Adult Patients Research Articles

Clinical and genetic characteristics of Chinese pediatric and adult patients with hereditary spherocytosis

ObjectiveThis study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype–phenotype correlations in Chinese patients with hereditary spherocytosis (HS).MethodsRetrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (< 14 and ≥ 14 years).ResultsA total of 34 HS patients were included in this study, comprising 22 children (64.70%) and 12 adults (35.30%). The probands who underwent genetic testing were derived from 34 unrelated families. Thirty-two variants were tested and 9 of them are novel. Eighteen cases had ANK1 variants, 15 had SPTB variants, and 1 had SLC4A1 variant. 25 patients performed core family members underwent genetic testing, 17 (68.0%, 17/25) were de novo, 5 (20.0%, 5/25) were maternally inherited, and 3 (12.0%, 3/25) were paternally inherited. ANK1-HS patients exhibited more severe anemia compared to cases with SPTB-HS, showing lower levels of RBC and HB (P < 0.05). Anemia was more severe in patients diagnosed in childhood than in those diagnosed in adulthood. Within the ANK1-HS group, MCH levels in adult patients was significantly higher than those in children (P < 0.05), while there were no significant differences in RBC, HB, MCV, and MCHC levels between two groups. Adult patients with SPTB-HS had significantly higher levels of RBC, HB, and MCH than pediatric patients (P < 0.05), while MCV and MCHC levels showed no significant statistical differences.ConclusionThis study conducted a comparative analysis of phenotypic characteristics and molecular genetics in adult and pediatric patients diagnosed with HS, confirming that pediatric ANK1-HS patients exhibit a more severe anemic phenotype compared to SPTB-HS patients, while the severity of HS in adults does not significantly differ between different causative genes.

Area Deprivation and Disease Severity in Adult Patients With Discoid Lupus Erythematosus.

The association of area deprivation with outcomes in discoid lupus erythematosus (DLE) remains poorly understood. To determine the association between US Census block measures of deprivation and disease severity in adult patients with DLE. This cross-sectional study included 154 patients with DLE seen between January 1, 2007, and January 1, 2024, at a single-center referral-based specialty rheumatologic-dermatology clinic in Philadelphia, Pennsylvania. Patients were aged 18 to 73 years and were enrolled in the University of Pennsylvania's Cutaneous Lupus Erythematosus Database study. Data were analyzed between January 1, 2024, and May 8, 2024. Residence in a highly disadvantaged area as geocoded by a state area deprivation index (ADI). The main outcome was DLE disease severity as codified by the validated Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) damage and activity scores. A total of 154 adult patients with DLE (128 women [83%] and 26 men [17%]; mean [SD] age, 43 [13] years; 6 [4%] Asian individuals, 98 [64%] Black individuals, 2 [1%] Hispanic individuals, 46 [30%] White individuals, and 2 individuals [1%] with other race or ethnicity; 78 [51%] with an ADI >5; 43 who currently smoked [28%];and 56 [36%] with concurrent systemic lupus erythematosus) were included in the analysis. By multivariable logistic regression, residence within communities with an ADI greater than 5 was associated with nearly 4-fold greater odds of moderate to severe damage (odds ratio [OR], 3.90; 95% CI, 1.27-12.69] and activity (OR, 3.31; 95% CI, 1.27-9.44). Concurrent cigarette smoking was similarly associated with greater odds of moderate to severe damage (OR, 3.15; 95% CI, 1.09-10.29). After controlling for ADI and other confounders, race was not significantly associated with DLE disease severity. The results of this cross-sectional study suggest that geospatial disadvantage is associated with DLE disease severity independent of race. This invites a paradigm shift that considers the social context within which racial disparities are observed, highlighting the potential for geographically targeted interventions and policy changes to improve patient outcomes in DLE.

A prospective observational cohort study comparing the treatment effectiveness and safety of ciclosporin, dupilumab and methotrexate in adult and paediatric patients with atopic dermatitis: results from the UK-Irish A-STAR register.

