Therapy For People Research Articles

The comparison of Pilates with cognitive functional therapy in adults with chronic neck pain: a protocol for randomized controlled trial

Background Chronic Neck Pain is one of the main musculoskeletal problems in the general population that negatively affects the lives of patients. Its treatment can include various treatment methods, such as Pilates and Cognitive Functional Therapy. The purpose of this research was to investigate the effectiveness of Pilates in relation to Cognitive Functional Therapy in people with Chronic Neck Pain. Methods This single-blind randomized controlled study included 60 patients with Chronic Neck Pain who were randomly divided into two groups (Group 1: Pilates, Group 2: Cognitive Functional Therapy). All patients will undergo 16 sessions over 8 weeks. Outcome measures (pain, disability, fear perception, functionality, quality of life, cervical range of motion, and neck muscle isometric strength) will be evaluated at baseline, at the end of the treatment (week 8) and three months after randomization (week 12). Outcome measures will be analyzed via random effects at the three assessment time points, and the interactions of the treatment groups with the assessment points will be included in the results of the fixed model. Discussion This is the first Randomized Controlled Trial to compare the effectiveness of Pilates and Cognitive Functional Therapy in patients with chronic neck pain. The results of this research will provide information on the effectiveness of each intervention separately and whether one of the two can outperform the other.

Microbiota modulation by teriflunomide therapy in people with multiple sclerosis: An observational case-control study

Multiple sclerosis (MS) is a chronic immune-mediated and heterogeneous disease characterized by demyelination, axonal damage, and physical and cognitive impairment. Recent studies have highlighted alterations in the microbiota of people with MS (pwMS). However, the intricate nature of the disease and the wide range of treatments available make it challenging to identify specific microbial populations or functions associated with MS symptoms and disease progression. This study aimed to characterize the microbiota of pwMS treated with the oral drug teriflunomide (TF) and compare it with that of pwMS treated with beta interferons (IFNβ), pwMS treated with no previous disease modifying therapies (naïve), and healthy controls. Our findings demonstrate significant alterations in both the composition and function of the gut microbiota in pwMS that are further influenced by disease-modifying therapies. Specifically, oral treatment with TF had a notable impact on the gut microbiota of pwMS. Importantly, the dysregulated microbial environment within the gut was associated with symptoms commonly experienced by pwMS, including fatigue, anxiety, and depression.

6531 Assessing the Risk of Recurrence in Acute Pancreatitis Among Patients with Type 2 Diabetes Initiating GLP-1 Receptor Agonists Therapy

Abstract Disclosure: M. Nassar: None. H. Abosheaishaa: None. P. Dandona: None. H. Ghanim: None. A. Chaudhuri: None. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recognized therapeutic agents for patients with type 2 diabetes mellitus and obesity. However, due to concerns about pancreatitis, clinicians do not recommend these agents for patients with a history of pancreatitis. Existing research presents conflicting evidence about this association. Our primary aim was to evaluate the risk of recurrence of acute pancreatitis (AP) associated with initiating GLP-1 RAs in patients with a history of AP. Methods: Our retrospective cohort study deployed the TriNetX platform, leveraging a large dataset from 106 healthcare organizations and approximately 127 million patients across 15 countries. We obtained data specific to our research on September 21, 2023. Using the ICD-10-CM code, we identified groups of adults with AP. We investigated the effect of GLP-1 RA vs. SGLT2i, DPP4i, and no medication (GLP-1 RA, SGLT2i, and DPP4i) on the recurrence of AP within 5 years of starting treatment. We ensured comparability between cohorts by employing propensity score matching, which focused on critical variables such as age, gender, body mass index (BMI), cholelithiasis, tobacco use, serum triglyceride, and HbA1c levels. Results: We matched the GLP-1 and SGLT2i cohorts, which initially had 4,680 and 7,212 patients, respectively, down to 3,926 in each group. Similarly, the GLP-1 vs. DPP4i comparison matched both cohorts to 3,324 patients from initial counts of 4,680 and 5,723 patients. In the matched cohorts, the GLP-1 group showed a lower AP recurrence risk (15.2%) than the SGLT2i group (24%). This difference was significant (-8.9%, 95% CI: -0.106, -0.071), with a notable risk ratio of 0.630 and an odds ratio of 0.564. For the GLP-1 vs. DPP4i comparison, the GLP-1 group's AP recurrence risk was 14.4%, lower than the 23.3% in the DPP4i group. This difference (-8.9%, 95% CI: -0.108 to -0.071) was also significant, with a risk ratio of 0.616 and an odds ratio of 0.552. For the GLP-1 vs. no medication (GLP-1RA, DPP4i, and SGLT2i) comparison, the GLP-1 group's AP recurrence risk was 14.5%, lower than the 51.6% in the comparison group. This difference (-37.1%, 95% CI: -0.388 to -0.353) was also significant, with a risk ratio of 0.282 and an odds ratio of 0.16. Conclusion: Our research showed that starting GLP-1 RA therapy in people who have had a history of AP does not increase and may potentially lower the risk of recurrence of AP than starting SGLT2i or DPP4i therapy and no medication group. These findings highlight the potential of GLP-1 RA therapy as a safer therapeutic option in this patient population, which requires further investigation. Presentation: 6/1/2024

