Clin Transl Oncol. 2024 Apr 16. doi: 10.1007/s12094-024-03455-y. Online ahead of print.

ABSTRACT

BACKGROUND: Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations.

METHODS: From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable.

RESULTS: A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events.

CONCLUSION: NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.

PMID:38627317 | DOI:10.1007/s12094-024-03455-y

Eur Radiol. 2024 Apr 16. doi: 10.1007/s00330-024-10730-7. Online ahead of print.

ABSTRACT

PURPOSE: To determine whether switching to contrast media based on the sharing of N-(2,3-dihydroxypropyl) carbamoyl side chain reduces the recurrence of iodinated contrast media (ICM)-associated adverse drug reactions (ADRs).

MATERIALS AND METHODS: This single-center retrospective study included 2133 consecutive patients (mean age ± SD, 56.1 ± 11.4 years; male, 1052 [49.3%]) who had a history of ICM-associated ADRs and underwent contrast-enhanced CT examinations. The per-patient and per-exam-based recurrence ADR rates were compared between cases of switching and non-switching the ICM from ICMs that caused the previous ADRs, and between cases that used ICMs with common and different carbamoyl side chains from ICMs that caused the previous ADRs. Downgrade rates (no recurrence or the occurrence of ADR less severe than index ADRs) were also compared. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were additionally performed.

RESULTS: In per-patient analysis, switching of ICM showed a lower recurrence rate (switching, 10.4% [100/965] vs. non-switching, 28.4% [332/1168]), with the adjusted odds ratio (OR) of 0.27 (95% CI: 0.21, 0.34; p < 0.001). The result was consistent in PSM (OR, 0.29 [95% CI: 0.22, 0.39]; p < 0.001), IPTW (OR, 0.28 [95% CI: 0.22, 0.36]; p < 0.001), and in per-exam analysis (5.5% vs. 13.8%; OR, 0.32 [95% CI: 0.27, 0.37]; p < 0.001). There was lower per-exam recurrence (5.0% [195/3938] vs. 7.8% [79/1017]; OR, 0.63 [95% CI: 0.47, 0.83]; p = 0.001) and higher downgrade rates (95.6% [3764/3938] vs. 93.3% [949/1017]; OR, 1.51 [95% CI: 1.12, 2.03]; p = 0.006) when using different side chain groups.

CONCLUSION: Switching to an ICM with a different carbamoyl side chain reduced the recurrent ADRs and their severity during subsequent examinations.

CLINICAL RELEVANCE STATEMENT: Switching to an iodinated contrast media with a different carbamoyl side chain reduced the recurrent adverse drug reactions and their severity during subsequent examinations.

PMID:38625610 | DOI:10.1007/s00330-024-10730-7

Low Urin Tract Symptoms. 2024 May;16(3):e12513. doi: 10.1111/luts.12513.

ABSTRACT

OBJECTIVES: This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 μg in Japanese men with nocturia due to nocturnal polyuria.

METHODS: Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set.

RESULTS: The mean age was 74.5 ± 9.9 years and 88.7% of the survey participants were aged ≥65 years. Desmopressin was started at a dose of 25 μg in 153 cases (44.3%). There were 102 adverse drug reactions (ADRs) reported in 71 cases, including 6 serious ADRs in 3 cases (0.9%). The most common ADR was hyponatremia occurring in 29 cases (8.4%). Eight of the hyponatremic cases were asymptomatic. Symptoms were resolved or slightly improved within 4 weeks of onset in 13 of 29 cases of hyponatremia. In addition, hyponatremia occurred in 11 of 217 cases (5.1%), with a serum sodium level before the administration of desmopressin of ≥140 mmol/L, and in 13 of 87 cases (14.9%), with a level of 135-139 mmol/L, and was not measured in 5 hyponatremia cases. Patient characteristics that showed significant differences in the occurrence of hyponatremia included body weight, body mass index, renal function, and pretreatment serum sodium level. Regular monitoring of serum sodium is necessary for early detection of hyponatremia.