The main conventional systemic atopic dermatitis (AD) treatments are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomised controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA. The aim of this study was to compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD. We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). Minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression was used to compare the hazards of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits. 488 patients (n=311 adults and n=177 children/adolescents) on dupilumab (n=282), methotrexate (n=149), or CyA (n=57) were included. CyA and MTX were primarily used first line, while dupilumab was mainly a second line systemic as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared to MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared to MTX. In severe patients the reduction in EASI, POEM, and PP-NRS was even greater with CyA. The incidence of AEs was similar across groups (734, 654 and 594 per 10,000 person-month on CyA, dupilumab and MTX respectively). This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within one follow-up year.

Identification of the most relevant aspects of spinal muscular atrophy (SMA) with impact on the quality of life of SMA patients and their caregivers: the PROfuture project, a qualitative study

BackgroundSMA is a hereditary neuromuscular disease that causes progressive muscle weakness and atrophy. Several studies have shown that the burden of SMA is very high at many levels. Functional assessment tools currently used do not completely address the impact of the disease in patients’ life. The objective of this qualitative study was to identify aspects of SMA that are relevant to patients and to design items useful for assessment purposes.ResultsFive focus group sessions were run during an annual SMA families meeting in Madrid, Spain. Focus groups were composed by parents of SMA type I children, sitter children type II-III, parents of sitter children type II-III, adult patients, and parents of walker children. Two trained facilitators conducted the focus groups using a semi-structured guideline to cover previously agreed topics based on the input of a Scientific and Patient Advisory Committee. The guideline was adapted for the different groups. According to what was communicated by participants, SMA entails a high burden of disease for both patients and their parents. Burden was perceived in physical, psychological, and social areas. Patient’s physical domain was the most relevant for participants, especially for parents of non-ambulant children, followed by limitations of motor scales to capture all changes, parents psychological burden, treatment expectations and patient’s psychological burden. Ten domains were the main areas identified as impacted by the disease: mobility and independence, fatigue and fatigability, infections and hospital consultations, scoliosis and contractures, vulnerability, pain, feeding, time spent in care, breathing, and sleep and rest.ConclusionsThis study confirms the necessity of evaluating other aspects of the disease that are not assessed in the functional motor scale. Measures of other aspects of the disease, such as pain, fatigue, feeding, should be also considered. A patient-reported outcomes instrument measuring such aspects in a valid and reliable way would be very useful. This study generated a list of new items relevant to be systematically measured in the assessment of the impact of SMA on the patients’ everyday life.

Investigating the therapeutic efficacy of psilocybin in advanced cancer patients: A comprehensive review and meta-analysis

BACKGROUND Psilocybin, a naturally occurring psychedelic compound found in certain species of mushrooms, is known for its effects on anxiety and depression. It has recently gained increasing interest for its potential therapeutic effects, particularly in patients with advanced cancer. This systematic review and meta-analysis aim to evaluate the effects of psilocybin on adult patients with advanced cancer. AIM To investigate the therapeutic effect of psilocybin in patients with advanced cancer. METHODS A comprehensive search of electronic databases was conducted in PubMed, Cochrane Central Register of Controlled Trials, and Google Scholar for articles published up to February 2023. The reference lists of the included studies were also searched to retrieve possible additional studies. RESULTS A total of 7 studies met the inclusion criteria for the systematic review, comprising 132 participants. The results revealed significant improvements in quality of life, pain control, and anxiety relief following psilocybin-assisted therapy, specifically results on anxiety relief. Pooled effect sizes indicated statistically significant reductions in symptoms of anxiety at both 4 to 4.5 months [35.15 (95%CI: 32.28-38.01)] and 6 to 6.5 months [33.06 (95%CI: 28.73-37.40)]. Post-administration compared to baseline assessments (P &lt; 0.05). Additionally, patients reported sustained improvements in psychological well-being and existential distress following psilocybin therapy. CONCLUSION The findings provided compelling evidence for the potential benefits of psilocybin-assisted therapy in improving quality of life, pain control, and anxiety relief in patients with advanced cancer.

Real-world effectiveness and safety of macitentan in patients with pulmonary artery hypertension: a multicenter, retrospective, observational study in China.

