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Men having postoperative radiotherapy after radical prostatectomy usually have a favourable outcome. The results of RADICALS-HD will help patients and their clinicians decide on the duration of androgen deprivation therapy with postoperative radiotherapy. Future trials should focus on patients at a higher risk of metastases. The use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) have been uncertain. RADICALS-HD compared adding no ("None"), 6-months ("Short"), or 24-mo ("Long") ADT to study efficacy in the long term. Participants with prostate cancer were indicated for postoperative RT and agreed randomisation between all durations. ADT was allocated for 0, 6, or 24 mo. The primary outcome measure (OM) was metastasis-free survival (MFS). The secondary OMs included freedom from distant metastasis, overall survival, and initiation of nonprotocol ADT. Sample size was determined by two-way comparisons. Analyses followed standard time-to-event approaches and intention-to-treat principles. Between 2007 and 2015, 492 participants were randomised one of three groups: 166 None, 164 Short, and 162 Long. The median age at randomisation was 66 yr; Gleason scores at surgery were as follows: <7 = 64 (13%), 3+4 = 229 (47%), 4+3 = 127 (26%), and 8+ = 72 (15%); T3b was 112 (23%); and T4 was 5 (1%). The median follow-up was 9.0 yr and, with MFS events reported for 89 participants (32 None, 31 Short, and 26 Long), there was no evidence of difference in MFS overall (logrank p = 0.98), and, for Long versus None, hazard ratio = 0.948 (95% confidence interval 0.54–1.68). After 10 yr, 80% None, 77% Short, and 81% Long patients were alive without metastatic disease. The three-way randomisation was not powered to conventional levels for assessment, yet provides a fair comparison. Long-term outcomes after radical prostatectomy are usually favourable. In those indicated for postoperative RT and considered suitable for no, short-term, or long-term ADT, there was no evidence of improvement with addition of ADT. Future research should focus on patients at a higher risk of metastases in whom improvements are required more urgently. [ABSTRACT FROM AUTHOR]

Since the appropriate antibiotic duration for uncomplicated Staphylococcus aureus (S. aureus) bacteremia (u-SAB) in an immunocompromised state is still unclear, physicians are likely to extend antibiotic therapy from 2 weeks to 4–6 weeks. To examine the appropriate duration of antibiotic therapy for u-SAB, we performed this study. We reviewed all patients with u-SAB at our institute seen between January 2020 and August 2023. A total of 51 patients were enrolled, and they were divided into the following two groups by antibiotic duration: longer duration group ≥28 days after blood culture negativity, and shorter duration group. Then, the patients were matched by a propensity score using the covariates of age, sex, qSOFA, and CCI. The primary outcome was to identify the prognosis by duration of antibiotic treatment. After propensity score matching, all-cause 30-day mortality was 0 % in both groups. Hence, there was no significant difference in all-cause 90 days mortality (19.0% vs 9.5%, p = 0.33) or recurrence (9.5%% vs 0%, p = 0.22). Before propensity-score matching, we found that a serum level of CRP 2.0 mg/dL and greater after intravenous antibiotic treatment was one of the poor prognostic factors. The cut-off value of serum CRP level was 2.0 mg/dL with a sensitivity of 82.1% and a specificity of 75.0%. We suggested that 4–6 weeks of antibiotic treatment for immunodeficient u-SAB patients was unnecessary. Moreover, the serum level of CRP after completion of IV antibiotic treatment could be a prognostic marker for u-SAB. [ABSTRACT FROM AUTHOR]

Opportunities to decrease the toxicity and cost of approved treatment regimens with lower dose, less frequent, or shorter duration alternative regimens have been limited by the perception that alternatives must be non-inferior to approved regimens. Non-inferiority trials are large and expensive to do, because they must show statistically that the alternative and approved therapies differ in a single outcome, by a margin far smaller than that required to demonstrate superiority. Non-inferiority's flaws are manifest: it ignores variability expected to occur with repeated evaluation of the approved therapy, fails to recognise that a trial of similar design will be labelled as superiority or non-inferiority depending on whether it is done prior to or after initial registration of the approved treatment, and relegates endpoints such as toxicity and cost. For example, while a less toxic and less costly regimen of 3 months duration would typically be required to demonstrate efficacy that is non-inferior to that of a standard regimen of 6 months to displace it, the longer duration therapy has no such obligation to prove its superiority. This situation is the tyranny of the non-inferiority trial: its statistics perpetuate less cost-effective regimens, which are not patient-centred, even when less intensive therapies confer survival benefits nearly identical to those of the standard, by placing a disproportionately large burden of proof on the alternative. This approach is illogical. We propose that the designation of trials as superiority or non-inferiority be abandoned, and that randomised, controlled trials should henceforth be described simply as "comparative". [ABSTRACT FROM AUTHOR]

