Stability evaluation of morphine, hydromorphone, metamizole and esketamine containing analgesic mixtures applied for patient-controlled analgesia in hospice and palliative care.

In this study, different injection solutions containing opioid and nonopioid compounds used for patient-controlled analgesia in hospice and palliative care were evaluated in terms of analyte stability. Investigated injection solutions contained different combinations of morphine, hydromorphone, metamizole and esketamine. For the practical implementation, samples from infusion pumps were daily drawn over a period of 7 days at 22 and 37°C. Quantitative measurements were performed on a high-performance liquid chromatography system with ultraviolet detection applying a validated analytical method. All compounds apart from morphine showed no evident changes in concentration. However, a significant loss of morphine was observed for injection mixtures containing both morphine and metamizole at 37°C. After 7 days, only 72% of the initially measured morphine concentration was measured in the binary and 77% in the ternary mixture. Furthermore, an additional compound was detected that could represent the morphine-metamizole-adduct, "metamorphine". Based on these results, a significantly reduced morphine concentration must be expected after only 3 days if an injection solution mixture containing both morphine and metamizole is administered to a patient at 37°C. Since the analgesic effects of morphine-metamizole adducts have not yet been thoroughly investigated, further clinical studies are necessary before accurate conclusions can be drawn in this regard.

Overcoming limitations in the availability of swabs systems used for SARS-CoV-2 laboratory diagnostics.

The diagnosis of COVID-19 relies on the direct detection of SARS-CoV-2 RNA in respiratory specimens by RT-PCR. The pandemic spread of the disease caused an imbalance between demand and supply of materials and reagents needed for diagnostic purposes including swab sets. In a comparative effectiveness study, we conducted serial follow-up swabs in hospitalized laboratory-confirmed COVID-19 patients. We assessed the diagnostic performance of an in-house system developed according to recommendations by the US CDC. In a total of 96 serial swabs, we found significant differences in the accuracy of the different swab systems to generate a positive result in SARS-CoV-2 RT-PCR, ranging from around 50 to 80%. Of note, an in-house swab system was superior to most commercially available sets as reflected by significantly lower Ct values of viral genes. Thus, a simple combination of broadly available materials may enable diagnostic laboratories to bypass global limitations in the supply of swab sets.

Anidulafungin and Micafungin Concentrations in Cerebrospinal Fluid and in Cerebral Cortex.

Anidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin levels (<0.01 to 0.66 µg/ml) and micafungin levels (<0.01 to 0.16 µg/ml) were lower than those in plasma concentrations (0.77 to 5.07 and 1.21 to 8.70 µg/ml, respectively) drawn simultaneously. In cerebral cortex, anidulafungin and micafungin levels were 0.21 to 2.34 and 0.18 to 2.88 µg/g, respectively. Thus, MIC values of several pathogenic Candida strains exceed concentrations in CSF and in brain.

Prospective Risk Assessment of Medicine Shortages in Europe and Israel: Findings and Implications.