Background: Macitentan, either as monotherapy or part of combination therapy, improved clinical outcomes in patients with pulmonary artery hypertension (PAH) in clinical trials. Evidence on the effectiveness and safety of macitentan administered in real-world clinical practice in China is limited. Methods: This real-world, retrospective, multicenter chart review study was conducted at seven hospitals in China. Adult patients with a diagnosis of PAH who initiated macitentan and had medical assessments at 3-7 months after macitentan initiation were included. The primary outcomes were changes in the World Health Organization functional class (WHO-FC), 6-minute walk distance (6MWD), and N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptide (NT-proBNP/BNP) from baseline to first follow-up visit (months 3-7). Serious adverse events (SAEs) and adverse drug reactions (ADRs) of macitentan were collected. Results: From 30 August 2021 to 31 March 2022, 214 eligible patients were included in the safety analysis set and 105 patients were included in the analysis of effectiveness. At the first follow-up visit compared with baseline, significant changes in WHO-FC were observed (p = .04), 93.5% patients had their WHO-FC improved (25.8%) or maintained (67.7%). 6MWD changed by a mean (standard deviation [SD]) of 45.0 (81.4) meters (p < .001), with 94.7% having their 6MWD improved (34.7%) or maintained (60.0%). The mean (SD) of NT-proBNP decreased from 1667.4 (3233.0) ng/L to 1090.0 (2230.1) ng/L (p < .001). In the safety analysis set, 24 (11.2%) patients experienced at least one ADR and/or SAE. ADRs and SAEs were reported in 11 (5.1%) and 18 (8.4%), respectively. No deaths or unexpected safety events were observed. Conclusion: This study provided real-world evidence on the clinical benefits and good tolerance of macitentan in Chinese patients with PAH treated in routine clinical practice.

Early Burst Suppression Similarity Association with Structural Brain Injury Severity on MRI After Cardiac Arrest.

Identical bursts on electroencephalography (EEG) are considered a specific predictor of poor outcomes in cardiac arrest, but its relationship with structural brain injury severity on magnetic resonance imaging (MRI) is not known. This was a retrospective analysis of clinical, EEG, and MRI data from adult comatose patients after cardiac arrest. Burst similarity in first 72h from the time of return of spontaneous circulation were calculated using dynamic time-warping (DTW) for bursts of equal (i.e., 500ms) and varying (i.e., 100-500ms) lengths and cross-correlation for bursts of equal lengths. Structural brain injury severity was measured using whole brain mean apparent diffusion coefficient (ADC) on MRI. Pearson's correlation coefficients were calculated between mean burst similarity across consecutive 12-24-h time blocks and mean whole brain ADC values. Good outcome was defined as Cerebral Performance Category of 1-2 (i.e., independence for activities of daily living) at the time of hospital discharge. Of 113 patients with cardiac arrest, 45 patients had burst suppression (mean cardiac arrest to MRI time 4.3days). Three study participants with burst suppression had a good outcome. Burst similarity calculated using DTW with bursts of varying lengths was correlated with mean ADC value in the first 36h after cardiac arrest: Pearson's r: 0-12h: -0.69 (p = 0.039), 12-24h: - 0.54 (p = 0.002), 24-36h: - 0.41 (p = 0.049). Burst similarity measured with bursts of equal lengths was not associated with mean ADC value with cross-correlation or DTW, except for DTW at 60-72h (- 0.96, p = 0.04). Burst similarity on EEG after cardiac arrest may be associated with acute brain injury severity on MRI. This association was time dependent when measured using DTW.

Controlling nutritional status score in the prediction of cardiovascular disease prevalence, all-cause and cardiovascular mortality in chronic obstructive pulmonary disease population: NHANES 1999–2018