9232 Assessing the Risk of Recurrence in Acute Pancreatitis Among Patients with Type 2 Diabetes Initiating GLP-1 Receptor Agonists Therapy

Abstract Disclosure: M. Nassar: None. H. Abosheaishaa: None. P. Dandona: None. H. Ghanim: None. A. Chaudhuri: None. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recognized therapeutic agents for patients with type 2 diabetes mellitus and obesity. However, due to concerns about pancreatitis, clinicians do not recommend these agents for patients with a history of pancreatitis. Existing research presents conflicting evidence about this association. Our primary aim was to evaluate the risk of recurrence of acute pancreatitis (AP) associated with initiating GLP-1 RAs in patients with a history of AP. Methods: Our retrospective cohort study deployed the TriNetX platform, leveraging a large dataset from 106 healthcare organizations and approximately 127 million patients across 15 countries. We obtained data specific to our research on September 21, 2023. Using the ICD-10-CM code, we identified groups of adults with AP. We investigated the effect of GLP-1 RA vs. SGLT2i, DPP4i, and no medication (GLP-1 RA, SGLT2i, and DPP4i) on the recurrence of AP within 5 years of starting treatment. We ensured comparability between cohorts by employing propensity score matching, which focused on critical variables such as age, gender, body mass index (BMI), cholelithiasis, tobacco use, serum triglyceride, and HbA1c levels. Results: We matched the GLP-1 and SGLT2i cohorts, which initially had 4,680 and 7,212 patients, respectively, down to 3,926 in each group. Similarly, the GLP-1 vs. DPP4i comparison matched both cohorts to 3,324 patients from initial counts of 4,680 and 5,723 patients. In the matched cohorts, the GLP-1 group showed a lower AP recurrence risk (15.2%) than the SGLT2i group (24%). This difference was significant (-8.9%, 95% CI: -0.106, -0.071), with a notable risk ratio of 0.630 and an odds ratio of 0.564. For the GLP-1 vs. DPP4i comparison, the GLP-1 group's AP recurrence risk was 14.4%, lower than the 23.3% in the DPP4i group. This difference (-8.9%, 95% CI: -0.108 to -0.071) was also significant, with a risk ratio of 0.616 and an odds ratio of 0.552. For the GLP-1 vs. no medication (GLP-1RA, DPP4i, and SGLT2i) comparison, the GLP-1 group's AP recurrence risk was 14.5%, lower than the 51.6% in the comparison group. This difference (-37.1%, 95% CI: -0.388 to -0.353) was also significant, with a risk ratio of 0.282 and an odds ratio of 0.16. Conclusion: Our research showed that starting GLP-1 RA therapy in people who have had a history of AP does not increase and may potentially lower the risk of recurrence of AP than starting SGLT2i or DPP4i therapy and no medication group. These findings highlight the potential of GLP-1 RA therapy as a safer therapeutic option in this patient population, which requires further investigation. Presentation: 6/1/2024

Baseline characteristics and predictors for early implantation of vagus nerve stimulation therapy in people with drug-resistant epilepsy: Observations from an international prospective outcomes registry (CORE-VNS).