Current guidelines recommend at least 2 weeks duration of antibiotic therapy (DOT) for patients with uncomplicated Staphylococcus aureus bacteraemia (SAB) but the evidence for this recommendation is unclear. To perform a systematic literature review assessing current evidence for recommended DOT for patients with SAB. The following are the methods used for this study. We searched MEDLINE, ISI Web of Science, the Cochrane Database and clinicaltrials.gov from inception to March 30, 2024. References of eligible studies were screened and experts in the field contacted for additional articles. All clinical studies, regardless of design, publication status and language. Adult patients with uncomplicated SAB. Long (>14 days; >18 days; 11–16 days) vs. short (≤14 days; 10–18 days; 6–10 days, respectively) DOT with the DOT being defined as the first until the last day of antibiotic therapy. Risk of bias was assessed using the ROBINS-I-tool. The primary outcome was 90-day all-cause mortality. Only studies presenting results of adjusted analyses for mortality were included. Data synthesis could not be performed. Eleven nonrandomized studies were identified that fulfilled the pre-defined inclusion criteria, of which three studies reported adjusted effect ratios. Only these were included in the final analysis. We did not find any RCT. Two studies with 1230 patients reported the primary endpoint 90-day all-cause mortality. Neither found a statistically significant superiority for longer (>14 days; 11–16 days) or shorter DOT (≤14 days; 6–10 days, respectively) for patients with uncomplicated SAB. Two studies investigated the secondary endpoint 30-day all-cause mortality (>18 days; 11–16 days vs. 10–18 days; 6–10 days, respectively) and did not find a statistically significant difference. All included studies had a moderate risk of bias. Sound evidence that supports any duration of antibiotic treatment for patients with uncomplicated SAB is lacking. [ABSTRACT FROM AUTHOR]

Comparisons between bona fide psychological therapies generally report no effects or small effects favoring cognitive behavioral therapy (CBT), suggesting that differences between therapy modalities are of little importance. An observational, cohort study of patients (N = 11,116), drawn from the English Talking Therapies program. Patients presented with depression and were treated by CBT or person-centered experiential therapy (PCET), 67 % were female and the age range was 15–94. Multilevel modeling was used to identify variables associated with outcomes and CBT and PCET outcomes were compared dependent on the number of sessions patients attended and the severity of their depression at intake. Although overall a small effect size of 0.14 (0.10, 0.18) favored CBT, we found differing effect sizes depending on patient severity and the number of sessions they had attended at outcome. For non-clinical and moderately depressed patients no significant differences between therapies were found. For moderately-severe and severe patients there was a crossover in effectiveness with PCET more effective up to 5 or 6 sessions and CBT more effective thereafter. However, small effects in favour of PCET were unreliable. The largest effects were found for CBT for patients who were moderately-severe and had >10 sessions (d = 0.30, 0.12, 0.48) or were severe and had >12 sessions (d = 0.26 (0.02, 0.49). No data was available on therapy allocation decisions or therapists and the results may not be generalizable to non-NHS Talking Therapies services. Small effects can mask important contextual differences between therapies and their study can inform allocation decisions. • The benefits of longer therapy duration were moderated by therapy type • Little difference between PCET and CBT for non-clinical or moderately depressed patients • The therapy type*sessions interaction yielded a crossover in effectiveness in the full sample and the more severe subgroups • CBT especially effective with moderately-severe and severely depressed patients who had over 10 sessions • Small effects translate to large numbers of patients in large routine services [ABSTRACT FROM AUTHOR]

