Intensive Treatment Research Articles

Hematopoietic Stem-Cell Transplantation: Exploring the Latest Advances and Gaps in Disparities, Psychosocial and Symptom Management Interventions, and Chronic Graft-Versus-Host Disease Care.

Although allogeneic hematopoietic cell transplantation (HCT) offers a potential for cure for many patients with advanced hematologic malignancies and bone marrow failure or immunodeficiency syndromes, it is an intensive treatment and accompanied by short- and long-term physical and psychological symptoms requiring specialized care. With substantial advances in therapeutic approaches for HCT and supportive care, HCT survivors experience less morbidity and mortality. However, disparities in both HCT access and outcomes persist, and HCT survivors and their caregivers often lack access to much-needed psychosocial care. Additionally, more medical and psychosocial resources are needed to holistically care for HCT survivors with chronic graft-versus-host disease (GVHD). Hence, this chapter focuses on three areas pertaining to advances and gaps in HCT care: disparities in access to and outcomes of HCT, psychosocial and physical symptom management with supportive care interventions, and GVHD prevention and management.

Developing a remotely delivered intensive outpatient program adapted for hospitalized patients with opioid use disorder: A qualitative study

IntroductionIndividuals with opioid use disorder (OUD) who inject drugs have an elevated risk of experiencing serious injection-related infections. While such infections can be treated, treatment for the underlying OUD is often limited. One potential strategy for more intensive addiction treatment is to offer a remotely delivered intensive outpatient program (IOP), adapted from an existing remote IOP (“Smart IOP”). We aimed to conduct a qualitative study to gather feedback on Smart IOP and identify adaptations needed for hospitalized patients. MethodsIndividuals with OUD and a history of serious injection-related infections completed a semi-structured interview and were shown samples of the videos and program content. The interviews were transcribed verbatim and coded to conduct a thematic analysis. ResultsSeventeen individuals participated. The mean age was 40.8 years and 70.6% were men. Participants reported that IOP during the hospitalization would have been helpful to their recovery. The themes that emerged were the importance of medications for OUD, having a relapse prevention plan, engaging with a recovery coach, and ensuring treatment linkage post-discharge. Other themes included the recognition of the severity of one’s illness and the emotional experiences related to the hospitalization. ConclusionsParticipants expressed the value of an IOP during hospitalization and provided insights into the support needed while hospitalized. The tailored IOP is now being developed and will undergo a pilot feasibility trial.

Identifying Giant Cell Arteritis patients with higher risk of relapse and vascular events: a cluster analysis.

Giant cell arteritis (GCA) is one of the most common large vessel (LVV) vasculitis and is associated with a high risk of relapse and cardiovascular complications. Improving risk stratification remains a significant issue in this patient population. We aimed to perform a cluster analysis among GCA to identify clusters and evaluate their prognostic value. In a multicenter cohort study, we performed hierarchical cluster analysis on the factor analysis of mixed data coordinates results with 283 GCA patients' characteristics to generate clusters and assess incidence of relapse, cardiovascular events and death. Three clusters were identified: "Vascular relapsing profile" (23.0%), "Typical GCA profile" (47.7%), and "Ophthalmologic elderly profile" (29.3%). The "Vascular relapsing profile" cluster included younger patients with more frequent relapses and cardiovascular events, particularly thoracic aortic aneurysms. The "Typical GCA profile" was the largest, with classic cranial manifestations and frequently associated polymyalgia rheumatica. The "Ophthalmologic elderly profile" had the oldest patients with more visual loss and the highest mortality rate. Our findings underline the varied prognostic landscape within GCA, emphasizing the poor cardiovascular prognosis of younger patients with LV involvement and the higher mortality among elderly patients. This reinforces the need for further research regarding the screening of aortic abnormalities and whether those patients might benefit from intensive treatment with biotherapy and cardiovascular risk factors management.