BackgroundMalnutrition is prevalent in chronic obstructive pulmonary disease (COPD) and associated with adverse outcomes, while COPD is intricately linked to cardiovascular disease (CVD), sharing common risk factors. The controlling nutritional status (CONUT) score, a promising tool for assessing malnutrition, warrants investigation into its predictive ability for cardiovascular disease prevalence and mortality in COPD patients.MethodsBased on the National Health and Nutrition Examination Survey (NHANES), this study analyzed 1501 adult COPD patients from 1999 to 2018. The endpoints were CVD prevalence, mortality related to CVD, and overall mortality. We evaluated the correlation of the CONUT score with each outcome using logistic regression and Cox regression models. The prognostic evaluation of patients was conducted using Kaplan-Meier curves in accordance with the CONUT score. We formed the receiver operating characteristic (ROC) curves for evaluating the CONUT score's discriminative capability.ResultsThe prevalence of malnutrition was 21.31% in COPD populations. Logistic analyses suggested a distinct connection between the CONUT score and CVD prevalence (OR:1.86, 95%CI:1.28-2.70) in individuals with COPD. The CONUT score demonstrated a significant correlation with a heightened risk of CVD mortality (HR: 1.86, 95%CI: 1.27-2.74) and overall mortality (HR: 1.50, 95%CI: 1.18-1.91). The prognostic outcomes might be effectively discriminated by the CONUT score, as seen by the Kaplan-Meier curves.ConclusionsIn summary, the CONUT score provides an uncomplicated and readily attainable marker for forecasting CVD prevalence, total mortality, and mortality from CVD among COPD patients.

Symptom burden and quality of life among patient and family caregiver dyads in advanced cancer.

Symptom management among patients diagnosed with advanced cancer is a high priority in clinical care that often involves the support of a family caregiver. However, limited studies have examined parallel patient and caregiver symptom burden and associations with their own and each other's quality of life (QOL). This study seeks to identify patient and caregiver symptom clusters and investigate associations between identified clusters and demographic, clinical, and psychosocial factors (cognitive appraisals and QOL). This study was a secondary analysis of self-reported baseline survey data collected from a randomized clinical trial of 484 adult advanced cancer patients and their caregivers. Latent class analysis and factor analysis were used to identify symptom clusters. Bivariate statistics tested associations between symptom clusters and demographic, clinical, and psychosocial variables. The most prevalent symptom for patients was energy loss/fatigue and for caregivers, mental distress. Low, moderate, and high symptom burden subgroups were identified at the patient, caregiver, and dyad level. Age, gender, race, income, chronic conditions, cancer type, and treatment type were associated with symptom burden subgroups. Higher symptom burden was associated with more negative appraisals of the cancer and caregiving experience, and poorer QOL (physical, social, emotional, functional, and overall QOL). Dyads whose caregivers had more chronic conditions were more likely to be in the high symptom burden subgroup. Patient and caregiver symptom burden influence their own and each other's QOL. These findings reinforce the need to approach symptom management from a dyadic perspective.

A decision tree model for predicting high mono-N-desethylamiodarone concentrations and reducing tissue toxicity in patients with low-dose amiodarone therapy: A multicentral retrospective cohort study.

High plasma levels of mono-N-desethylamiodarone (MDEA), an active amiodarone metabolite, may be associated with tissue toxicity in heart failure (patients with heart rhythm disturbances); therefore, a tool that can identify patients for whom therapeutic drug monitoring (TDM) of MDEA is required. This multicenter study aimed to develop a decision tree (DT) model that can identify patients with heart rhythm disturbances at high MDEA concentrations. A multicenter retrospective cohort study was conducted, including 157 adult patients with heart failure who received oral amiodarone treatment. A χ2 automatic interaction-detection algorithm was used to construct a DT model. In the DT analysis, the dependent variable was set as an MDEA trough plasma concentration of ≥0.6 μg/mL during the steady-state period. Explanatory variables were selected as factors with p < 0.05 in multivariate logistic regression analysis. The adjusted odds ratios for the daily dose of amiodarone and body mass index were 1.01 (95% coefficient interval: 1.008-1.021, p<0.001) and 0.91 (95% confidence interval: 0.834-0.988, p=0.025), respectively. For DT analysis, the risk of reaching plasma MDEA concentrations ≥0.6μg/mL was relatively high, combined with a daily dose of amiodarone >100 mg and body mass index ≤22.3 kg/m2 at 69.0% (20/29), and its trend was also detected in the sensitivity analysis. Patients taking a daily amiodarone dose > 100 mg and with a body mass index ≤22.3 kg/m2 warrant TDM implementation for MDEA to minimize the risk of MDEA-induced tissue toxicity.

