Dose Changes Research Articles

Impact of metabolic and bariatric surgery on weight loss and insulin requirements in type 1 and insulin-treated type 2 diabetes.

Metabolic and Bariatric Surgery (MBS) is effective in improving metabolic outcomes and reducing weight in patients with obesity and diabetes, with less explored benefits in type 1 diabetes (T1D). This study aimed to evaluate the impact of MBS on weight loss and insulin requirements in T1D patients compared to insulin-treated type 2 diabetes (T2D) patients over a 5-year period. This retrospective analysis included patients who underwent primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) with a confirmed preoperative diagnosis of either T1D or insulin-treated T2D. Primary endpoints focusing on weight loss and secondary outcomes assessing changes in insulin dosage and glycemic control. After 5 years, weight loss was similar across groups, with total weight loss at 14.2% for T1D and 17.6% for insulin-treated T2D in SG, and 22.6% for T1D vs. 26.8% for insulin-treated T2D in RYGB. Additionally, there was a significant reduction in median daily insulin doses from 140.5 units at baseline to 77.5 units at 1 year postoperatively, sustained at 90 units at 5 years. The differential impact of MBS procedure was also highlighted, where RYGB patients showed a more pronounced and enduring decrease in insulin requirements compared to SG.

Reduced dose helical CT scout imaging on next generation wide volume CT system decreases scan length and overall radiation exposure

PurposeTraditional CT acquisition planning is based on scout projection images from planar anterior-posterior and lateral projections where the radiographer estimates organ locations. Alternatively, a new scout method utilizing ultra-low dose helical CT (3D Landmark Scan) offers cross-sectional imaging to identify anatomic structures in conjunction with artificial intelligence based Anatomic Landmark Detection (ALD) for automatic CT acquisition planning. The purpose of this study is to quantify changes in scan length and radiation dose of CT examinations planned using 3D Landmark Scan and ALD and performed on next generation wide volume CT versus examinations planned using traditional scout methods. We additionally aim to quantify changes in radiation dose reduction of scans planned with 3D Landmark Scan and performed on next generation wide volume CT. MethodsSingle-center retrospective analysis of consecutive patients with prior CT scan of the same organ who underwent clinical CT using 3D Landmark Scan and automatic scan planning. Acquisition length and dose-length-product (DLP) were collected. Data was analyzed by paired t-tests. Results104 total CT examinations (48.1 % chest, 15.4 % abdomen, 36.5 % chest/abdomen/pelvis) on 61 individual consecutive patients at a single center were retrospectively analyzed. 79.8 % of scans using 3D Landmark Scan had reduction in acquisition length compared to the respective prior acquisition. Median acquisition length using 3D Landmark Scan was 26.7 mm shorter than that using traditional scout methods (p < 0.001) with a 23.3 % median total radiation dose reduction (245.6 (IQR 150.0–400.8) mGy cm vs 320.3 (IQR 184.1–547.9) mGy cm). CT dose index similarly was overall decreased for scans planned with 3D Landmark and ALD and performed on next generation CT versus traditional methods (4.85 (IQR 3.8–7) mGy vs. 6.70 (IQR 4.43–9.18) mGy, respectively, p < 0.001). ConclusionScout imaging using reduced dose 3D Landmark Scan images and Anatomic Landmark Detection reduces acquisition range in chest, abdomen, and chest/abdomen/pelvis CT scans. This technology, in combination with next generation wide volume CT reduces total radiation dose.

Effect of on-demand vs continuous prescription of proton pump inhibitors on symptom burden and quality of life: results of a real-world randomized controlled trial in primary care patients with gastroesophageal reflux disease.

