Optimizing pharmaceutical management of clinical trials.

OBJECTIVES: The clinical trials pharmacists have an essential role in managing the pharmaceutical part of interventional studies. The primary objective of this article was to provide a template for improving trials management for the growing number of studies without increasing personnel resources. MATERIAL AND METHODS: A retrospective study was conducted between 2016 and 2020 at the service of pharmacy at Lausanne University Hospital in Switzerland. RESULTS: The number of clinical trials (in progress) managed at the pharmacy increased from 77 to 115 (+49%) between 2016 and 2020. The majority of these studies were in oncology and were sponsored by industry. Therefore, different changes in routine tasks were decided during the 5 years term to meet the above challenge. These modifications allowed to improve pharmaceutical and administrative management of clinical trials, without increasing personnel resources. The management template was accepted by the sponsors, and no issues were mentioned by national and international audit authorities. CONCLUSION: Changes could be made in the routine practice of the clinical trials pharmacists to improve the management of studies, while the number of trials is increasing every year.

Parenteral Nutrition Process Management for Newborn and Preterm Infants - A Preliminary Risk Analysis.

BACKGROUND: There are variable practices in the management of the parenteral nutrition (PN) process in hospitals having a neonatal intensive care unit (NICU). In our hospital, PN is prepared partially on the neonatal ward by nurses but also at the central pharmacy by trained pharmacy technicians. A previous study showed a concentration non-conformity of 34% of on-ward PN preparations potentially resulting in under- or overfeeding of the patients. OBJECTIVE: The objectives were to perform preliminary risk analyses (PRA) in preparation for our hospital's transition to universal central pharmacy PN compounding. METHODS: A working group including pharmacists, neonatologists, nurses, and pharmacy technicians performed two PRA. The risks of 9 management steps of the PN process were identified, evaluated, and quoted. A comparison of the number of risks and their criticality index (CI) was conducted. RESULTS: A total of 36 and 39 risks were identified for PN preparation in the NICU and the pharmacy, respectively. For the NICU, ten risks (28%) had an "acceptable" CI, 15 risks (42%) were "under control" and eleven (31%) were defined as "non-acceptable". For the pharmacy, 14 risks (36%) had an "acceptable" CI, 19 risks (49%) were "under control" and six (15%) were defined as "non-acceptable". Risks directly related to the preparation process, including the steps preparation hood, PN preparation and analytical quality control, represented a cumulated CI of 145 for eleven NICU-risks vs 108 for twelve pharmacy risks (-26%). The implementation of immediate improvement measures, eg, an electronic prescription form, reduces the total CI by 5.7% and 2.2% for the NICU and the pharmacy, respectively. CONCLUSION: This PRA highlighted the safety differences between PN preparation in the NICU vs the pharmacy at our institution, and facilitated our moving forward with a process change that should improve the care of our neonatal patients. Nevertheless, long-term improvement measures have to be implemented to further reduce risks related to the PN management process.

Quality and safety of parenteral nutrition for newborn and preterm infants as an on-ward preparation.

BACKGROUND: For newborn and preterm infants, standardised and individual parenteral nutrition (PN) is used. PN preparation is at risk for contamination and dosing errors. The quality of PN is crucial for infants and has a direct impact on their health status and safety. PURPOSE: The aim of this study is to evaluate the physicochemical and microbial quality of PN for newborn and preterm infants prepared on a neonatal ward. METHODS: Sampling of various individual PN prepared by nurses on a neonatal ward was performed. Formulations included maximal four electrolytes, variable dextrose and amino acid concentrations. Depending on the sample volume, up to three quality analyses were performed: (1) test for bacterial endotoxins by kinetic-chromogenic method, (2) sterility according to the European and US Pharmacopoeia, and (3) quantification of electrolytes by capillary electrophoresis and of dextrose by ultraviolet detection after enzymatic reaction of hexokinase. The concentrations obtained were evaluated based on the US and Swiss Pharmacopoeia specifications for compounded preparations and compared to the widened pharmacy specifications. RESULTS: The composition of 86% of the 110 analysed PN prepared by nurses on the neonatal ward corresponded to their medical prescription. 14% were out of the acceptable widened pharmacy ranges. We found no microbial contamination in the samples. All PN were free from endotoxins. CONCLUSION: Component concentrations of PN prepared on wards by nurses differed frequently and significantly from their medical prescription, and the deviation can be critical depending on the component and its mode of action. The sample size is too small to evaluate the microbial contamination.

