not affect actigraphy-recorded motor activity nor sleep in patients with acute alcohol withdrawal. There were no findings indicating that actigraphy can be used to evaluate the degree of withdrawal symptoms during detoxification. However, patients undergoing acute alcohol withdrawal had a motor activity pattern different from than in healthy controls.

Neonatal adaptation following intrauterine antidepressant exposure: assessment, drug assay levels, and infant development outcomes.

BackgroundAlthough a meta-analysis has confirmed the association between antidepressant exposure in utero and subsequent poor neonatal adaptation, few identified studies included drug levels or standardized measures and only two studies followed up children who developed symptoms beyond infancy.MethodsThe study draws on the Mercy Pregnancy and Emotional Wellbeing Study and reports on 42 women/infant pairs at delivery. In all, 31 women continued to take antidepressants until delivery and 11 ceased earlier in pregnancy. Poor neonatal adaptation was assessed twice daily for up to 6 days by using the Neonatal Abstinence Scoring System (NASS). Drug levels were analyzed in umbilical cord blood and maternal blood obtained at delivery.ResultsIn total, 76% (32 of 42) of neonates exposed to antidepressants had symptoms observed on the NASS. These symptoms occurred up to 5 days postpartum with 25% having symptoms that persisted for more than 3 days. The most frequent symptoms were correlated most closely to antidepressant drug levels. Elevated NASS scores were found to be associated with poorer fine motor development at 6 months of age.ConclusionsPoor neonatal adaptation may be more common than previously recognized. The NASS was observed to be an effective assessment and monitoring measure. Research following symptomatic infants beyond the neonatal period is required.

Quality assessment of structure and language elements of written responses given by seven Scandinavian drug information centres.

PURPOSE: The aim of this study was to identify structure and language elements affecting the quality of responses from Scandinavian drug information centres (DICs). METHODS: Six different fictitious drug-related queries were sent to each of seven Scandinavian DICs. The centres were blinded for which queries were part of the study. The responses were assessed qualitatively by six clinical pharmacologists (internal experts) and six general practitioners (GPs, external experts). In addition, linguistic aspects of the responses were evaluated by a plain language expert. RESULTS: The quality of responses was generally judged as satisfactory to good. Presenting specific advice and conclusions were considered to improve the quality of the responses. However, small nuances in language formulations could affect the individual judgments of the experts, e.g. on whether or not advice was given. Some experts preferred the use of primary sources to the use of secondary and tertiary sources. Both internal and external experts criticised the use of abbreviations, professional terminology and study findings that was left unexplained. The plain language expert emphasised the importance of defining and explaining pharmacological terms to ensure that enquirers understand the response as intended. In addition, more use of active voice and less compressed text structure would be desirable. CONCLUSIONS: This evaluation of responses to DIC queries may give some indications on how to improve written responses on drug-related queries with respect to language and text structure. Giving specific advice and precise conclusions and avoiding too compressed language and non-standard abbreviations may aid to reach this goal.

Drug Information Services Today: Current Role and Future Perspectives in Rational Drug Therapy.

Polypharmacy and complex drug treatment regimens are becoming increasingly common, which may lead to adverse drug reactions, drug interactions, medication nonadherence, and increasing costs and thus challenge the rational use of drugs. At the same time, the accessibility of drug information increases, and health care professionals may have limited opportunities and capabilities to search and critically evaluate drug information. Clinicians have reported difficulties in searching the best evidence and translating study findings into clinically meaningful information applicable to specific patients. Consequently, it remains a challenge to ensure the rational use of drugs in the years to come. Drug information centers (DICs) have been established to promote the rational use of drugs. One of the most important tasks of DICs is the question and answer services for health care professionals posing drug-related questions. DICs staffed by pharmacists and clinical pharmacologists hold expertise in searching for drug information and critical evaluation of the literature. The uniqueness in this service lies not only in the identification and interpretation of the scientific literature but also in the adaptation of the findings into specific clinical situations and the discussion of possible solutions with the enquirer. Thus, DICs could provide valuable decision support to the clinic. Taking into account the increasing number of possible drug-related questions that will arise today and in the future, the DICs will remain highly relevant in the years to come. However, the DICs must follow the developments in health information technology to disseminate relevant, unbiased drug information to old and new users of the service. Moreover, the DICs are important tools to counterbalance the drug information published by the pharmaceutical industry.

[Written pharmaceutical advertising--still unreliable?]. / Skriftlig legemiddelreklame--fremdeles ikke til å stole på?

BACKGROUND: Marketing by the pharmaceutical industry affects doctors' prescribing habits. MATERIAL AND METHOD: All pharmaceutical advertising received by nine doctors in two GP offices over a period of three months was collected. The advertising material was sorted by compound. For each compound, the advert with the highest number of references was selected. The cited references were obtained, and the claims in the adverts were assessed in terms of their consistency with the source data based on the provisions in the Norwegian regulations on pharmaceuticals. The references were also assessed with regard to the incidence of conflicts of interest among authors. RESULTS: The doctors received a total of 270 shipments of advertising for 46 different compounds. Altogether 95% of the 173 references cited in the 46 selected adverts could be obtained. The adverts contained a total of 156 claims. Of these, 56% were assessed as correct when compared to the source data and as having clinical relevance. Altogether 75% of the journal articles reported relevant conflicts of interest for the authors. INTERPRETATION: About half the claims in the adverts were found to be correct and clinically relevant. These results concur with those from a methodologically identical study based on advertising material collected in 2004. The cited literature was of varying quality and often funded by the pharmaceutical companies. The findings indicate that the target group should be sceptical of this type of marketing.

