Tag: pubmed

Int J Clin Pharm. 2024 Nov 21. doi: 10.1007/s11096-024-01836-5. Online ahead of print.

ABSTRACT

BACKGROUND: Neutropenia can easily progress to febrile neutropenia and is a risk factor for life-threatening infections. Predicting and preventing severe neutropenia can help avoid such infections.

AIM: This study aimed to develop an optimal model using advanced statistical methods to predict neutropenia after 5-fluorouracil/cisplatin chemotherapy for esophageal cancer and to create a nomogram for clinical application.

METHOD: Patients who received 5-fluorouracil/cisplatin chemotherapy at Chiba University Hospital, Japan, between January 2011 and March 2021 were included. Clinical parameters were measured before the first, second, and third chemotherapy cycles and were randomly divided by patient into a training cohort (60%) and test cohort (40%). The predictive performance of Logistic, Stepwise, Lasso, and GLMMLasso models was evaluated by the area under the receiver-operating characteristic curve (AUC). A nomogram based on GLMMLasso was developed, and the accuracy of probabilistic predictions was evaluated by the Brier score.

RESULTS: The AUC for the first cycle of chemotherapy was 0.781 for GLMMLasso, 0.751 for Lasso, 0.697 for Stepwise, and 0.669 for Logistic. The respective AUCs for GLMMLasso in the second and third cycles were 0.704 and 0.900. The variables selected by GLMMLasso were cisplatin dose, 5-fluorouracil dose, use of leucovorin, sex, cholinesterase, and platelets. A nomogram predicting neutropenia was created based on each regression coefficient. The Brier score for the nomogram was 0.139.

CONCLUSION: We have developed a predictive model with high performance using GLMMLasso. Our nomogram can represent risk visually and may facilitate the assessment of the probability of chemotherapy-induced severe neutropenia in clinical practice.

PMID:39570570 | DOI:10.1007/s11096-024-01836-5

Drug Saf. 2024 Nov 21. doi: 10.1007/s40264-024-01487-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Risk minimisation measures (RMMs) aim to ensure safe use of medicines, but their implementation in clinical practice is complicated by the diversity of stakeholders whose clinical decision making they seek to inform. Clinical practice guidelines (CPGs) are considered integral in clinical decision making.

OBJECTIVES: To determine the extent to which RMMs are included in the relevant CPGs and to describe factors that determine RMM inclusion.

METHODS: A multi-case study design using quantitative document analysis of CPGs combined with qualitative interviews with informants from organisations that issue CPGs. Cases from five therapeutic areas (TAs) with a regulatory requirement for further RMMs were studied individually in six EU member states (Denmark, Greece, Latvia, Netherlands, Portugal and Slovenia). Clinical practice guidelines were analysed using pre-defined coding frameworks. Interviewees were sampled purposively for experience and knowledge about CPG development and RMM inclusion. Verbatim interview transcripts were analysed inductively.

RESULTS: In total, 136 CPGs were analysed, and RMM information about TAs was included in 25% of CPGs. Based on 71 interviews we found that factors that determine RMM inclusion in CPGs include clinicians’ low awareness of RMMs despite awareness of RMMs’ safety concern, low expectation of RMMs’ clinical utility, and unfamiliarity with pharmacovigilance data supporting RMMs and perceived incompatibility of CPGs’ scope and purpose and RMM information.

CONCLUSIONS: The inclusion of RMM information in relevant CPGs is remarkably limited. It may be explained by characteristics of CPGs and of RMMs as well as lack of connection between national regulators and organisations and authors developing CPGs. More collaboration between stakeholders, national regulators and the EMA may advance implementation.

PMID:39570566 | DOI:10.1007/s40264-024-01487-5

Adv Ther. 2024 Nov 21. doi: 10.1007/s12325-024-03050-1. Online ahead of print.

ABSTRACT

INTRODUCTION: There is no information on the incidence of severe hypoglycemia in real-world patients with diabetes receiving ultra-rapid lispro (URLi). This post-marketing, observational, safety study assessed the incidence proportion and incidence rate of the first severe hypoglycemia event requiring a hospital visit in URLi-treated patients. It also compared the risk of severe hypoglycemia between patients treated with URLi or other rapid-acting insulin analogs (RAIAs).

METHODS: Claims data were obtained from a nationwide hospital-based administrative database in Japan (Medical Data Vision). Adults with diabetes who initiated URLi or other RAIA on/after June 01, 2020, were followed up through May 31, 2023. Severe hypoglycemia was identified using a validated algorithm. Incidence proportion and incidence rate of the first severe hypoglycemia event requiring a hospital visit was described in URLi-treated patients (descriptive analysis). These outcomes were also compared against propensity score (PS)-matched other RAIA-treated patients (comparator; comparative analysis). Hazard ratio (HR) and 95% confidence interval (CI) was estimated with a Cox proportional hazards model.