CONCLUSIONS: Hyponatremia was the most common ADR when desmopressin orally disintegrating tablets were used to treat nocturia due to nocturnal polyuria over a 12-week period.

PMID:38616722 | DOI:10.1111/luts.12513

Rev Med Suisse. 2024 Apr 10;20(869):766-767. doi: 10.53738/REVMED.2024.20.869.766.

ABSTRACT

Asymptomatic bacteriuria is frequently encountered in clinical practice and should be treated only in pregnant women and before invasive urological procedures. Inappropriate treatment of asymptomatic bacteriuria is associated with numerous adverse effects including allergic reactions, increased antibiotics resistance and increase risk of Clostridioides difficile infection. Positive urinary culture often leads to antimicrobial treatment, irrespective of urinary symptoms. Therefore, urine analysis and culture should be performed only in symptomatic individuals or in asymptomatic individuals with a clear indication for treatment.

PMID:38616688 | DOI:10.53738/REVMED.2024.20.869.766

Eur J Hosp Pharm. 2024 Apr 15:ejhpharm-2023-004047. doi: 10.1136/ejhpharm-2023-004047. Online ahead of print.

ABSTRACT

OBJECTIVES: Drug shortages are of increasing concern to worldwide public health. The consequences of drug shortages for patient safety have been little studied, especially from a pharmacovigilance point of view. In this context, the network of French pharmacovigilance centres conducted the CIRUPT study (Conséquences Iatrogènes des RUPTures de stock/iatrogenic consequences of drug shortages) based on a prospective campaign of adverse effects occurring in the context of drug shortage notifications.

METHODS: All notifications involving a shortage drug submitted to the French pharmacovigilance centres between 1 January 2020 and 30 June 2021 were collected and registered in the French national pharmacovigilance database with the standardised high level term 'product supply and availability issues' and with predefined keywords in the narrative section.

RESULTS: 224 cases were included, involving mainly adverse drug reactions (ADRs) (n=131/224, 59%) and medication errors (n=51/224, 23%); 29% of the cases were serious. The most represented classes of shortage drugs were: vaccines (n=78/224, 35%); drugs for acid-related disorders (H2-receptor antagonists) (n=27/224, 12%); antineoplastic agents (n=17/224, 8%); and antiepileptics (n=15/224, 7%). In 82% of cases, the involved shortage drug was the subject of information delivered to health professionals by the National Agency for the Safety of Medicines and Health Products. Drug shortages were associated with an ADR related to replacement drugs in 59% (n=131/224) of the cases, drug inefficacy in 18% (n=41/224), and/or an aggravation of the underlying disease in 11% (n=25/224).

CONCLUSIONS: From a pharmacovigilance point of view, a large diversity of anatomical therapeutic classes is involved and the risk related to drug shortages is not limited to drugs registered on 'major therapeutic interest or essential drug' lists. Information from health agencies is not sufficient to avoid the risks, and further strategies should be developed.

PMID:38621957 | DOI:10.1136/ejhpharm-2023-004047

Lancet HIV. 2024 Apr 12:S2352-3018(23)00327-2. doi: 10.1016/S2352-3018(23)00327-2. Online ahead of print.

ABSTRACT

BACKGROUND: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg.

METHODS: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with ClinicalTrials.gov, NCT02881320.

FINDINGS: Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUCtau for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7-119·7); Ctau was 34·6% lower than adults (65·4%, 49·1-87·2). Both parameters were within the target exposure range previously found in adults, children, or both". Grade 3-4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3-4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48.

INTERPRETATION: Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg.

FUNDING: Gilead Sciences.

PMID:38621393 | DOI:10.1016/S2352-3018(23)00327-2

Int J Cancer. 2024 Apr 15. doi: 10.1002/ijc.34962. Online ahead of print.

ABSTRACT

The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication-related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of "Osteonecrosis of jaw" were detected only in females using palbociclib (cROR025: 2.08). Other signals detected included stomatitis-related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib-induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0025: 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug-related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors.

