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Aims Methods Results Conclusions Previous work has identified several limitations in “Summaries of Product Characteristics” (SmPCs), which are associated with risks for patients. The aim of this study was to evaluate pharmacists' and physicians' interpretation of contraindications in SmPCs and reasons for their nonadherence in clinical routine.For 20 commonly missed or ignored absolute contraindications, an anonymous online survey providing 24 clinical example cases (one or two per contraindication) for physicians and pharmacists was developed. Experts in medication safety were asked whether the respective case fulfilled the definition of the contraindication in the SmPC: (a) formally, irrespective of the clinical relevance of the contraindication (17 cases), and (b) whether the contraindication was deemed clinically relevant in each respective case (24 cases).Twenty‐seven pharmacists and 27 physicians completed the survey. For only one case (1/17; 5.8%) did all experts agree on the same answer option regarding the formal fulfilment of a given contraindication statement. Experts gave heterogeneous answers regarding the interpretation of a contraindication. For instance, among 10 predefined answer options for the contraindication “active liver disease” in the SmPC of simvastatin, every option was selected by at least six experts. In 17/24 (70.8%) clinical example cases a majority of experts agreed on the clinical relevance of a given contraindication. Key reasons for nonadherence to contraindications were “patient monitoring possible”, “lack of alternative treatment” and “acute/severe situations”.Experts' disagreement on the interpretation of contraindications in SmPCs using clinical example cases indicates that further efforts are needed to improve their usability in clinical routine. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions The optimal mode of delivery for vaginal breech presentation remains a clinical dilemma. Planned vaginal delivery offers maternal advantages because it avoids major abdominal surgery and has no consequences for following pregnancies, while elective cesarean delivery proves advantageous for the neonate because adverse outcomes are less frequent. Patient selection for vaginal breech delivery is important based on the individual risk balance. A lack of consensus exists regarding the specific contraindications for vaginal breech delivery, largely due to limited scientific evidence. This systematic review aims to give an overview of contraindications for vaginal breech delivery, as presented in guidelines, analyze relevant literature, and offer evidence‐based recommendations for the contraindications stated in the guidelines.To identify national guidelines PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, NICE, UpToDate, and ClinicalKey were searched using two keywords: “breech presentation” and “vaginal delivery.” We systematically reviewed the literature for existing evidence for contraindications for term vaginal breech delivery. The following databases were searched: PubMed (April 2024), the Cochrane Central Register of Controlled Trials, and EMBASE (1947 to 2024).Our search identified eight guidelines that stated a total of 11 contraindications for vaginal breech delivery. Among these guidelines, agreement was limited, with the sole consensus in all guidelines on the contraindication of footling breech. Our comprehensive literature search yielded 43 articles discussing 14 potential contraindications. We found supportive evidence for 7 of 11 contraindications from the guidelines, with only substantial and satisfactory evidence for two contraindications.The findings of this study underscore the lack of consensus among national guidelines regarding contraindications for term vaginal breech delivery. Furthermore, we found a notable lack of substantial scientific evidence to support these contraindications. In light of these findings, we suggest a reduced list of contraindications in vaginal breech deliveries. [ABSTRACT FROM AUTHOR]

Purpose: The study validates a rule-based system for identifying contraindications to exercise therapy in a medical context. It evaluates accuracy and performance by comparing it with physical therapists' assessments and patients' characteristics. Method: The dataset included 80 patient cases with clinical characteristics assessed by 20 physical therapists for contraindications to exercise therapy. Fleiss kappa and pooled kappa values measured agreement between physical therapists and AI. AI performance was assessed by sensitivity, specificity, accuracy and F1 score. Clinical characteristics were compared between therapists' votes using ANOVA and Bonferroni post-hoc test. Results: The physical therapists had a mean age of 40.85 (8.23) years and a mean experience of 14.53 (8.20) years. Out of 64 patient cases, there was consensus on 35 cases with no contraindication and 29 cases with a consensus on "contraindication exists" for exercise therapy. In 16 cases there was no consensus between therapists. Overall, therapists had 87.5% agreement with Fleiss Kappa κπ =.43. The pooled kappa value between therapists and AI was κpooled =.63. AI achieved perfect values (1) for sensitivity, specificity, accuracy and F1 score. Statistically, consensus-based comparisons by therapists revealed significant differences in pain intensity, duration, timing, and quality. Conclusion: The study shows significant agreement between physical therapists and the AI, consistent with similar musculoskeletal studies. Various clinical characteristics highlight the importance of clinical reasoning and contraindication detection. In conclusion, advanced technologies such as decision support and expert systems could have a profound impact on clinical practice, improving accuracy, personalized exercises and telemedicine referrals for efficient care and improved patient decisions. Trial registration: 30.12.2021 via OSF Registries, https://doi.org/10.17605/OSF.IO/YCNJQ. [ABSTRACT FROM AUTHOR]

Background: Few data are available concerning the outcome of patients denied venovenous extracorporeal membrane oxygenation (VV-ECMO) relative to severe acute respiratory distress syndrome (ARDS) due to COVID-19. Methods: We compared the 90-day survival rate of consecutive adult patients for whom our center was contacted to discuss VV-ECMO indication. Three groups of patients were created: patients for whom VV-ECMO was immediately indicated (ECMO-indicated group), patients for whom VV-ECMO was not indicated at the time of the call (ECMO-not-indicated group), and patients for whom ECMO was definitely contraindicated (ECMO-contraindicated group). Results: In total, 104 patients were referred for VV-ECMO support due to severe COVID-19 ARDS. Among them, 32 patients had immediate VV-ECMO implantation, 28 patients had no VV-ECMO indication, but 1 was assisted thereafter, and 44 patients were denied VV-ECMO for contraindication. Among the 44 patients denied, 30 were denied for advanced age, 24 for excessive prior duration of mechanical ventilation, and 16 for SOFA score >8. The 90-day survival rate was similar for the ECMO-indicated group and the ECMO-not-indicated group at 62.1 and 61.9%, respectively, whereas it was significantly lower (20.5%) for the ECMO-contraindicated group. Conclusions: Despite a low survival rate, 50% of patients were at home 3 months after being denied for VV-ECMO for severe ARDS due to COVID-19. [ABSTRACT FROM AUTHOR]