Vagus nerve stimulation (VNS) Therapy is routinely indicated for people with drug-resistant epilepsy (DRE). We analyzed the baseline characteristics of individuals receiving the recently released VNS models and identified factors associated with early or late implantation. The Comprehensive Outcomes Registry of subjects with Epilepsy (CORE-VNS), a prospective observational study evaluating the clinical and psychosocial outcomes of VNS Therapy®, is following participants for up to 60 months after VNS implantation. In this analysis, we used Cox proportional hazards model to identify baseline characteristics associated with the time from diagnosis to first implantation. Of the 819 enrolled, 792 (96.7%) participants implanted with a VNS device were evaluated. 529 (64.6%) underwent the first implantation and 263 (32.1%) a re-implantation. Participants' median age at first implant was 24 years; 492 (62.1%) were ≥18 years old and 166 (20.3%) were < 12 years old. The average number of failed ASMs prior to VNS implantation was 7.1, and 145 (17.7%) had undergone previous epilepsy-related surgery. Epilepsy was classified as focal in 47.7% of participants, generalized in 16.1% and combined focal and generalized in 34.2%. Many of the participants (40.9%) had epilepsy of unknown etiology. The median time from diagnosis to first implantation was 10.33 years and was significantly shorter in participants with combined focal and generalized epilepsy compared to those with focal epilepsy alone, and in participants with genetic and immune epilepsy compared to those with unknown etiologies. In people with DRE, VNS Therapy is provided after multiple failures of ASMs and after failure of epilepsy surgery in one in six individuals. Time from diagnosis to first implantation is associated with epilepsy type and etiology, likely reflecting variable treatment pathways. Clearer guidelines on when and how non-drug therapies should be deployed in people with DRE related to different epilepsy factors are needed. Neuromodulation can be a very helpful treatment in people who have seizures that do not respond to medications. The most widely utilized neuromodulation therapy is vagus nerve stimulation (VNS). We present data from a large, global study to show that people use an average of seven anti-seizure medications before attempting VNS Therapy and that it takes about 10 years for people to get their first VNS implant. We advocate for clearer treatment guidelines on how and when to consider VNS Therapy in people with seizures that are resistant to medication.

Individualized Versus General Exercise Therapy in People with Subacromial Pain Syndrome: A Randomized Controlled Trial

ObjectiveTo evaluate the effect of individualized exercises based on movement fault (MF) control on pain intensity and disability in subjects with chronic subacromial pain syndrome (SAPS). DesignRandomized Controlled Trial (IRCT20221126056621N1) SettingRehabilitation clinics ParticipantsThirty-eight participants with chronic SAPS (aged 52.23(8.47), 60 %woman). InterventionsThe participants were randomly allocated to one of the intervention groups (individualized exercises based on MFs control test designed to target specific movement faults) or the control group (commonly prescribed general scapular stabilization exercises). Both groups received exercise sessions twice a week for four weeks. Main Outcome MeasuresThe primary outcome measures were pain intensity at rest (PR) and during arm raising (PAR) using a visual analog scale. Disability was assessed as a key secondary outcome, including the disabilities of the arm, shoulder, and hand (DASH) questionnaire and the Shoulder Pain and Disability Index (SPADI). ResultsFollowing completion of all exercise sessions, PAR was significantly lower in the intervention group compared to the control group (mean [CI]: 9.17 [0.31 to 18.03], p=0.04), with a large effect size [0.68]. The reduction of PAR remained significantly lower in the intervention group than in the control group after four months of follow-up (mean [CI]: 18.29 [9.09 to 27.48], p=0.00) with a large effect size [1.27]. Disability significantly decreased at two month (mean=14.58, p=0.002 on SPADI index; mean=10.26, p=0.006 on DASH index) and four month (mean=19.85, p=0.00 on SPADI index; mean=12.09, p=0.001 on DASH index) follow ups in the intervention group compared to the control group. ConclusionIndividualized exercises based on MFs control of the shoulder region was accompanied by decreased PAR and disability in subjects with SAPS.

Impact of mental disorders on low adherence to antiretroviral therapy in people living with HIV in Spain

ABSTRACT The relationship between mental disorders other than depression or anxiety, and low adherence to both antiretroviral treatment (ART) and linkage to HIV care are unclear. The aim of our study was to compare the prevalence of mental disorders in people living with HIV (PLHIV) in Spain who present low versus high adherence to ART. We performed a cross-sectional study comparing two groups of PLHIV: 20 PLHIV with low adherence and 80 PLHIV with high adherence to ART. PLHIV who met at least one of the following criteria were included in the low-adherence group: virological failure (HIV-VL > 50 copies/mL in two consecutive blood samples); low attendance to scheduled clinical visits (≥2 missed visits in last year); irregular administration of ART (≥10 forgotten doses in the last month); and interruption of ART for more than 1 week. Inclusion criteria for high adherence were: PLHIV who had been on stable ART for more than 1 year with an HIV-VL below 50 copies/mL and without missed visits over the previous 12 months. The Millon Clinical Multiaxial Inventory was administered to participants. PLHIV with low adherence showed higher scores for all mental disorders compared with those with high adherence. And, in the multivariate binary logistic regression analysis, drug dependence and post-traumatic stress disorder were independently associated with low adherence (Nagelkerke R2 = 0.0686). In conclusion, PLHIV with poorly controlled HIV infection presented important psychological vulnerabilities. Mental health should be checked at the beginning of ART and during follow-up, especially in PLHIV with low adherence or low linkage to the health care system.