INTRODUCTION: While medicine shortages are complex, their mitigation is more of a challenge. Prospective risk assessment as a means to mitigate possible shortages, has yet to be applied equally across healthcare settings. The aims of this study have been to: 1) gain insight into risk-prevention against possible medicine shortages among healthcare experts; 2) review existing strategies for minimizing patient-health risks through applied risk assessment; and 3) learn from experiences related to application in practice. METHODOLOGY: A semi-structured questionnaire focusing on medicine shortages was distributed electronically to members of the European Cooperation in Science and Technology (COST) Action 15105 (28 member countries) and to hospital pharmacists of the European Association of Hospital Pharmacists (EAHP) (including associated healthcare professionals). Their answers were subjected to both qualitative and quantitative analysis (Microsoft Office Excel 2010 and IBM SPSS Statistics®) with descriptive statistics based on the distribution of responses. Their proportional difference was tested by the chi-square test and Fisher's exact test for independence. Differences in the observed ordinal variables were tested by the Mann-Whitney or Kruskal-Wallis test. The qualitative data were tabulated and recombined with the quantitative data to observe, uncover and interpret meanings and patterns. RESULTS: The participants (61.7%) are aware of the use of risk assessment procedures as a coping strategy for medicine shortages, and named the particular risk assessment procedure they are familiar with failure mode and effect analysis (FMEA) (26.4%), root cause analysis (RCA) (23.5%), the healthcare FMEA (HFMEA) (14.7%), and the hazard analysis and critical control point (HACCP) (14.7%). Only 29.4% report risk assessment as integrated into mitigation strategy protocols. Risk assessment is typically conducted within multidisciplinary teams (35.3%). Whereas 14.7% participants were aware of legislation stipulating risk assessment implementation in shortages, 88.2% claimed not to have reported their findings to their respective official institutions. 85.3% consider risk assessment a useful mitigation strategy. CONCLUSION: The study indicates a lack of systematically organized tools used to prospectively analyze clinical as well as operationalized risk stemming from medicine shortages in healthcare. There is also a lack of legal instruments and sufficient data confirming the necessity and usefulness of risk assessment in mitigating medicine shortages in Europe.

A nationwide computerized patient medication history: evaluation of the Austrian pilot project "e-Medikation".

PURPOSE: To manage medication treatment and to assure medication safety, health care professionals need a complete overview of all drugs that have been prescribed or are taken by a patient. In 2009, Austria launched the pilot project "e-Medikation" in three pilot regions. E-Medikation gives access to a patient's nationwide medication list and includes medication safety checks. The objective of this paper is to report on the evaluation results and lessons learnt. METHODS: A formative evaluation study performed between July and December 2011 comprised a standardized survey of participating physicians, pharmacists, and patients, as well as an analysis of the e-Medikation log files. RESULTS: During the evaluation period, 18,310 prescriptions and 13,797 dispensings were documented, and 22,359 medication safety checks were performed. Overall, 61 physicians, 68 pharmacists, and 553 patients responded to a written survey. The results showed high acceptance of the idea of e-Medikation among pharmacists and patients and mixed acceptance among physicians. The satisfaction with the quality of the software used in the pilot project was low. CONCLUSIONS: The overall aim to increase medication safety seems achievable through e-Medikation, but several limitations of the pilot project need to be solved before a national rollout. Based on the evaluation results and after redesign of e-Medikation, Austria is now planning a nationwide introduction of e-Medikation starting in 2015.

Prevalence of hypovitaminosis D and folate deficiency in healthy young female Austrian students in a health care profession.

PURPOSE: We performed a single-day cross-sectional study to assess the prevalence of vitamin D deficiency as well as folate status in healthy young female volunteers well educated with respect to health information. METHODS: We assessed dietary intake of vitamin D and calcium, serum concentrations of 25-OH-vitamin D(3), folate, red blood cell folate and other dietary, laboratory, and lifestyle parameters in 215 young healthy women (age 18-30 years) on a single day at the end of the winter months. Primary aim was to investigate the prevalence of hypovitaminosis D. Folic acid status was a secondary study aim. RESULTS: Mean daily ingestion of vitamin D was 2.25 µg/day with a daily calcium intake of 749 mg/day. 6.9% had hypovitaminosis D (25-OH-vitamin D(3) <30 nmol/L) and 89.3% were vitamin D insufficient (<75 nmol/L). Preplanned subpopulation comparison (lower vs. upper quartile) revealed a significant negative correlation (P = 0.048) between plasma PTH and 25-OH-vitamin D(3) levels. Fifteen individuals (6.9%) were folic acid deficient (<140 ng/mL RBC folate). Only 9.3% reached RBC folate concentrations regarded as optimal for the prevention of fetal neural tube defects (>400 ng/mL). CONCLUSIONS: The prevalence of hypovitaminosis D in healthy young women trained in health care professions is low but 89.3% can be classified as vitamin D insufficient in spring. Folate status can also be considered not sufficient. Considering the emerging role of higher vitamin D plasma levels for many health conditions, a timely correction of vitamin D status in the general Austrian population appears appropriate.