Background: Poor Bell's phenomenon is often considered a relative contraindication for ptosis surgery, as it increases the risk of corneal exposure and dry eye symptoms after surgery. However, the Bell's phenomenon may vary in different individuals and sleep stages, making it inaccurate to predict the position of the eye during sleep based on awake examination. This study aimed to investigate the role of Bell's phenomenon in ptosis surgery and the management of nocturnal lagophthalmos. Methods: We conducted a retrospective case series of 23 patients with ptosis and poor Bell's phenomenon who underwent different surgical techniques at Xijing Hospital from April 2020 to June 2021. We assessed Bell's phenomenon at different stages of sleep and collected data on ptosis degree, surgical approach, lagophthalmos, complications, and outcomes. Results: Of the total 23 patients originally considered for study, 9 with frontalis muscle advancement technique, 8 with conjoint fascial sheath suspension, 4 with levator resection technique, and 2 with levator aponeurosis plication technique. All patients achieved satisfactory correction of ptosis. One patient had prolonged lagophthalmos and underwent reoperation to lower the eyelid height. Other complications were minor and resolved with conservative treatment. Conclusion: We conclude that poor Bell's phenomenon is not a relative contraindication for ptosis surgery. Nocturnal lagophthalmos should be monitored after ptosis surgery regardless of the Bell's phenomenon results. Tape eyelid closure can be an effective solution to protect the corneal surface during nocturnal lagophthalmos. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the use of pyridostigmine in presence of contraindications, and the use of concomitant potentially contraindicated drugs in a cohort of patients affected by Myasthenia Gravis (MG) in the Italian Regions of Lazio, Tuscany, and Umbria. Methods: This is a retrospective cohort study. A multivariate logistic regression model was used to evaluate the determinants of pyridostigmine and of potentially contraindicated drugs use in MG patients. Results: Among 591 incident pyridostigmine users affected by MG, 91 (15.4%) had at least one of the contraindications considered at the first prescription of pyridostigmine. Patients prescribed with pyridostigmine in presence of contraindications were more frequently affected by diabetes, obesity, and renal diseases. Age 75+ years (odds ratio, OR 4.94, 95% confidence interval, CI 1.60-15.22 for Latium; OR 3.78, 95%CI: 1.26-11.34 for Tuscany; OR 5.83, 95%CI 1.19-28.52 for Umbria), the presence of at least one specific comorbidity (OR 3.93; 95%CI 1.68-9.17 for Latium), and polytherapy (6+ drugs, OR 4.90, 95%CI: 1.35-17.85 for Tuscany) were found to be significantly associated with pyridostigmine use in presence of contraindications. Among patients affected by MG, 1,483 (62.6%) were treated with potentially contraindicated drugs in the first year of follow-up (67.06.9% in Latium; 59% in Tuscany; 57.6% in Umbria). Patients aged 75+ years, those with at least one specific complication or comorbidity, and those exposed to polytherapy were more likely to be treated with a potential contraindicated drug. Conclusion: Among incident users of pyridostigmine, more than 15% of patients have at least one of the contraindications considered, and among patients diagnosed with MG, in the first year of follow-up >60% of subjects were treated with potentially contraindicated drugs. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the surgical outcome in terms of safety, efficacy, predictability, and retreatment rate of LASIK surgery in patients with controlled systemic diseases in comparison with healthy individuals. Methods: The retrospective study included data from 1936 eyes of 976 patients with stable systemic diseases who underwent LASIK surgery between January 2016 and June 2019. The safety, efficacy, predictability of the surgery, and retreatment rate were evaluated in comparison with a control group comprising 1951 patients. The study was approved by the local ethics committee and adhered to the principles of the Declaration of Helsinki. Statistical analysis was performed using R team and the level of statistical significance was set at p < 0.05. Results: All treatment groups demonstrated high safety and efficacy indices after LASIK surgery. Furthermore, the study arms demonstrated comparable predictability and retreatment rates to the control group in nearly all cases. Retreatment rates were significantly higher in the rheumatoid arthritis group (p = 0.03), while safety indices were significantly lower in the hay fever group compared to the control group (p = 0.004). No intra- or postoperative sight-threatening complications were documented. Conclusion: Our findings suggest that selected patients with stable systemic conditions can safely undergo LASIK surgery and achieve comparable outcomes to healthy individuals. Further research is needed to better understand the treatment outcomes in this challenging patient population. [ABSTRACT FROM AUTHOR]

The use of live attenuated vaccines in patients with immunosuppressive agents is contraindicated in package inserts and guidelines in Japan and other countries. However, patients receiving immunosuppressants have a high risk of infectious disease becoming severe, and the necessity to prevent infectious disease is high. To date, 2,091 vaccinations have been reported in 25 reports of live attenuated vaccines in people receiving immunosuppressants. Twenty-three patients (1.1%) became infected with the virus strain used in the vaccine, which was varicella virus in 21 patients. No reports have described life-threatening complications. A prospective study at the National Center for Child Health and Development conducted under certain immunological conditions (CD4 cell count ≥ 500/mm3, stimulation index of lymphocyte blast transformation by phytohemagglutinin (PHA) ≥ 101.6, serum immunoglobulin G ≥ 300 mg/dL) confirmed the serological effectiveness and safety. The evidence suggests that live attenuated vaccines can be used even in combination with immunosuppressants. Further evidence must be gathered and immunological criteria investigated to determine the conditions for safe use. Depending on the results of these investigations, the wording in package inserts and guidelines may need to be revised. [ABSTRACT FROM AUTHOR]

Background: Nirmatrelvir/ritonavir is authorized for the treatment of COVID-19 but has several contraindications and potential drug–drug interactions (pDDIs) due to ritonavir-induced irreversible inhibition of cytochrome P450 3A4. We aimed to assess the prevalence of individuals with one or more risk factors for severe COVID-19 along with contraindications and pDDIs due to ritonavir- containing COVID-19 therapy. Methods: Retrospective observational study of individuals with one or more risk factors according to Robert Koch Institute criteria for severe COVID-19 according to German statutory health insurance (SHI) claims data from the pre-pandemic years 2018–2019 based on the German Analysis Database for Evaluation and Health Services Research. Prevalence was extrapolated to the entire SHI population using age-adjusted and sex-adjusted multiplication factors. Results: Nearly 2.5 million fully insured adults, representing 61 million people in the German SHI population, were included in the analysis. In 2019, prevalence of individuals that would have been at risk of severe COVID-19 was 56.4%. Amongst them, the prevalence of contraindications for treatment with ritonavir-containing COVID-19 therapy was approximately 2% according to presence of somatic comorbidities (severe liver or kidney disease). Prevalence of intake of medicines contraindicated for their potential interactions with ritonavir-containing COVID-19 therapy was 16.5% according to Summary of Product Characteristics and 31.8% according to previously published data. The prevalence of individuals at risk of pDDIs during ritonavir- containing COVID-19 therapy without adjustment of their concomitant therapy was 56.0% and 44.3%, respectively. Prevalence data for 2018 were similar. Conclusion: Administering ritonavir-containing COVID- 19 therapy can be challenging as thorough medical record review and close monitoring are required. In some cases, ritonavir-containing treatment may not be appropriate due to contraindications, risk of pDDIs, or both. For those individuals, an alternative ritonavir-free treatment should be considered.