Treatment trajectories for Danish individuals with type 2 diabetes in the era of emerging glucose-lowering therapies.

To analyse patterns of glucose-lowering therapies among people with type 2 diabetes (T2D) in Denmark from 2016 to 2023. We examined time trends in the clinical profiles of people with T2D who initiated different glucose-lowering therapy classes for the first time. We furthermore investigated individual-level treatment trajectories following first-ever glucose-lowering therapy in people with or without cardiorenal disease. The study utilized data from the nationwide Danish health registries and included all individuals who filled a first-ever prescription for metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose co-transporter-2 inhibitors (SGLT-2is) or insulin, excluding those without HbA1c-confirmed T2D or probable type 1 diabetes. We included 260 393 individuals initiating a new glucose-lowering therapy class from 2016 to 2023, during which there were 6- and 3-fold increases in initiators of GLP-1RAs and SGLT-2is, respectively. The median HbA1c level at treatment initiation with GLP-1RAs or SGLT-2is decreased, from 67-68 mmol/mol in 2016-2017 to 57-58 mmol/mol in 2022-2023. Among individuals who initiated metformin as first-line therapy, the proportion who started additional glucose-lowering therapy within 2 years increased from 25% in 2016 to 40% in 2021. Among the 38% of individuals who had established cardiorenal disease when they initiated first-ever glucose-lowering therapy in 2020, 22% used SGLT-2is and 18% GLP-1RAs after 2.5 years, compared with 17% and 21% among initiators without cardiorenal disease, respectively. Our study documents a trend towards earlier T2D treatment intensification and an increase in the use of GLP-1RAs and SGLT-2is in Denmark. However, optimal T2D treatment is still not received by most individuals with early T2D and established cardiorenal disease.

The influence of therapy quality on outcomes from behavioural activation and guided self-help treatments for depression in adults with intellectual disabilities.

We report the effect of quality of therapy delivery on outcomes in a randomized, controlled trial of behavioural activation (BA) and guided self-help (GSH) for depression in adults with intellectual disabilities. A study specific measure of quality was used in a linear mixed effect model to determine the effects therapy and therapy quality on therapy outcome. There was a significant interaction between quality and treatment type, with lower quality therapy associated with better outcome for GSH but poorer outcome for BA, with little difference in outcomes at higher levels of therapy quality. Factors suggesting high quality in individualized BA may indicate problematic engagement for GSH. More research into processes in therapy for people with intellectual disabilities is required.

Real-world effectiveness and tolerability of switching to doravirine-based antiretroviral therapy in people with HIV: a nationwide, matched, prospective cohort study

Currently, real-world data on doravirine are scarce. In a national prospective cohort, we assessed the effectiveness and tolerability of switching to doravirine-based antiretroviral therapy (ART) in people with HIV. We did a nationwide, matched, prospective cohort study of people with HIV without previous virological failure and stable for at least 12 months on non-doravirine-containing triple or dual ART switching to doravirine before Sept 1, 2020 (exposed group). Participants in the exposed group were matched 1:2 to individuals continuing stable non-doravirine-containing ART, on age, sex, HIV acquisition category, time since ART initiation, calendar time, pre-ART CD4-count, pre-ART plasma viral load (PVL) and anchor drug class before switching. The primary outcome was protocol-defined virological failure (PDVF; PVL of ≥200 copies per mL) in the intention-to-treat (ITT) population at week 104, with participants modifying their regimen or becoming lost to follow-up considered as PDVF (non-inferiority margin +5%). In contrast, in the on-treatment population, those who modified their regimen or became lost to follow-up were censored from that moment onwards. Tolerability was a secondary outcome. In total, 590 participants in the exposed group and 1180 participants in the unexposed group (of whom 55·3% used integrase strand transfer inhibitor-based regimens) were included. In the ITT analysis, PDVF occurred in 135 (22·9%) exposed participants and in 295 (25·0%) unexposed participants (risk difference -2·12%, upper limit of the one-sided 95% CI +1·40%). In the on-treatment analysis, 10 (2·2%) of 455 non-censored exposed participants and 26 (2·9%) of 885 non-censored unexposed participants had PDVF (risk difference -0·70%, upper limit of the one-sided 95% CI +0·73%). All exposed participants with a PVL of 200 copies or more per mL resuppressed without regimen modification: no confirmed virological failure (two consecutive PVLs of ≥200 copies per mL) was observed. 104 (17·6%) exposed participants and 211 (17·9%) unexposed participants modified their regimen. 73 (12.4%) exposed participants discontinued doravirine due to adverse events: abnormal dreams (1·7%) and insomnia (1·5%) were most common. Switching to doravirine in well suppressed people with HIV without previous virological failure was non-inferior compared with continuing non-doravirine-containing regimens after 2 years in a real-world setting. None.

Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with hemophilia B

BackgroundLittle information regarding the management of invasive procedures in people with hemophilia B (HB) after undergoing gene therapy is available. Here, we report the management of invasive procedures in people with severe or moderately severe HB who had previously been treated with etranacogene dezaparvovec in the phase 2b and phase 3 HOPE-B clinical trials (NCT03489291 and NCT03569891). Objectives▪. MethodsThis retrospective analysis included invasive procedures performed within 3 and 2 years following a single infusion of 2 × 1013 gc/kg of etranacogene dezaparvovec in participants in the phase 2b and HOPE-B trials, respectively. Data for factor (F)IX dosing, duration of postoperative FIX use, FIX activity prior to invasive procedures, and postoperative bleeds were collected and analyzed. ResultsThe analysis included 64 procedures in 29 participants: 9 major surgeries, 24 minor surgeries, 11 endoscopies, 3 endoscopies with biopsy/polypectomy, and 17 dental procedures. Uncontaminated endogenous FIX activity corresponded to mild hemophilia or normal levels prior to 98% of all procedures, with a median endogenous FIX activity of 43.8 IU/dL (range, 3.1-113 IU/dL). All major surgeries were managed with exogenous FIX, 67% with ≤4 days of FIX infusion. Most minor surgeries (88%), endoscopies (82%), and dental procedures (94%) were managed with no or a single FIX infusion. Postoperative bleeds occurred after 1 minor surgery and 4 dental procedures. There were no symptomatic thrombotic events or FIX inhibitor developments. ConclusionEtranacogene dezaparvovec has the potential to facilitate perioperative management in people with HB by reducing the need for perioperative exogenous FIX and its associated risks.

Efficacy and safety of statins, ezetimibe and statins-ezetimibe therapies for children and adolescents with heterozygous familial hypercholesterolaemia: Systematic review, pairwise and network meta-analyses of randomised controlled trials

Background and aimsStatins, ezetimibe and statins-ezetimibe combination therapy are recommended lipid-lowering therapies (LLTs) in children with heterozygous familial hypercholesterolaemia (HeFH). However, their relative effectiveness is not well understood. We aimed to compare the safety and efficacy of these therapies using direct and indirect comparisons. MethodsWe conducted systematic review, pairwise and network meta-analyses (NMAs) of randomised-controlled trials (RCTs) of statins, ezetimibe and statins-ezetimibe combination therapy in people <18 years with HeFH. Comprehensive bibliographic searches were conducted in December 2022, and a Medline update in January 2024. NMA models accounted for drug class, statin type and dosage. ResultsThirteen RCTs were included (n = 1649, median age 13 years, follow-up 6 weeks-2 years). All LLTs reduced low-density lipoprotein cholesterol (LDL-C) and total cholesterol; statins led to increases in high-density lipoprotein cholesterol and reductions in triglycerides. Statins reduced LDL-C by 33.61 % against placebo (95 % CI 27.58 to 39.63, I2 = 83 %). Adding ezetimibe to statins reduced LDL-C by an additional 15.85 % (95 % CI 11.91 to 19.79). NMAs showed intermediate-dose statins reduced LDL-C by an additional 4.77 % compared with lower-doses statins (95 % CrI −11.22 to 1.05); higher-dose statins and intermediate-dose statins + ezetimibe may be similarly effective and are probably superior to ezetimibe, intermediate-and lower-dose statins. There was no evidence of differences in maturation, safety or tolerability between LLTs and placebo. ConclusionsStatins, ezetimibe and statins-ezetimibe are all effective treatments for children with HeFH, but the magnitude of LDL-C reductions varies and may depend on treatment dosage and combination. No safety or tolerability issues were found. Longer-term safety and effectiveness are uncertain.