Dealing with the Unexpected: Stercoral Perforation – A Surgical Conundrum

Stercoral colon perforation is a rare surgical emergency primarily linked to chronic constipation and advanced age. Diagnosis is challenging and requires established criteria and imaging. Urgent surgery is the modality of choice, typically involving Hartmann's procedure. Mortality rates can be as high as 60%, emphasising the need for early diagnosis and intervention. We presented a case of a 71-year-old bedridden female with a history of stroke, diabetes, and hypertension presenting with abdominal pain, fever and diarrhoea. Initial evaluation indicated dehydration, sepsis, and abdominal tenderness. An urgent imaging revealed a suspected rectal perforation, prompting emergency surgery. Intraoperatively, stercoral perforation due to impacted hard faeces was identified. Despite prompt and intensive treatment, the patient's condition deteriorated, ultimately resulting in her demise. Stercoral colon perforation is a critical condition requiring rapid diagnosis. Symptoms include abdominal distension, tenderness, cramps, fever, and anorectal pain. Healthcare providers should consider the possibility of stercoral perforation in individuals exhibiting these symptoms alongside a background of persistent constipation. Treatment involves peritoneal lavage and surgery. Early recognition is vital for proper management and improved outcomes.

Quality of life, diabetes-related stress and treatment satisfaction are correlated with glycemia risk index (GRI), time in range and hypoglycemia/hyperglycemia components in type 1 diabetes.

To evaluate the relationship between the GRI -component of hypoglycemia (CHypo) and hyperglycemia (CHyper)- with diabetes quality of life (DQoL), diabetes-related stress (DDS), perception of hypoglycemia (Clarke Test), visual analogic scale (VAS) and diabetes-knowledge (DKQ2) in T1D. Cross-sectional study in 92 patients with T1D under intensive insulin treatment (21.7% CSII) and flash glucose monitoring (isCGM). Clinical, metabolic and glycometric parameters and quality of life/satisfaction questionnaires were analyzed. 92 patients (54.3% male, BMI 25.4 ± 4.5 kg/m2, HbA1c 7.5 ± 1.0%, TIR 53.9 ± 15.9%) with mean age 36.1 ± 12.6years and 17.8 ± 11.3 T1D duration. The mean GRI was 60.6 ± 22.2 with a CHypo and CHyper of 5.9 ± 4.8 and 27.3 ± 14.4, respectively. 19.1% presented a pathological Clarke's test. Patients with TIR > 70% and GRI < 40 showed better VAS (8.8 ± 1.3 vs 9.3 ± 0.9, p < 0.05) and DDS (46.4 ± 22.1 vs 36.7 ± 16.6, p < 0.05) scores, showing no differences between groups. CHyper > 15 and Chypo > 3.4 were related to worse levels of DQoL (91.1 ± 23.9 vs 76.6 ± 18.6 and 94.6 ± 24.8 vs 79.8 ± 20.1, p < 0.01), DDS(49.8 ± 22.4 vs 35.7 ± 16.5 and 49.8 ± 22.4 vs 35.7 ± 16.5, p < 0.01),and DKQ2 (24.4 ± 4.3 vs 26.8 ± 5.2 and 24.1 ± 4.8 vs 26.0 ± 4.6, p < 0.05), respectively. Worse metabolic control defined by GRI correlated with worse scores in VAS (r = -0.209, p < 0.05), DQoL (r = 0.205, p < 0.05), and DDS (r = 0.205, p < 0.05). No difference was observed in knowledge´s scale. CHyper correlated with worse scores in VAS (r = -0.231, p < 0.05), DQoL (r = 0.422, p < 0.01), and DDS (r = 0.341, p < 0.01) and lower degree of knowledge DKQ2 (r = -0.231, p < 0.05). When analyzing DQoL as a dependent variable in a multiple lineal regression, only age (β = 0.747; p < 0.001) and CHyper (β = 0.717; p < 0.001) maintained statistical significance. Higher GRI was related to worse quality of life, diabetes-related stress and satisfaction with treatment, analogous to the TIR results.CHyper an Chypo were related to a greater decline in quality of life, diabetes-related stress, and lower satisfaction with treatment.However, in a multiple linear regression, only CHyper maintained statistical significance.