RESULTS: The descriptive analysis’ URLi-treated cohort included 17,838 patients [mean (standard deviation, SD) age 65.9 (15.7) years; 58.3% male]. The majority had type 2 diabetes (75.7%). The incidence proportion of the first severe hypoglycemia event requiring a hospital visit was 0.6% (95% CI 0.5, 0.8) and the incidence rate was 1.7 per 100 person-years (95% CI 0.7, 4.3). The comparative analysis included 10,592 URLi-treated and 52,917 comparator-treated patients. The incidence rate of severe hypoglycemia did not significantly differ between these cohorts (HR 0.8; 95% CI 0.5, 1.1; p = 0.132;.

CONCLUSION: This study did not show a statistically significant increase in the incidence and risk of the first severe hypoglycemia event requiring a hospital visit in real-world URLi-treated patients in Japan, compared with a PS-matched cohort of other RAIA-treated patients.

PMID:39570544 | DOI:10.1007/s12325-024-03050-1

Sports Med. 2024 Nov 21. doi: 10.1007/s40279-024-02144-8. Online ahead of print.

ABSTRACT

BACKGROUND: Several factors such as acute symptom severity, premorbid anxiety, and depression have been associated with concussion recovery. Elevated kinesiophobia has been associated with recovery from musculoskeletal conditions, as well as increased reaction time and vestibular-ocular motor dysfunction following concussion. However, kinesiophobia has yet to be evaluated as a modifier of concussion recovery time.

OBJECTIVES: This study was designed to evaluate the role of acute kinesiophobia levels on days until clinical recovery in collegiate athletes with concussion. We hypothesized that collegiate athletes with elevated Tampa Scale of Kinesiophobia (TSK) scores would take a greater number of days to achieve clinical recovery compared with athletes with lower values.

METHODS: Division I collegiate athletes diagnosed with a concussion (N = 113, 19.9 ± 1.5 years, 42% female) participated in this descriptive laboratory study. Participants were assigned to high [≥ 37 (H-TSK, n = 54)] or low [< 37 (L-TSK, n = 59)] TSK groups on the basis of the first TSK values recorded within 72 h of their concussion. Participants were also administered the Revised Head Injury Scale (HIS-r) to assess symptom severity within 72 h of injury. The Immediate Postconcussion and Cognitive Test (ImPACT) battery was administered at baseline and used to gather demographic variables such as biological sex, age, history of anxiety/depression, and concussion history, and as part of the athletes’ symptom-free assessment. Days until clinical recovery between H-TSK and L-TSK groups were compared using a Mann-Whitney U test. Spearman’s rank correlation coefficients were calculated to determine the relationship between TSK and days until clinical recovery in addition to other modifiers of recovery. Multiple linear regression was used to evaluate days until clinical recovery as a function of the TSK total score, controlling for the HIS-r and ImPACT variables.

RESULTS: Days until clinical recovery was significantly longer in the H-TSK group (median difference = 2.5 days, p < 0.001) compared with the L-TSK group. A significant, moderate positive correlation between the TSK score and days to clinical recovery (ρ = 0.45, p < 0.001) was observed, which was also the strongest correlation among all variables. Our regression model demonstrated that for every point increase on the TSK, days until clinical recovery increased by 0.23 while controlling for total symptom severity, age, concussion history, psychiatric history, and biological sex (β = 0.23, p = 0.018). All other variables entered into the regression were not statistically significant.

CONCLUSIONS: Our data suggest that athletes with TSK scores above 37 within 72 h of a concussion had a greater number of days until clinical recovery when compared with athletes with TSK values below 37. The TSK score had the highest correlation with days until clinical recovery when compared with other known modifiers of recovery, including total symptom severity. The TSK score was also the strongest predictor of days until clinical recovery. Collectively, these findings suggest that the TSK score should be considered by healthcare professionals to help inform effective management strategies for collegiate athletes with concussion.

PMID:39570534 | DOI:10.1007/s40279-024-02144-8

Environ Sci Pollut Res Int. 2024 Nov 21. doi: 10.1007/s11356-024-35558-y. Online ahead of print.

ABSTRACT

The chemical behavior of mercury (Hg) and its interactions with naturally occurring ligands shape its environmental fate and impact. The neurotoxic properties of Hg are widely known and studied both in vitro and in vivo. However, there continues to be limited information on the influence of chelation with large organic ligands on the toxicity to marine macro-organisms. This work examined the effect of Hg complexed with various types of dissolved organic matter (DOM) on the mortality and hatching success of Artemia sp. nauplii under varying marine media conditions. The results confirmed both, an alleviating as well as additive, DOM-specific, effect on mortality. DOM coexposure resulted in a compound specific decreased or increased toxicity in comparison with single exposure in artificial seawater, with LC₅₀ values ranging from 2.11 to 62.89 µM. Hatching success under conditions of Hg exposure was almost two orders of magnitude more sensitive than toxicity in hatched individuals. Elevated DOM concentrations had no statistically significant impact on hatching success with computed EC₅₀ values ranging from 196 to 324 nM.