PMID:38619193 | DOI:10.1002/ijc.34962

Hong Kong Med J. 2024 Apr 15. doi: 10.12809/hkmj2310708. Online ahead of print.

NO ABSTRACT

PMID:38618912 | DOI:10.12809/hkmj2310708

Clin Exp Dermatol. 2024 Apr 15:llae135. doi: 10.1093/ced/llae135. Online ahead of print.

ABSTRACT

BACKGROUND: No trial of supramolecular salicylic acid (SSA) for chloasma is available yet.

OBJECTIVE: The purpose of this study was to assess the efficacy and safety of Bole DA 30% supramolecular salicylic acid (SSA) combined with 10% niacinamide in treating chloasma.

METHODS: This multicenter (n=15), randomized, double-blind, parallel placebo-controlled trial randomized the subjects (1:1) to Bole DA 30% SSA or placebo. The primary endpoint was the effective rate after 16 weeks using the modified melasma area severity index (mMASI) [(pretreatment-posttreatment)/pretreatment×100%].

RESULTS: This study randomized 300 subjects (150/group in the full analysis set, 144 and 147 in the per-protocol set). The total mMASI score, overall Griffiths 10 score, left Griffiths 10 score, and right Griffiths 10 score were significantly lower in the Bole DA 30% SSA group than in the placebo group (all P<0.001). One study drug-related AE and one study drug-unrelated adverse events (AE) were reported in the Bole DA 30% SSA group. No AE was reported in the placebo group.

CONCLUSION: Bole DA 30% SSA combined with 10% niacinamide is effective and safe for treating chloasma.

CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065346.

PMID:38618759 | DOI:10.1093/ced/llae135

Vet Rec. 2024 Apr 14:e4149. doi: 10.1002/vetr.4149. Online ahead of print.

ABSTRACT

BACKGROUND: Isoxazolines are rarely reported to be associated with neurological adverse events in cats and dogs, but information about the onset and duration of neurological signs is lacking in the summary of product characteristics of these medicines.

METHODS: The Veterinary Poisons Information Service and the Dutch Poisons Information Center databases were searched using the Veterinary Dictionary for Drug-Related Affairs terms for ataxia, muscle tremor, convulsions or hyperesthesia in cats and dogs exposed to isoxazolines.

RESULTS: There were 22 cases with and 57 cases without outcome information, mostly involving fluralaner or sarolaner. In both groups, muscle tremors and convulsions were the most common signs. In dogs, neurological signs occurred with oral therapeutic dose and overdosage. In cats, most fluralaner cases involved therapeutic topical exposure, and all sarolaner cases involved oral exposure. In all cases with outcome information, the animals recovered.

LIMITATIONS: Cases discussed with poison centres tend to involve more severe signs.

CONCLUSION: The true incidence of neurological adverse effects from isoxazolines remains unclear. The delay between the administration and onset of signs can be long, and the association may be missed. A lack of timing information in the summary of product characteristics could also contribute to missed attribution of adverse effects.

PMID:38616548 | DOI:10.1002/vetr.4149

Clin Med (Lond). 2023 Mar;23(2):173-174. doi: 10.7861/clinmed.2022-0431.

ABSTRACT

A 45-year-old woman presented to the hospital with bloody diarrhoea and significant weight loss over the past 1 month. On admission and evaluation, she was found to have acute ulcerative colitis. She was started on prednisolone and mesalamine therapy. Within 24 hours of initiation of this therapy, the patient complained of giddiness and chest discomfort and was found to have sinus bradycardia on ECG with no acute coronary event. After withdrawing mesalamine, her heart rate normalised within 24 hours and she remained symptom-free. This is a rare case report of severe symptomatic sinus bradycardia due to mesalamine therapy; to our knowledge, only four cases of mesalamine-induced bradycardia have been reported in the literature.

PMID:38614550 | DOI:10.7861/clinmed.2022-0431

Cancers (Basel). 2024 Apr 8;16(7):1440. doi: 10.3390/cancers16071440.