#3018 Aciclovir or valaciclovir neurotoxicity in renal patients: increasing number of neurotoxicity cases are diagnosed in Sweden by a blood test

Abstract Background and Aims Kidney transplant patients are at high risk for developing zoster infections, as well as patients with impaired renal function. Aciclovir (ACV) and its prodrug valaciclovir are effective medications to treat these herpes infections. The medications typically have mild side effects such as nausea and vomiting, headache, and skin rash. More uncommon but serious side effects include elevated creatinine, acute kidney failure, and aciclovir-induced neuropsychiatric symptoms (AINS). The latter is difficult to distinguish from the viral infection treated, thus prolonged treatment with ACV may cause further deterioration and increase the chance for coma and need for intensive care treatment. ACV is excreted by glomerular filtration and tubular secretion and should be doses according to renal function. A small part is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase to its main metabolite 9-carboxymethoxymethylguanine (CMMG), but as renal function decreases more CMMG is found in the urine, serum, and CSF. We have earlier shown that a serum CMMG cut-off level of 10.8 µmol/L is predictive of AINS. Hemodialysis alleviates the symptoms dramatically, but AINS need to be diagnosed first. The knowledge about our method has increased in Sweden, but has more AINS cases been diagnosed in Sweden now than for 10 years ago? Method Data from our therapeutic drug monitoring (TDM) database of ACV and CMMG levels were studied during the period 2013 to 2023. Serum samples with a CMMG concentration above 10.8 µmol/L were collated and compared to the total number of samples per year. Some patients were monitored with more than one blood sample during the treatment period and the number of single patients was also included. Results The database consisted of 4521 serum ACV and CMMG samples during the study period with 727 samples with a CMMG concentration above 10.8 µmol/L. The number of CMMG serum samples increased from 278 in 2013 to 601 in 2023. A total of 363 patients had at least one sample above 10.8 µmol/L. A median of 33 (range 17 to 59) single patients were diagnosed with AINS per year. Conclusion Measurement of both ACV and CMMG has increased the number of AINS cases in Sweden and are requested to a higher extent now than 10 years ago. Two more laboratories in Sweden measure or will start to measure ACV and CMMG, one laboratory in Bristol have had the method since 2007, but there are too few laboratories performing the analysis in other countries, causing severe suffering for patients and high costs for healthcare.

Narrative analysis in individuals with Parkinson’s disease following intensive voice treatment: secondary outcome variables from a randomized controlled trial

Narrative analysis in individuals with Parkinson’s disease following intensive voice treatment: secondary outcome variables from a randomized controlled trial

Veterans’ 12-month PTSD and depression outcomes following 2- and 3-week intensive cognitive processing therapy-based treatment

ABSTRACT Background: Growing evidence indicates that daily delivery of evidence-based PTSD treatments (e.g. Cognitive Processing Therapy (CPT)), as part of intensive PTSD treatment programmes (ITPs), is feasible and effective. Research has demonstrated that a 2-week CPT-based ITP can produce equivalent outcomes to a 3-week ITP, suggesting shorter treatment can also be highly effective. However, the extent to which ITP length and composition impact longer-term outcomes needs further study. Objective: We examined whether PTSD and depression symptoms 3-, 6-, and 12-months following completion of a 2-week ITP could be considered non-inferior, or equivalent, to those of a 3-week ITP. Method: Data from 638 veterans who participated in a 2-week CPT-based ITP were evaluated against 496 veterans who participated in a 3-week CPT-based ITP. A Bayes factor approach was used to examine whether PTSD and depression severity outcomes of the 2-week ITP could be considered equivalent to the 3-week ITP. Results: Participants across both ITPs reported large PTSD (d = 0.98) and moderate to large depression symptom reductions (d = 0.69) from baseline to 12-month follow-up. The PTSD and depression symptom reductions seen in the 2-week ITP were determined to be equivalent to those of the 3-week ITP. Conclusions: Low follow-up completion was a limitation. Future research might replicate the present findings using samples with greater follow-up rates and explore whether adjunctive services impact other relevant constructs, such as quality of life and functioning.

Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea.

Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Symptom clusters and unplanned hospital readmission in Chinese patients with acute myocardial infarction on admission

