Adjusting for switches to multiple treatments: Should switches be handled separately or combined?

Treatment switching is common in randomised controlled trials (RCTs). Participants may switch onto a variety of different treatments, all of which may have different treatment effects. Adjustment analyses that target hypothetical estimands - estimating outcomes that would have been observed in the absence of treatment switching - have focused primarily on a single type of switch.

The Striking Power of Amniotic Fluid and Its Exosomes Collected at the End of a Normal Pregnancy on Severe Inflammation and Tissue Repair.

With this short communication, which contains a new case report on diabetic ulcer, we summarize our research progress in treating several complex conditions at a point where currently available treatments were failing to help the affected patients. We review the first case of lower back pain due to severe spondylitis (T12-L1) treated with intravenous injections of a sterile fraction of human purified amniotic fluid (ViX001) obtained from thoroughly screened volunteers at the time of planned c-section at the term of normal pregnancies. Then, we review the first case of recalcitrant diabetic ulcer treated successfully by twice-daily applications of ViX001 directly on the wound and describe another case of diabetic ulcer treated successfully with ViX001.

A Meta-Analysis of Levofloxacin for Contacts of Multidrug-Resistant Tuberculosis.

Background: Data from randomized trials evaluating the effectiveness of tuberculosis (TB) preventive treatment for contacts of multidrug-resistant (MDR)-TB are lacking. Two recently published randomized trials that did not achieve statistical significance provide the opportunity for a meta-analysis.

Methods: We conducted combined analyses of two phase 3 trials of levofloxacin MDR-TB preventive treatment - Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis (VQUIN) trial and the Levofloxacin preventive treatment in children exposed to MDR-TB (TB-CHAMP) trial.

Sample-to-answer detection of miRNA from whole blood using thermally responsive alkane partitions.

Circulating miRNA offers a tremendous opportunity as a biomarker paradigm for many applications in disease diagnostics, including point-of-care diagnostics for global health needs. However, despite the numerous miRNA detection schemes reported, there still does not exist a solution for highly sensitive sample-to-answer detection of miRNA directly from complex samples, such as whole blood. We recently developed thermally responsive alkane partitions (TRAPs), which - when combined with magnetic microbeads - enable the complete assay automation from whole blood.

Is inverse probability of censoring weighting a safer choice than per-protocol analysis in clinical trials?

Deviation from the treatment strategy under investigation occurs in many clinical trials. We term this intervention deviation. Per-protocol analyses are widely adopted to estimate a hypothetical estimand without the occurrence of intervention deviation.

Factors Associated With Biologic Therapy After Ileal Pouch-Anal Anastomosis in Patients With Ulcerative Colitis.

Background: Patients with ulcerative colitis (UC) undergoing proctocolectomy and ileal pouch-anal anastomosis (IPAA) may eventually require biologic therapy. Factors associated with biologic therapy after IPAA have not been previously studied.

Methods: All patients with UC after total proctocolectomy and IPAA who were followed at Rabin Medical Center comprehensive pouch clinic and who consented to prospective observational follow-up were included.

Impact of Seton Use on Clinical, Patient-Reported, and Healthcare Resource Utilization Outcomes in Complex Crohn's Perianal Fistulas: A Systematic Literature Review.

Background: Optimal treatment strategies for seton use in patients with Crohn's perianal fistulas (CPF) remain elusive. This systematic literature review aimed to summarize clinical, patient-reported, and healthcare resource utilization (HCRU) outcomes associated with seton use for symptomatic relief and treatment of complex CPF.

Methods: Electronic databases (MEDLINE, Embase, EBM Reviews, EconLit) were searched.

Saliva-STAT: Sample-to-answer saliva test for COVID-19.

Highly accessible and highly accurate diagnostics are necessary to combat rapidly-spreading infectious diseases, such as the recent COVID-19 pandemic. While lateral flow antigen tests have become pervasive, they are insufficiently sensitive to detect early or asymptomatic disease. Nucleic acid amplification tests provide the needed sensitivity, but accessibility of these tests continues to be a challenge due to the need for precise sample processing steps.

Proactive integrated consultation-liaison psychiatry and time spent in hospital by older medical inpatients in England (The HOME Study): a multicentre, parallel-group, randomised controlled trial.

Background: Older people admitted to hospital in an emergency often have prolonged inpatient stays that worsen their outcomes, increase health-care costs, and reduce bed availability. Growing evidence suggests that the biopsychosocial complexity of their problems, which include cognitive impairment, depression, anxiety, multiple medical illnesses, and care needs resulting from functional dependency, prolongs hospital stays by making medical treatment less efficient and the planning of post-discharge care more difficult. We aimed to assess the effects of enhancing older inpatients' care with Proactive Integrated Consultation-Liaison Psychiatry (PICLP) in The HOME Study.

Estimation of Treatment Policy Estimands for Continuous Outcomes Using Off-Treatment Sequential Multiple Imputation.

The estimands framework outlined in ICH E9 (R1) describes the components needed to precisely define the effects to be estimated in clinical trials, which includes how post-baseline 'intercurrent' events (IEs) are to be handled. In late-stage clinical trials, it is common to handle IEs like 'treatment discontinuation' using the treatment policy strategy and target the treatment effect on outcomes regardless of treatment discontinuation. For continuous repeated measures, this type of effect is often estimated using all observed data before and after discontinuation using either a mixed model for repeated measures (MMRM) or multiple imputation (MI) to handle any missing data.