PMID:39570530 | DOI:10.1007/s11356-024-35558-y

Biochem Genet. 2024 Nov 21. doi: 10.1007/s10528-024-10949-5. Online ahead of print.

ABSTRACT

Cervical cancer (CC) remains a real public health problem in low- and middle-income countries, where technical resources and competent personnel are insufficient. Persistent cervix infection by high-risk human papillomavirus (Hr-HPV) is the main cause of CC development. In the current study, we examined the distribution of Hr-HPV in the general healthy Malian population using cervicovaginal self- sampling. A total of 354 women were recruited, with a median age of 34 ± 11.37 years, IQR (27-43). We found that 100% of participants agreed to self-sample at the health center. For result announcement 99.2% expressed their preference to be contacted by cell phone. Furthermore, 100% of study participants showed their willingness to undergo confirmatory CC test in case of Hr-HPV test proved positive, and to receive treatment in the event of the presence of cervical lesions. The overall prevalence of Hr-HPV was 21.2% (95% CI: 17-25.8). HPV31/35/33/52/58 with 11.9% (95% CI: 8.7-15.7) and HPV39/68/56/66 with 5.9% (95% CI: 3.7-8.9) were the most common Hr-HPV subtypes. We noted that Hr-HPV genotypes were more prevalent among women under 25 years, 36.1% (N = 61). In addition, the distribution of Hr-HPV was statistically associated with age, W = 12,374, p = 0.015. Our data showed that 25.3% (N = 19) of Hr-HPV-positive women were tested positive by VIA/VILI. Among the 19 VIA/VILI-positive women, histological examination showed that 4 were CIN1, 4 were CIN2, and 2 were CIN3 grades. In addition, the median age of participants with CIN2 and CIN3 was statistically higher than the median of those with CIN1 grade, 25 years IQR (21-26.75) versus 50 years, IQR (40.25-55), W = 24, p = 0.009. In sum, end-users are very satisfied with the cervicovaginal self-sampling device for identifying HR-HPV genotypes as part of CC screening. In addition, it enables hospital practitioners to take the necessary action after triaging women according to their HR-HPV genotype.

PMID:39570507 | DOI:10.1007/s10528-024-10949-5

J Endocrinol Invest. 2024 Nov 21. doi: 10.1007/s40618-024-02502-3. Online ahead of print.

ABSTRACT

BACKGROUND: Induction of puberty in boys with constitutional delay of growth and puberty (CDGP) through a short course of low-dose testosterone therapy indicates the critical interaction between testosterone and the androgen receptor (AR) during the activation and maturation of the hypothalamic-pituitary-gonadal axis at puberty onset. Previous studies have shown an inverse relationship between the CAG repeat length and the transactivation function or expression level of the AR gene.

OBJECTIVE: We aimed to investigate whether the AR CAG repeat polymorphism has any implications on pubertal delay.

SUBJECTS AND METHODS: Thirty-three male patients with CDGP were enrolled in the study group, while 53 age-matched healthy individuals who had entered puberty on time were included in the control group. The CAG repeat length was determined through direct DNA sequencing analysis.

RESULTS: The median chronological age of boys with CDGP was 14.2 (14.1-14.6) years, compared to 14.2 (13.65-14.8) years for healthy subjects (p = 0.5). In the CDGP group, 22 (66.7%) children had a family history of the condition. There was no significant difference between the groups in terms of AR CAG repeat length (median AR CAG repeat length: 21 (20-24.5) and 20 (20-24), respectively, p = 0.1). However, in boys with CDGP with a similar family history (n = 22), a significantly longer AR CAG repeat length was found compared to the control group (n = 53) (median AR CAG repeat length: 22 (20-25) and 20 (20-24), respectively, p = 0.03). The median AR CAG repeat length in boys without a family history was 21 (20-22) triplets. Although boys with a family history had a slightly longer AR CAG repeat length than those without, the difference was not statistically significant (p = 0.07). Additionally, no significant differences were observed between boys with non-familial CDGP and control subjects (p = 0.8). Furthermore, no significant differences in anthropometric characteristics or hormonal parameters were found when patients with CDGP were categorized by AR CAG repeat length quartiles.

CONCLUSION: This is the first study to investigate the role of AR CAG polymorphism in the etiopathogenesis of CDGP. Our findings suggest that the AR CAG repeat length may be associated with familial CDGP.