ABSTRACT

The landscape of cancer treatment has undergone a significant transformation with the introduction of Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit with a potential risk of developing immune-related adverse events (irAEs). Here, we reviewed and discussed the mechanisms of action of ICIs and their pivotal role in regulating the immune system to enhance the anti-tumor immune response. We scrutinized the intricate pathogenic mechanisms responsible for irAEs, arising from the evasion of self-tolerance checkpoints due to drug-induced immune modulation. We also summarized the main clinical manifestations due to irAEs categorized by organ types, detailing their incidence and associated risk factors. The occurrence of irAEs is more frequent when ICIs are combined; with neurological, cardiovascular, hematological, and rheumatic irAEs more commonly linked to PD1/PD-L1 inhibitors and cutaneous and gastrointestinal irAEs more prevalent with CTLA4 inhibitors. Due to the often-nonspecific signs and symptoms, the diagnosis of irAEs (especially for those rare ones) can be challenging. The differential with primary autoimmune disorders becomes sometimes intricate, given the clinical and pathophysiological similarities. In conclusion, considering the escalating use of ICIs, this area of research necessitates additional clinical studies and practical insights, especially the development of biomarkers for predicting immune toxicities. In addition, there is a need for heightened education for both clinicians and patients to enhance understanding and awareness.

PMID:38611115 | DOI:10.3390/cancers16071440

J Clin Med. 2024 Apr 1;13(7):2040. doi: 10.3390/jcm13072040.

ABSTRACT

Background: The comparison of the efficacy of zoledronate and denosumab for treating osteoporosis is controversial, and few randomized controlled trials have compared these two drugs in practical patients with acute osteoporotic vertebral compression fractures (OVCFs). We conducted a randomized controlled study to compare the efficacy of zoledronate and denosumab in patients with acute OVCF, with a focus on the occurrence of new OVCF. Methods: We enrolled 206 subjects who had their first acute OVCF, without any previous history of osteoporosis medication. The patients were randomly assigned to receive either intravenous zoledronate once a year or subcutaneous denosumab twice a year. We investigated the OVCF recurrence, clinical outcome, bone mineral density (BMD), and bone turnover markers over 12 months. Results: The final cohort comprised 89 participants (mean age of 75.82 ± 9.34 years, including 74 women [83.15%]) in the zoledronate group and 86 patients (mean age of 75.53 ± 10.23 years, including 71 women [82.56%]) in the denosumab group. New OVCFs occurred in 8 patients (8.89%) in the zoledronate group and 11 patients (12.79%) in the denosumab group (odds ratio, 1.485 [95% confidence interval, 0.567-3.891], p = 0.419). No significant difference was observed in the survival analysis between the two groups (p = 0.407). The clinical outcome, including the visual analog scale score for pain and simple radiographic findings, did not differ between the two groups. The changes in BMD and bone turnover markers were also not significantly different between the two groups. Additionally, drug-related adverse events did not differ between the groups in terms of safety. Conclusions: The efficacy of zoledronate was comparable to that of denosumab in terms of the occurrence of new OVCFs, as well as of the overall clinical course in patients with their first acute OVCF. Notably, this study represents the first comparison of these two drugs in patients with acute OVCF. However, further research with large-scale and long-term follow-up is necessary.

PMID:38610804 | DOI:10.3390/jcm13072040

J Clin Med. 2024 Mar 22;13(7):1840. doi: 10.3390/jcm13071840.

ABSTRACT

Background: Intrathecal baclofen (ITB) is used for the treatment of intractable spasticity. The burden of traveling for ITB screening and aftercare is problematic for nursing home residents with severe spasticity and seems to result in undertreatment of spasticity. The aim of this study is to evaluate the effectiveness, safety, and feasibility of ITB for nursing home residents treated in their home, describing the selection phase, the initial trial of ITB, and aftercare up to 3 months after implantation of an ITB pump. Methods: This retrospective database study included immobile, adult nursing home residents with severe spasticity, referred to an Ambulatory Care Clinic between 2016 and 2021. When eligible, an ITB trial was performed by ITB experts in the nursing home. If a permanent pump was implanted, dose titration and aftercare were performed on location. Results: A total of 102 patients were referred; 80 underwent an ITB trial on location, and 94% improved significantly on the Modified Ashworth Scale and clonus scale pre-ITB trial versus post-ITB trial, as well as at 3 months post-implantation. There was a low incidence of adverse events, mostly procedure- and drug-related. Conclusions: This study indicates that selection, testing, and aftercare for ITB on location is effective and safe.