This study aimed to assess the impact of on-demand versus continuous prescribing of proton pump inhibitors (PPIs) on symptom burden and health-related quality of life in patients with gastroesophageal reflux disease (GERD) presenting to primary care. Thirty-six primary care centres across Europe enrolled adult GERD patients from electronic health records. Participants were randomised to on-demand or continuous PPI prescriptions and were followed for 8 weeks. PPI intake, symptom burden, and quality of life were compared between the two groups using mixed-effect regression analyses. Spearman's correlation was used to assess the association between changes in PPI dose and patient-reported outcomes. A total of 488 patients (median age 51 years, 58% women) completed the initial visit, with 360 attending the follow-up visit. There was no significant difference in PPI use between the continuous and on-demand prescription groups (b=.57, 95%CI:0.40-1.53), although PPI use increased in both groups (b = 1.33, 95%CI:0.65 - 2.01). Advice on prescribing strategy did not significantly affect patient-reported outcomes. Both symptom burden (Reflux Disease Questionnaire, b=-0.61, 95%CI:-0.73 - -0.49) and quality of life (12-item Short Form Survey physical score b = 3.31, 95%CI:2.17 - 4.45) improved from baseline to follow-up in both groups. Increased PPI intake correlated with reduced reflux symptoms (n = 347, ρ=-0.12, p = 0.02) and improved quality of life (n = 217, ρ = 0.16, p = 0.02). In real-world settings, both continuous and on-demand PPI prescriptions resulted in similar increases in PPI consumption with no difference in treatment effects. Achieving an adequate PPI dose to alleviate reflux symptom burden improves quality of life in GERD patients. EudraCT number 2014-001314-25.

Characterizing Lipid Changes and Use of Lipid-Lowering Medications in Patients With Alopecia Areata Treated With Baricitinib: Integrated Results From the BRAVE-AA1 and -AA2 Clinical Trials

Introduction. Elevations in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) can occur with baricitinib treatment, consistent with a class effect of JAK inhibitors. In this analysis, we characterized changes in lipid levels and use of lipid-lowering medication among patients with severe alopecia areata (AA) treated with baricitinib through 152-weeks of treatment. Methods. Two integrated datasets from the BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) trials were analyzed: 1. Extended BARI AA includes patients treated with continuous baricitinib 2 mg (N=383) and 4 mg (N=565) from baseline and censored at dose change: 2. ALL BARI AA (N=1303) includes data for patients who received ≥1 dose of baricitinib at any time. Outcomes included abnormal changes in lipid parameters, mean change from baseline in lipids, and concomitant use of lipid-lowering medications. Results. At time of enrollment, 43% of patients had hypercholesterolemia. Incidence rates for categorical increases in total cholesterol (TC; ≥240mg/dL), LDL-C (≥130 mg/dL), and HDL-C (&gt;60 mg/dL) were 11.8, 13.3, and 12.9 per 100 patients-years of exposure, respectively in the ALL BARI AA dataset. In the Extended BARI AA the mean maximal increase in lipids (mg/dL) for baricitinib 4 mg was 20.9 for TC, 12.4 for LDL-C, and 8.5 for HDL-C. Changes occurred early and stabilized by one year for TC and LDL-C and by 12 weeks for HDL-C. 6.1% (n=79) of patients in the ALL BARI AA dataset used lipid-lowering medication at baseline; post-baseline, 3.9% (n=51) discontinued this medication and 4.7% (n=61) initiated lipid lowering medication. No patients discontinued baricitinib treatment due to treatment-emergent adverse events related to hyperlipidemia. Conclusions. Elevations in TC, LDL-C, and HDL-C, but not triglycerides were associated with baricitinib treatment in patients with AA, consistent with a class effect of JAK inhibitors. The relatively low use of lipid-lowering medications at baseline despite the prevalence of hypercholesterolemia may reflect undermanagement of this condition in the population. Notably, the mean maximal magnitude of increase in lipid levels on baricitinib was modest. Initiation of lipid-lowering medication was infrequent, and no patients discontinued due to lipid abnormalities.

Anticoagulation with warfarin for paediatric cardiac indications: a retrospective study.

Warfarin is used as anticoagulation for children for a wide range of cardiac indications but carries the disadvantage of requiring international normalised ratio monitoring and dose adjustment. Management of warfarin therapy is challenging due to its narrow therapeutic window and is further complicated in children by dietary changes, frequent illnesses, and developing systems of metabolism and haemostasis.A retrospective review was performed of patients' medical records to assess the indication for warfarin use, percentage of international normalised ratio values in target range (%ITR), and frequency of phlebotomy.Twenty-six patients were identified. The most common indication for warfarin use was in patients post-total cavo-pulmonary connection (n = 19, 73%). We demonstrated a variability in duration of warfarin therapy following total cavo-pulmonary connection (median of 11.1 months). Nineteen (73%) patients had used the CoaguChek machine for home measurement of international normalised ratio. The median frequency of phlebotomy for all indications was once every 10 days, and the median %ITR was 55.4 % (29.7-86.4%). Of note, the percentage under target range in the patients with mechanical mitral (n = 2) and aortic valves (n = 1) was found to be 23% and 33%, respectively.These data demonstrate a high frequency of international normalised ratio values outside of the target range as seen in previous studies of warfarin in children. This necessitates frequent phlebotomy and dose changes, which can have a significant effect on the quality of life of these patients and their families highlighting the need to focus on quality improvement in the area of anticoagulation in paediatric cardiac patients.