[Potentially addictive drugs on reimbursable prescription for chronic severe pain]. / Potensielt vanedannende legemidler på blåresept ved kroniske sterke smerter.

BACKGROUND: Changes in the Norwegian drug reimbursement system in 2008 included the establishment of a new reimbursement code (-71) which authorises coverage of expenditures for potentially addictive drugs in patients with severe, predominantly non-malignant, chronic pain. This reform has hitherto not been evaluated. MATERIAL AND METHOD: We assessed national data on drug reimbursements in accordance with code -71 for the period 2008-2011, and anonymised copies of all confirmation letters granting reimbursements according to code -71 in Central Norway (three counties) for 2010. Approximately 1300 individual applicants' gender and age, diagnosis, potentially addictive drug applied for, drug dose, and identity and specialty of the prescribing physician, were recorded. RESULTS: From the time of establishment, reimbursement code -71 has been utilised by an increasing number of individuals, encompassing close to 10,000 subjects in 3rd quarter 2011. Almost one-third of the approved applications were for pregabalin, and the rest were for various opioids. The diagnoses were most often derived from the musculoskeletal and nervous systems, and were often nonspecific. A considerable number of treatment regimens were not in accordance with current principles for the management of chronic non-malignant pain, and drug doses were at times remarkably high. INTERPRETATION: Aspects of this drug reimbursement regulation should be closely monitored, and may be in need of changes.

[Drug-related claims in the Norwegian system of compensation to patients]. / Legemiddelsaker i Norsk pasientskadeerstatning.

BACKGROUND: Patients subjected to drug-related injuries can, in accordance with Norwegian legislation, seek compensation from the Norwegian System of Patient Injury Compensation (NPE). The aim of this study was to examine what drugs and injuries instigate claims against NPE, and how these cases are resolved. MATERIAL AND METHODS: We have assessed anonymised summaries of 992 consecutive indemnity applications received and evaluated by NPE over the period 2003-2009. We recorded the age and gender of applicants, treatment diagnosis, drugs implicated, outcome, and NPE's decision in each case. RESULTS: A total of 964 claims were included. The most commonly implicated drugs were those affecting the nervous system (34.6%) and the musculoskeletal system (26.1%). Rofecoxib at 18.9% was the predominant single drug implicated. In two-thirds of the cases, adverse effects were given as the reason for the claim, whereas the last one-third consisted of claims for medication errors. The most common injuries were related to cardiovascular diseases (28.7%) or non-specific conditions (17.5%). 8.4% of the cases related to fatalities. In all, 26.3% of the claims resulted in compensations. INTERPRETATION: Few patients made use of the NPE. Most of the compensation claims in the years 2003-2009 involved rofecoxib and psychoactive drugs, and the majority of claims were rejected.

Venous thromboembolism in recipients of antipsychotics: incidence, mechanisms and management.

Since chlorpromazine was introduced to the market in the early 1950s, the use of antipsychotic drugs has been associated with venous thromboembolism (VTE) in a number of reports. During the last decade the evidence has been strengthened with large epidemiological studies. Whether all antipsychotics increase the risk for VTE or the risk is confined to certain drugs is still unclear. The aim of this article is to present an updated critical review focusing on the incidence, mechanisms and management of VTE in users of antipsychotics. After searching the databases PubMed and Scopus for relevant articles we identified 12 observational studies, all of which were published after the year 2000. In most of these studies an elevated risk of VTE was observed for antipsychotic drugs, with the highest risk for clozapine, olanzapine and low-potency first-generation antipsychotics. The risk seems to be correlated with dose. The elderly, who mainly use lower doses, do not show an increased risk of VTE to the same extent as younger subjects. The underlying biological mechanisms explaining the association between antipsychotic medication and VTE are to a large extent unknown. Several hypotheses have been proposed, such as body weight gain, sedation, enhanced platelet aggregation, increased levels of antiphospholipid antibodies, hyperprolactinaemia and hyperhomocysteinaemia. The risk of VTE in schizophrenia and other psychotic disorders may also be related to the underlying disease rather than the medication. Very limited evidence exists to guide how cases of VTE in subjects using antipsychotics should be handled. An attempt to compile an algorithm where the patients' individual risk of VTE is assessed and preventive clinical measures are suggested has been published recently. Strong consideration should be given to discontinuation of the offending antipsychotic drug in patients experiencing a VTE, and another antipsychotic drug with a presumably lower risk should be chosen if antipsychotic drug treatment is still indicated. It is essential that physicians and patients are aware that VTE may be an adverse drug reaction to the antipsychotic treatment so the condition is identified early and treated appropriately.