PMID:38610605 | DOI:10.3390/jcm13071840

BMC Health Serv Res. 2024 Apr 12;24(1):458. doi: 10.1186/s12913-024-10888-2.

ABSTRACT

BACKGROUND: Due to unidentified geriatric needs, elderly patients have a higher risk for developing chronic conditions and acute medical complications. Early geriatric screenings and assessments help to identify geriatric needs. Holistic and coordinated therapeutic approaches addressing those needs maintain the independence of elderly patients and avoid adverse effects. General practitioners are important for the timely identification of geriatric needs. The aims of this study are to examine the spatial distribution of the utilization of outpatient geriatric services in the very rural Federal State of Mecklenburg-Western Pomerania in the Northeast of Germany and to identify regional disparities.

METHODS: Geographical analysis and cartographic visualization of the spatial distribution of outpatient geriatric services of patients who are eligible to receive basic geriatric care (BGC) or specialized geriatric care (SGC) were carried out. Claims data of the Association of Statutory Health Insurance Physicians in Mecklenburg-Western Pomerania were analysed on the level of postcode areas for the quarter periods between 01/2014 and 04/2017. A Moran's I analysis was carried out to identify clusters of utilization rates.

RESULTS: Of all patients who were eligible for BGC in 2017, 58.3% (n = 129,283/221,654) received at least one BCG service. 77.2% (n = 73,442/95,171) of the patients who were eligible for SGC, received any geriatric service (BGC or SGC). 0.4% (n = 414/95,171) of the patients eligible for SGC, received SGC services. Among the postcode areas in the study region, the proportion of patients who received a basic geriatric assessment ranged from 3.4 to 86.7%. Several regions with statistically significant Clusters of utilization rates were identified.

CONCLUSIONS: The widely varying utilization rates and the local segregation of high and low rates indicate that the provision of outpatient geriatric care may depend to a large extent on local structures (e.g., multiprofessional, integrated networks or innovative projects or initiatives). The great overall variation in the provision of BGC services implicates that the identification of geriatric needs in GPs' practices should be more standardized. In order to reduce regional disparities in the provision of BGC and SGC services, innovative solutions and a promotion of specialized geriatric networks or healthcare providers are necessary.

PMID:38609972 | PMC:PMC11010346 | DOI:10.1186/s12913-024-10888-2

BMC Psychiatry. 2024 Apr 12;24(1):272. doi: 10.1186/s12888-024-05695-2.

ABSTRACT

BACKGROUND: Personal values of Thai medical students have been observed to be diverging from those of their seniors, but the differences remain uncharacterized. Despite its potential association with mental wellbeing, the issue remain unexplored in the population. This study aimed to explore (1) the difference in personal values between medical students and instructors and (2) the association between student's value adherence to mental well-being and the interaction by gender.

METHODS: An online survey was performed in 2022. Participants rated their adherence to five groups of values, namely, Self-Direction, Hedonism, Achievement & Power, Universalism & Benevolence, and Tradition. Participants also rated their mental wellbeing. Comparisons were made between the personal values of students and instructors. The association between the personal values of students and their mental wellbeing and the interaction between values and gender were analyzed in linear regression.

RESULTS: Compared to instructors, students rated higher on Universalism & Benevolence, marginally higher on Hedonism, and lower on Tradition. Students' ratings on Self-Direction, Universalism & Benevolence, and Tradition predicted better mental wellbeing. Their rating on Hedonism predicted poorer mental wellbeing, the effect of which was marginally stronger in males. Ratings on Achievement & Power marginally predicted poorer mental wellbeing in females.