Abstract 4137768: Evaluation of Therapeutic Intensification for Uncontrolled Hypertension Using Different Sources of Electronic Health Records

Background: Healthcare system level interventions to monitor therapeutic intensification for uncontrolled blood pressure (BP) may address potential therapeutic inertia, however, the best methods to evaluate therapeutic intensification using different sources of electronic health records are unknown. Question: To what extent do medication orders and pharmacy data provide comparable or distinct evaluations of therapeutic intensification? Methods: We identified adults with uncontrolled hypertension (systolic BP ≥140 or diastolic BP ≥90 mm Hg) in an outpatient encounter (index) from Kaiser Permanente Southern California in 2018. We included patients with new antihypertensive medication orders at the index encounter. We calculated therapeutic intensification score (TIS), a proportional measure of prescribed daily dose to maximum recommended daily dose of antihypertensive medications using two data sources: (1) medication orders including dose, directions for use, discontinuation order; (2) pharmacy fill data including strength, days’ supply, and quantity within 14 days after the index. Therapeutic intensification was determined by comparing the new dose at index and the previous dose [delta TIS (new dose – previous dose) &gt;0]. Differences in TIS and the percentage of concordance using two methods were compared using descriptive statistics. Results: We included 75,935 patients with medication orders at the index encounter. Using medication order data, 84% increased the dose of antihypertensive medications with a median TIS (25 th , 75 th ) of 0.25 (0.13, 0.50). Among the total, 80% (n=61,485) filled their prescriptions. Among those who filled their prescriptions, 84% and 85% increased the dose using medication order and pharmacy data, respectively, with 95% concordance between the two methods. Mean (SD) differences in dose change was -0.06 (0.55) between the two methods ( p &lt;0.001). Conclusion: A large portion of patients with uncontrolled BP failed to fill their new prescriptions, underscoring the value of utilizing medication order data to evaluate therapeutic intensification. For those who filled prescriptions, only minimal differences were observed between the evaluations using medication orders and pharmacy data.

Abstract 4128919: A Study Using Team Based Hypertension Care Focused on Black Patients to Inform a Future Randomized Trial

Background: Current telemedicine programs to manage hypertension are less effective in Black patients perhaps due to insufficient support for self-care skills and social needs. We describe a tailored program for Black patients emphasizing self-management support and social needs to inform future studies. Method: We piloted a 12-week telemedicine intervention comprising home blood pressure (BP) guided pharmacotherapy, frequent self-management support and social support using pharmacist, nurses, community health workers (CHW) and social workers (SW) among 20 patients in 2 clinics. At enrollment, we trained patients to use a BP monitor and a telemonitoring app that transmits BP real-time via a smartphone and provided a pill box to facilitate medication adherence. We asked patients to measure BP at least once daily and used 6 weeks average to guide pharmacotherapy. Trained nurses helped patients achieve self-care goals and provided 8-12 self-management support calls discussing hypertension, medication adherence, diet, physical activity, weight management, sleep, and BP measurement techniques. SWs and CHWs provided social support to address social needs such as food, transportation, and housing, and also offered home visits. Result: Eighteen patients completed the study of which 15 were Black, 2 White, and 1 Korean (9 were women). Mean age was 61.7 ± 11.8 years. Patients measured BP 10 ± 8.6 times/week and completed 8.3 ± 2.5 self-management calls. Over 12 weeks, SBP/DBP decreased by 16.5 ± 26.2/10.2 ± 18.5 mmHg without safety events (Table). There were 1.1 ± 0.8 (range 0-3) medication adjustments (dose or medication changes) per patient. Patients had 8 minor technical difficulties that were promptly resolved. 17 patients used pill boxes to improve medication adherence. Conclusion: Our tailored telemedicine program to manage hypertension is feasible among Black patients and offer valuable insights for future research.