BackgroudAcute myocardial infarction (AMI) has a high morbidity rate, high mortality rate, high readmission rate, high health care costs, and a high symptomatic, psychological, and economic burden on patients. Patients with AMI usually present with multiple symptoms simultaneously, which are manifested as symptom clusters. Symptom clusters have a profound impact on the quality of survival and clinical outcomes of AMI patients.ObjectiveThe purpose of this study was to analyze unplanned hospital readmissions among cluster groups within a 1-year follow-up period, as well as to identify clusters of acute symptoms and the characteristics associated with them that appeared in patients with AMI.MethodsBetween October 2021 and October 2022, 261 AMI patients in China were individually questioned for symptoms using a structured questionnaire. Mplus 8.3 software was used to conduct latent class analysis in order to find symptom clusters. Univariate analysis is used to examine characteristics associated with each cluster, and multinomial logistic regression is used to analyze a cluster membership as an independent predictor of hospital readmission after 1-year.ResultsThree unique clusters were found among the 11 acute symptoms: the typical chest symptom cluster (64.4%), the multiple symptom cluster (29.5%), and the atypical symptom cluster (6.1%). The cluster of atypical symptoms was more likely to have anemia and the worse values of Killip class compared with other clusters. The results of multiple logistic regression indicated that, in comparison to the typical chest cluster, the atypical symptom cluster substantially predicted a greater probability of 1-year hospital readmission (odd ratio 8.303, 95% confidence interval 2.550–27.031, P &amp;lt; 0.001).ConclusionOut of the 11 acute symptoms, we have found three clusters: the typical chest symptom, multiple symptom, and atypical symptom clusters. Compared to patients in the other two clusters, those in the atypical symptom cluster—which included anemia and a large percentage of Killip class patients—had worse clinical indicators at hospital readmission during the duration of the 1-year follow-up. Both anemia and high Killip classification suggest that the patient's clinical presentation is poor and therefore the prognosis is worse. Intensive treatment should be considered for anemia and high level of Killip class patients with atypical presentation. Clinicians should focus on patients with atypical symptom clusters, enhance early recognition of symptoms, and develop targeted symptom management strategies to alleviate their discomfort in order to improve symptomatic outcomes.

Fetal Hepatic Hemangioma Diagnosed in Utero Using Doppler Microvascular Imaging.

A 35-year-old pregnant woman was referred to our institution at 33 weeks' gestation for evaluation of a fetal abdominal tumor. B-mode ultrasonography demonstrated a massive lesion. Bidirectional power Doppler mode showed abundant blood flow surrounding the tumor. On superb micro-vascular imaging, various Doppler signal patterns were observed within the tumor, including diffuse fine dotted-like signals, linear flow, and internal shunt flow. Sequential observations of the tumor and cardiac cycles also revealed pulsatile flow beneath the edges of the tumor and continuous fine flow in the central area, resembling a 'centripetal fill-in' appearance on contrast computed tomography. Therefore, we assumed the fetal tumor to be a hepatic hemangioma. Fetal heart failure was detected at 37 weeks' gestation, and a 2,484-g female infant was delivered with 1- and 5-min Apgar scores of 7 and 8, respectively. A postnatal contrast computed tomography examination showed a progressive centripetal fill-in appearance, leading to a diagnosis of hepatic hemangioma. Kasabach-Merritt syndrome was also noted. Intensive treatment was performed, and the infant was discharged at 3 months after birth. In summary, we experienced a case of hepatic hemangioma diagnosed in utero using superb micro-vascular imaging. And basing seamless postnatal treatments on prenatal imaging findings may help to reduce the perinatal mortality.

Effectiveness and safety of granulocyte colony-stimulating factor priming regimen for acute myeloid leukemia: A systematic review and meta-analysis of the Clinical Practice Guideline for the use of G-CSF 2022 from the Japan Society of Clinical Oncology.

The outcomes of relapsed or refractory acute myeloid leukemia (AML) remain poor. Although the concomitant use of granulocyte colony-stimulating factor (G-CSF) and anti-chemotherapeutic agents has been investigated to improve the antileukemic effect on AML, its usefulness remains controversial. This study aimed to investigate the effects of G-CSF priming as a remission induction therapy or salvage chemotherapy. We performed a thorough literature search for studies related to the priming effect of G-CSF using PubMed, Ichushi-Web, and the Cochrane Library. A qualitative analysis of the pooled data was performed, and risk ratios (RRs) with confidence intervals (CIs) were calculated and summarized. Two reviewers independently extracted and accessed the 278 records identified during the initial screening, and 62 full-text articles were assessed for eligibility in second screening. Eleven studies were included in the qualitative analysis and 10 in the meta-analysis. A systematic review revealed that priming with G-CSF did not correlate with an improvement in response rate and overall survival (OS). The result of the meta-analysis revealed the tendency for lower relapse rate in the G-CSF priming groups without inter-study heterogeneity [RR, 0.91 (95% CI 0.82-1.01), p=0.08; I2=4%, p=0.35]. In specific populations, including patients with intermediate cytogenetic risk and those receiving high-dose cytarabine, the G-CSF priming regimen prolonged OS. G-CSF priming in combination with intensive remission induction treatment is not universally effective in patients with AML. Further studies are required to identify the patient cohort for which G-CSF priming is recommended.

