Is blinding in studies of manual soft tissue mobilisation of the back possible? A feasibility randomised controlled trial with Swiss graduate students

Study design Single-centre, two-parallel group, methodological randomised controlled trial to assess blinding feasibility. Background Trials of manual therapy interventions of the back face methodological challenges regarding blinding feasibility and success. We assessed the feasibility of blinding an active manual soft tissue mobilisation and control intervention of the back. We also assessed whether blinding is feasible among outcome assessors and explored factors influencing perceptions about intervention assignment. Methods On 7–8 November 2022, 24 participants were randomly allocated (1:1 ratio) to active or control manual interventions of the back. The active group (n = 11) received soft tissue mobilisation of the lumbar spine. The control group (n = 13) received light touch over the thoracic region with deep breathing exercises. The primary outcome was blinding of participants immediately after a one-time intervention session, as measured by the Bang blinding index (Bang BI). Bang BI ranges from –1 (complete opposite perceptions of intervention received) to 1 (complete correct perceptions), with 0 indicating ‘random guessing’—alanced ‘active’ and ‘control’ perceptions within an intervention arm. Secondary outcomes included blinding of outcome assessors and factors influencing perceptions about intervention assignment among both participants and outcome assessors, explored via thematic analysis. Results 24 participants were analysed following an intention-to-treat approach. 55% of participants in the active manual soft tissue mobilisation group correctly perceived their group assignment beyond chance immediately after intervention (Bang BI: 0.55 [95% confidence interval (CI), 0.25 to 0.84]), and 8% did so in the control group (0.08 [95% CI, −0.37 to 0.53]). Bang BIs in outcome assessors were 0.09 (−0.12 to 0.30) and −0.10 (−0.29 to 0.08) for active and control participants, respectively. Participants and outcome assessors reported varying factors related to their perceptions about intervention assignment

Is blinding in studies of manual soft tissue mobilisation of the back possible? A feasibility randomised controlled trial with Swiss graduate students

STUDY DESIGN Single-centre, two-parallel group, methodological randomised controlled trial to assess blinding feasibility. BACKGROUND Trials of manual therapy interventions of the back face methodological challenges regarding blinding feasibility and success. We assessed the feasibility of blinding an active manual soft tissue mobilisation and control intervention of the back. We also assessed whether blinding is feasible among outcome assessors and explored factors influencing perceptions about intervention assignment. METHODS On 7-8 November 2022, 24 participants were randomly allocated (1:1 ratio) to active or control manual interventions of the back. The active group (n = 11) received soft tissue mobilisation of the lumbar spine. The control group (n = 13) received light touch over the thoracic region with deep breathing exercises. The primary outcome was blinding of participants immediately after a one-time intervention session, as measured by the Bang blinding index (Bang BI). Bang BI ranges from -1 (complete opposite perceptions of intervention received) to 1 (complete correct perceptions), with 0 indicating 'random guessing'-balanced 'active' and 'control' perceptions within an intervention arm. Secondary outcomes included blinding of outcome assessors and factors influencing perceptions about intervention assignment among both participants and outcome assessors, explored via thematic analysis. RESULTS 24 participants were analysed following an intention-to-treat approach. 55% of participants in the active manual soft tissue mobilisation group correctly perceived their group assignment beyond chance immediately after intervention (Bang BI: 0.55 [95% confidence interval (CI), 0.25 to 0.84]), and 8% did so in the control group (0.08 [95% CI, -0.37 to 0.53]). Bang BIs in outcome assessors were 0.09 (-0.12 to 0.30) and -0.10 (-0.29 to 0.08) for active and control participants, respectively. Participants and outcome assessors reported varying factors related to their perceptions about intervention assignment. CONCLUSIONS Blinding of participants allocated to an active soft tissue mobilisation of the back was not feasible in this methodological trial, whereas blinding of participants allocated to the control intervention and outcome assessors was adequate. Findings are limited due to imprecision and suboptimal generalisability to clinical settings. Careful thinking and consideration of blinding in manual therapy trials is warranted and needed. TRIAL REGISTRATION ClinicalTrials.gov: NCT05822947 (retrospectively registered)

Validation of a new optical diagnosis training module to improve dysplasia characterization in inflammatory bowel disease:a multicenter international study

