A description of pharmacists' interventions to optimise the treatment of adults with orally available Covid-drug, Paxlovid.

Paxlovid ®, the only orally available COVID drug, consists of two main components: Nirmatrelvir and Ritonavir. Ritonavir is known for the potent inhibition of CYP (cytochrome P450) enzymes in the liver mainly of CYP3A4, resulting in a large number of clinically significant drug-drug interactions (DDIs). This results in an increased number of adverse events, raising concerns for patient safety. Since numerous instances of inappropriate prescribing, particularly with co-medications, were noted at the pharmacy despite prescriber consideration at the point of prescribing, a pharmaceutical service was introduced to perform medication reviews. The aim was to describe the frequency, type, and severity of detected DDIs in Paxlovid® recipients identified during pharmacy screening. A retrospective monocentric quantitative data analysis was performed in an Austrian clinic in Vienna. Ethics approval was obtained. All patients prescribed Paxlovid® were included and data collected from the patients' electronic records. A data collection tool was developed and piloted to ensure inter-rater reliability. Drug drug interactions including prescribing recommendations were determined using the COVID 19 Drug Interactions checker developed by the University of Liverpool. 122 of 140 (87.1%) patients whose records were reviewed required dose reduction, alternative COVID medication and/or interventions to prevent interactions or overdosing. In 33 (23.5%) cases the necessary action was performed by the doctors at the point of prescribing. However, in 89 (63.6%) cases the required action was not identified at the point of prescribing but identified during the pharmaceutical medication review after Paxlovid® was ordered in the pharmacy. Since interventions were made prior to the patient receiving the supply, all patients in this group benefitted from the pharmaceutical service leading to enhancement of patient safety. This study demonstrated that many drug related problems were identified through the pharmaceutical intervention This shows that pharmacist involvement in prescribing highly interacting drugs such as Paxlovid® is beneficial to enhance patient safety and mitigate risks

Using self-drilling screws in volar plate osteosynthesis for distal radius fractures: a feasibility study

Background: Symptomatic extensor tendon irritation is a frequent complication in volar plate osteosynthesis of distal radius fractures. It is typically caused by dorsal screw protrusion and overdrilling of the dorsal cortex. The use of self-drilling locking screws (SDLS) could overcome both causes. The practical applicability of SDLS depends on two prerequisites: (1) the feasibility of preoperative distal screw length determination, and (2) sufficient primary biomechanical stability of SDLS compared to standard locking screws (SLS). Methods: We first assessed the feasibility of preoperative screw length determination (1): Distal radius width, depth and distal screw lengths were measured in 38 human radii. Correlations between distal radius width and depth were assessed, a cluster analysis (Ward's method and squared Euclidean distance) for distal radius width conducted, and intra-cluster screw lengths analyzed (ANOVA). The biomechanical performance of SDLS (2) was assessed by comparison to SLS in a distal radius fracture model (AO-23 A3). 75 % distal screw length was chosen for both groups to simulate a worst-case scenario. Uniaxial compression tests were conducted to measure stiffness, elastic limit, maximum force and residual tilt. Statistics comprised of independent sample t-tests and a Bonferroni correction (p 36.9 mm. ANOVA and Tukey post-hoc analysis revealed significantly different volar-dorsal depths (p < 0.05) for nearly all screws. (2) To assess biomechanical stability nine specimens were tested each;no significant differences were found between the SDLS and SLS groups. Conclusions: This feasibility study demonstrates that (1) distal radius width can be used as a predictor for distal screw length and (2) that SDLS provides mechanical stability equivalent to SLS. These results highlight the feasibility of applying SDLS screws in volar plate osteosynthesis at least in extraarticular fractures

Prevalence of second victims, risk factors and support strategies among young German physicians in internal medicine (SeViD-I survey)

Background: Second victims, defined as healthcare team members being traumatised by an unanticipated clinical event or outcome, are frequent in healthcare. Evidence of this phenomenon in Germany, however, is sparse. Recently, we reported the first construction and validation of a German questionnaire. This study aimed to understand this phenomenon better in a sample of young (<= 35 years) German physicians. Methods: The electronic questionnaire (SeViD-I survey) was administered for 6 weeks to a sample of young physicians in training for internal medicine or a subspecialty. All physicians were members of the German Society of Internal Medicine. The questionnaire had three domains - general experience, symptoms, and support strategies - comprising 46 items. Binary logistic regression models were applied to study the influence of various independent factors on the risk of becoming a second victim, the magnitude of symptoms and the time to self-perceived recovery. Results: The response rate was 18% (555/3047). 65% of the participants were female, the mean age was 32 years. 59% experienced second victim incidents in their career so far and 35% during the past 12 months. Events with patient harm and unexpected patient deaths or suicides were the most frequent key incidents. 12% of the participants reported that their self-perceived time to full recovery was more than 1 year or have never recovered. Being female was a risk factor for being a second victim (odds ratio (OR) 2.5) and experiencing a high symptom load (OR 2). Working in acute care was promoting a shorter duration to self-perceived recovery (OR 0.5). Support measures with an exceptionally high approval among second victims were the possibility to discuss emotional and ethical issues, prompt debriefing/crisis intervention after the incident and a safe opportunity to contribute insights to prevent similar events in the future. Conclusion: The second victim phenomenon is frequent among young German physicians in internal medicine. In general, these traumatic events have a potentially high impact on physician health and the care they deliver. A better understanding of second victim traumatisations in Germany and broad implementation of effective support programs are warranted

Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program

Background: Drug-induced liver injury is a common cause of liver damage and the most frequent reason for withdrawal of a drug in the United States. The symptoms of drug-induced liver damage are extremely diverse, with some patients remaining asymptomatic. Methods: This observational study is based on data of Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries (Austria, Germany, and Switzerland) recording severe drug reactions in psychiatric inpatients. Of 184 234 psychiatric inpatients treated with antidepressants between 1993 and 2011 in 80 psychiatric hospitals, 149 cases of drug-induced liver injury (0.08%) were reported. Results: The study revealed that incidence rates of drug-induced liver injury were highest during treatment with mianserine (0.36%), agomelatine (0.33%), and clomipramine (0.23%). The lowest probability of drug-induced liver injury occurred during treatment with selective serotonin reuptake inhibitors ([0.03%), especially escitalopram [0.01%], citalopram [0.02%], and fluoxetine [0.02%]). The most common clinical symptoms were nausea, fatigue, loss of appetite, and abdominal pain. In contrast to previous findings, the dosage at the timepoint when DILI occurred was higher in 7 of 9 substances than the median overall dosage. Regarding liver enzymes, duloxetine and clomipramine were associated with increased glutamat-pyruvat-transaminase and glutamat-oxalat-transaminase values, while mirtazapine hardly increased enzyme values. By contrast, duloxetine performed best in terms of gamma-glutamyl-transferase values, and trimipramine, clomipramine, and venlafaxine performed worst. Conclusions: Our findings suggest that selective serotonin reuptake inhibitors are less likely than the other antidepressants, examined in this study, to precipitate drug-induced liver injury, especially in patients with preknown liver dysfunction

Macular atrophy in patients with long-term anti-VEGF treatment for neovascular age-related macular degeneration.

PURPOSE To identify the prevalence and progression of macular atrophy (MA) in neovascular age-related macular degeneration (AMD) patients under long-term anti-vascular endothelial growth factor (VEGF) therapy and to determine risk factors. METHOD This retrospective study included patients with neovascular AMD and ≥30 anti-VEGF injections. Macular atrophy (MA) was measured using near infrared and spectral-domain optical coherence tomography (SD-OCT). Yearly growth rate was estimated using square-root transformation to adjust for baseline area and allow for linearization of growth rate. Multiple regression with Akaike information criterion (AIC) as model selection criterion was used to estimate the influence of various parameters on MA area. RESULTS Forty-nine eyes (47 patients, mean age 77 ± 14) were included with a mean of 48 ± 13 intravitreal anti-VEGF injections (ranibizumab:37 ± 11, aflibercept:11 ± 6, mean number of injections/year 8 ± 2.1) over a mean treatment period of 6.2 ± 1.3 years (range 4-8.5). Mean best-corrected visual acuity improved from 57 ± 17 letters at baseline (= treatment start) to 60 ± 16 letters at last follow-up. The MA prevalence within and outside the choroidal neovascularization (CNV) border at initial measurement was 45% and increased to 74%. Mean MA area increased from 1.8 ± 2.7 mm(2) within and 0.5 ± 0.98 mm(2) outside the CNV boundary to 2.7 ± 3.4 mm(2) and 1.7 ± 1.8 mm(2) , respectively. Multivariate regression determined posterior vitreous detachment (PVD) and presence/development of intraretinal cysts (IRCs) as significant factors for total MA size (R(2) = 0.16, p = 0.02). Macular atrophy (MA) area outside the CNV border was best explained by the presence of reticular pseudodrusen (RPD) and IRC (R(2) = 0.24, p = 0.02). CONCLUSION A majority of patients show MA after long-term anti-VEGF treatment. Reticular pseudodrusen (RPD), IRC and PVD but not number of injections or treatment duration seem to be associated with the MA size

The impact of ganglion cell layer cysts in diabetic macular oedema treated with anti-vascular endothelial growth factor.