For years, there have been many discussions about the optimal/beneficial threshold for transfusion of blood products in subarachnoid hemorrhage (SAH), and it remains to be established. Over the period spent by patients who are recuperating from such acute intracranial bleeding, they often become anemic. This is a rationale why these patients are considered candidates for transfusion to restore normal hemoglobin levels and optimal arterial oxygen content. After a comprehensive review of multidisciplinary studies, it becomes evident that the benefits of blood transfusion may vary greatly depending on the situation. The objective here is to summarize the reported outcomes following administration of blood products, i.e., platelets, tranexamic acid, prothrombin complex concentrate, red blood cells, and colloids/crystalloids for optimal oxygenation and to minimize rebleeding. These treatments are reviewed in the context of how they interact with the brain during the early brain injury, the vasospasm, microthrombus formation, inflammation, brain edema, and the delayed cerebral ischemic phases. In severe SAH, cardiac dysfunction and hyponatremia are not uncommon, and the transfusion-associated circulatory overload should be monitored. Thus, continuous hemodynamic monitoring is necessary to prevent pulmonary edema, along with the maintenance of euvolemia. The paper also highlights conditions when transfusion is contraindicated. Patient blood management programs should be promoted to develop clearer hospital transfusion guidelines to strive for optimization of patient hemoglobin and iron stores, and to train for more restrictive RBC policy. The results reported thus far need to be critically reviewed by a panel of experts, along with the need to design novel rigorous prospective parallel-group studies to establish SAH-specific guidelines.

IntroductionTo evaluate the use of pyridostigmine in presence of contraindications, and the use of concomitant potentially contraindicated drugs in a cohort of patients affected by Myasthenia Gravis (MG) in the Italian Regions of Lazio, Tuscany, and Umbria.MethodsThis is a retrospective cohort study. A multivariate logistic regression model was used to evaluate the determinants of pyridostigmine and of potentially contraindicated drugs use in MG patients.ResultsAmong 591 incident pyridostigmine users affected by MG, 91 (15.4%) had at least one of the contraindications considered at the first prescription of pyridostigmine. Patients prescribed with pyridostigmine in presence of contraindications were more frequently affected by diabetes, obesity, and renal diseases. Age 75+ years (odds ratio, OR 4.94, 95% confidence interval, CI 1.60–15.22 for Latium; OR 3.78, 95%CI: 1.26–11.34 for Tuscany; OR 5.83, 95%CI 1.19–28.52 for Umbria), the presence of at least one specific comorbidity (OR 3.93; 95%CI 1.68–9.17 for Latium), and polytherapy (6+ drugs, OR 4.90, 95%CI: 1.35–17.85 for Tuscany) were found to be significantly associated with pyridostigmine use in presence of contraindications. Among patients affected by MG, 1,483 (62.6%) were treated with potentially contraindicated drugs in the first year of follow-up (67.06.9% in Latium; 59% in Tuscany; 57.6% in Umbria). Patients aged 75+ years, those with at least one specific complication or comorbidity, and those exposed to polytherapy were more likely to be treated with a potential contraindicated drug.ConclusionAmong incident users of pyridostigmine, more than 15% of patients have at least one of the contraindications considered, and among patients diagnosed with MG, in the first year of follow-up >60% of subjects were treated with potentially contraindicated drugs.

BackgroundThere are limited data on the safety of intravenous recombinant tissue plasminogen activator (rtPA) for treating acute ischemic stroke in patients with gastrointestinal malignancy or recent gastrointestinal bleeding within 21 days of their index stroke.AimsTo evaluate clinical outcomes in patients treated with rtPA for acute ischemic stroke who had gastrointestinal malignancy or recent gastrointestinal bleeding.MethodsWe identified patients who were treated with rtPA for acute ischemic stroke between 2/2009 and 12/2015 from the Get With The Guidelines-Stroke linked to Medicare claims data. Gastrointestinal malignancy and recent gastrointestinal bleeding were defined as any gastrointestinal malignancy hospitalisation within one year prior to acute ischemic stroke and gastrointestinal bleeding hospitalisation within 21 days prior to acute ischemic stroke, respectively. Outcomes of interest included in-hospital mortality and bleeding complications.ResultsAmong 40,396 patients aged 65 years or older treated with rtPA for acute ischemic stroke from 1522 sites (mean age [SD] 81.0 [8.1] years; 41.9% women), 136 (0.3%) had gastrointestinal malignancy (n = 96) or recent gastrointestinal bleeding (n = 43). Patients with gastrointestinal malignancy or bleeding had more severe stroke than those without (median NIHSS [interquartile range]: 14.0 [8.0-19.0] vs. 11.0 [6.0-18.0]). The rates of in-hospital mortality and life-threatening systemic haemorrhage were not significantly different between those with and without gastrointestinal malignancy or bleeding (mortality: 10.3% vs. 9.0%, adjusted odds ratio [aOR] 1.01, 95%CI 0.58-1.75; bleeding: 2.3% vs. 1.2%, aOR 1.72, 95%CI 0.58-5.11).ConclusionsIn this observational cohort, we did not find increased risk of in-hospital mortality and bleeding in rtPA-treated patients with gastrointestinal malignancy or recent gastrointestinal bleeding.

Background/Aim. Diclofenac, a non-selective inhibitor of cyclooxygenase with analgesic, anti-inflammatory, and antipyretic effects, is one of the most prescribed nonsteroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to analyze the prescription patterns of diclofenac systemic formulations at primary health care (PHC) level in Montenegro, in patients with cardiovascular (CV) diseases (CVD) and patients with risk factors for CVD, from 2016 to 2020. Methods. A retrospective national drug utilization study was conducted and it included patients with CVD, to whom prescribing diclofenac was contraindicated, and patients with risk factors for CVD, to whom diclofenac could be prescribed but with increased precaution. PHC information system has been used as a source of medical data for these patients. Results. Within the observed period, prescribing diclofenac systemic formulations, dominantly oral formulations in 75 mg dose, increased by 36.9% [from 4.6 of defined daily doses (DDD) /1,000 inhabitants/day in 2016 to 6.3 DDD/1,000 inhabitants/day in 2020]. A rising trend in prescribing diclofenac was also recorded in patients with CVD or those with risk factors for CVD, to whom diclofenac prescribing is contraindicated. Out of the overall number of patients who were prescribed diclofenac in 2016, 2017, 2018, 2019, and 2020, 16%, 18%, 24%, 15%, and 20% of them, respectively, already had a CVD or some risk factor for CVD. Most CV patients (39.7%), for whom the use of diclofenac was contraindicated, had ischemic heart disease and were prescribed 40.7% of the total amount of diclofenac prescribed for this group of patients (expressed in DDD/1,000 inhabitants/day for the given medicine). The majority (77.4%) of CV patients to whom the drug could be prescribed, but with increased precautions, had hypertension, and they were prescribed 77.2% of the total amount of diclofenac prescribed for this group of patients (expressed in DDD/1,000 inhabitants/day for the given medicine). Conclusion. Despite the undertaken regulatory measures aimed at a safer prescription of diclofenac to patients with CVD or at high risk of developing CVD, this medicine is still widely prescribed at the level of PHC in Montenegro, even in cases that represent a contraindication for its use. This article has been corrected. Link to the correction 10.2298/VSP2310892E