Background and aims Inflammatory bowel disease (IBD) increases risk of dysplasia and colorectal cancer. Advanced endoscopic techniques allow for the detection and characterization of IBD dysplastic lesions, but specialized training is not widely available. We aim to develop and validate an online training platform to improve the detection and characterization of colonic lesions in IBD: OPTIC-IBD. Methods We designed a web-based learning module that includes surveillance principles, optical diagnostic methods, approach to characterization, classifications of colonic lesions, utilizing still images and videos. We invited gastroenterologists from Canada, Italy, and the UK, with a wide range of experience. Participants reviewed 24 educational videos of IBD colonic lesions, predicted histology, and rated their confidence. The primary endpoint was to improve accuracy in detecting dysplastic lesions following training on the platform. Furthermore, participants were randomized 1:1 to get additional training or not, with a final assessment occurring after 60 days. Diagnostic performance for dysplasia and rater confidence were measured. Results One hundred seventeen participants completed the study and were assessed for the primary endpoint. Diagnostic accuracy improved from 70.8% to 75.0% (p 0.002) following training, with the greatest improvements seen in less experienced endoscopists. Improvements in both accuracy and confidence were sustained after 2 months of assessment, although the group randomized to receive additional training did not improve further. Similarly, participants’ confidence in characterizing lesions significantly improved between pre- and post-course (

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Characterization And Determinants Of Long-term Immune Recovery Under Suppressive Antiretroviral Therapy

Objective. We developed a robust characterization of immune recovery trajectories in people living with HIV (PWH) on antiretroviral treatment (ART) and relate our findings to epidemiological risk factors and bacterial pneumonia. Methods. Using data from the Swiss HIV Cohort Study and the Zurich Primary HIV Infection Cohort Study (n = 5907), we analyzed the long-term trajectories of CD4 cell and CD8 cell counts and their ratio in PWH on ART for at least eight years by fitting nonlinear mixed effects models. The determinants of long-term immune recovery were investigated using generalized additive models. In addition, prediction accuracy of the modeled trajectories and their impact on the fit of a model for bacterial pneumonia was assessed. Results. Overall, our population showed good immune recovery (median plateau [IQR]-CD4: 718 [555, 900] cells/µl, CD8: 709 [547, 893] cells/µl, CD4/CD8: 1.01 [0.76, 1.37]). The following factors were predictive of recovery: Age, sex, nadir/zenith value, pre-ART HIV-1 viral load, Hepatitis C, ethnicity, acquisition risk and timing of ART-initiation. The fitted models proved to be an accurate and efficient way of predicting future CD4+ and CD8+ cell recovery dynamics: Compared to carrying forward the last observation, mean squared errors of the fitted values were lower by 1.3% to 18.3% across outcomes. When modeling future episodes of bacterial pneumonia, using model-derived predictors improved most model fits. Conclusion. We described and validated a method to characterize individual immune recovery trajectories of PWH on suppressive ART. These trajectories accurately predict long-term immune recovery and the occurrence of bacterial pneumonia

Is blinding in studies of manual soft tissue mobilisation of the back possible? : a feasibility randomised controlled trial with Swiss graduate students

Study design: Single-centre, two-parallel group, methodological randomised controlled trial to assess blinding feasibility. Background: Trials of manual therapy interventions of the back face methodological challenges regarding blinding feasibility and success. We assessed the feasibility of blinding an active manual soft tissue mobilisation and control intervention of the back. We also assessed whether blinding is feasible among outcome assessors and explored factors influencing perceptions about intervention assignment. Methods: On 7–8 November 2022, 24 participants were randomly allocated (1:1 ratio) to active or control manual interventions of the back. The active group (n = 11) received soft tissue mobilisation of the lumbar spine. The control group (n = 13) received light touch over the thoracic region with deep breathing exercises. The primary outcome was blinding of participants immediately after a one-time intervention session, as measured by the Bang blinding index (Bang BI). Bang BI ranges from –1 (complete opposite perceptions of intervention received) to 1 (complete correct perceptions), with 0 indicating ‘random guessing’—balanced ‘active’ and ‘control’ perceptions within an intervention arm. Secondary outcomes included blinding of outcome assessors and factors influencing perceptions about intervention assignment among both participants and outcome assessors, explored via thematic analysis. Results: 24 participants were analysed following an intention-to-treat approach. 55% of participants in the active manual soft tissue mobilisation group correctly perceived their group assignment beyond chance immediately after intervention (Bang BI: 0.55 [95% confidence interval (CI), 0.25 to 0.84]), and 8% did so in the control group (0.08 [95% CI, −0.37 to 0.53]). Bang BIs in outcome assessors were 0.09 (−0.12 to 0.30) and −0.10 (−0.29 to 0.08) for active and control participants, respectively. Participants and outcome assessors reported varying factors related to their perceptions about intervention assignment. Conclusions: Blinding of participants allocated to an active soft tissue mobilisation of the back was not feasible in this methodological trial, whereas blinding of participants allocated to the control intervention and outcome assessors was adequate. Findings are limited due to imprecision and suboptimal generalisability to clinical settings. Careful thinking and consideration of blinding in manual therapy trials is warranted and needed. Trial registration: ClinicalTrials.gov: NCT05822947 (retrospectively registered

CHARACTERIZATION AND DETERMINANTS OF LONG-TERM IMMUNE RECOVERY UNDER SUPPRESSIVE ANTIRETROVIRAL THERAPY.