Low testing rates and high BRCA prevalence: Poly (ADP-ribose) polymerase inhibitor use in Middle East BRCA/homologous recombination deficiency-positive cancer patients

BACKGROUND Poly (ADP-ribose) polymerase inhibitors (PARPis) are approved as first-line therapies for breast cancer gene (BRCA )-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. They are also effective for new and recurrent ovarian cancers that are BRCA - or homologous recombination deficiency (HRD)-positive. However, data on these mutations and PARPi use in the Middle East are limited. AIM To assess BRCA /HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer. METHODS This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations, and 25 of 65 ovarian cancer patients tested for HRD. These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023. Data were summarized using descriptive statistics and compared using counts and percentages. Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria. RESULTS Among the 472 breast cancer patients, 12.1% underwent BRCA testing, and 38.5% of 65 ovarian cancer patients received HRD testing. Pathogenic mutations were found in 25.6% of the tested patients: 26.3% breast cancers had germline BRCA (gBRCA ) mutations and 24.0% ovarian cancers showed HRD. Notably, 40.0% of gBRCA -positive breast cancers and 66.0% of HRD-positive ovarian cancers were Middle Eastern and Asian patients, respectively. PARPi treatment was used in 5 (33.3%) gBRCA -positive breast cancer patients as first-line therapy (n = 1; 7-months progression-free), for maintenance (n = 2; &gt; 15-months progression-free), or at later stages due to compliance issues (n = 2). Four patients (66.6%) with HRD-positive ovarian cancer received PARPi and all remained progression-free. CONCLUSION Lower testing rates but higher BRCA mutations in breast cancer were found. Ethnicity reflected United Arab Emirates demographics, with breast cancer in Middle Eastern and ovarian cancer in Asian patients.

Comparison of Pain With Ultrasound-Guided Intra-Articular Hip Injections With and Without Prior Subcutaneous Local Anesthesia.

To compare pain levels of intra-articular hip steroid injections performed with and without prior subcutaneous local anesthesia (LA) injection. Randomized prospective study. University-based musculoskeletal clinic. Forty-one adult patients undergoing a first-time ultrasound-guided unilateral intra-articular hip steroid injection. Subjects were randomized into 1 of 2 groups: intra-articular hip injection with prior subcutaneous LA with 2 mL of lidocaine 1% (With LA) or hip injection without prior subcutaneous LA (Without LA). Visual analog scale (VAS) pain scores (0-100) were collected before and after each injection. Visual analog scale pain score for the intra-articular hip injection. Of the 41 total subjects, 18 were randomized to the Without LA group and 23 to the With LA group. There was no significant difference in baseline (preprocedure) VAS scores between the Without LA (mean ± SD = 39.2 ± 27.2) and With LA (41.2 ± 24.0) groups (P = 0.864). The mean ± SD VAS score for the subcutaneous LA injection in the With LA group was 20.4 ± 16.1. There was no significant difference in VAS scores for the intra-articular hip injection between the Without LA (48.5 ± 27.7) and With LA (39.5 ± 25.7) groups (P = 0.232). Subcutaneous injection of lidocaine before an intra-articular hip injection did not significantly decrease pain from the intra-articular hip injection. Providers may perform intra-articular hip injections with a 22-gauge 3.5-inch spinal needle without the need for an extra subcutaneous LA injection.

The clinical efficacy of a daratumumab-based regimen in relapsed/refractory acute leukemia: a single-center experience.

Relapsed/refractory acute leukemia (R/R-AL) is associated with a low remission rate, short survival rate, and poor prognosis. Treating R/R-AL remains challenging as there is no standardized effective regimen; hence, there is a need for efficient therapies. CD38 expression has been observed in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Daratumumab is a humanized anti-CD38 monoclonal antibody used to treat multiple myeloma and has been reported to treat R/R-AL safely and effectively. The clinical data of 10 adult patients with R/R-AL who were treated with a daratumumab-based salvage regimen between July 2018 and May 2023 at our center were analyzed retrospectively. Seven AML and three ALL cases were included in the analysis. Seven (70%) patients showed responses to the treatments (complete response [CR], 60%; partial response [PR], 10%). Of the seven responders, three underwent allogenic stem cell transplantation (ASCT), including one who underwent a second ASCT. Among the five patients with R/R AML who had prior exposure to venetoclax, three achieved a therapeutic response (two CR and one PR) when re-treated with venetoclax in combination with daratumumab. The median follow-up time was 6.15 months (0.9-21 months). Overall survival and event-free survival rates at 12 months were 68.6% and 40.0%, respectively. The main adverse events included grade 3 febrile neutropenia (20%) and grade 3 hematological toxicities (60%). The daratumumab-based salvage regimen offers patients with R/R-AL the opportunity of remission with acceptable tolerability, creating the possibility of bridging ASCT.