Background Intravenous recombinant tissue-type plasminogen activator (rtPA) remains the only medical therapy to improve outcomes for acute ischemic stroke (AIS), but the safety of rtPA in AIS patients with a history of recent myocardial infarction (MI) remains controversial. Methods and Results We sought to determine whether the presence of recent MI would alter the risk of mortality and rtPA-related complications. Multivariate logistic regression models were used to compare in-hospital outcomes between rtPA-treated AIS patients with recent MI within 3 months and those with no history of MI from the Get With The Guidelines-Stroke hospitals between February 2009 and December 2015. Among 40 396 AIS patients aged ≥65 years treated with rtPA, 241 (0.6%) had recent MI, of which 19.5% were ST-segment-elevation myocardial infarction. Patients with recent MI had more severe stroke than those without (median National Institutes of Health Stroke Scale [interquartile range]: 13.0 [7.0-20.0] versus 11.0 [6.0-18.0]). Recent MI was associated with an increased risk of mortality compared with no history of MI (17.4% versus 9.0%; adjusted odds ratio 1.60 [95% CI, 1.10-2.33]; P=0.014), but no statistically significant differences in rtPA-related complications (13.5% versus 9.4%; adjusted odds ratio 1.28 [0.88-1.86]; P=0.19). Recent ST-segment-elevation myocardial infarction was associated with higher risk of death and rtPA-related complications, but non-ST-segment-elevation myocardial infarction was not. Conclusions Among older AIS patients treated with rtPA, recent MI was associated with an increased risk of in-hospital mortality. Further investigations are necessary to determine whether the benefit of rtPA outweighs its risk among AIS patients with recent MI.

Abstract Background Allergen immunotherapy (AIT) is the only treatment that has modified the natural history of allergic diseases. However, since its overall effect on the immune system has not been elucidated, AIT is either absolutely or relatively contraindicated in patients with rheumatic autoimmune diseases (RADs). Therefore, there have been no long-term observations of patients with RADs receiving AIT; thus, the effectiveness and safety of AIT in these patients remain unclear. Methods This was a single-center retrospective observational study. RAD patients receiving AIT for allergic rhinitis at our institution were selected. Changes in the activity of RAD patients were investigated for 2 years from baseline, including those who discontinued AIT. The effectiveness of AIT was also investigated using the Japan Allergic Rhinitis Standard Quality of Life Questionnaire. Results Thirteen patients with RADs were enrolled in the study. All patients received sublingual immunotherapy, of which four discontinued AIT owing to adverse events. Among all patients, the symptoms of RADs in three patients worsened during the observation period; however, none of them were causally related to AIT. Most of the adverse events associated with AIT were mild, in which only one patient required drug intervention due to worsening rhinitis symptoms. In the nine patients who were able to continue AIT, their eye and nasal symptom scores showed a significant improvement from 1.67 (1.5–2.0) at baseline to 0.67 (0–1.17) in the 2nd year of treatment (p = 0.0141). Conclusions AIT is a safe and effective treatment modality for patients with allergic rhinitis complicated by RADs.

Aims: Automated checks for medication‐related problems have become a cornerstone of medication safety. In many clinical settings medication checks remain confined to drug–drug interactions because only medication data are available in an adequately coded form, leaving possible contraindicated drug–disease combinations unaccounted for. Therefore, we devised algorithms that identify frequently contraindicated diagnoses based on medication patterns related to these diagnoses. Methods: We identified drugs that are associated with diseases constituting common contraindications based on their exclusive use for these conditions (such as allopurinol for gout or salbutamol for bronchial obstruction). Expert‐based and machine learning algorithms were developed to identify diagnoses based on highly specific medication patterns. The applicability, sensitivity and specificity of the approach were assessed by using an anonymized real‐life sample of medication and diagnosis data excerpts from 3506 discharge records of geriatric patients. Results: Depending on the algorithm, the desired focus (i.e., sensitivity vs. specificity) and the disease, we were able to identify the diagnoses gout, epilepsy, coronary artery disease, congestive heart failure and bronchial obstruction with a specificity of 44.0–99.8% (95% CI 41.7–100.0%) and a sensitivity of 3.8–83.1% (95% CI 1.0–86.1%). Using only medication data, we were able to identify 123 (51.3%) of 240 contraindications identified by experts with access to medication data and diagnoses. Conclusion: This study provides a proof of principle that some key diagnosis‐related contraindications can be identified based on a patient's medication data alone, while others cannot be identified. This approach offers new opportunities to analyse drug–disease contraindications in community pharmacy or clinical routine data. [ABSTRACT FROM AUTHOR]

The purpose of this study was to suggest appropriate indications and contraindications for full endoscopic surgery and to predict the prognosis for the incidence of complications by reviewing the literature on full endoscopic lumbar decompression for various spinal stenoses and systematically analyzing the contraindications and complications of endoscopic surgery. We searched the PubMed/MEDLINE database to identify articles on full endoscopic decompression for lumbar spinal stenosis. The levels of evidence in all studies were classified according to the method adopted by the North American Spine Society (NASS) 2005. Full endoscopic lumbar decompression was divided into interlaminar and transforaminal decompressions. We selected articles that contained preoperative contraindications and complications during and after surgery. We analyzed the evidence level and classified the prescribed contraindications and complications according to the literature. We identified 362 articles, of which 57 met our criteria, with evidence ranging from levels I to V. After reviewing the literature on full endoscopic lumbar decompression, pure back pain without neurogenic symptoms and instability/deformities requiring stabilization were found to be contraindications. Also, in transforaminal decompression, central stenosis or complex foraminal stenoses were contraindications. Dysesthesia (most common), untreated pain, dural tear, disc herniation, infection, incomplete decompression, and other complications have been reported as complications of transforaminal decompression. On the other hand, dural tear (most common), epidural hematoma, transient dysesthesia, untreated pain, motor weakness, and other complications have been reported in interlaminar decompression. Full endoscopic lumbar surgery, including transforaminal and interlaminar decompression, is a safe and effective surgical option for treating lumbar spinal stenosis; however, it is important to select the transforaminal or interlaminar approach according to the indication. [ABSTRACT FROM AUTHOR]