Antipsychotic-induced weight gain (AIWG) is a significant but frequently neglected adverse effect of first- and second-generation antipsychotic therapy, which may lead to cardiovascular disturbances. The present network meta-analysis (NMA) was conducted to evaluate and compare the effects of available treatment options in antipsychotic-induced weight gain (AIWG). The data was extracted from 68 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases and clinical trial registries. Random-effects Bayesian NMA was done to pool the effects across the interventions for the change in body weight from baseline. A network graph was built, a consistency model was run, node split analysis was performed, treatments were ranked as per the SUCRA score and meta-regression was done for the duration of therapy, baseline body weight and treatment strategy as the predictor variables. Finally, the results were sorted based on the certainty of evidence. The drugs showing significant reduction in body weight in order of magnitude of effect size include sibutramine 10 mg (−8.0 kg; −16. to −0.21), metformin 750 mg + lifestyle modification (−7.5 kg; −12 to −2.8), topiramate 200 mg (−7 kg; −10 to −3.4), metformin 750 mg (−5.7 kg; −9.3 to −2.1), topiramate 100 mg (−5.7 kg; −8.8 to −2.5), topiramate 50 mg (−5.2 kg; −10 to −0.57), liraglutide 1.8 mg (−5.2 kg; −10., −0.080), sibutramine 15 mg (−4.5 kg; −8.9 to −0.59), nizatidine 300 mg (−3.0 kg; −5.9 to −0.23) and metformin 1000 mg (−2.3 kg; −4.6 to −0.0046). There was no effect of duration of follow-up, baseline body weight and, preventive versus therapeutic strategy on weight reduction in AIWG. Metformin 750 mg with lifestyle modification was the most effective treatment for AIWG, followed by topiramate 200 mg, metformin 750 mg, and topiramate 100 mg with moderate certainty of evidence. • This network meta-analysis compared pharmacological agents used for antipsychotic-induced weight gain (AIWG) in schizophrenia. • Metformin (750 mg) with lifestyle modification is the best available treatment for AIWG, followed by topiramate (200 mg) and metformin (750 mg). • Other interventions which had a significant weight reduction effect were topiramate (50 mg and 100 mg), nizatidine 300 mg and metformin 1000 mg. • Liraglutide 3 mg had the highest magnitude of weight reduction as compared to placebo when meta-regression with baseline mean weight was done. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the length of stay (LOS) in patients who had adjunct middle meningeal artery embolization (MMAE) for chronic subdural hematoma after conventional surgery and determine the factors influencing the LOS in this population. A retrospective review of 107 cases with MMAE after conventional surgery between September 2018 and January 2024 was performed. Factors associated with prolonged LOS were identified through univariable and multivariable analyses. The median LOS for MMAE after conventional surgery was 9 days (interquartile range = 6–17), with a 3-day interval between procedures (interquartile range = 2–5). Among 107 patients, 58 stayed ≤ 9 days, while 49 stayed longer. Univariable analysis showed the interval between procedures, type of surgery, MMAE sedation, and the number of complications associated with prolonged LOS. Multivariable analysis confirmed longer intervals between procedures (odds ratio [OR] = 1.52; P < 0.01), ≥2 medical complications (OR = 13.34; P = 0.01), and neurological complications (OR = 5.28; P = 0.05) were independent factors for lengthier hospitalizations. There was a trending association between general anesthesia during MMAE and prolonged LOS (P = 0.07). Subgroup analysis revealed diabetes (OR = 5.25; P = 0.01) and ≥2 medical complications (OR = 5.21; P = 0.03) correlated with a LOS over 20 days, the 75th percentile in our cohort. The interval between procedures and the number of medical and neurological complications were strongly associated with prolonged LOS in patients who had adjunct MMAE after open surgery. Reducing the interval between the procedures and potentially performing both under 1 anesthetic may decrease the burden on patients and shorten their hospitalizations. [ABSTRACT FROM AUTHOR]

Many articles suggest that clozapine was strongly associated with a higher incidence of new-onset diabetes mellitus, and the issue has remained unsettled. Many articles have compared clozapine with FGAs, but few have compared clozapine with SGAs. We aimed to compare the risk of new-onset diabetes mellitus in adults with schizophrenia treated with clozapine and other SGAs. We conducted a comprehensive search of databases from their inception up until August 26, 2023. The specific databases include PubMed, Embase and others. We included non-randomized controlled trials involving the use of SGAs such as clozapine, olanzapine, risperidone, quetiapine, amisulpride, and zotepine, with a focus on new-onset diabetes mellitus as an outcome. We utilized odds ratio with 95 % credible intervals (95 % CI) as our effect size measures. The study protocol is registered with PROSPERO, number CRD42024511280. We included 7 studies with sufficient data to include in the meta-analysis. A total of eight studies with 641,48 participants met the eligibility criteria. The OR of the incidence rates of new-onset diabetes between clozapine and olanzapine was 0.95 (95 % CI:[0.82–1.09]), between clozapine and risperidone was 1.25 (95 % CI: [1.09–1.44]), between clozapine and quetiapine was 1.44 (95 % CI: [0.92–2.25]). In patients with schizophrenia, clozapine has been found to have a higher rate of new-onset diabetes mellitus compared to risperidone. However, there was no significant difference in incidence rate between clozapine versus olanzapine and quetiapine. These findings can assist clinicians in balancing the risks and benefits of those drugs. • Differences in the incidence of new-onset diabetes caused by second-generation antipsychotics were compared. • Clozapine and olanzapine cause a similar incidence of new-onset diabetes. • Clozapine is more likely to cause new-onset diabetes than risperidone. • Explored relationship between therapy duration and incidence [ABSTRACT FROM AUTHOR]

The number needed to treat (NNT) is the inverse of the absolute risk difference, which is used as a secondary outcome to clinical trials as a measure relevant to a positive trial, supplementing statistical significance. The NNT requires dichotomous outcomes and is influenced by the baseline disease or symptom severity, the particular population, the type and intensity of the interventional, the duration of treatment, the time period to assessment of response, and the comparator response. Confidence intervals should always accompany NNT for the precision of its estimate. In this review, three meta-analyses are reviewed, which included the NNT in the analysis of response. [ABSTRACT FROM AUTHOR]