Abstract 4137636: Cardiac radiation dose and changes in physical activity and quality of life in patients with locally advanced lung cancer

Background: Physical activity is associated with prognosis in cancer. However, in non-small cell lung cancer (NSCLC), a high cardiovascular (CV) population, the relationships between RT dose, physical activity, and CV patient-reported outcomes remain unclear. We determined the associations between cardiac radiation dose-volume metrics and changes in physical activity and quality-of-life (QoL) in patients treated with definitive chemoradiation. Methods: NSCLC participants treated with chemoradiation were enrolled in a multi-center longitudinal cohort study. Self-reported physical activity via Godin–Shephard Leisure-Time Physical Activity Questionnaire (Godin) and QoL via Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue and Dyspnea Scales were collected at baseline, end of RT, 6, and 12 months post-RT. Changes in Godin and FACIT scores over time were examined using linear mixed-effects models. Multivariable linear regression via generalized estimating equations assessed the associations between: 1) mean heart dose (MHD) and longitudinal changes in physical activity and QoL, and 2) concurrent changes in physical activity and FACIT scores. Results: Across 101 participants, the mean age was 66 years, with 57% male, 66% White, and 25% Black. The median (Q1, Q3) MHD was 10.8 Gy (6.1,16.3). Very low physical activity [9 (0, 25)], high dyspnea [4 (1, 9)], and low fatigue [39 (31,46)] were reported at baseline. With chemoRT, there was a significant worsening of physical activity ( P = 0.03), fatigue ( P &lt; 0.001), and dyspnea ( P &lt; 0.001). Each 1-Gy increase in MHD was associated with a modest decline in physical activity (-0.28; 95% CI -0.53, -0.02, P = 0.03), and higher physical activity was associated with a concurrent decrease in fatigue ( P &lt; 0.001) and dyspnea ( P = 0.007) (Table). Conclusions: In locally advanced NSCLC, physical activity levels prior to RT were very low, and higher cardiac radiation dose was associated with a further decline in physical activity. Increased physical activity was associated with concurrent decreases in fatigue and dyspnea. Strategies to promote physical activity may result in improved QoL in this high CV group.

TMOD-18. FUNCTIONAL DISSECTION OF RECURRENT COPY-NUMBER-ALTERATIONS INFORMS MECHANISMS OF LOW-GRADE-GLIOMA PROGRESSION

Abstract Low-grade gliomas (LGG) are slowly growing brain cancers that ultimately undergo a malignant progression to lethal secondary glioblastomas with a dismal prognosis. Despite intensive research, very little progress has been made in our understanding of this transformation. Hence, outside of known alternations in well-characterized driver genes CDKN2A, PTEN and PDGFRA, genetic drivers that underlie LGG transformation are largely unknown. Contrary to other types of cancer, LGGs exhibit very few driver mutations (30-40 mutations) as they progress. Interestingly, LGGs also exhibit a highly prevalent and heterogenous pattern of copy-number-alterations (CNAs) suggesting that they might be driven by changes in gene dosages that result from widespread chromosomal instability observed within these tumors. Through analysis of the human Mayo Clinic and TCGA LGG datasets (~1500 patients), we have identified eleven highly recurrent CNAs affecting LGG patients, many of which correlate with patient survival. We hypothesized that these CNAs contain driver genes that confer a growth advantage resulting in the highly recurrent CNA pattern and prognostic associations. To investigate the tumor suppressive potential of the ~1800 genes located in recurrently deleted regions and the oncogenic potential of the ~1200 genes located in recurrently amplified regions, our lab developed a novel in vivo ‘CRISPR-Knock Out and Activation Linked Assay’ (CRISPR-KOALA). Stereotaxic delivery of arm-level CNA lentiviral gRNA libraries targeting the mouse orthologs of genes in CNAs into the brain of our animal model (rs557mut;IDHmut;P53KO;AtrxKO;Cas9GFP: Yanchus et. al Science 2022) resulted in rapid formation of tumors compared to animals injected with control libraries. Deconvoluting the screen revealed enrichment of immune modulators such as Them6 as well as a modulator of NMDA receptors (Grina) implicating immune system and glutamate dysregulation in LGG malignant transformation. Taken together, our study provides insights into mechanisms underlying LGG progression which may serve to inform intervention strategies for this lethal disease.