Reimagining care: effectiveness of modifying an adolescent eating disorder intensive service.

The COVID-19 pandemic prompted a surge in adolescent eating disorders and rapid changes in the delivery of intensive community treatments. This study investigates the modification from a group-based day programme to an intensive family treatment approach. A retrospective chart review was performed on data from 190 patients who accessed the intensive service for anorexia nervosa in the past 6 years. Outcomes from the traditional model were compared with the new intensive family model, namely length of admission, percentage median body mass index difference and transfers to in-patient services. There was a significant reduction in the length of intensive treatment (from 143.19 to 97.20 days). The number of transfers to specialist eating disorder in-patient services also significantly reduced, and is decreasing year on year. The findings hold particular relevance as intensive services for adolescent eating disorders continue to be established within health services, with no clear unified approach to treatment.

Speeding up Glioblastoma Cancer Research: Highlighting the Zebrafish Xenograft Model

Glioblastoma multiforme (GBM) is a very aggressive and lethal primary brain cancer in adults. The multifaceted nature of GBM pathogenesis, rising from complex interactions between cells and the tumor microenvironment (TME), has posed great treatment challenges. Despite significant scientific efforts, the prognosis for GBM remains very poor, even after intensive treatment with surgery, radiation, and chemotherapy. Efficient GBM management still requires the invention of innovative treatment strategies. There is a strong necessity to complete cancer in vitro studies and in vivo studies to properly evaluate the mechanisms of tumor progression within the complex TME. In recent years, the animal models used to study GBM tumors have evolved, achieving highly invasive GBM models able to provide key information on the molecular mechanisms of GBM onset. At present, the most commonly used animal models in GBM research are represented by mammalian models, such as mouse and canine ones. However, the latter present several limitations, such as high cost and time-consuming management, making them inappropriate for large-scale anticancer drug evaluation. In recent years, the zebrafish (Danio rerio) model has emerged as a valuable tool for studying GBM. It has shown great promise in preclinical studies due to numerous advantages, such as its small size, its ability to generate a large cohort of genetically identical offspring, and its rapid development, permitting more time- and cost-effective management and high-throughput drug screening when compared to mammalian models. Moreover, due to its transparent nature in early developmental stages and genetic and anatomical similarities with humans, it allows for translatable brain cancer research and related genetic screening and drug discovery. For this reason, the aim of the present review is to highlight the potential of relevant transgenic and xenograft zebrafish models and to compare them to the traditionally used animal models in GBM research.

The Contribution of Psychological Symptoms to Cognitive Difficulties in Youth With Postural Orthostatic Tachycardia Syndrome and Chronic Pain.

Subjectively experienced cognitive difficulties are common in youth with postural orthostatic tachycardia syndrome. The pathophysiological and psychological contributions of these cognitive impairments remain unclear. Participants were 96 adolescents and young adults diagnosed with postural orthostatic tachycardia syndrome and admitted to an intensive pain treatment program. Participants completed cognitive assessment and measures of postural orthostatic tachycardia syndrome symptoms, pain intensity, pain catastrophizing, anxiety, depression, and functional disability. Self-reported autonomic symptom intensity, but not severity of heart rate change, was associated with cognitive performance. Symptoms of depression were associated with decreases in most measures of cognitive functioning. Pain intensity, pain catastrophizing, and depression but not cognitive scores and physiological measures, were significant predictors of disability. Depression appears to be a significant contributor to the cognitive difficulties in youth with postural orthostatic tachycardia syndrome. These findings highlight the importance of assessing and treating affective symptoms in this population along with medical and lifestyle approaches to treating postural orthostatic tachycardia syndrome symptoms.

Safety and Efficacy of High-Dose Chemotherapy with TreoMel 200 vs. TreoMel 140 in Acute Myeloid Leukemia Patients Undergoing Autologous Stem Cell Transplantation.