Despite total shoulder arthroplasty (TSA) and reverse TSA (rTSA) being fundamentally different procedures, and indicated in different pathologies (rTSA for rotator cuff deficiency [RCD] and proximal humeral fractures [PHFx] and anatomic TSA [aTSA] for glenohumeral osteoarthritis [GHOA]), they have the same Current Procedural Terminology (CPT) code (23472). This paper's aim is to investigate differences in operative time and work-related value units (wRVUs) per hour among these pathologies, and ultimately determine if there is a need to assign separate CPTs for aTSA and rTSA. A retrospective cohort of data from the American College of Surgeons–National Surgical Quality Improvement Program was collected, all patients who underwent aTSA or rTSA (CPT: 23472) between the years of 2006 and 2019 for diagnoses of GHOA, RCD, and PHFx were included. Data collected included patient age, body mass index, operative time, and wRVUs per hour. Compared to GHOA (reference group), the average operative time for the RCD cohort was 12.242 minutes shorter (P <.001), while the wRVUs were higher by 1.627 (P <.001). The average operative time for rTSAs in the PHFx cohort were 17.615 minutes longer (P <.001), while the wRVUs were lower by 2.205 (P <.001). The average operative time for rTSAs for both RCDs and PHFx were longer than that for aTSAs for GHOA. Additionally, wRVUs were lower for rTSAs for RCD and PHFx compared to aTSAs for GHOA. This elucidates inconsistency in reimbursement structure for the procedures, which should be revisited. [ABSTRACT FROM AUTHOR]

Healthcare practitioners will encounter children who use orthoses to improve or maintain body structures and functions, activities and participation. Orthotic interventions involve complex science and the benefits need to outweigh the burden. Interdisciplinary collaborative family centred goal setting, from birth to adulthood is essential. An understanding of why and when orthoses are helpful allows a deeper discussion with families and can improve adherence. This article presents a systematic 'Inside-Out Approach' incorporating the International Classification of Functioning, Disability and Health and the International Organization for Standardization objectives for orthotic interventions. Pictorial and Table Tools identify potential goals for bones and joints, muscles, motor control of standing and walking, activities and participation, and prevention of pain which is an indicator of quality of life. Achieving short and long term goals requires early intervention. The design, alignments and dosage, the duration and frequency the child needs to wear the orthosis, required to achieve goals will be determined by an understanding of natural history and prognosis, the agreed goals and the child's schedule of activities. A Dosage Tool is presented. Recent improved understanding of the contribution of the footwear, individualized and optimized joint and segment alignments and segment proportion is discussed. [ABSTRACT FROM AUTHOR]

• Pulmonary exacerbations are less frequent in the era of highly effective CFTR modulator therapy but remain clinically impactful. • For individuals who experience an early symptomatic and spirometric response to intravenous antibiotics, 10 days is not inferior to 14 days of treatment. • Evidence does not support the routine use of systemic corticosteroids as an adjunctive treatment strategy to improve pulmonary exacerbation outcomes. • Ongoing clinical trials are evaluating more tailored and rational approaches to the use of oral and intravenous antibiotics. Pulmonary exacerbations in people with cystic fibrosis are associated with significant morbidity and reduced quality of life. Pulmonary exacerbation treatment guidelines, published by an expert panel assembled by the Cystic Fibrosis Foundation nearly 15 years ago, were primarily consensus-based as there were several gaps in the evidence base. In particular, limited evidence existed regarding optimal pulmonary exacerbation treatment strategies, including duration of antibiotic therapy, treatment location, antibiotic selection, and the role of systemic corticosteroids. Over the last decade, results from observational studies and large multi-center randomized controlled trials have begun to answer important questions related to pulmonary exacerbation treatment. This review focuses on the diagnosis, etiology, and changing epidemiology of pulmonary exacerbations, and also summarizes the most recent and up-to-date studies describing pulmonary exacerbation treatment. Finally, this review provides consideration for future pulmonary exacerbation research priorities, particularly in the current highly effective modulator therapy era. [ABSTRACT FROM AUTHOR]

What is the effect of a 4-week regimen of Mulligan manual therapy (MMT) plus exercise compared with exercise alone for managing cervicogenic headache? Is MMT plus exercise more effective than sham MMT plus exercise? Are any benefits maintained at 26 weeks of follow-up? A three-armed, parallel-group, randomised clinical trial with concealed allocation, blinded assessment of some outcomes and intention-to-treat analysis. Ninety-nine people with cervicogenic headache as per International Classification of Headache Disorders (ICHD-3). Participants were randomly allocated to 4 weeks of: MMT with exercise, sham MMT with exercise or exercise alone. The primary outcome was headache frequency. Secondary outcomes were headache intensity, headache duration, medication intake, headache-related disability, upper cervical rotation range of motion, pressure pain thresholds and patient satisfaction. Outcome measures were collected at baseline and at 4, 13 and 26 weeks. MMT plus exercise reduced headache frequency more than exercise alone immediately after the intervention (MD between groups in change from baseline: 2 days/month, 95% CI 2 to 3) and this effect was still evident at 26 weeks (MD 4 days, 95% CI 3 to 4). There were also benefits across all time points in several secondary outcomes: headache intensity, headache duration, headache-related disability, upper cervical rotation and patient satisfaction. Pressure pain thresholds showed benefits at all time points at the zygapophyseal joint and suboccipital areas but not at the upper trapezius. The outcomes in the sham MMT with exercise group were very similar to those of the exercise alone group. In people with cervicogenic headache, adding MMT to exercise improved: headache frequency, intensity and duration; headache-related disability; upper cervical rotation; and patient satisfaction. These benefits were not due to placebo effects. CTRI/2019/06/019506. [ABSTRACT FROM AUTHOR]