OBJECTIVE We developed a robust characterization of immune recovery trajectories in people living with HIV (PWH) on antiretroviral treatment (ART) and relate our findings to epidemiological risk factors and bacterial pneumonia. METHODS Using data from the Swiss HIV Cohort Study and the Zurich Primary HIV Infection Cohort Study (n = 5907), we analyzed the long-term trajectories of CD4 cell and CD8 cell counts and their ratio in PWH on ART for at least eight years by fitting nonlinear mixed effects models. The determinants of long-term immune recovery were investigated using generalized additive models. In addition, prediction accuracy of the modeled trajectories and their impact on the fit of a model for bacterial pneumonia was assessed. RESULTS Overall, our population showed good immune recovery (median plateau [IQR]-CD4: 718 [555, 900] cells/µl, CD8: 709 [547, 893] cells/µl, CD4/CD8: 1.01 [0.76, 1.37]). The following factors were predictive of recovery: Age, sex, nadir/zenith value, pre-ART HIV-1 viral load, Hepatitis C, ethnicity, acquisition risk and timing of ART-initiation. The fitted models proved to be an accurate and efficient way of predicting future CD4+ and CD8+ cell recovery dynamics: Compared to carrying forward the last observation, mean squared errors of the fitted values were lower by 1.3% to 18.3% across outcomes. When modeling future episodes of bacterial pneumonia, using model-derived predictors improved most model fits. CONCLUSION We described and validated a method to characterize individual immune recovery trajectories of PWH on suppressive ART. These trajectories accurately predict long-term immune recovery and the occurrence of bacterial pneumonia

Female reproductive health and inflammatory bowel disease: A practice-based review

Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, occur worldwide and affect people of all ages, with a high impact on their quality of life. Sex differences in incidence and prevalence have been reported, and there are also gender-specific issues that physicians should recognize. For women, there are multiple, important concerns regarding issues of body image and sexuality, menstruation, contraception, fertility, pregnancy, breastfeeding and menopause. This practice-based review focuses on the main themes that run through the life of women with inflammatory bowel diseases from puberty to menopause. Gastroenterologists who specialize in inflammatory bowel diseases and other physicians who see female patients with inflammatory bowel diseases should provide support for these problems and offer adequate therapy to ensure that their patients achieve the same overall well-being and health as do women without inflammatory bowel diseases. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Quantifying and predicting ongoing Human Immunodeficiency Virus Type 1 (HIV-1) transmission dynamics in Switzerland using a distance-based clustering approach

BACKGROUND: Despite effective prevention approaches, ongoing HIV-1 transmission remains a public health concern indicating a need for identifying its drivers. METHODS: We combine a network-based clustering method using evolutionary distances between viral sequences with statistical learning approaches to investigate the dynamics of HIV-1 transmission in the Swiss HIV Cohort Study and to predict the drivers of ongoing transmission. RESULTS: We find that only a minority of clusters and patients acquire links to new infections between 2007 and 2020. While the growth of clusters and the probability of individual patients acquiring new links in the transmission network was associated with epidemiological, behavioral and virological predictors, the strength of these associations decreased substantially when adjusting for network characteristics. Thus, these network characteristics can capture major heterogeneities beyond classical epidemiological parameters. When modeling the probability of a newly diagnosed patient being linked with future infections, we found that the best predictive performance (median AUCROC = 0.77) was achieved by models including characteristics of the network as predictors and that models excluding them performed substantially worse (median AUCROC = 0.54). CONCLUSIONS: These results highlight the utility of molecular epidemiology-based network approaches for analysing and predicting ongoing HIV-1-transmission dynamics. This approach may serve for real-time prospective assessment of HIV-1-transmission

Quantifying and predicting ongoing Human Immunodeficiency Virus Type 1 (HIV-1) transmission dynamics in Switzerland using a distance-based clustering approach.

BACKGROUND Despite effective prevention approaches, ongoing HIV-1 transmission remains a public health concern indicating a need for identifying its drivers. METHODS We combine a network-based clustering method using evolutionary distances between viral sequences with statistical learning approaches to investigate the dynamics of HIV-1 transmission in the Swiss HIV Cohort Study and to predict the drivers of ongoing transmission. RESULTS We find that only a minority of clusters and patients acquire links to new infections between 2007 and 2020. While the growth of clusters and the probability of individual patients acquiring new links in the transmission network was associated with epidemiological, behavioral and virological predictors, the strength of these associations decreased substantially when adjusting for network characteristics. Thus, these network characteristics can capture major heterogeneities beyond classical epidemiological parameters. When modeling the probability of a newly diagnosed patient being linked with future infections, we found that the best predictive performance (median AUCROC = 0.77) was achieved by models including characteristics of the network as predictors and that models excluding them performed substantially worse (median AUCROC = 0.54). CONCLUSIONS These results highlight the utility of molecular epidemiology-based network approaches for analysing and predicting ongoing HIV-1-transmission dynamics. This approach may serve for real-time prospective assessment of HIV-1-transmission