NIMG-85. RADIATION DOSE IS ASSOCIATED WITH CHANGE IN MAGNETIC RESONANCE FINGERPRINTING PROPERTIES OF ANATOMICALLY DISTINCT REGIONS OF INTEREST IN GLIOBLASTOMA MULTIFORME PATIENTS

Abstract Magnetic Resonance Fingerprinting (MRF) is an investigational imaging technique that provides spatially-resolved quantification of tissue properties, in contrast to qualitatively weighted conventional MR imaging. Intentional sequential variation of acquisition parameters throughout the MRF acquisition produces a unique quantitative signal timecourse for each tissue, which generates a spatial “fingerprint” for individual voxels. This study applies MRF to quantitatively correlate radiation dose with MR signal intensity changes, specifically T1, T2, and M0 maps across regions of interest (ROIs) that are involved in cognitive speed and processing. Three patients who underwent radiation therapy for resected glioblastoma multiforme participated in this study. MRF scans were conducted at pre-radiotherapy (pre-RT), mid-radiotherapy (mid-RT), and post-radiotherapy (post-RT) timepoints. ROIs (bilateral hippocampi, amygdalae, dorsolateral prefrontal cortices, and corpus callosum) were contoured and radiation dose to the ROI contours at mid-RT and post-RT timepoints were obtained using MIM treatment planning software (MIM Software, Beachwood, OH). Spearman’s rank correlation test was conducted in MATLAB (MATLAB R2024a, Natick, MA) for mean radiation dose to ROIs against MRF T1 relaxation time, T2 relaxation time, and M0 proton density. Mean radiation dose exhibited statistically significant correlation with absolute changes from pre-RT to post-RT T1 relaxation time, T2 relaxation time, and M0 proton density values across the ROIs. Mid-RT scans showed intermediate changes, suggesting a progressive alteration in tissue characteristics with accumulating radiation dose. The hippocampus and amygdala received lower radiation doses than other ROIs and exhibited less pronounced changes in T1, T2, and M0 values. These results demonstrate a novel application of MRF in quantitative characterization of imaging changes in anatomically distinct ROIs. The correlation between radiation dose and absolute changes in MRF signal values from pre-RT to post-RT MRF scans reflect progressive changes as a result of radiation exposure.

A PHARMACOEPIDEMIOLOGICAL STUDY OF NEW DRUG APPROVAL PATTERN OF JAPAN

Objectives: The objective of the study was to study the drug development and drug approval pattern of a developed Asian country: Japan. Methods: Data available on official website of Japan government health authority was compiled for the duration of January 2017–December 2021. The new approved drugs were classified based on different parameters such as active ingredient, drug approval date, review category, new approval or partial change, Indication of drugs, and WHO anatomic thoracic classification. The descriptive analysis of data was done using LibreOffice Calc. Results: Out of 545 drugs approved, 46% were anti-neoplastic and immunomodulating agent, 10% were anti-infective and 9% were Nervous system category. Furthermore, among all approved drugs, 51.38% were new approved drugs while 48.62% of drugs were approved with partial change in dosage, route, or indications. Conclusion: This study showed new drug development and approval was done significantly for anti-cancer agents and agents for non-communicable diseases.

Dynamic readout of the Hh gradient in the Drosophila wing disc reveals pattern-specific tradeoffs between robustness and precision.

Understanding the principles underlying the design of robust, yet flexible patterning systems is a key problem in developmental biology. In the Drosophila wing, Hedgehog (Hh) signaling determines patterning outputs using dynamical properties of the Hh gradient. In particular, the pattern of collier (col) is established by the steady-state Hh gradient, whereas the pattern of decapentaplegic (dpp), is established by a transient gradient of Hh known as the Hh overshoot. Here we use mathematical modeling to suggest that this dynamical interpretation of the Hh gradient results in specific robustness and precision properties. For instance, the location of the anterior border of col, which is subject to self-enhanced ligand degradation is more robustly specified than that of dpp to changes in morphogen dosage, and we provide experimental evidence of this prediction. However, the anterior border of dpp expression pattern, which is established by the overshoot gradient is much more precise to what would be expected by the steady-state gradient. Therefore, the dynamical interpretation of Hh signaling offers tradeoffs between.