Cystatin C vs creatinine eGFR in advanced CKD: an analysis of the STOP-ACEi trial

ABSTRACT Background In this secondary analysis of the STOP-ACEi trial, we explored the impact of discontinuing or continuing renin–angiotensin system inhibitor therapy in people with advanced chronic kidney disease on cystatin C estimated glomerular filtration rate (eGFR). Methods Cystatin C eGFRs were calculated at baseline, 12, 24 and 36 months using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin 2012, European Kidney Function Consortium and CKD-EPI Combined 2021 equations. We excluded samples obtained after the initiation of kidney replacement therapy. Primary analysis used complete case analysis and mixed-effects linear regression model, adjusting for minimization variables, baseline value, time-point and treatment by time interaction. Sensitivity analysis was conducted using a pattern mixture model to account for missing data that was not at random. To model the longitudinal cystatin C data with time-to-event data, a joint model was utilized which incorporated the cystatin C measurements at various time points and accounted for the occurrence of kidney replacement therapy. Results The mean cystatin C eGFRs (CKD-EPI 2012) at baseline were 17.8 mg/L [standard deviation (SD 6.3)] and 17.9 mL/min/1.73 m2 (SD 6.3) in the STOP and CONTINUE arms, respectively. The estimated least squares mean difference at 12 months between STOP and CONTINUE arm was –1.46 [95% confidence interval (CI) –2.39 to –0.52, P = .002]. The estimated least squares mean difference at 24 months was –2.27 (95% CI –3.48 to –1.06, P &amp;lt; .001). The estimated least squares mean difference at 36 months was –1.72 (95% CI –3.48 to 0.03, P = .05). Conclusion Our results are consistent with the primary study's analysis and sensitivity analyses support these findings and provide additional insights. Our findings demonstrate the similarity of creatinine and cystatin eGFR results and therefore support the use of cystatin C as an alternative marker of eGFR in advanced CKD, particularly in those in whom creatinine is likely to be less accurate.

Use of Complementary and Alternative Therapies in People with Inflammatory Bowel Disease.

Complementary and alternative medicines (CAMs) are frequently discussed by people with Inflammatory Bowel Disease (IBD). The aim of this study is to explore CAM use in Australians with IBD. This cross-sectional study was conducted via an anonymous online survey, predominantly distributed through IBD-specific social media accounts. Data collection occurred over a three-month period in 2021. Descriptive statistics, Chi-Square tests, and binary logistic regression were used to analyse quantitative data. A simple thematic analysis was conducted for qualitative free-text responses. Of the 123 responses, acupuncture (12.2%) and chiropractors (8.9%) were common CAM practitioners accessed. CAM practitioners were perceived to be 'very helpful' compared to mainstream health practitioners. The most common CAM products reported were vitamins (51.2%), probiotics (43.9%), and herbal medicine (30.9%). Common reasons for use were improved perceived improvements to wellbeing or for long-term management of IBD. Females were more likely to access CAM practitioners (OR 12.6, 95% CI 1.62-98.1, p = 0.02). Doctors were the participants' primary source of information (64.2%), although many expressed dissatisfaction with conventional therapy and the desire for a more holistic approach to care. The use of CAMs in this sample was high. Limited research into the efficacy and safety of these therapies may prevent health professionals from discussing their use with patients. Improved communication with health professionals will allow patients to be active partners in their healthcare plans and can heighten patient satisfaction with conventional therapy.

Kidney effects of triple CFTR modulator therapy in people with cystic fibrosis.