Efficacy and safety of a self-expandable retainer in endoscopic ear surgery.

During endoscopic ear surgery (EES), it is important to maintain a clear view of the endoscopic camera to achieve a clean field. In this study, a self-expandable external auditory canal (EAC) retainer was developed to enable a more efficient and safer EES. This study aimed to evaluate the retainer's efficacy and safety in EES. Among adult patients scheduled for endoscopic tympanoplasty, 50 participants were recruited. They were assigned to either the retainer or control group in a 1:1 ratio. The anatomical characteristics, number of endoscopic cleanings during surgery, surgeon's satisfaction, and other factors were evaluated. No differences were observed in the surgical direction, EAC size measured on preoperative temporal bone computed tomography scans, location and size of tympanic membrane perforation, or bleeding degree between the two groups. When comparing the surgical time, including retainer insertion and removal, the time was similar between groups (retainer group, 35min; control group, 33.2min). The frequency of endoscopic cleaning per minute was statistically significantly lower in the retainer group than in the control group (0.18 times per minute, p = 0.048). No side effects, including sensory abnormalities or allergic reactions, were reported in any patient who used the retainer. A reduction in unnecessary endoscopic cleaning during EES was observed while using the self-expandable retainer, leading to increased surgeon satisfaction and efficiency. Furthermore, as a safe method without side effects, the retainer could be widely used to various indications for EES beyond tympanoplasty.

Population pharmacokinetic modeling of sufentanil in adult Korean patients undergoing cardiopulmonary bypass surgery.

Sufentanil is frequently used as an anesthetic agent in cardiac surgery owing to its cardiovascular safety and favorable pharmacokinetics. However, the pharmacokinetics profiles of sufentanil in patients undergoing cardiopulmonary bypass (CPB) surgery remain less understood, which is crucial for achieving the desired level of anesthesia and mitigating surgical complications. Therefore, this study aimed to develop a population pharmacokinetic model of sufentanil in patients undergoing CPB surgery and elucidate the clinical factors affecting its pharmacokinetic profile. Adult patients who underwent cardiac surgery with CPB and were administered sufentanil for anesthesia were enrolled. Arterial blood samples were collected to quantify plasma concentrations of sufentanil and clinical laboratory parameters, including inflammatory cytokines. A population pharmacokinetic model was established using nonlinear mixed-effects modeling. Simulations were performed using the pharmacokinetic parameters of the final model. Overall, 20 patients were included in the final analysis. Sufentanil pharmacokinetics were modeled using a two-compartment model, accounting for CPB effects. Sufentanil clearance increased 2.80-fold during CPB and warming phases, while the central compartment volume increased 2.74-fold during CPB. CPB was a significant covariate affecting drug clearance and distribution volume. No other significant covariates were identified despite increased levels of the inflammatory cytokines, including IL-6, IL-8, and TNF-α during CPB. The simulation indicated a 30 μg loading dose and 40 μg/h maintenance infusion for target-controlled infusion. Additionally, a bolus dose of 60 μg was added at CPB initiation to adjust for exposure changes during this phase. Considering the target sufentanil concentrations, a uniform dosing regimen was acceptable for effective analgesia.

Iodine-123-Iomazenil Single-Photon Emission Computed Tomography Revealed Recovery of Neuronal Viability in Association With Improvement of Cognitive Dysfunction After Revascularization in Moyamoya Disease.