This systematic review provides an update on outcomes for patients with spinal muscular atrophy (SMA) type 1 to 4 treated with approved therapeutics, including the most recent, risdiplam, for an observation period of up to 48 months. A systematic literature search was conducted in July 2023 in four databases. Selected publications were assessed for internal validity and risk of bias by two authors and relevant data were extracted into standardised tables. Results were summarised narratively as substantial heterogeneity of studies prevents meaningful quantitative analysis. Twenty observational studies and one RCT were included in the analysis, fifteen studies on nusinersen, one on onasemnogene abeparvovec and two on risdiplam. Evidence supports the effectiveness of the therapies in motor function improvement for up to 48 months of follow-up in the SMA types specified in their respective indications. Better results were observed with earlier treatment initiation and higher baseline function. Whilst motor improvement was consistently observed, regardless of SMA type or treatment used, we noted no significant improvements in respiratory and nutritional outcomes. Quality of life endpoints were rarely investigated. Adverse events were common but seldom classified as treatment–related except for post–lumbar puncture syndrome, which was frequently reported across nusinersen studies. The treatment of SMA with the new therapies changes the disease phenotype with changes in motor function far exceeding any improvement in respiratory and nutritional function. Questions persist on long-term efficacy, potential regressions, impact on quality of life and social functioning, therapy duration, and discontinuation indicators. • SMA patients treated with novel therapies show improved motor skills but no change in respiratory and nutritional outcomes. • Early treatment initiation and/or high baseline function results in better outcomes, highlighting screening importance. • Influence of SMN2 copies remains inconclusive. • Questions remain on permanence of improvements, quality-of-life and changing medical needs of the changed disease phenotypes. [ABSTRACT FROM AUTHOR]

• Adherence to Ketogenic Diet Therapies (KDT) is challenging for subjects. • The measurement of adherence lacks standardization, despite being essential. • The average adherence rates across age groups range from 63.9 to 71.5%. • Adherence is higher in short-therm KDT treatment. Treatment adherence, defined as the degree to which the patient actively follows the plan of care, is very difficult for subjects undergoing ketogenic dietary therapies (KDTs). This is a relevant issue because adherence to dietary therapies is considered 1 of the primary determinants of the treatment's success. This paper aimed to review the literature evidence about KDT adherence according to age and diagnosis of patients. Performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method, this systematic review included clinical trials and observational studies. The risk of bias was assessed by the RoB 2.0 Cochrane tool and the quality of evidence according to the Mixed Methods Appraisal Tool system. Twenty-two articles were included, with more than half (n = 12) having average quality (2–3 stars). The studies' heterogeneity in measuring adherence and diagnosis made it difficult to compare results. Mean adherence rates were 71.5%, 66%, and 63.9% for children, adolescents, and adults, respectively. Adherence and compliance rates varied according to the follow-up period (79.7%, 66.7%, and 37.7% at 6, 24, and 36 months, respectively). The most frequent reasons for low adherence were linked to inefficacy in seizure control, adverse effects, food refusal, difficulty in preparing KDT meals or diet restrictiveness, lack of motivation, poor parental compliance, or cost of the diet. To conclude, there is a lack of standardized tools to measure adherence. Several studies highlighted the families' challenges in adhering to KDTs. These factors should be considered when creating strategies and resources on family education. A systematic review of 22 articles on ketogenic diet therapy adherence showed high heterogeneity, challenging comparisons with other studies. Mean adherence rates were similar across age groups: 71.5% for children, 66% for adolescents, and 63.9% for adults. Adherence varied over time: 79.7%, 66.7%, and 37.7% at 6, 24, and 36 months, respectively. Adherence was influenced by inefficacy in seizure control, adverse effects, food refusal, meal preparation challenges, diet restrictions, lack of motivation, poor parental compliance, and cost of the diet. Abbreviations: KDT, ketogenic diet therapies; mo, months. [Display omitted] [ABSTRACT FROM AUTHOR]

Since 2013, Flanders has introduced a screening programme for colorectal cancer for all citizens aged between 50 and 74 years. The objective of this study was to assess the cost-utility of an expansion of the colorectal cancer screening policy in Flanders (Belgium) and to place these findings in the international context. Cost-utility analysis using high-detail data about screening participation, screening results, and epidemiological data, a Markov cohort model has been constructed to study long-term costs and effects. A cost-utility analysis was performed as a three-way comparison between current, expanded (from age 45 years), and no screening scenarios, from a societal and healthcare perspective. Robustness was assessed by both one-way and probabilistic sensitivity analyses. Analyses show that both current and expanded screening result in quality-adjusted life years (QALY) gains and are mostly cost-saving. Overall, 97.5% of Incremental Cost-Effectiveness Ratios (ICERs) remained well below € 2000 per QALY for all comparisons. Parameters related to the colonoscopy that follows a positive test result such as compliance and cost are especially impactful on the cost-effectiveness. Screening participation and screening costs have remained comparatively stable, making colorectal cancer screening a cost-effective (dominant) policy. Expanding the screen age to 45 years is also cost-effective (dominant) compared with current screening, albeit with a slimmer margin. [ABSTRACT FROM AUTHOR]