Elexacaftor/tezacaftor/ivacaftor (ETI) is a new cystic fibrosis transmembrane conductance regulator (CFTR) modulator that has transformed the respiratory prognosis of people with cystic fibrosis (pwCF). However, its impact on other organs such as the kidneys, where CFTR is expressed, remains unclear. Since pwCF are risk of both kidney disease and urolithiasis, we aimed to study the potential effects of ETI on renal function, volume status, and risk factors for urolithiasis. This prospective, observational, single-center, before-after cohort study, involved adult pwCF eligible for ETI. The changes in plasma and urinary profiles were assessed by comparing renal function (using 2021 CKD-EPIcreatinine and 2021 CKD-EPIcreatinine-cystatin C formulas), volume status (using aldosterone/renin ratio and blood pressure), and risk factors for urolithiasis, at the time of ETI introduction (M0) and 7 months after (M7). Nineteen pwCF were included. No significant change in renal function was observed between M0 and M7 (2021 CKD-EPIcreatinine: 105.5ml/min/1.73 m² at M0 vs. 103.3ml/min/1.73 m² at M7; P=.17). There was a significant reduction in aldosterone level (370.3pmol/l at M0 vs. 232.4pmol/l at M7; P=.02) and aldosterone/renin ratio (33.6 at M0 vs. 21.8 at M7; P=.03). Among the risk factors for urolithiasis, a significant reduction in magnesuria level was found (4.6mmol/d at M0 vs. 3.8mmol/d at M7; P=.01). These findings suggest that ETI seem to have no short-term impact on the renal function of adult pwCF and appears to correct secondary hyperaldosteronism due to excessive sweat losses. Further investigations are needed to determine the potential impact of decreased magnesuria observed under ETI therapy on the risk of urolithiasis.

No increased risk of tuberculosis-related immune reconstitution inflammatory syndrome with integrase inhibitor-based antiretroviral therapy in people with HIVwith profound immunosuppression.

The issue of whether integrase inhibitors (INSTIs) may confer a higher risk of paradoxical tuberculosis-related immune reconstitution inflammatory syndrome (TB-IRIS) compared with other classes of antiretroviral in people with HIV with a profound level of immunosuppression remains insufficiently explored. We aimed to assess whether such a higher risk exists by examining a cohort of patients with TB-HIV initiating antiretroviral therapy (ART) in Hong Kong. This was a retrospective review of 133 patients registered in the TB-HIV Registry of the Department of Health during the period 2014-2021. Sixteen of 70 patients (22.9%; 95% confidence interval [CI] 13.0-32.7) and 14 of 63 patients (22.2%; 95% CI 12.0-32.5) from the INSTI and non-INSTI groups experienced TB-IRIS (p = 0.920). The median intervals between ART initiation and IRIS among patients from the two groups were similar (3 weeks [interquartile range IQR 2.0-7.8] vs. 4 weeks [IQR 2.0-5.1], p = 0.620). The proportion of patients requiring steroid therapy were similar, as were the hospitalization rates. There was no IRIS-related death in either group. The risk of TB-IRIS with INSTI versus non-INSTI was also similar in a stratified analysis in a subgroup of patients with a baseline CD4 count of <50 μL (10/33 [30.3%; 95% CI 14.6-46.0] vs. 10/22 [45.5%; 95% CI 24.7-66.3], p = 0.252) and another subgroup of patients with ART initiated within 4 weeks of anti-TB treatment (10/26 [38.5%; 95% CI 19.8-57.2] vs. 10/23 [43.5%; 95% CI 23.2-63.7], p = 0.721). Our cohort study did not offer support for an increased risk of TB-IRIS with INSTIs compared with non-INSTIs, even in severely immunocompromised people with HIV.

A plain language summary of the results from the phase 2b HERIZON-BTC-01 study of zanidatamab in participants with HER2-amplified biliary tract cancer.

Researchers wanted to study whether the research drug zanidatamab could help people with a type of cancer called biliary tract cancer. In some people, biliary tract cancer cells make extra copies of a gene called HER2 (also called ERBB2). This is known as being HER2-amplified. Zanidatamab is an antibody designed to destroy cancer cells that have higher-than-normal HER2 protein or gene levels. Zanidatamab is currently under research and is not yet approved for any diseases. Participants in this phase 2b clinical study had tumors that were HER2-amplified and at the advanced or metastatic stage. Participants also had cancer which had become worse after previous chemotherapy or had side effects that were too bad to continue chemotherapy. They also had to meet other requirements to be enrolled. Researchers measured the amount of HER2 protein in the tumor samples of the participants who were enrolled. There were 80 participants with tumors that were both HER2 amplified and had higher-than-normal HER2 protein amounts (considered to be 'HER2-positive'). There were 7 participants with tumors that were HER2-amplified, but had little-to-no levels of the HER2 protein (considered to be 'HER2-low'). All participants in the study were treated with zanidatamab and no other cancer treatments once every 2weeks. In the HER2-positive group, 33 of 80 (41%) participants had their tumors shrink by 30% or more of their original size. In half of these participants, their tumors did not grow for 13months or longer. No participant in the HER2-low group had their tumors shrink by 30% or more. In total, 63 of 87 participants (72%) had at least one side effect believed to be related to zanidatamab treatment. Most side effects were mild or moderate in severity. No participant died from complications related to zanidatamab. Diarrhea was one of the more common side effects and was experienced by 32 of 87 participants (37%). Side effects related to receiving zanidatamab through the vein, such as chills, fever, or high blood pressure, were experienced by 29 of 87 participants (33%). The results of this study support the potential for zanidatamab as a new therapy for people with HER2-positive biliary tract cancer after they had already received chemotherapy. More research is occurring to support these results.Clinical Trial Registration: NCT04466891 (HERIZON-BTC-01 study).