Stability of N-Acetylcysteine (NAC) in Standardized Pediatric Parenteral Nutrition and Evaluation of N,N-Diacetylcystine (DAC) Formation.

The ESPGHAN/ESPEN/ESPR-Guidelines on pediatric parenteral nutrition (PPN) recommend the administration of the semiessential amino acid (AA) cysteine to preterm neonates due to their biochemical immaturity resulting in an inability to sufficiently synthetize endogenous cysteine. The soluble precursor N-acetylcysteine (NAC) is easily converted into bioavailable cysteine. Its dimer N,N-diacetylcystine (DAC) is almost unconvertable to cysteine when given intravenously resulting in a diminished bioavailability of cysteine. This study aims to understand the triggers and oxidation process of NAC to DAC to evaluate possibilities of reducing DAC formation in standardized PPN. Therefore, different air volumes (21% O2) were injected into the AA compartment of a standardized dual-chamber PPN. O2 concentrations were measured in the AA solution and the headspaces of the primary and secondary packaging. NAC and DAC concentrations were analyzed simultaneously. The analysis showed that O2 is principally delivered from the primary headspace. NAC oxidation exclusively delivers DAC, depending on the O2 amount in the solution and the headspaces. The reaction of NAC to DAC being containable by limiting the O2 concentration, the primary headspace must be minimized during manufacturing, and oxygen absorbers must be added into the secondary packaging for a long-term storage of semipermeable containers.

Measuring anger in patients experiencing chronic pain - A systematic review.

Anger is prevalent in chronic pain and has been associated with pain perception, disability, behavior and treatment outcome. Objectives were (1) to survey in the context of chronic pain the application (and omission) of validated anger self-report instruments, (2) to discuss the instruments found in the context of emotion theories and (3) to identify a possible instrument preference. A systematic search of textbooks and review articles was first performed on validated instruments designed to measure the cognitive, the motivational and the subjective feeling component of anger. Thereafter, a systematic review aimed at finding chronic pain studies from 2005 to 2019 reporting on these instruments. Textbooks and reviews listed 16 validated self-report anger measurement instruments. 28 papers applying four of these were identified and two new instruments were additionally detected. The State-Trait Anger Expression (STAXI) and its precursors were most commonly used. Studies on chronic low back pain patients prevailed. In conclusion, anger in chronic pain patients is reliably measurable at low cost with self-report tools. The STAXI-II qualifies best for this purpose based on its extensive validation history. The majority of instruments lack sufficient theoretical and psychometric adequacy. A more detailed exploration of the cognitive anger component in chronic pain patients in future research is recommended.

Design, construction, and technical implementation of a web-based interdisciplinary symptom evaluation (WISE) - a heuristic proposal for orofacial pain and temporomandibular disorders.

BACKGROUND: Medical symptoms independent of body location burden individuals to varying degrees and may require care by more than one expert. Various paper and computer-based tools exist that aim to comprehensively capture data for optimal clinical management and research. METHODS: A web-based interdisciplinary symptom evaluation (WISE) was newly designed, constructed, and technically implemented. For worldwide applicability and to avoid copyright infringements, open source software tools and free validated questionnaires available in multiple languages were used. Highly secure data storage limits access strictly to those who use the tool for collecting, storing, and evaluating their data. Concept and implementation is illustrated by a WISE sample tailored for the requirements of a single center in Switzerland providing interdisciplinary care to orofacial pain and temporomandibular disorder patients. RESULTS: By combining a symptom- burden checklist with in-depth questionnaires serving as case-finding instruments, an algorithm was developed that assists in clarifying case complexity and need for targeted expert evaluation. This novel modular approach provides a personalized, response-tailored instrument for the time- and cost-effective collection of symptom-burden focused quantitative data. The tool includes body drawing options and instructional videos. It is applicable for biopsychosocial evaluation in a variety of clinical settings and offers direct feedback by a case report summary. CONCLUSIONS: In clinical practice, the new instrument assists in clarifying case complexity and referral need, based on symptom burden and response -tailored case finding. It provides single-case summary reports from a biopsychosocial perspective and includes graphical symptom maps. Secure, centrally stored data collection of anonymous data is possible. The tool enables personalized medicine, facilitates interprofessional education and collaboration, and allows for multicenter patient-reported outcomes research.