(1) Background: Treosulfan and melphalan (TreoMel)-based high-dose chemotherapy (HDCT) has shown promising safety and efficacy as a conditioning regimen for acute myeloid leukemia (AML) patients undergoing autologous stem cell transplantation (ASCT). However, despite intensive first-line induction treatment and upfront consolidation with HDCT and ASCT, AML relapse rates are still high, and further efforts are needed to improve patient outcomes. The aim of this study was to compare two melphalan dose schedules in regard to the safety of TreoMel HDCT and patient outcomes. (2) Methods: We retrospectively analyzed the safety and efficacy of two melphalan dose schedules combined with standard-dose treosulfan in AML patients undergoing HDCT and ASCT at the University Hospital of Bern, Switzerland, between August 2019 and August 2023. Patients received treosulfan 42 g/m2 combined with either melphalan 140 mg/m2 (TreoMel 140) or melphalan 200 mg/m2 (TreoMel 200). Co-primary endpoints were progression-free survival (PFS), overall survival (OS), as well as safety profile. (3) Results: We included a total of 51 AML patients: 31 (60.8%) received TreoMel 140 and 20 (39.2%) TreoMel 200. The patients' basal characteristics were comparable between both cohorts. No significant differences in the duration of hospitalization or the adverse event profile were identified. There were no statistically significant differences in relapse (0.45 vs. 0.30, p = 0.381) and mortality rates (0.42 vs. 0.15, p = 0.064) between the melphalan 140 mg/m2 and 200 mg/m2 cohorts, nor for PFS (HR: 0.81, 95% CI: 0.29-2.28, p = 0.70) or OS (HR: 0.70, 95% CI: 0.19-2.57, p = 0.59) for the TreoMel 140 vs. TreoMel 200 cohort. (4) Conclusions: A higher dose of melphalan (TreoMel 200) was well tolerated overall. No statistically significant differences for patient outcomes could be observed, possibly due to the relatively small patient cohort and the short follow-up. A longer follow-up and prospective randomized studies would be required to confirm the safety profile and clinical benefit.

Diabetes mellitus in older persons with neurocognitive disorder: overtreatment prevalence and associated structural brain MRI findings

BackgroundTight diabetes control is often applied in older persons with neurocognitive disorder resulting in increased hypoglycemic episodes but little is known about the pattern of brain injury in these overtreated patients. This study aims to: (a) quantify the prevalence of diabetes overtreatment in cognitively impaired older adults in a clinical population followed in an academic memory clinic (b) identify risk factors contributing to overtreatment; and (c) explore the association between diabetes overtreatment and specific brain region volume changes.MethodsRetrospective study of older patients with type 2 diabetes and cognitive impairment who were diagnosed in a memory clinic from 2013 to 2020. Patients were classified into vulnerable and dependent according to their health profile. Overtreatment was defined when glycated hemoglobin was under 7% for vulnerable and 7.6% for dependent patients. Characteristics associated to overtreatment were examined in multivariable analysis. Grey matter volume in defined brain regions was measured from MRI using voxel-based morphometry and compared in patients over- vs. adequately treated.ResultsAmong 161 patients included (median age 76.8 years, range 60.8–93.3 years, 32.9% women), 29.8% were considered as adequately treated, 54.0% as overtreated, and 16.2% as undertreated. In multivariable analyses, no association was observed between diabetes overtreatment and age or the severity of cognitive impairment. Among patients with neuroimaging data (N = 71), associations between overtreatment and grey matter loss were observed in several brain regions. Specifically, significant reductions in grey matter were found in the caudate (adj β coeff: -0.217, 95%CI: [-0.416 to -0.018], p = .033), the precentral gyri (adj βcoeff:-0.277, 95%CI: [-0.482 to -0.073], p = .009), the superior frontal gyri (adj βcoeff: -0.244, 95%CI: [-0.458 to -0.030], p = .026), the calcarine cortex (adj βcoeff:-0.193, 95%CI: [-0.386 to -0.001], p = .049), the superior occipital gyri (adj βcoeff: -0.291, 95%CI: [-0.521 to -0.061], p = .014) and the inferior occipital gyri (adj βcoeff: -0.236, 95%CI: [-0.456 to – 0.015], p = .036).ConclusionA significant proportion of older patients with diabetes and neurocognitive disorder were subjected to excessively intensive treatment. The association identified with volume loss in several specific brain regions highlights the need to further investigate the potential cerebral damages associated with overtreatment and related hypoglycemia in larger sample.

Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis: A Multi-center, Double-Blinded and Randomized Controlled Trial.