Treatment satisfaction and effectiveness of Lurasidone on quality of life and functioning in adult patients with schizophrenia in the real-world Italian clinical practice: a prospective 3-month observational study.

Although second-generation antipsychotics (SGAs) have proven to be effective therapeutic options for patients with schizophrenia, there is a notable lack of evidence on patients' subjective perspectives regarding their well-being, quality of life, and satisfaction with these medications. This study aimed to evaluate the treatment satisfaction and effectiveness of lurasidone on quality of life and functioning in adult patients with schizophrenia in real-world Italian clinical practice. This was a multicentre, national, non-interventional, single-arm, 3-month prospective study. Patients who were naive to lurasidone treatment and whose treating physician had decided to start them on this medication were enrolled and evaluated over a 3-month period. Eligible patients were adults (≥ 18 years of age) with a primary diagnosis of schizophrenia who were being treated with lurasidone (for the first time [i.e., they were lurasidone naive]) as part of routine clinical practice. Efficacy endpoints were changes in patient/caregiver treatment satisfaction (seven-point Likert scale from the Treatment Satisfaction Questionnaire for Medication), patient quality of life and functioning (QLS), investigator-rated global assessment of functioning (CGI-S, IAQ) after 6 weeks and 3 months of lurasidone, and number of relapses and hospitalizations. Sixty-one patients were enrolled and 59 completed the study. The median dosage of lurasidone at baseline was 37.00mg/day. The median duration of titration was 86.0 days (Min 28; Max 115 days); the median number of dosage changes was 1.0. At the end of 3-month observation period, the median dose of lurasidone was 74.00mg/day. QoL and Functioning Score showed a trend of improvement over time, reaching a mean change from baseline of 9.8 at the end of the study. According to the CGI-S, the percentage of patients who were "markedly or severely ill" showed a continuous decrease from baseline to 3 months, from 62.29% to 8.20%. Patient satisfaction increased over time, with 80.32% of patients reporting that they were somewhat, fairly, or very satisfied (including 63.93% who were completely or very satisfied) at the end of the study. No relapses/hospitalizations for psychiatric reasons were reported. Lurasidone was well tolerated with no safety concerns or discontinuations due to AEs. Lurasidone represents a valid option for the treatment of schizophrenia and positively affects subjective well-being, quality of life and satisfaction. NCT06527885 retrospectively registered (01/08/2024).

Heart Failure Part 3: Diuretic Management in Older People.

Heart failure is a common condition in the older population. As severity progresses, fluid accumulates resulting in congestive symptoms. Loop diuretics are the cornerstone of managing fluid overload and dosing should target euvolemia and congestive symptoms. Volume status is difficult to assess but signs and symptoms such as dyspnea, orthopnea, edema, and weight changes can be evaluated even without specialized equipment in the outpatient setting. Pharmacists are capable of assessing diuretic response and making recommendations for dosing changes in older heart failure patients.

Fear of COVID-19 Diagnosis and Cannabis Use Patterns Among Adults with Chronic Health Conditions: Results from COVID-19 Cannabis Health Study

ABSTRACT Given the scarcity of literature regarding COVID-19 impacts on cannabis consumers with chronic illnesses who widely use cannabis to manage their health conditions, we aim to assess the effect of COVID-19 on cannabis use patterns among adults living with chronic diseases. Cannabis consumers with a chronic disease (N = 1,466) from COVID-19 Cannabis Health Study were included in this analysis. The primary outcomes were change in cannabis dosage, past 30-day cannabis usage, and change in route of cannabis administration, with the main exposure being self-reported fear of COVID-19 diagnosis. Significant differences were found between changes in cannabis dose by fear of COVID-19 diagnosis (p = .03) where 41.5% of adults fearing diagnosis reported an increase in their cannabis dosage since the pandemic. Multinomial logistic regression showed that individuals who feared COVID-19 diagnosis had 50% greater odds [aOR = 1.50, 95% CI: 1.02–2.24 of decreasing their cannabis in reference to their dose staying the same, than those without fear of COVID-19, adjusting for socio-demographics. Our findings highlight the significant association between fear of COVID-19 diagnosis and changes in cannabis usage patterns among adults with chronic diseases. This underscores the pandemic’s impact on health-related behaviors and the role of cannabis as a coping mechanism during uncertain times.