Interstitial high-dose-rate brachytherapy (HDR-BT) is an effective therapy modality for patients with localized prostate carcinoma. The objectives of the study were to optimise the therapy regime variables using two models: response surface methodology (RSM) and artificial neural network (ANN). Thirty-one studies with 5651 patients were included (2078 patients presented as low-risk, 3077 patients with intermediate-risk, and 496 patients with high-risk). A comparison of these therapy schedules was carried out using an effective biologically effective dose (BED ef) that was calculated assuming the number of treatment days and dose (D) per day. The modelling and optimization of therapy parameters (BED ef and risk level) in order to obtain the maximum biochemical free survival (BFS) were carried out by the RSM and ANN models. An optimal treatment schedule (BFS = 97%) for patients presented with low-risk biochemical recurrence would be D = 26 Gy applied in one application, 2 fractions at least 6 h apart, within an overall treatment time of 1 day (BED ef = 251 Gy) by the RSM and ANN model. For patients presented with intermediate- or high-risk an optimal treatment regime (BFS = 94% and 90%, respectively) would be D = 38 Gy applied in one application, 4 fractions at least 6 h apart, with an overall treatment time of 2 days (BED ef = 279 Gy) by the RSM and ANN models. The RSM and ANN models determine almost the same optimal values for the set of predicted therapy parameters that make a feasible selection of an optimal treatment regime. • HDR-BT is an effective therapy modality for patients with localised prostate carcinoma. • Optimisation of HDR-BT regime variables was carried out by the RSM and ANN models. • The RSM and ANN models determined almost the same optimal values. [ABSTRACT FROM AUTHOR]

The Scottish Medical Consortium recently approved first-line pembrolizumab monotherapy or in combination with chemotherapy for head and neck squamous cell carcinoma in the palliative setting, contrasting with the decision made by the National Institute for Health and Care Excellence, who approved monotherapy alone in England and Wales. The aim of this study was to provide real-world performance data for first-line pembrolizumab-containing treatments for head and neck squamous cell carcinoma in the palliative setting in Scotland. We analysed the electronic records of patients who started pembrolizumab-containing treatment between 1 March 2020 and 30 September 2021. Outcomes included overall survival, progression-free survival (PFS), the duration of response and the disease control rate. Data were compared with the KEYNOTE-048 study and clinical factors were evaluated for association with survival. Our cohort included 91 patients (median follow-up 10.8 months). Patient characteristics were similar to those in the KEYNOTE-048 study, although our cohort had a higher proportion of patients with newly diagnosed, non-metastatic disease. For patients receiving monotherapy (n = 76), 12- and 24-month overall survival were 45% and 27%, respectively. For patients receiving pembrolizumab–chemotherapy (n = 15), 12-month overall survival was 60% (24-month overall survival had not yet been reached). Experiencing one or more immune-related adverse event (irAE; versus no irAEs), of any grade, was associated with favourable overall survival and PFS for patients receiving monotherapy in both univariable Log-rank analysis (median overall survival 17.4 months versus 8.6 months, respectively, P = 0.0033; median PFS 10.9 months versus 3.0 months, respectively, P < 0.0001) and multivariable analysis (Cox proportional hazards regression: overall survival hazard ratio 0.31, P = 0.0009; PFS hazard ratio 0.17, P < 0.0001). Our real-world data support the KEYNOTE-048 study findings and the value of combination treatment options. Additionally, our data show that irAEs of any grade, as reported in routine clinical records, are associated with better outcomes in this patient group, adding to the growing body of evidence showing that irAEs are generally a positive marker of programmed death-ligand 1 (PD-L1) inhibitor response. • Pembrolizumab efficacy and toxicity were similar between our real-world and KEYNOTE-048 data. • Locally advanced, treatment-naïve patients had comparable outcomes to other groups. • irAEs were associated with better outcomes when receiving pembrolizumab. [ABSTRACT FROM AUTHOR]