To assess the efficacy and safety of Bufei Jiedu (BFJD) ranules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB). A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups (1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months (6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life (QoL) of patients. Adverse reactions were monitored during and after the trial. A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as an adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo (58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion (5 months vs. 11 months). The cavity closure rate of the BFJD Granules group (50.6%, 43/85) was higher than that of the placebo group (32.1%, 26/81; P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group (all P<0.01). Overall, the death rates in the two groups were not significantly different; 5.1% (8/156) in the BFJD Granules group and 2.6% (4/156) in the placebo group. Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rates, and rapidly improved QoL of patients with MDR-PTB (Registration No. ChiCTR-TRC-12002850).

Screening for eating disorders in adolescents with chronic pain: the Eating Attitudes Test–16–Chronic Pain

BackgroundFew measures have been validated to screen for eating disorders (ED) in youth with chronic pain. We conducted confirmatory (CFA) of two established factor structures of the Eating Attitudes Test-26 (EAT-26) in a sample of youth with chronic pain attending an intensive interdisciplinary pain treatment (IIPT) program and examined the validity of the best-fitting model in predicting ED diagnoses in this sample.MethodsParticipants were 880 adolescents (M age = 16.1, SD = 2.1) consecutively admitted into an IIPT program who completed the EAT-26 upon admission. CFA was conducted and in the case of inadequate fit, EFA was planned to identify alternative models. Factors of the best-fitting model were included in a logistic regression analysis to predict ED diagnoses.ResultsThe TLIs (0.70; 0.90), RMSEAs (0.09; 0.07) and CFIs (0.73; 0.92) suggested poor fit of one model and adequate of the second model. Goodness of fit indices from EFA (TLI:0.85, RMSEA:0.06) did not outperform the fit of the second CFA. As such, the second model was retained with the exception of one factor. The items loaded onto a 16-item, five factor model: Fear of Getting Fat, Social Pressure to Gain Weight, Eating-Related Control, Eating-Related Guilt and Food Preoccupation. Based on chart review, 19.1% of the participants were diagnosed with an eating disorder. Logistic regression analyses indicated the new 16-item measure and Fear of Getting Fat, significantly predicted an ED diagnosis that did not include avoidant restrictive food intake disorder (ARFID) and Social Pressure to Gain Weight significantly predicted a diagnosis of ARFID.ConclusionsAn alternative 16-item, 5-factor structure of the EAT-26 should be considered in screening for EDs with youth with chronic pain.

Intensive antihypertensive treatment does not lower cerebral blood flow or cause orthostatic hypotension in frail older adults

AbstractThis study aimed to examine the effects of intensive antihypertensive treatment (AHT), i.e., systolic blood pressure target ≤ 140 mmHg, on cerebral blood flow, cerebral autoregulation, and orthostatic hypotension, in a representative population of frail older adults. Fourteen frail hypertensive patients (six females; age 80.3 ± 5.2 years; Clinical Frailty Scale 4–7; unattended SBP ≥ 150 mmHg) underwent measurements before and after a median 7-week AHT targeting SBP ≤ 140 mmHg. Transcranial Doppler measurements of middle cerebral artery velocity (MCAv), reflecting changes in cerebral blood flow (CBF), were combined with finger plethysmography recordings of continuous BP. Transfer function analysis assessed cerebral autoregulation (CA). ANCOVA analysed AHT-induced changes in CBF and CA and evaluated non-inferiority of the relative change in CBF (margin: -10%; covariates: pre-AHT values and AHT-induced relative mean BP change). McNemar-tests analysed whether the prevalence of OH and initial OH, assessed by sit/supine-to-stand challenges, increased with AHT. Unattended mean arterial pressure decreased by 15 mmHg following AHT. Ten (71%) participants had good quality TCD assessments. Non-inferiority was confirmed for the relative change in MCAv (95%CI: -2.7, 30.4). CA remained normal following AHT (P &gt; 0.05), and the prevalence of OH and initial OH did not increase (P ≥ 0.655). We found that AHT in frail, older patients does not reduce CBF, impair autoregulation, or increase (initial) OH prevalence. These observations may open doors for more intensive AHT targets upon individualized evaluation and monitoring of hypertensive frail patients.Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05529147; September 1, 2022) and EudraCT (2022-001283-10; June 28, 2022).