[Routines for first prescription of oral contraceptives]. / Rutiner ved førstegangsforskrivning av p-piller.

BACKGROUND: There is an increasing awareness about the risk of thromboembolic disease caused by combination oral contraceptives. This study assesses routines associated with prescription of an oral contraceptive, with an emphasis on venous thromboembolic disease. MATERIAL AND METHODS: A questionnaire requesting information about medical history, examinations, and general routines when an oral contraceptive was prescribed for the first time was sent to general practitioners, public health nurses and midwives in two Norwegian counties in 2008. A slightly different questionnaire was distributed to a group of female medical students. They were requested to describe the queries, procedures and information they were subjected to when oral contraceptives was first prescribed for themselves. RESULTS: In total, 99-100% of the prescribers reported that they asked about smoking habits and venous thromboembolic disease in the family. 94% of the doctors and 100% of the public health nurses/midwives informed about the risk of venous thromboembolic disease (p=0.028). The students reported that they had been asked, examined and informed less often than that reported by health professionals. 54% of the physicians and 11% of the public health nurses /midwives most often prescribed third generation oral contraceptives (p < 0.001). INTERPRETATION: Doctors, midwives and public health nurses seem to examine and inform their patients thoroughly about the risk of venous thromboembolic complications when prescribing combination oral contraceptives for the first time. Public health nurses and midwives seem to have a more rational prescription pattern of combined oral contraceptives than doctors.

Norwegian medical students' attitudes towards the pharmaceutical industry.

OBJECTIVE: Whereas there is a considerable body of information on the interaction between physicians and the pharmaceutical industry, little is known about the pharmaceutical industry-medical student relationship. We have assessed the extent of contact between Norwegian medical students and the pharmaceutical industry as well as the attitudes of these students towards the pharmaceutical industry. METHODS: A self-assessment questionnaire was distributed to fifth- and sixth-year students attending the four medical schools in Norway and to Norwegian medical students attending selected universities abroad. RESULTS: A total of 65.8% of all eligible students returned a completed questionnaire. Of these, 73.9% had been exposed to various levels of contact with the pharmaceutical industry, but only 17.5% reported having a generally positive attitude towards the industry. The level of exposure did not correlate in students' attitudes; rather, it correlated positively to a feeling of competence in terms of being able to handle such interactions. A majority of students responded that while they would decline accepting monetary gifts, they would welcome receiving reimbursements for meeting expenses, meals and educational material. Students favoured a practice of full disclosure of potential industry-related conflicts of interest among the university teaching staff. There were considerable differences in the students' attitudes between universities, suggesting that medical students are prone to influence from university lecturers. CONCLUSIONS: Norwegian medical students are opinionated, critical and curious with respect to pharmaceutical industry relations. This interest can be explored and probably also modified by educational initiatives.

[Medication errors in hospitalised patients]. / Feilmedisinering hos pasienter innlagt i sykehus.

BACKGROUND: Medication errors can arise both during prescription and administration (dispensing and distribution) of drugs. Little is known about types of medication errors in Norwegian hospitals. MATERIAL AND METHOD: All medication errors reported at St. Olav's Hospital from 1 July 2002 to 30 June 2006 were reviewed and analysed. RESULTS: 610 reports were identified. The most common cause of reporting (39 %) was prescription of a different dose from the one prescribed. Other frequent causes were administration of a different drug than the one prescribed (17 %), inadvertent subcutaneous infusion of an intravenous drug (15 %), and that the drug was given to another patient (12 %). The errors were almost exclusively reported by nurses. In 107 cases (18 %), precautions had been taken to reduce the extent of injury after the error had been identified. The causes of errors could be classified in three main categories: Nonvigilance caused by stress, lack of appropriate routines or violation of them, and lack of appropriate skills/negligence. INTERPRETATION: Changes of routines, improved education in existing routines, and increased pharmacological competence may contribute to prevention of medication errors.

[Written drug advertisements--are they reliable?]. / Skriftlig legemiddelreklame--til å stole på?

BACKGROUND: Drug advertisements affect the practice and continuous education of physicians. We assessed whether drug advertisements in Norway were in accordance with national regulations in the field. METHODS: All drug advertisements received by three general practitioners during a period of three months were collected. One advertisement for each of the 50 pharmaceutical products most frequently advertised was reviewed, available references obtained, and the information evaluated in relation to Norwegian regulations. RESULTS: A total of 294 advertisements for 77 different products were reviewed. The 50 chosen advertisements contained 191 reference citations, of which 93% were retrieved. The originator of the advertisement in question provided 72% of the references we asked for. We identified 262 promotional claims for which the regulations require a reference citation. Of these, 135 (52%) did not comply with the regulations, including 15 (6%) that were false. CONCLUSION: Only half of the information presented in drug advertisements was correct and clinically relevant. Relatively few statements were false, but a considerable proportion of statements gave an excessively positive picture of the product; hence, in general, this kind of information has no value as a source of information.