Usage status of biologics for the chronic treatment of optic neuritis in neuromyelitis optica spectrum disorders in Japan.

To investigate the usage status of biologics for the chronic treatment of optic neuritis including neuromyelitis optica spectrum disorders in Japan. Multicenter retrospective case series. Patients diagnosed with anti-aquaporin 4 antibody (AQP4-Ab) positive optic neuritis and had been initiated on biologics (satralizumab, eculizumab, and inebilizumab) between January 2020 and August 2022 were identified at 30 facilities in Japan. These patients were investigated regarding changes in oral steroid doses, optic neuritis relapse, and adverse events after initiation of biologics. Eighty-eight patients with AQP4-Ab positive optic neuritis initiated on biologics were included. Satralizumab was the most common biologic used (79 patients), followed by eculizumab (6 patients) and inebilizumab (3 patients). In the satralizumab group, during the observation period (10.0±7.0months) until February 2023, the oral steroid dose was reduced significantly from 13.8 ± 8.6mg/day at the time of initiation to 5.3 ± 4.8mg/day (p < 0.001). No relapse of optic neuritis was observed in 76 of 79 patients (96.2%) after initiation of satralizumab. Furthermore, in 15 patients who succeeded in discontinuing steroids during 8.5 ± 5.8months after initiation of satralizumab, no relapse of optic neuritis was observed throughout the observation period. Adverse events occurred in 7 patients with satralizumab and 2 patients with eculizumab, but no serious infections were observed. Satralizumab was the most commonly used biologic for AQP4-Ab positive optic neuritis in Japan. This study demonstrates the efficacy and safety of satralizumab in preventing the relapse of optic neuritis.

Dose and time dependent morphodynamic changes in the ovary of nano-nickel treated rats A SEM study

AimsPresent study demonstrates dose and time dependent effects of NiONPs (<30 nm) on the ovaries of Wistar rat. MethodsFemale rats were gavaged NiONPs or NiOMPs (5 mg/kg b.w.) for 24 h, 15 days and 30 days, euthanized and ovaries thus removed were analyzed for nickel bioaconcentration and processed for scanning electron microscopy. Serum samples were analyzed to compare the effects of nickel nano & microparticles on progesterone and estradiol values. ResultsResults confirmed the bioaccumulation of Ni in ovarian tissue. Its concentration was higher in NiONPs treated rats than NiOMPs treated rats. Progesterone level increased whereas estradiol values decreased in NiONPs and NiOMPs treated rats. SEM results also exhibited dose dependent effects on the morphology of corpoluteal complex. The structural changes varied from formation of blebs to distorted microvilli and germinal epithelium. ConclusionIt is hypothesized that NiONPs/NiOMPs are biodegraded into smaller fragments that conjugate with amino acids and or alter downstream signaling pathways, generate ROS and modulate protein structure activity relationships. Finally, these processes manifest into morphological alterations in the ovary. Biopersistence of nickel in female reproductive system may compromise with fertility and reproductive performance of exposed population.

Switching from Premixed Insulin to Insulin Degludec/Insulin Aspart for the Management of Type 2 Diabetes Mellitus: Implications of a Real-World Study on Insulin Degludec Dosing.

When switching from premixed insulin to insulin degludec/aspart (IDegAsp), IDegAsp usually starts at the same dose as the premixed insulin according to limited clinical experience or at a dose according to clinician discretion. The dose of insulin degludec used in the real world after switching has been poorly investigated. A retrospective analysis was conducted on patients with type 2 diabetes who switched from premixed insulin to IDegAsp from October 2016 to December 2023. Repeated measures analysis of variance was used to compare changes in insulin dose, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and postprandial blood glucose (PBG) before and after switching. Sixty-six patients with prior low-ratio premixed insulin and 22 with prior mid-ratio premixed insulin were included. Among the low-ratio insulin users, the total daily dose of insulin degludec (IDeg) decreased by 21.43% and 19.05% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). Conversely, among mid-ratio insulin users, the IDeg daily dose increased by 10.71% and 32.14% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). In all patients, HbA1c levels decreased by 0.70%, FBG decreased by 1.00mmol/l, and PBG decreased by 1.61mmol/l after 6months of switching (all p < 0.05); the total daily insulin dose and injection frequency significantly decreased after switching (both p < 0.05); age and disease duration did not affect IDegAsp effects on HbA1c reduction. In the setting of transition to IDegAsp from premixed insulin, the dose of basal insulin in the premixed formulation can be a valuable reference for adjusting insulin degludec dose. IDegAsp is superior to premixed insulin in blood glucose control with reduced total daily dose and injection frequency. IDegAsp could be the best choice for the management of diabetes in elderly patients.