Plain language summary of the CARTITUDE-4 study of ciltacabtagene autoleucel for the treatment of people with relapsed or refractory multiple myeloma.

This is a summary of a phase 3 clinical trial called CARTITUDE-4. This trial compared the anti-cancer therapy ciltacabtagene autoleucel (or cilta-cel) with standard therapies in people who have multiple myeloma, a cancer that affects specific kinds of blood cells called plasma cells. The people in the study had been treated with 1 to 3 previous treatments for multiple myeloma, including a common anti-myeloma treatment called lenalidomide, but their multiple myeloma did not get better. About half of the 419 participants in this study received cilta-cel, while the other half received standard therapies, or therapies that are commonly used to treat multiple myeloma. Participants who received cilta-cel had a type of immune cell called T cells collected from their blood and genetically modified to recognize a specific protein found on myeloma cells. These modified T cells, which comprise cilta-cel, were then infused back into the bloodstream. After approximately 1year in the study, more participants were alive without their cancer getting worse in the cilta-cel group (76%) than in the standard therapies group (49%). The most common side effects in both groups were infections and low blood cell counts. Cytokine release syndrome (a potentially serious side effect caused by overactivation of the immune system) was common but mostly mild. Neurotoxicities (including immune effector cell-associated neurotoxicity syndrome, which can cause symptoms such as headaches, changes in consciousness, and difficulty with memory, attention, speaking, or understanding others) were less common and were reported in 20.5% of participants treated with cilta-cel. In CARTITUDE-4, more participants treated with cilta-cel showed improvements and were alive with control of their disease 12months after receiving cilta-cel compared with participants who received standard therapies.Clinical Trial Registration: NCT04181827 (CARTITUDE-4) (ClinicalTrials.gov).

Dosage effects of psychodynamic and schema therapy in people with comorbid depression and personality disorder: four-arm pragmatic randomised controlled trial: commentary, Mulder.

Dosage effects of psychodynamic and schema therapy in people with comorbid depression and personality disorder: four-arm pragmatic randomised controlled trial: commentary, Mulder.

Sodium-glucose cotransporter 2 inhibitors reduce the risk of incident type 2 diabetes in people with heart failure without diabetes: An analysis of real-world, cohort data.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is), used as a glucose-lowering therapy in people with type 2 diabetes (T2D), have significant cardiorenal benefits, reducing hospitalization for heart failure (HF) and cardiovascular mortality in patients with and without T2D. Recent clinical trial evidence suggests their potential utility in preventing incident T2D among the high-risk HF populations. Therefore, we aimed to assess whether this finding was reproducible in a real-world setting. We performed a retrospective cohort analysis of 484 643 patients with HF, without baseline diabetes, prescribed either angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers with/without SGLT2is (treatment, n = 42 018; reference, n = 442 625) across 95 global health care organizations, using a large real-world ecosystem. Propensity score matching balanced arms 1:1 for confounders (n = 39 168 each arm). Subgroup analysis further evaluated the impact on patients with prediabetes and the efficacy of dapagliflozin/empagliflozin, specifically, on incident T2D and secondary outcomes, including all-cause mortality, acute pulmonary oedema and hospitalization. Treatment with SGLT2is significantly reduced incident T2D {hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.63, 0.75]} in patients with HF. The analysis of patients with prediabetes found that SGLT2is further reduced incident T2D [HR 0.62 (95% CI 0.45, 0.80)]. The magnitude of reduction in incident T2D was higher in patients prescribed dapagliflozin [HR 0.47 (95% CI 0.39, 0.56)] versus empagliflozin [HR 0.81 (95% CI 0.70, 0.93)]. Treatment with SGLT2is in patients with HF was associated with a reduced risk of incident T2D, most strikingly in people with prediabetes.