Background/purpose: To investigate the impact of pharmaceutical care programs for the management of contraindicated drug–drug interactions (DDIs) in direct-acting antivirals (DAAs) therapy. Methods: A prospective observational study was performed at Dalin Tzu Chi Hospital between January 2018 and December 2019. Pharmacists screened DDIs for all hepatitis C patients before DAA therapy. The study outcome included the frequency of contraindicated DDIs, acceptance rate, and cost avoidance of the pharmaceutical care program. Results: A total of 1053 patients were enrolled in the study, with a mean age of 67.1 ± 11.9 years. Most patients received therapy with sofosbuvir/ledipasvir (37.1%; n = 391), elbasvir/grazoprevir (23.8%; n = 251), or glecaprevir/pibrentasvir (21.1%; n = 222). A total of 796 (75.6%) patients received at least one co-medication, with the average number of co-medications being 5.2 per patient (SD: 4.4/patient). In total, 1356 DDIs were identified, with the average DDIs per patient of 1.3 (SD: 1.7). For patients with contraindicated DDIs (2%, n = 102), statins and amiodarone were the most common co-medications. Physicians often accepted pharmacists’ recommendations (acceptance rate of 72.5%) or withheld co-medication to avoid severe adverse drug events (ADEs). The estimated cost avoidance of preventable ADEs was USD 14,033 for contraindicated DDIs with pharmaceutical care programs. Conclusion: The implementation of pharmaceutical care programs in DAA therapy provides a favorable outcome and substantial cost avoidance.

Coronary arteries coursing behind the aortic root may get compressed when nitinol septal occluders are used to close an atrial septal defect. Hence, echocardiographic recognition of a retroaortic linear vessel is important during preinterventional evaluation. While the left circumflex arising from the right coronary artery is the most common cause, a similar finding is sometimes observed in a single left or right coronary artery and rarely with small sinus nodal branches from the left circumflex artery. Complex three-dimensional relations between the defect and the aortic root may be understood only after a postdeployment selective coronary angiography. Two patients with anomalous retroaortic left circumflex from the right coronary artery underwent uneventful device closure with clearly documented separation between the edges of the occluder and the anomalous vessel. Follow-up imaging and exercise testing confirmed the safety of the intervention. A selective postdeployment and postrelease coronary angiography are mandatory in every patient with retroaortic coronaries.

Background: This study aimed to compare the surgical outcomes of vaginal hysterectomy based on the number of previous cesarean delivery. Methods: A retrospective chart review was performed for all patients who underwent vaginal hysterectomy for non-prolapsed uterus between January 2016 and December 2019. Women with a history of other abdominal surgeries were excluded. Patient characteristics and surgical outcomes were compared based on the number of previous cesarean deliveries. Results: Among 610 women, 541 had no cesarean delivery, 39 had one cesarean delivery, and 30 had two or more cesarean deliveries. Patient characteristics, such as parity, body mass index, and uterine weight were similar, except for age (no section 49.2 ± 8.6 years old vs. one section 46.5 ± 5.2 years old vs. two sections 44.9 ± 4.4 years old; p = 0.004) and preoperative hemoglobin level (no section 12.0 ± 1.23 g/dL vs. one section 11.5 ± 1.44 g/dL vs. two sections 11.9 ± 1.13 g/dL; p = 0.014). Surgical outcomes, including surgery time, postoperative hospital stay and drop in hemoglobin level, and estimated blood loss were similar among the three groups. The intra- or post-operative transfusion rate was the highest in the one cesarean delivery group (no cesarean delivery 8.1% vs. one cesarean delivery 20.5% vs. two or more cesarean deliveries 3.3%; p = 0.017). Conclusion: Our data suggest that the number of previous cesarean deliveries did not affect the outcomes of vaginal hysterectomy. Vaginal hysterectomy can be performed safely even in women with two or more prior cesarean deliveries, when patients are selected appropriately by skilled surgeons.

The exact rate of contraindications to anti-TNF therapy and physician perspectives on treatment choices facing to anti-TNF contraindication, are poorly reported. A two-week cross-sectional study was conducted in 31 centres. Physicians completed a questionnaire for a total of 1,314 consecutive outpatients with Crohn's disease, assessing each patient's potential contraindications to anti-TNF therapy, the choice of alternative therapy to anti-TNFs, and their preference in an unrestricted reimbursement setting. Among the 1,293 responses to the first item, 148 (11.5%) reported 32 absolute contraindications (2.5%) and 116 relative contraindications (9.0%) to anti-TNF therapy. When asked about their preference of alternative therapies in those cases with contraindications to anti-TNF, physicians chose ustekinumab and vedolizumab, 75.6% and 23.9%, respectively. In multivariable analysis, the choice of vedolizumab was the preferred choice for patients aged > 60 years with the L2 phenotype and the absence of perianal lesions. In a hypothetical setting of unrestricted reimbursement, anti-TNFs remained physicians' preferred first-line biological therapy choice for 78.2%. Anti-TNF contraindications occurred in up to 11.5% of patients with Crohn's disease. Physicians' choices for alternative therapy to anti-TNF relied on ustekinumab in 75.6% and vedolizumab in 23.9% of these cases. This choice was driven mainly by phenotypical criteria and age. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19, the 7th coronavirus) was a pandemic infectious disease with significant morbidity and mortality in the world. The respiratory system is often involved in COVID-19 infection. Underlying disorders such as uncontrolled asthma are a risk factor for COVID-19 infection. For protecting against COVID-19, we need vaccination-associated social care such as facial masks, distance, and sanitizers.

Background: Allergen immunotherapy (AIT) is the only treatment that has modified the natural history of allergic diseases. However, since its overall effect on the immune system has not been elucidated, AIT is either absolutely or relatively contraindicated in patients with rheumatic autoimmune diseases (RADs). Therefore, there have been no long-term observations of patients with RADs receiving AIT; thus, the effectiveness and safety of AIT in these patients remain unclear. Methods: This was a single-center retrospective observational study. RAD patients receiving AIT for allergic rhinitis at our institution were selected. Changes in the activity of RAD patients were investigated for 2 years from baseline, including those who discontinued AIT. The effectiveness of AIT was also investigated using the Japan Allergic Rhinitis Standard Quality of Life Questionnaire. Results: Thirteen patients with RADs were enrolled in the study. All patients received sublingual immunotherapy, of which four discontinued AIT owing to adverse events. Among all patients, the symptoms of RADs in three patients worsened during the observation period; however, none of them were causally related to AIT. Most of the adverse events associated with AIT were mild, in which only one patient required drug intervention due to worsening rhinitis symptoms. In the nine patients who were able to continue AIT, their eye and nasal symptom scores showed a significant improvement from 1.67 (1.5–2.0) at baseline to 0.67 (0–1.17) in the 2nd year of treatment (p = 0.0141). Conclusions: AIT is a safe and effective treatment modality for patients with allergic rhinitis complicated by RADs. [ABSTRACT FROM AUTHOR]