Recent studies indicate that 123I-iomazenil (123I-IMZ) single-photon emission computed tomography (SPECT) can demonstrate neuronal viability. Although cognitive dysfunction has been recognized as an important issue in adult patients with moyamoya disease (MMD), no standard neuroradiological methods to define such conditions have been established. We examined the relationship between cognitive function and 123I-IMZ SPECT before and after revascularization in patients with MMD. The study participants were 16 adult patients with MMD whose cerebrovascular reactivities were decreased only on the surgical sides of combined revascularization. Cognitive function was examined using the Mini-Mental State Examination (MMSE; cutoff: 27) and the Frontal Assessment Battery (FAB; cutoff: 16) before and at 3 to 6 months after surgery. 123I-iodoamphetamine (123I-IMP) SPECT with acetazolamide challenge and 123I-IMZ SPECT were performed concurrently while evaluating cognitive function. The radioreactivities of 123I-IMZ SPECT in regions with decreased cerebrovascular reactivities on 123I-IMP SPECT were investigated using affected-to-contralateral side asymmetry ratio (IMZ-ACR). Twelve patients showed normal cognitive function (MMSE: 29.8 ± 0.4, FAB: 18 ± 0) before surgery. No evident laterality of 123I-IMZ uptake was seen (IMZ-ACR: 0.98 ± 0.04). Neither cognitive function nor 123I-IMZ SPECT worsened after surgery (MMSE: 29.8 ± 0.3, FAB: 18 ± 0, IMZ-ACR: 1.00 ± 0.04). By contrast, 4 patients presented cognitive dysfunction (MMSE: 24.3 ± 3.9, FAB: 14.8 ± 2.7) before revascularization. Preoperative imaging of these patients showed decreased 123I-IMZ uptake, and their IMZ-ACRs (0.83 ± 0.08) were significantly lower than those of the normal group. After revascularization, cognitive functions and 123I-IMZ uptake tended to ameliorate (MMSE: 27.5 ± 1.7, FAB: 16.3 ± 2.2, IMZ-ACR: 0.94 ± 0.09). Preoperative cognitive function was associated with 123I-IMZ uptake in adult patients with MMD. After revascularization, cognitive function could be recovered in the viable areas of the brain, which is consistent with 123I-IMZ SPECT findings.

Efficacy of planned moderate to severe torque changes in maxillary central incisors with the Invisalign appliance: A retrospective investigation

This study aimed to investigate whether there was a difference between the planned and achieved lingual root torque of the maxillary central incisors in patients treated with an initial series of Invisalign (Align Technology, Santa Clara, Calif) aligners in which>10° change in the inclination of these teeth was prescribed via the ClinCheck facility. The pretreatment, planned, and the digital models after wear of the initial series of aligners regarding adult patients who satisfied selection criteria and were treated using the Invisalign appliance were measured using the Geomagic Control X software (version 2017.0.3; 3D systems, Rock Hill, SC). A sample of 63 patients with 126 maxillary central incisors satisfied the inclusion criteria. The mean accuracy of the planned torque change of the maxillary central incisors that was achieved was 41.9%. A clinically significant shortfall (≥5°) was detected in 78.6% of the incisors, with the majority showing an underexpression between 10°-15°. Linear regression analyses indicated that weekly or biweekly wear protocols or the presence or absence of power ridges did not influence the accuracy of planned torque expression (P>0.05). The changes in torque expression with an initial series of Invisalign aligners were less than half of what was planned in patients in which at least a 10° change in lingual root torque of these teeth was prescribed. The presence of power ridges and the aligner change protocol did not appear to significantly affect the accuracy of maxillary central incisor torque expression.

The natural history of dihydrolipoamide dehydrogenase deficiency in Israel.