CONCLUSION: Difference in personal values between medical students and instructors have been observed. Some of these values hold potentials over student's mental wellbeing. Curricular and medical school environmental accommodation for the changes in the characters of learners may be necessary to mitigate the adverse effects on their mental wellbeing and foster development of desirable professional characteristics.

PMID:38609919 | PMC:PMC11010319 | DOI:10.1186/s12888-024-05695-2

Sci Rep. 2024 Apr 13;14(1):8572. doi: 10.1038/s41598-024-58005-x.

ABSTRACT

Unfractionated heparin (UFH) is an effective antithrombotic during surgery but has known adverse effects, in particular on platelets. A marked increase in platelet responsiveness has previously been observed in patients within minutes of receiving UFH, despite adequate inhibition by aspirin prior to heparin. We studied this phenomenon in patients undergoing cardiac artery bypass grafting (n = 17) to determine whether the effects of heparin were systemic or platelet-specific. All patients' platelets were fully inhibited by aspirin prior to surgery, but within 3 min of receiving heparin spontaneous aggregation and responses to arachidonic acid (AA) and ADP increased significantly (p ≥ 0.0002), and activated platelets were found in the circulation. While there was no rise in thromboxane in the plasma following heparin, levels of the major platelet 12-lipoxygenase product, 12-HETE, rose significantly. Mixing experiments demonstrated that the changes caused by heparin resided primarily in the platelets, while addition of AA pathway inhibitors, and analysis of oxylipins provided evidence that, following heparin, aggregating platelets regained their ability to synthesise thromboxane. These findings highlight potentially unrecognised pro-thrombotic and pro-inflammatory changes during CABG surgery, and provide further evidence of adverse effects associated with UFH.

PMID:38609431 | PMC:PMC11015001 | DOI:10.1038/s41598-024-58005-x

BMJ Ment Health. 2024 Apr 12;27(1):e300876. doi: 10.1136/bmjment-2023-300876.

ABSTRACT

BACKGROUND: Use of psychostimulants and relative drugs has increased worldwide in treatment of attention-deficit hyperactivity disorder (ADHD) in adolescents and adults. Recent studies suggest a potential association between use of psychostimulants and psychotic symptoms. The risk may not be the same between different psychostimulants.

OBJECTIVE: To assess whether amphetamine or atomoxetine use is associated with a higher risk of reporting symptoms of psychosis than methylphenidate use in adolescents and adults, particularly in patients with ADHD.

METHODS: Using VigiBase, the WHO's pharmacovigilance database, disproportionality of psychotic symptoms reporting was assessed among adverse drug reactions related to methylphenidate, atomoxetine and amphetamines, from January 2004 to December 2018, in patients aged 13-25 years. The association between psychotic symptoms and psychostimulants was estimated through the calculation of reporting OR (ROR).

FINDINGS: Among 13 863 reports with at least one drug of interest, we found 221 cases of psychosis with methylphenidate use, 115 with atomoxetine use and 169 with a prescription of an amphetamine drug. Compared with methylphenidate use, amphetamine use was associated with an increased risk of reporting psychotic symptoms (ROR 1.61 (95% CI 1.26 to 2.06)]. When we restricted the analysis to ADHD indication, we found a close estimate (ROR 1.94 (95% CI 1.43 to 2.64)). No association was found for atomoxetine.

CONCLUSION: Our study suggests that amphetamine use is associated with a higher reporting of psychotic symptoms, compared with methylphenidate use.

CLINICAL IMPLICATIONS: The prescription of psychostimulants should consider this potential adverse effect when assessing the benefit-risk balance.

PMID:38609318 | DOI:10.1136/bmjment-2023-300876

Pneumologie. 2024 Apr;78(4):236-243. doi: 10.1055/a-2267-2074. Epub 2024 Apr 12.

ABSTRACT

INTRODUCTION: Pirfenidone was the first anti-fibrotic drug approved in Europe in 2011 for the treatment of mild-to-moderate idiopathic pulmonary fibrosis.

OBJECTIVES: To investigate the clinical course of mild-to-moderate idiopathic pulmonary fibrosis in pirfenidone-treated patients in a real-world setting.