Objective: We sought to investigate the prevalence of triptan use among patients with migraine who have contraindications to triptan usage, and to explore specifics of the medication prescribed, dosage, and route of administration. Background: Triptan medications are a mainstay of acute migraine therapy, but little is known about prevalence and patterns of triptan prescribing among patients with contraindications in the United States. Methods: In this retrospective cohort study, we used data from the IBM Marketscan database to identify patients aged ≥ 18 years with migraine from January 1, 2016, to December 31, 2017, using International Classification of Diseases, Clinical Modification 10 codes. Contraindications to triptan medications were identified by review of package labels as listed on the US Food and Drug Administration website. Triptan medications were identified from the IBM Micromedex Redbook linked to prescription claims along with route of administration and dosage. Results: Of 1,038,472 individuals diagnosed with migraine, 400,112 (38.5%) were prescribed triptan medication, and of those who were prescribed a triptan, 55,707 (13.9%) had at least one contraindication, with the most common contraindication being cardiac arrhythmia (33,696/400,112 individuals, 8.4%) followed by cerebrovascular disease (14,787/400,112, 3.7%) and coronary artery disease (10,236/400,112, 2.6%). Sumatriptan was the most prescribed triptan (261,736/1,038,472, 25.2%), and the subcutaneous and intranasal routes were more commonly prescribed among those with contraindications compared with those without contraindications. Discussion: A substantial proportion of patients with migraine with contraindications were prescribed triptan medications. These findings call for further research on the outcomes of patients with medical contraindications who are prescribed triptan medications, and for greater clarity in prescribing guidelines about the optimal approach for acute therapy among patients with migraine. [ABSTRACT FROM AUTHOR]

Introduction: As 5-HT1B receptor agonists, triptans produce vasoconstriction and have cardiovascular contraindications and precautions. Lasmiditan, a selective 5-HT1F receptor agonist, has a low affinity for 5-HT1B receptors, does not cause vasoconstriction, and is free of cardiovascular contraindications and precautions. The objective of this post hoc analysis was to evaluate the efficacy and safety of lasmiditan in patients with and without at least one triptan contraindication. Methods: Patient subgroups, with and without triptan contraindications, were analyzed from pooled patient data from four randomized, double-blind, placebo-controlled clinical trials (SAMURAI, SPARTAN, CENTURION, and MONONOFU). Patients experiencing a single migraine attack of moderate or severe intensity were treated with lasmiditan 50 mg (SPARTAN and MONONOFU only), 100 mg, 200 mg, or placebo, and efficacy data were recorded in an electronic diary. Results: Of 5704 patients, 207 (3.6%) patients had at least one contraindication to triptans. Overall subgroup analysis revealed that the effects of lasmiditan on pain freedom, pain relief, freedom from most bothersome symptom, disability freedom, and Patient Global Impression of Change at 2 h post-dose did not differ in patient groups with and without triptan contraindications. These outcomes generally showed a similar benefit pattern for lasmiditan in both subgroups, with all results being statistically significant in patients without contraindications, and pain relief being statistically significant in patients with contraindications. The safety and tolerability profiles of patients with triptan versus without triptan contraindications were similar, including dizziness in 18.3 to 22.8% and somnolence in 7.9 to 9.9% of patients at the highest dose of lasmiditan. Conclusions: In pooled analyses from four trials, patients with and without triptan contraindications did not differ in their patterns of lasmiditan efficacy. Lasmiditan may be a treatment option in patients with contraindications to triptans. Trial Registration Numbers: SAMURAI, NCT:02439320; SPARTAN, NCT:02605174; CENTURION, NCT:03670810; and MONONOFU, NCT:03962738. [ABSTRACT FROM AUTHOR]

Agustín Falco,1 Thiago Bueno de Oliveira,2 Jon Cacicedo,3 Aylen Vanessa Ospina,4 Miguel Ángel Ticona,5 Héctor Galindo,6 Marcos David Pereira,7 José Luis Aguilar-Ponce,8 Antonio Rueda-Domínguez,9 Tannia Soria,10 Miren Taberna,11 Lara Iglesias,12 Taysser Sowley,13 Ricard Mesía14 On behalf of TTCC group (Spanish Group for the Treatment of the Head and Neck Cancer)1Instituto Alexander Fleming, Asociación Argentina de Oncología Clínica (AAOC), Buenos Aires, Argentina; 2AC Camargo Cancer Center, Sociedade Brasileira de Oncologia Clínica (SBOC), São Paulo, Brazil; 3Hospital Universitario Cruces/Biocruces Bizkaia Health Research Institute, Barakaldo, Bizkaia, Spain; 4ICCAL, Hospital Universitario Fundación Santa Fe de Bogotá, Asociación Colombiana de Hematología y Oncología (ACHO), Bogotá, Colombia; 5Hospital Nacional Edgardo Rebagliati Martins de Lima, Sociedad Peruana de Oncología Médica (SPOM), Lima, Perú; 6Pontificia Universidad Católica de Chile, Sociedad Chilena de Oncología Médica (SCOM), Santiago, Chile; 7Instituto de Oncología Ángel H. Roffo, Asociación Argentina de Oncología Clínica (AAOC), Buenos Aires, Argentina; 8Instituto Nacional de Cancerología, Sociedad Mexicana de Oncología (SMeO), Mexico City, Mexico; 9UGC Oncología Médica, Hospital Universitario Regional y Virgen de la Victoria, IBIMA, Málaga, Spain; 10Hospital SOLCA de Quito, Sociedad Ecuatoriana de Oncología (SEO), Quito, Ecuador; 11Institut Català d’Oncologia, ICO L’Hospitalet, Barcelona, Spain; 12Hospital 12 de Octubre, Madrid, Spain; 13Instituto Oncológico Nacional (ION) de Panamá, Sociedad Panameña de Oncología (SPO), Panama City, Panama; 14Institut Català d’Oncologia, ICO Badalona, Barcelona, SpainCorrespondence: Ricard MesíaInstitut Català d´Oncologia, ICO Badalona, Barcelona, SpainEmail rmesia@iconcologia.netAbstract: Cisplatin is the standard of treatment for squamous cell carcinoma of the head and neck (SCCHN) that has demonstrated efficacy, either in locally advanced disease when combined with radiotherapy at high doses, or in metastatic/recurrent disease when combined with other agents. However, the usual toxicities related to cisplatin, such as neurotoxicity, nephrotoxicity, ototoxicity, and hematologic toxicities, especially when high doses have been administered, have important implications in the patients’ quality of life. The decision to administer cisplatin depends on several patient factors, such as age, performance status, weight loss, comorbidities, previous toxicities, chronic viral infection, or even the current SARS-CoV-2 pandemic. In order to establish recommendations for the management of patients with SCCHN, a group of experts in medical and radiation oncology from Spain and Latin-American discussed how to identify patients who are not candidates for cisplatin to offer them the most suitable therapeutic alternative.Keywords: age, cisplatin, comorbidities, contraindication, frailty, toxicity