What is the effect of a protocol targeted at the various stages of labour – with a peanut ball, positioning and pelvic mobility – on the duration of labour, pain severity, fatigue, maternal outcomes, neonatal outcomes and satisfaction in parturients without analgesia? A randomised trial with concealed allocation, blinding of assessors and intention-to-treat analysis. One hundred women in active labour. The experimental group received the protocol targeted at the various stages of labour, with a peanut ball, positioning and pelvic mobility, whilst the control group received usual care. The primary outcomes were the duration of labour and pain severity. The secondary outcomes were maternal fatigue, mode of delivery, risk of perineal laceration, severity of perineal laceration, use of synthetic oxytocin, satisfaction with delivery, Apgar scores, admission of the neonate to an intensive care unit and resuscitation of the neonate in the delivery room. In the active phase of labour, the numerical rating scale and maternal perception of childbirth fatigue questionnaire were applied; they were taken again when the parturient had 8 to 10 cm of dilation. The numerical rating scale was also applied postpartum to evaluate satisfaction with childbirth. The use of the protocol with a peanut ball reduced the duration of active and expulsive phases and the total duration of labour, with mean differences of 82 minutes (95% CI 41 to 125), 8 minutes (95% CI 0 to 18) and 89 minutes (95% CI 45 to 132), respectively. Maternal satisfaction was better in the experimental group: mean between-group difference on the 10-point scale was 1.1 (95% CI 0.4 to 1.8). The effects on the other outcomes were either similar between groups or unclear. A protocol with a peanut ball, positioning and pelvic mobility reduced the duration of labour and improved maternal satisfaction with childbirth. RBR-74wcnjc. [ABSTRACT FROM AUTHOR]

To investigate whether two brands of intravenous immunoglobulin (IVIG) from the same manufacturer lead to varied effects when administered to patients with Kawasaki disease. (KD) Clinical characteristics, laboratory data, IVIG response, and coronary arteries change were analyzed between two groups. We included 158 KD cases. The mean age at KD diagnosis was 23 ± 1.39 (range, 2–95) months. In the first IVIG course, 18 (11.4 %) patients were unresponsive. TBSF (brand T) and Privigen (brand P) were administered to 94 and 64 patients, respectively. The brand P group had a significantly longer fever (P < 0.001) and hospitalization (P = 0.007) durations after the therapy and a higher number of IVIG unresponsiveness (P = 0.016) than the brand T group. In the multivariate logistic regression analysis, a high Formosa score (≥3, Odds ratio [OR], 4.939; 95 % confidence interval [CI], 1.199–20.337; P = 0.027), high levels of CRP (≥12 mg/L, OR: 4.257,95 % CI,1.265–14.322; P = 0.019), and treatment with brand P (OR, 3.621; 95 % CI, 1.029–12.677; P = 0.045) were independent risk factors for IVIG unresponsiveness. Compared with brand T, brand P prolonged the fever and hospitalization durations after IVIG treatment and increased the proportion of IVIG treatment unresponsiveness, but it did not infer the coronary arteries sequelae. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to evaluate the evidence for ultrahypofractionated pelvic nodal irradiation in patients with prostate cancer, with a focus on reported acute and late toxicities. A comprehensive search was conducted in 5 electronic databases (PubMed, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov) from inception until March 23, 2023. Eligible publications included patients with intermediate- and high-risk and node-positive prostate cancer who underwent elective or therapeutic ultrahypofractionated pelvic nodal irradiation. Primary outcomes included the presence of grade ≥2 rates of acute and late gastrointestinal and genitourinary toxicity based on the Common Terminology Criteria for Adverse Events or Radiation Therapy Oncology Group scales. Quality assessment was performed using National Institutes of Health tools for noncontrolled beforeand after (single arm) clinical trials, as well as single-arm observational studies. Because all outcomes were categorical variables, proportion was calculated to estimate the effect size and compare the outcomes after the intervention. We identified 16 publications that reported the use of ultrahypofractionated radiation therapy to treat the pelvis in prostate cancer. Seven publications met our criteria and were included in the meta-analysis, including 417 patients. The median total dose to the pelvic lymph nodes was 25 Gy (range, 25-28.5 Gy), with a median of 5 fractions. The prostate received a median dose of 40 Gy (range, 35-47.5 Gy). All studies used androgen deprivation therapy for a median duration of 18 months. The median follow-up period was 3 years (range, 0.5-5.6 years). The rates of acute grade ≥2 gastrointestinal and genitourinary toxicity were 8% (95% CI, 1%-15%) and 29% (95% CI, 18%-41%), respectively. For late grade ≥2 gastrointestinal and genitourinary toxicity, the rates were 13% (95% CI, 5%-21%) and 29% (95% CI, 17%-42%), respectively. Ultrahypofractionated pelvic nodal irradiation appears to be a safe approach in terms of acute and late genitourinary and gastrointestinal toxicity. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infections are common opportunistic infections in solid organ transplants (SOT) with increased health care resource USE and costs. Costs are further increased with ganciclovir-resistance (GR). This study aimed to evaluate the real-world impact of conversion to oral step-down therapy on duration of foscarnet and hospital length of stay (LOS) for treatment of GR-CMV infections in SOT. This study included adult recipients of kidney or lung transplants who received foscarnet for genotypically documented GR-CMV while admitted at the University of Wisconsin Hospital from October 1, 2015, to January 31, 2022. Patients in the oral step-down group were converted from standard of care (SOC; foscarnet) to maribavir or letermovir; patients in the historical control group were treated with SOC. Twenty-six patients met the inclusion criteria: 5 in the intervention group and 21 in the SOC group. The median viral load at foscarnet initiation was 11,435 IU/mL. Patients who received oral step-down conversion had shorter mean foscarnet duration than those who received SOC (7 ± 4 vs 37 ± 25 days, P =.017). Mean hospital LOS in the oral step-down group (16 ± 3 days) was shorter than the SOC group (33 ± 21 days; P <.001). In the SOC group, 9 patients lost their graft, and 9 patients died; 2 deaths were attributed to CMV. There were 2 deaths in the oral step-down group, neither of which was attributed to CMV. In this real-world case series of patients receiving treatment for GR-CMV infection, oral step-down conversion decreased foscarnet therapy duration and hospital LOS. Future studies are needed to evaluate better the effect of oral step-down in treating GR-CMV infection on treatment duration and cost-savings. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the impact of a nonopioid multimodal pain protocol on the amount of opioids prescribed, pain level, and complications in patients undergoing total shoulder arthroplasty (TSA) compared to a standard opioid regimen. We retrospectively reviewed 2 consecutive cohorts who underwent either primary anatomic or reverse TSA by a single surgeon. The opioid cohort included patients from 2016 to 2020 who received an intraoperative periarticular injection (Ropivacaine, Epinephrine, and Ketorolac cocktail) and were prescribed Oxycodone/Acetaminophen 5/325 mg on discharge. The nonopioid cohort included patients from 2020 to 2022, consisting of preoperative oral analgesics (Celecoxib, Pregabalin, and Tramadol); intraoperative intravenous Dexamethasone and Acetaminophen and periarticular injection; and postoperative oral Dexamethasone and oral analgesics (Pregabalin, Tizanidine, Magnesium, Ibuprofen, and Acetaminophen). The nonopioid cohort had the option to ask for an opioid prescription postoperatively if needed. Patient-reported outcomes collected included visual analog scale scores for pain and Patient-Reported Outcome Measurement Information System up to 1 year after surgery. Opioid consumption using Morphine Milligram Equivalents were compared up to 3 months postoperatively. There were 232 patients in the opioid and 112 in the nonopioid cohorts, respectively. The nonopioid protocol had lower mean visual analog scale scores at preoperative (6.4 vs. 7.4, P <.05), 10-day (3.5 vs. 4.2, P <.05), and 6-week postoperative time points (2.1 vs. 2.8, P <.05), but no differences between the groups were noted 3 months postoperatively. No differences in Patient-Reported Outcome Measurement Information System–upper extremity, pain interference, or depression were found preoperatively and up to 1 year after surgery. Opioid consumption was lower in the nonopioid cohort at all time periods (P <.01). Patients in the nonopioid cohort had significantly lower Morphine Milligram Equivalents at discharge, 10-day, 6-week, and 90-day time periods (P <.01) when compared to the opioid cohort. When analyzing risk factors for continued opioid prescriptions for the whole cohort, preoperative opioid use within 90 days before surgery (relative risk 4.69 [95% confidence interval 3.18-6.91; P <.01) and current tobacco use (relative risk 2.61 [95% confidence interval 1.50-4.54]; P =.01) were associated with continued refills >30 days. Complications in the perioperative period and 90-day hospital readmissions were not significantly different between the groups. A nonopioid postoperative regimen for patients undergoing TSA significantly reduces opioid prescriptions with similar patient-reported outcomes, subjective pain scores, and without increased complication rates compared to an opioid-only regimen. [ABSTRACT FROM AUTHOR]