PURPOSE To investigate the prevalence and impact of ganglion cell layer cysts (GCLC) in patients with diabetic macular oedema (DME) under continuous anti-vascular endothelial growth factor (VEGF) therapy. METHODS The clinical findings and spectral domain optical coherence devices of baseline visits and follow-up after 12-24 and 36 months of DME patients under continuous anti-VEGF therapy were retrospectively collected and analysed for the impact of GCLC cysts. Previously established prognostic parameters were also assessed. RESULTS A total of 110 eyes of 110 DME patients (mean age 64 ± 10 years) were included. At baseline, 17% eyes had GCLC. With GCLC, the best-corrected visual acuity (BCVA) improvement was in mean 8.4 ± 2.4 Early-Treatment-Diabetic-Retinopathy-Study (ETDRS) letters less over the course of 36 months compared to the group lacking GCLC (p = 0.0009). Eyes with GCLC showed 68 ± 23.4 μm less central retinal thickness (CRT) decrease than eyes lacking GCLC (p < 0.0001). In the linear mixed effect models including external limiting membrane disruption, disintegration of inner retinal layer and epiretinal membrane, GCLC remained a statistical significant factor for the outcome parameter CRT, but missed statistical significance for BCVA. CONCLUSION Ganglion cell layer cysts (GCLC) seem to impact outcome in DME in patients receiving long-term treatment. This prognostic factor warrants further evaluation in the context of already well-established outcome parameters

Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program

Background: Drug-induced liver injury is a common cause of liver damage and the most frequent reason for withdrawal of a drug in the United States. The symptoms of drug-induced liver damage are extremely diverse, with some patients remaining asymptomatic. Methods: This observational study is based on data of Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries (Austria, Germany, and Switzerland) recording severe drug reactions in psychiatric inpatients. Of 184 234 psychiatric inpatients treated with antidepressants between 1993 and 2011 in 80 psychiatric hospitals, 149 cases of drug-induced liver injury (0.08%) were reported. Results: The study revealed that incidence rates of drug-induced liver injury were highest during treatment with mianserine (0.36%), agomelatine (0.33%), and clomipramine (0.23%). The lowest probability of drug-induced liver injury occurred during treatment with selective serotonin reuptake inhibitors ([0.03%), especially escitalopram [0.01%], citalopram [0.02%], and fluoxetine [0.02%]). The most common clinical symptoms were nausea, fatigue, loss of appetite, and abdominal pain. In contrast to previous findings, the dosage at the timepoint when DILI occurred was higher in 7 of 9 substances than the median overall dosage. Regarding liver enzymes, duloxetine and clomipramine were associated with increased glutamat-pyruvat-transaminase and glutamat-oxalat-transaminase values, while mirtazapine hardly increased enzyme values. By contrast, duloxetine performed best in terms of gamma-glutamyl-transferase values, and trimipramine, clomipramine, and venlafaxine performed worst. Conclusions: Our findings suggest that selective serotonin reuptake inhibitors are less likely than the other antidepressants, examined in this study, to precipitate drug-induced liver injury, especially in patients with preknown liver dysfunction

Evaluation of vascular changes in intermediate uveitis and retinal vasculitis using swept-source wide-field optical coherence tomography angiography.

PURPOSE To evaluate vascular changes in patients with intermediate uveitis with or without retinal vasculitis using swept-source wide-field optical coherence tomography angiography (OCTA). METHODS This is a prospective cross-sectional study. Consecutive patients with intermediate uveitis were evaluated using wide-field OCTA. Wide-field OCTA and en-face OCT images were analysed for the presence of capillary non-perfusion and reduced perfusion, disruption of ellipsoid zone, and abnormalities on en-face wide-field retinal thickness maps, respectively, and compared with fluorescein angiography (FA) findings in a subcohort. RESULTS 164 eyes of 88 patients with intermediate uveitis were included. Areas of capillary non-perfusion and reduced perfusion were more frequently observed in the choroidal OCTA slab (33.3% and 49.4%), choriocapillaris (CC; 31.4% and 48%) and deep capillary plexus (DCP; 9.6% and 34.6%) than in the superficial capillary plexus (SCP; 5% and 26.3%), respectively. Intermediate uveitis with vasculitis presented more frequently with non-perfusion and hypoperfusion in the DCP (p=0.003 and p=0.05, respectively) and SCP (p=0.007 and p=0.005, respectively) than intermediate uveitis without vasculitis. Peripheral capillary leakage on FA correlated with the presence of perivascular, macular and generalised thickening on en-face wide-field thickness maps (p=0.007). Ischaemia on FA was significantly associated with non-perfusion on wide-field OCTA in SCP and DCP (p=0.019 and p=0.027, respectively). CONCLUSION Changes in the choroid, CC and DCP are more frequently found than in the SCP on wide-field OCTA in intermediate uveitis. While wide-field OCTA is a reliable tool to detect capillary non-perfusion in intermediate uveitis, it was not helpful in determining disease activity. TRIAL REGISTRATION NUMBER NCT02811536