There has been a considerable controversy about vaccination practices in Children with congenital heart disease (CHD) in China. This study aims to identify the reasons for deferring vaccination among the patient population attending the Vaccination Consultation Clinic in Zhejiang Province and the safety of their vaccination. We analyzed the data of 2442 children with CHD, who visited to our clinic from January 2016 to March 2019. A questionnaire survey was conducted to investigate the reasons for their delayed vaccination. Information about the following vaccination and Adverse Events Following Immunization (AEFI) was collected. Most of the enrolled children did not receive vaccines on time before consultation. The reasons for their deferring vaccination included: 1. Providers in the community health center refused to administer vaccines (77.6%); 2. Parents’ concerns about the safety of vaccines (19.0%); 3. Parents’ doubts about the efficiency of vaccines after certain drug applications (3.4%). According to the evaluation reports issued by the Vaccination Consultation Clinic, 83.7% of CHD children were recommended to be vaccinated on the nationally recommended schedule, 14.4% were recommended to defer some specific vaccination, and 1.9% were recommended to defer all vaccination. Among the group who received vaccines on nationally recommended schedule, the AEFI rate was 33.5/100 000. No rare or serious rare vaccine reactions were observed. Our study provides evidence that routine vaccination is safe in the majority of this patient population.

Aims This study aims to estimate the cost-effectiveness of percutaneous left atrial appendage occlusion (LAAO) compared to standard stroke prevention care for patients with atrial fibrillation (AF) and contraindication to oral anticoagulation (OAC) in a Swedish healthcare and public sector perspective. Methods and results We used a combined decision tree and cohort Markov model to estimate costs and quality-adjusted life-years (QALYs) over a lifetime horizon with LAAO compared to standard of care where the treatment effect is based on a recent meta-analysis. According to our analysis, LAAO gives more QALYs than standard of care (7.11 vs. 6.12). Furthermore, LAAO treatment is related to the first-year cost of 14 984 Euro (EUR) and higher average healthcare costs over the lifetime by about 4010 EUR, which gives an incremental cost-effectiveness ratio of LAAO vs. standard of care at 4047 EUR per gained QALY. From a public sector perspective, LAAO reduces average costs due to substantial reductions in long-term care and, thus, implies that LAAO is dominant from a public sector perspective (lower average costs and better health outcomes). Conclusion From both Swedish healthcare and public sector perspectives, LAAO can be considered cost-effective compared to standard of care for individuals with AF and contraindication to OAC. However, these results must be confirmed in health economic evaluations alongside the ongoing randomized clinical trials. Key Question Is left atrial appendage occlusion (LAAO) cost-effective for patients with atrial fibrillation (AF) and contraindication to oral anticoagulation (OAC) compared to the standard of care from a Swedish healthcare and public sector perspective? Key Finding LAAO is associated with lower cost than the standard of care from a public sector perspective and an incremental cost of 4010 Euro from a healthcare perspective. Furthermore, LAAO is related to better health outcomes than the standard of care. Take Home Message Treatment with LAAO among individuals with AF and contraindication to OAC can be considered as cost-effective compared to the standard of care from a Swedish healthcare and public sector perspective. [ABSTRACT FROM AUTHOR]

Coronary arteries coursing behind the aortic root may get compressed when nitinol septal occluders are used to close an atrial septal defect. Hence, echocardiographic recognition of a retroaortic linear vessel is important during preinterventional evaluation. While the left circumflex arising from the right coronary artery is the most common cause, a similar finding is sometimes observed in a single left or right coronary artery and rarely with small sinus nodal branches from the left circumflex artery. Complex three-dimensional relations between the defect and the aortic root may be understood only after a postdeployment selective coronary angiography. Two patients with anomalous retroaortic left circumflex from the right coronary artery underwent uneventful device closure with clearly documented separation between the edges of the occluder and the anomalous vessel. Follow-up imaging and exercise testing confirmed the safety of the intervention. A selective postdeployment and postrelease coronary angiography are mandatory in every patient with retroaortic coronaries. [ABSTRACT FROM AUTHOR]

Background: Drug repurposing provides an effective method for high-speed, low-risk drug development. Clinical phenotype-based screening exceeded target-based approaches in discovering first-in-class small-molecule drugs. However, most of these approaches predict only binary phenotypic associations between drugs and diseases; the types of drug and diseases have not been well exploited. Principally, the clinical phenotypes of a known drug can be divided into indications (Is), side effects (SEs), and contraindications (CIs). Incorporating these different clinical phenotypes of drug–disease associations (DDAs) can improve the prediction accuracy of the DDAs. Methods: We develop Drug Disease Interaction Type (DDIT), a user-friendly online predictor that supports drug repositioning by submitting known Is, SEs, and CIs for a target drug of interest. The dataset for Is, SEs, and CIs was extracted from PREDICT, SIDER, and MED-RT, respectively. To unify the names of the drugs and diseases, we mapped their names to the Unified Medical Language System (UMLS) ontology using Rest API. We then integrated multiple clinical phenotypes into a conditional restricted Boltzmann machine (RBM) enabling the identification of different phenotypes of drug–disease associations, including the prediction of as yet unknown DDAs in the input. Results: By 10-fold cross-validation, we demonstrate that DDIT can effectively capture the latent features of the drug–disease association network and represents over 0.217 and over 0.072 improvement in AUC and AUPR, respectively, for predicting the clinical phenotypes of DDAs compared with the classic K-nearest neighbors method (KNN, including drug-based KNN and disease-based KNN), Random Forest, and XGBoost. By conducting leave-one-drug-class-out cross-validation, the AUC and AUPR of DDIT demonstrated an improvement of 0.135 in AUC and 0.075 in AUPR compared to any of the other four methods. Within the top 10 predicted indications, side effects, and contraindications, 7/10, 9/10, and 9/10 hit known drug–disease associations. Overall, DDIT is a useful tool for predicting multiple clinical phenotypic types of drug–disease associations. [ABSTRACT FROM AUTHOR]