The Association of Antidepressants in Late Pregnancy with Postpartum Hemorrhage: Systematic Review of Controlled Observational Studies.

Introduction: Despite advances in obstetric care, postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Prior reviews of studies published through 2016 suggest an association of antidepressant use during late pregnancy and increased risk of PPH. However, a causal link between prenatal antidepressants and PPH remains controversial. Objectives: This systematic literature review aimed to synthesize the empirical evidence on the association of antidepressant exposure in late pregnancy with the risk of PPH, including studies published before and after 2016. Methods: A systematic literature search was conducted using PubMed, OVID Medline, EMBASE, SCOPUS, PsycINFO, and CINAHL from inception to September 9, 2023. Original, peer-reviewed studies (published in English) that reported on the frequency or risk of PPH in women with evidence of antidepressant use during pregnancy and included at least one control group were included. Results: Twenty studies (eight published after 2016) met inclusion criteria, most of which focused on the risks of PPH associated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). The main findings from the individual studies were mixed, but the majority documented statistically significant associations of PPH with late prenatal exposure, especially for exposures occurring within 30 days of delivery, compared with unexposed deliveries. Fourteen studies addressed underlying antidepressant indications or their correlates. Few studies focused on prenatal antidepressants and the risk of well-defined severe PPH or on antidepressant dose changes and general PPH risk. None examined competing risks of antidepressant discontinuation on mental health outcomes. Conclusions: Late pregnancy exposure to antidepressants may be a minor risk factor for PPH, but it is unclear to what extent reported associations are causal in nature, as opposed to correlational (effects related to nonpharmacological factors including maternal indication). For patients needing antidepressants during pregnancy, current evidence does not favor routinely discontinuing antidepressants specifically to reduce the risk of PPH.

Effective Assessment of Rheumatoid Arthritis Disease Activity and Outcomes Using Monocyte Chemotactic Protein-1 (MCP-1) and Disease Activity Score 28-MCP-1.

The effectiveness of monocyte chemotactic protein-1 (MCP-1) and Disease Activity Score 28 (DAS28)-MCP-1 (DAS28-MCP-1) in assessing rheumatoid arthritis (RA) disease activity is unclear, although some studies have demonstrated their potential usefulness. The present study investigated relationships between MCP-1 and different DAS28 measures, the occurrence of residual swollen joints in different DAS28 remission statuses, changes in medication dosage in relation to the 2005 modified American Rheumatism Association and 2011 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) remission definitions, and the correlations between different DAS28-related scores and Health Assessment Questionnaire Disability Index (HAQ-DI) scores in two RA patient cohorts. The results revealed that the MCP-1 level was correlated with five disease activity measures (DAS28-erythrocyte sedimentation rate [DAS28-ESR], DAS28-C-reactive protein [CRP], Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and DAS28-MCP-1) in multivariable regression analysis (all p < 0.05; ESR, CRP, and MCP-1 as independent variables). However, ESR was not significantly associated with SDAI and CDAI scores (p = 0.343 and 0.323, respectively). Residual swollen joints were more frequently observed in patients who met the DAS28-ESR remission criteria (<2.6) compared with those meeting the other four remission criteria, with a difference ranging from 71% to 94%. Among patients meeting the DAS28-ESR remission criteria (<2.6), medication changes (dose increase by ≥30% or new medications prescribed) were less frequent in those who also met the 2011 ACR/EULAR remission criteria than in those who did not meet them (p = 0.006). Moreover, the correlation coefficients for the relationship between DAS28-ESR and HAQ-DI scores were the lowest among the five disease activity measures. In conclusion, MCP-1 and DAS28-MCP-1 are effective in assessing RA disease activity, with less residual joint swelling and less frequent medication increases observed in the DAS28-MCP-1 remission < 2.2 subgroup.