Dihydrolipoamide dehydrogenase (DLD) deficiency is an ultra-rare autosomal-recessive inborn error of metabolism, affecting no less than five mitochondrial multienzyme complexes. With approximately 30 patients reported to date, DLD deficiency was associated with three major clinical presentations: an early-onset encephalopathic phenotype with metabolic acidosis, a predominantly hepatic presentation with liver failure, and a rare myopathic phenotype. To elucidate the demographic, phenotypic, and molecular characteristics of patients with DLD deficiency within the Israeli population, data were collected from metabolic disease specialists in four large tertiary medical centers in the center and south of Israel. Pediatric and adult patients with biallelic variants in DLD were included in the study. A total of 53 patients of 35 families were included in the cohort. Age at presentation ranged between birth and 10 years. Wide phenotypic variability was observed, from asymptomatic individuals in their sixth decade of life, to severe, neonatal-onset disease with devastating neurological sequelae. Six DLD variants were noted, the most common of which was the c.685G>T (p.G229C) variant in homozygous form (24/53 patients, 45.3%; 13/35 families), observed mostly among patients of Ashkenazi-Jewish descent, followed by the homozygous c.1436A>T (p.D479V) variant, found in 20 patients of Bedouin descent (37.7%; 16/35 families). Overall, patients did not necessarily present as one of the previously described distinct clinical phenotypes. DLD deficiency is a panethnic disorder, with significant phenotypic variability, and comprises a continuum, rather than three distinct clinical presentations.

Impact of pharmacist managed oral epidermal growth factor receptor inhibitors.

Pharmacists are an integral part of medication management, with the positive impact of their clinical services in patient outcomes previously studied and reported in literature. The roles and responsibilities of pharmacists continue to expand, including optimizing patient medication and health outcomes related to complex oral anticancer drugs. To evaluate the impact of a pharmacist-managed oral chemotherapy clinic in patients with non-small cell lung cancer (NSCLC) taking oral epidermal growth factor receptor inhibitor (EGFRi) regimens within an integrated healthcare delivery system. This was an observational cohort study using data from Kaiser Permanente Northern and Southern California regions on adult patients who received oncology pharmacist-managed care compared to patients with usual care. Patients were newly initiated with EGFRi therapy to treat NSCLC between 2017 and 2019. The follow-up period was defined as the time from index date (first sold date of EGFRi) to December 2020 or end of membership or death, whichever occurred first. Primary outcome measures included adherence to EGFRi, frequency of imaging during drug exposure, and presence of imaging prior to treatment change. Outcomes were analyzed with Chi-square test for categorical variables, and Student's t-test or Wilcoxon rank-sum test for continuous variables. There were 613 patients in the pharmacist-managed group and 714 patients in the usual care group. Overall, the mean age was 68.2 ± 11.3 years, and 65.1% were female. In the pharmacist-managed group, there was a significantly higher mean proportion of days covered (PDC) during the first three months of therapy (0.86 ± 0.24 vs 0.82 ± 0.36, p = 0.01) and a higher percentage of patients who were adherent to EGFRi therapy (with PDC ≥0.80) during the drug exposure period (95.8% vs 92.4%, p = 0.01). The rate of computed tomography (CT) and magnetic resonance imaging (MRI) during drug exposure was higher in the pharmacist-managed group compared to the usual care group (31.8% vs 20.7%, p < 0.01) with a higher number of mean scans completed per patient (1.15 ± 2.42 vs 0.62 ± 1.63, p < 0.01) and per patient-year (2.60 ± 7.27 vs 1.58 ± 5.95, p < 0.01). Overall, 66.2% of patients had a treatment change, with a higher percentage of patients in the pharmacist-managed group who completed a CT or MRI scan prior to treatment change (36.3% vs 26.3%, p < 0.01). Additionally, the median time between the scan and treatment change was shorter for patients with pharmacist-managed care (1.8 vs 4 months, p = 0.04). Clinical pharmacy services contributed to improved adherence, higher rates of imaging, and shorter time between imaging and treatment changes in NSCLC patients who were taking EGFRi regimens.

Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: Results from the Phase 3 randomized, controlled trial (THRIVE-AA1)

BackgroundAlopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. ObjectiveThe Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. MethodsPatients aged 18–65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg BID, deuruxolitinib 12 mg BID, or placebo for 24 weeks. The primary endpoint was percentage of patients achieving Severity of Alopecia Tool (SALT) score ≤20. A key secondary endpoint was percentage of satisfaction of hair patient-reported outcome (SPRO) responders. ResultsSignificantly higher proportions of patients taking deuruxolitinib met the primary endpoint (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary endpoints versus placebo, including SPRO (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. LimitationsFurther studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. ConclusionBoth doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.