• Systematic comparison of 549 medications was conducted between FDA and EMA labeling. • Our analysis found limited discrepancies in hepatic safety information. • The discrepancies were mainly associated with non-severe or low-frequency hepatic adverse events. Drug labeling informs physicians and patients on the safe and effective use of medication. However, recent studies suggested discrepancies in labeling of the same drug between different regulatory agencies. Here, we evaluated the hepatic safety information in labeling for 549 medications approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Limited discrepancies were found regarding risk for hepatic adverse drug reactions (ADRs) (8.7% in hepatic ADR warnings and 21.3% in contraindication for liver disease), while caution should be exercised over drugs with inconsistencies in contraindications for liver disease and evidence for hepatotoxicity (4.9%). Most discrepancies were attributable to less-severe hepatic events and low-frequency hepatic ADR reports and had limited implication on clinical outcomes. [ABSTRACT FROM AUTHOR]

• Sharing a common target, both MG and BTX treatment can weaken the function of neuromuscular junction. • MG should not be considered to be an absolute contraindication for BTX. • Under proper management of MG, BTX could be used in patients presenting MG comorbidities. Botulinum toxin (BTX) is a neurotoxin that has been used to treat various disorders and has also become a popular choice for cosmetic indications, yet traditionally, myasthenia gravis (MG) is considered a contraindication for BTX. To determine whether BTX should be avoided in MG patients, clinical data from our MG and dystonia specialist clinic were analyzed retrospectively. In addition, a systematic literature review was conducted to identify all published cases associated with the co-existence of MG and BTX treatments. Here, we described one patient from our clinic, who received BTX injections before being given MG diagnosis. After the literature review, 8 cases with subclinical MG previously treated with BTX for dystonia or cosmetic reasons ("BTX injections before MG diagnosis") were identified. Markedly, 8 out of 8 (100%) patients developed obvious muscle weakness. In contrast, 10 patients presenting MG as comorbidity had received BTX for dystonia or overactive bladder ("BTX injection after MG diagnosis"), and 8 out of 10 (80%) experienced improved symptoms through appropriate dose modifications and adequate treatment for MG before receiving BTX injections. These findings support that, under proper management of co-existing MG, BTX could be used safely and successfully in patients presenting MG comorbidities in the future. [ABSTRACT FROM AUTHOR]

Background/purpose: To investigate the impact of pharmaceutical care programs for the management of contraindicated drug-drug interactions (DDIs) in direct-acting antivirals (DAAs) therapy.Methods: A prospective observational study was performed at Dalin Tzu Chi Hospital between January 2018 and December 2019. Pharmacists screened DDIs for all hepatitis C patients before DAA therapy. The study outcome included the frequency of contraindicated DDIs, acceptance rate, and cost avoidance of the pharmaceutical care program.Results: A total of 1053 patients were enrolled in the study, with a mean age of 67.1 ± 11.9 years. Most patients received therapy with sofosbuvir/ledipasvir (37.1%; n = 391), elbasvir/grazoprevir (23.8%; n = 251), or glecaprevir/pibrentasvir (21.1%; n = 222). A total of 796 (75.6%) patients received at least one co-medication, with the average number of co-medications being 5.2 per patient (SD: 4.4/patient). In total, 1356 DDIs were identified, with the average DDIs per patient of 1.3 (SD: 1.7). For patients with contraindicated DDIs (2%, n = 102), statins and amiodarone were the most common co-medications. Physicians often accepted pharmacists' recommendations (acceptance rate of 72.5%) or withheld co-medication to avoid severe adverse drug events (ADEs). The estimated cost avoidance of preventable ADEs was USD 14,033 for contraindicated DDIs with pharmaceutical care programs.Conclusion: The implementation of pharmaceutical care programs in DAA therapy provides a favorable outcome and substantial cost avoidance. [ABSTRACT FROM AUTHOR]

Ozone (O3) can be translated from the Greek as "smelly". The gas form was discovered in 1839 and its first medical use dates back to the First World War. Medical O3 treatment was discussed in the "Traditional and Complementary Medicine (GETAT) Practices Regulation" published in the Official Gazette in 2014 by the ministry of health in our country; indications, contraindications and routes of administration are reported in this regulation. O3 therapy; according to the current regulation, should be done by medical doctors, in appropriate therapeutic dose and with appropriate methods. Many studies have been conducted to investigate the primary or complementary therapy efficacy of O3, and these studies continue to be conducted in more detail today. According to studies, although O3 treatment may cause negative results in healthy tissues without oxidative stress, its use either alone or in combination with other therapeutic agents in cases of oxidative stress has an antioxidant effect and corrects the damage. These results show that the complementary therapy feature of O3 is at an effective level; but; there is a need for more healthy tissue studies on O3 and for more studies applied as a primary treatment protocol. [ABSTRACT FROM AUTHOR]

Delayed vaccination in children with seizures was common in China. This study aims to describe the vaccination status, reasons for vaccination deferral, vaccination recommendations and the safety for these patients in Zhejiang. 1539 children included were divided into febrile seizure (FS) group, epilepsy (EP) group, unclassified seizure group and other symptomatic seizure group. Medical records and reasons for the vaccination deferral were collected by questionnaire. Vaccination data and Adverse Event Following Immunization were retrieved from vaccination booklets. The main diseases of children enrolled were FS (756, 49.1%) and EP (443, 28.8%). Most of them (95.6%) were vaccinated on time before the onset of seizure, but their vaccination was delayed after seizure occurred. 76.1% were recommended to receive vaccines normally, of which the FS group accounted for the highest proportion (90.3%). 88.73% of them were vaccinated as recommended, and no serious side effects or seizure occurred. The main reason for vaccination deferral was providers' and parents' hesitation to have them vaccinated. Seizures were overestimated as a contraindication for vaccination in China. Routine vaccination was safe in most circumstances. It is essential to educate providers and parents about the benefits and contraindications of vaccination in children with seizures. [ABSTRACT FROM AUTHOR]

Median arcuate ligament syndrome (MALS) is a rare condition in which the median arcuate ligament (MAL) exerts external compression on the celiac trunk. Most cases are asymptomatic and diagnosed incidentally on radiographic imaging; however, some patients may experience gastrointestinal (GI) symptoms related to foregut ischemia and/or celiac neuropathy. In the following case, we present a patient with hemorrhagic peptic ulcer disease of the duodenum, which resulted in episodes of hemodynamic instability requiring multiple blood transfusions. Upon attempted transarterial angioembolization of the gastroduodenal artery (GDA), celiac stenosis and retrograde arterial flow from the superior mesenteric artery confirmed the presence of MALS. This rendered GDA angioembolization a contraindication, as the GDA became the dominant arterial supply for the distal celiac organs. The patient then received open surgical MAL release with concurrent surgical ligation of the hemorrhaging duodenal artery, which resolved his symptoms without the need for further intervention., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Almaguer et al.)