Sexual Health, sexuality and sexual intimacy in patients with head and neck cancer - A narrative review.

Sexuality and sexual intimacy are important aspects of cancer survivorship. In head and neck cancer (HNC), concerns around sexual health, sexuality and sexual intimacy are infrequently raised or addressed in standard HNC consultations, either before embarking on treatment or during survivorship. The changing demographic of HNC patients, largely due to the increasing proportion of patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPVOPSCC), has driven renewed interest in some specific survivorship issues, including sexual behaviours and lifestyles, which may account for both the primary mode of HPV transmission and the younger and less comorbid population affected by this disease.

Risk Factors for Rectal Cancer Recurrence after Local Excision of T1 Lesions from a Decade-Long Multicenter Retrospective Study.

Local surgical excision of T1 rectal adenocarcinoma is a well-established approach. Yet, there are still open questions regarding the recurrence rates and its risk factors. A retrospective multicenter study including all patients who underwent local excision of early rectal cancer with an open or MIS approach and had a T1 lesion from 2010 to 2020 in six academic centers.

An evaluation of sample size requirements for developing risk prediction models with binary outcomes.

Background: Risk prediction models are routinely used to assist in clinical decision making. A small sample size for model development can compromise model performance when the model is applied to new patients. For binary outcomes, the calibration slope (CS) and the mean absolute prediction error (MAPE) are two key measures on which sample size calculations for the development of risk models have been based.

Determining sample size in a personalized randomized controlled (PRACTical) trial.

In clinical settings with no commonly accepted standard-of-care, multiple treatment regimens are potentially useful, but some treatments may not be appropriate for some patients. A personalized randomized controlled trial (PRACTical) design has been proposed for this setting. For a network of treatments, each patient is randomized only among treatments which are appropriate for them.

Sample-to-Answer Detection of SARS-CoV-2 Viremia Using Thermally Responsive Alkane Partitions.

The diagnosis of bloodborne viral infections (viremia) is currently relegated to central laboratories because of the complex procedures required to detect viruses in blood samples. The development of point-of-care diagnostics for viremia would enable patients to receive a diagnosis and begin treatment immediately instead of waiting days for results. Point-of-care systems for viremia have been limited by the challenges of integrating multiple precise steps into a fully automated (i.

Exploring different objectives in non-inferiority trials.

Non-inferiority trials compare the efficacy of a new treatment with an existing one where the new treatment is expected to have broadly similar efficacy to the existing treatment, but where other benefits might make the new treatment desirable. These trials might aim to demonstrate that a new treatment is either an alternative to, or a replacement for, the current treatment. In this article, how treatment comparisons can be based only on efficacy, or on both efficacy and other benefits, is explained, and guidance on how to choose the correct objective for a trial is given.

Changes in the prevalence of mental health problems during the first year of the pandemic: a systematic review and dose-response meta-analysis.

Aim: To describe the pattern of the prevalence of mental health problems during the first year of the COVID-19 pandemic and examine the impact of containment measures on these trends.

Methods: We identified articles published until 30 August 2021 that reported the prevalence of mental health problems in the general population at two or more time points. A crowd of 114 reviewers extracted data on prevalence, study and participant characteristics.

Severely compromised supply of patch test allergens in Europe hampers adequate diagnosis of occupational and non-occupational contact allergy. A European Society of Contact Dermatitis (ESCD), European Academy of Allergy and Clinical Immunology (EAACI), European Academy of Dermatology and Venereology (EADV) task forces 'Contact Dermatitis' and 'Occupational Skin Disease' position paper.

Patch testing is the only clinically applicable diagnostic method for Type IV allergy. The availability of Type IV patch test (PT) allergens in Europe, however, is currently scarce. This severely compromises adequate diagnostics of contact allergy, leading to serious consequences for the affected patients.

Comparison of Post-Operative Outcomes of Right Colectomy between Crohn's Disease and Adenocarcinoma of the Right Colon: A Retrospective Cohort Study.

(1) Crohn's disease (CD) and right-sided colorectal-carcinoma (CRC) are two common indications for right colectomies. Many studies have tried to identify risk factors associated with post-operative complications for both CD and CRC. However, data directly comparing the outcomes of the two are sparse.

Insights into treatment of complex Crohn's perianal fistulas.

Complex perianal fistula is a common complication of Crohn's disease (CD) which leads to negative impact on patient's quality of life. Successful management of the disease requires a multidisciplinary approach, including a gastroenterologist and a colorectal surgeon, applying combined surgical and medical therapy. One of frequently practiced surgical procedures is seton placement in the fistula tract, which is used to control perianal sepsis and drain the fistula, while preventing recurrent abscess formation.

D3/Penta 21 clinical trial design: A randomised non-inferiority trial with nested drug licensing substudy to assess dolutegravir and lamivudine fixed dose formulations for the maintenance of virological suppression in children with HIV-1 infection, aged 2 to 15 years.

Background: There is increasing interest in utilising two-drug regimens for HIV treatment with the goal of reducing toxicity and improve acceptability. The D3 trial evaluates the efficacy and safety of DTG/3TC in children and adolescents and includes a nested pharmacokinetics(PK) substudy for paediatric drug licensing.

Methods: D3 is an ongoing open-label, phase III, 96-week non-inferiority randomised controlled trial(RCT) conducted in South Africa, Spain, Thailand, Uganda and the United Kingdom.