Review of self-reported instruments that measure sleep dysfunction in patients suffering from temporomandibular disorders and/or orofacial pain.

Patients with temporomandibular disorders (TMD) and/or orofacial pain (OFP) frequently experience poor sleep quality or suffer from comorbid sleep disorders. Study results suggest that in chronic pain patients, an improvement in sleep quality critically influences the outcomes of interventions on mood and pain. Yet, only a few studies have systematically sought to evaluate the sleep quality of TMD/OFP patients. Standardized and validated self-reported instruments designed for screening sleep disturbances or for the evaluation of treatment outcomes in this population would therefore enhance evidence and improve treatment options. The objectives of the present study were: (1) to review the self-reported instruments that measure sleep dysfunction in studies on TMD/OFP patients, by conducting a systematic literature search; (2) to evaluate their clinimetric evidence; and (3) to provide guidance for future research using such instruments. A total of 26 papers, using eight different instruments, were identified. The most frequently used questionnaires and the only ones with good clinimetric properties were the Insomnia Severity Index followed by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. They were most reliable, valid and time-effective for measuring sleep dysfunctions in patients with TMD/OFP, with only a few practical constraints. Yet, in future studies, an assessment of the relationship between sleep disturbances and chronic pain will have to include instruments measuring the effect of mediator variables such as cognitive or emotional arousal. Research is required to clarify if existing self-reported questionnaires measuring these aspects will promote further insights or if there is a need for new instruments. This future research direction would blend into the overall biopsychosocial concept of TMD/OFP diagnoses and treatment.

[Insomnia in the general practitioner's office: from diagnosis to initial interventions]. / Insomnie in der Hausarztpraxis: von der Diagnostik zu ersten Interventionen.

Insomnia is the most frequent type of sleeping disorder and - following pain - the second most common symptom reported in the general practitioner's office. The prevalence of insomnia increases with age. Untreated, insomnia is regarded as risk factor for other comorbid somatic and mental disorders. Therefore, it is important to make a thorough diagnostic and differential diagnostic assessment. Particularly interventions aiming at improving sleep hygiene and therapy using sleep restriction can help alleviate insomnia. Pharmacologically, herbal drugs and antidepressants with sleep inducing effects can be used, for short-term treatment also benzodiazepine/gaba-ergic agonists.

Parmi les troubles du sommeil, l'insomnie est considérée comme la forme la plus commune et représente ­ après la douleur ­ le problème le plus fréquent dans le cabinet du médecin généraliste. La prévalence de l'insomnie augmente avec l'âge. Une insomnie non traitée représente un facteur de risque pour le développement d'une maladie somatique ou mentale. Un diagnostic différentiel et détaillé est donc essentiel. La discussion de mesures d'hygiène du sommeil et la restriction du sommeil dans le contexte d'une thérapie comportementale et cognitive sont des techniques efficaces pour améliorer la qualité du sommeil. Au niveau pharmacologique il est possible de prescrire des médicaments à base de plantes, des antidépresseurs ou, à court terme, des benzodiazépines.

Adjustment to trauma exposure: prevalence and predictors of posttraumatic stress disorder symptoms in mountain guides.

OBJECTIVE: The present study was designed to assess the frequency of trauma exposure, the prevalence rates of posttraumatic stress disorder, comorbid symptoms, and sense of coherence (SOC) in Swiss mountain guides. METHOD: All mountain guides (n=1347) were surveyed using of the Posttraumatic Stress Diagnostic Scale (PDS), the General Health Questionnaire (GHQ-28), and the Sense of Coherence Self-Rating Scale (SOC-29). RESULTS: Although Swiss mountain guides are exposed to many traumatic situations, the prevalence rate of PTSD is very low (2.7%), and their SOC total scores are high (157.9+/-18.4). Subgroups differentiated by the extent of traumatic stress symptoms differ significantly in SOC and GHQ total scores. Regression analysis showed SOC total score to be a significant predictor, although it only accounted for 1% of the variance in the number of PTSD symptoms endorsed. CONCLUSION: The low prevalence rate of PTSD is not in line with findings in other high-risk populations for PTSD. SOC seems to be a marker for psychological health rather than a protective factor against PTSD.