PMID:39570490 | DOI:10.1007/s40618-024-02502-3

Mycopathologia. 2024 Nov 21;189(6):102. doi: 10.1007/s11046-024-00908-4.

ABSTRACT

During the last two decades, wound invasive fungal diseases (WIFDs) have reemerged as important causes of mortality and morbidity in military personnel and civilian casualties in war areas. Historically, mycotic infections acquired in combat operations during Vietnam War and were associated with burn wounds. Modern combat related WIFDs are almost exclusively associated with severe traumatic events which encompass blast exposure as the primary mechanism of injury and subsequent extremity amputation and extensive blood loss. Such infections often lead to deep tissue necrosis, long hospitalizations, extensive surgeries, and more severe amputation. Studies of combat related WIFDs among U.S. military personnel in Operation Enduring Freedom (Afghanistan) demonstrated incidence rates of approximately 7% and crude mortality of 8.5%. WIFDs were also seen in U.K. military personnel returning from Afghanistan and are common in the current Ukraine and Gaza conflicts. Mucorales, Aspergillus and Fusarium species are the predominant causes of WIFDs. These molds are opportunistic pathogens which thrive in patients with immune system imbalances following traumatic injury. They are ubiquitous environmental fungi found in a variety of soils but there are significant regional differences depending on the local soil type, vegetation, and climate. The management of WIFDs is complicated by the limited efficacy of current antifungals on many of these environmental species and by emerging antifungal resistance globally. This review provides an overview of the global burden, epidemiology, and clinical features of combat-related fungal infections with the aim to provide a better understanding of the threat posed for wounded Service Members and civilians.

PMID:39570484 | DOI:10.1007/s11046-024-00908-4

Int J Hematol. 2024 Nov 21. doi: 10.1007/s12185-024-03864-3. Online ahead of print.

ABSTRACT

Lenalidomide is an oral immunomodulatory agent approved for the treatment of relapsed/refractory adult T-cell leukemia/lymphoma (ATLL) in Japan. Post-marketing surveillance (PMS) was conducted to confirm its safety and effectiveness. From April 2017 until April 2020, safety data were obtained for 77 patients and effectiveness data for 65 patients (31.2% of patients had progressive disease as the best response to their most recent prior regimen). Forty-nine patients (63.6%) in the safety analysis set experienced an adverse drug reaction (ADR). Grade ≥ 3 ADRs occurred in 42.9%. The most common Grade ≥ 3 ADRs were neutrophil count decreased/neutropenia and platelet count decreased/thrombocytopenia (11.7% each). Serious ADRs occurred in 26 patients. Five patients had previously received allogeneic hematopoietic stem cell transplantation. Among these, one experienced acute graft versus host disease (GvHD) during lenalidomide administration and two responded to lenalidomide. Effectiveness analysis showed that an objective response was achieved in 29.2% of patients. No statistically significant differences were observed in the objective response rates of patients aged < 70 versus those aged ≥ 70 years (33.3% vs 28.0%, respectively; p = 0.6904). No new safety signals were observed in this PMS, and lenalidomide demonstrated a favorable benefit-risk balance in Japanese patients with ATLL.

PMID:39570473 | DOI:10.1007/s12185-024-03864-3

Support Care Cancer. 2024 Nov 21;32(12):813. doi: 10.1007/s00520-024-09023-y.

ABSTRACT

OBJECTIVES: Due to disease- or therapy-associated immunosuppression, oncological patients suffer from significantly higher morbidity and mortality due to infections transmitted by respiratory pathogens such as Streptococcus pneumoniae and influenza virus. Although the German Standing Committee on Vaccination (STIKO) provides specific recommendations for vaccination against these pathogens, there is no data on vaccination rates in this high-risk population.

METHODS: Data from the interventional EVO study were analyzed to provide information on vaccination rates against Streptococcus pneumoniae and influenza virus in oncological patients. Numbers presented in this publication summarize baseline and follow-up data of the control group; thus, data were not influenced by the intervention.

RESULTS: Data of 370 patients were analyzed; 20.5% of patients were treated for hematological malignancies and 79.5% for solid cancer. 28.1% of patients had received vaccination against influenza and 32.2% against Streptococcus pneumoniae; for the latter only 7.3% according recommendations. While vaccination rates where even lower for patients with thoracic carcinoma (influenza 26.7% and Streptococcus pneumoniae 6.0% according to STIKO recommendations), rates in patients with multiple myeloma were remarkably higher (39.0% and 14.6%).

CONCLUSIONS: Despite strong recommendations to vaccinate and the clear clinical need to prevent infections in the vulnerable group of oncological patients, only the minority was vaccinated against Streptococcus pneumoniae or influenza, underlining the urgent need for better vaccination strategies in this high-risk population.

PMID:39570461 | DOI:10.1007/s00520-024-09023-y