METHODS: The non-interventional study was conducted at 18 sites in Germany from 6/2014-12/2016. Adult patients with mild-to-moderate idiopathic pulmonary fibrosis were treated with pirfenidone (escalated from 3×1 to 3×3 capsules of 267 mg/day within 3 weeks) for 12 months. The observation period comprised 4 follow-up visits at months 3, 6, 9 and 12. Disease progression was defined as decrease of ≥10% in vital capacity or ≥15% in diffusing capacity of the lung for carbon monoxide (DLCO) and/or ≥50m in 6-minute walking distance vs. baseline, or "lack of response/progression" as reason for therapy discontinuation.

RESULTS: A total of 51 patients (80.4% male, mean age 70.6 years) were included in the full analysis set. Disease progression at any visit was reported for 23 (67.6%) of 34 patients with available data. Over the course of the study, lung function parameters, physical resilience, impact of cough severity on quality of life, and the mean Gender, Age and Physiology Index (stage II) remained stable. In total, 29 patients (56.9%) experienced at least one adverse drug reaction (11 patients discontinued due to adverse drug reactions); serious adverse reactions were reported in 12 patients (23.5%).

CONCLUSIONS: The results of this study are in line with the established benefit-risk profile of pirfenidone. Therefore, pirfenidone can be considered a valuable treatment option to slow disease progression in mild-to-moderate idiopathic pulmonary fibrosis. NCT02622477.

PMID:38608658 | PMC:PMC11014748 | DOI:10.1055/a-2267-2074

J Med Internet Res. 2024 Apr 12;26:e51428. doi: 10.2196/51428.

ABSTRACT

BACKGROUND: Panic disorder is a common and important disease in clinical practice that decreases individual productivity and increases health care use. Treatments comprise medication and cognitive behavioral therapy. However, adverse medication effects and poor treatment compliance mean new therapeutic models are needed.

OBJECTIVE: We hypothesized that digital therapy for panic disorder may improve panic disorder symptoms and that treatment response would be associated with brain activity changes assessed with functional near-infrared spectroscopy (fNIRS).

METHODS: Individuals (n=50) with a history of panic attacks were recruited. Symptoms were assessed before and after the use of an app for panic disorder, which in this study was a smartphone-based app for treating the clinical symptoms of panic disorder, panic symptoms, depressive symptoms, and anxiety. The hemodynamics in the frontal cortex during the resting state were measured via fNIRS. The app had 4 parts: diary, education, quest, and serious games. The study trial was approved by the institutional review board of Chung-Ang University Hospital (1041078-202112-HR-349-01) and written informed consent was obtained from all participants.

RESULTS: The number of participants with improved panic symptoms in the app use group (20/25, 80%) was greater than that in the control group (6/21, 29%; χ21=12.3; P=.005). During treatment, the improvement in the Panic Disorder Severity Scale (PDSS) score in the app use group was greater than that in the control group (F1,44=7.03; P=.01). In the app use group, the total PDSS score declined by 42.5% (mean score 14.3, SD 6.5 at baseline and mean score 7.2, SD 3.6 after the intervention), whereas the PDSS score declined by 14.6% in the control group (mean score 12.4, SD 5.2 at baseline and mean score 9.8, SD 7.9 after the intervention). There were no significant differences in accumulated oxygenated hemoglobin (accHbO2) at baseline between the app use and control groups. During treatment, the reduction in accHbO2 in the right ventrolateral prefrontal cortex (VLPFC; F1,44=8.22; P=.006) and the right orbitofrontal cortex (OFC; F1,44=8.88; P=.005) was greater in the app use than the control group.

CONCLUSIONS: Apps for panic disorder should effectively reduce symptoms and VLPFC and OFC brain activity in patients with panic disorder. The improvement of panic disorder symptoms was positively correlated with decreased VLPFC and OFC brain activity in the resting state.

TRIAL REGISTRATION: Clinical Research Information Service KCT0007280; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=21448.

PMID:38608270 | DOI:10.2196/51428