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Custom-made transparent facial orthoses (TFOs) (face masks) are used to improve facial burn scars. We conducted a systematic literature review on TFO manufacture and use. Pubmed and Cochrane databases were searched without restrictions for relevant articles. TFO manufacture details and use according to international recommendations (20–32 mmHg pressure, TFO worn 20–23 h/day for ≥2 months) were extracted. Of 279 retrieved articles, 11 published over the last 41 years (four in the last 5 years) discussed TFO manufacture/use. There were five technical notes, five case reports, and a patient-cohort study (total patients in the studies=21). TFO-manufacture methods could be categorized as classical, digital, or mixed classical-digital. Relative clinical efficacies and cost advantages were unclear. The plastics used, harness materials, harness-point number, and silicone-interface use differed from study to study. Target pressure, actual pressure, expected daily wearing time, and treatment duration ranged widely and often did not meet current guidelines. Actual wearing time and treatment duration were never measured. Although TFOs play an important global role in burn care, there is a grave paucity of research. Further research is needed to promote the standardization of TFO-related practices and thereby improve the outcomes of facial-burn patients. • Transparent facial orthotic (TFO) pressure therapy aims to improve facial burn scars. • Our systematic review identified only 11 papers on TFO manufacture/use in 41 years. • TFO manufacture methods included classical and recent digital/mixed approaches. • TFO materials differed and actual pressure was rarely measured. • The evidence base for TFO manufacture/use is very weak. More studies are needed. [ABSTRACT FROM AUTHOR]

Children receiving cancer therapy have particular dietary needs. Most have issues with eating. The combination of extended duration of treatment, high frequency admissions and prolonged length of stay impacts more on this group of children than most others. With advancements in more effective diagnosis and tailored multimodal therapy more children than ever are being treated with increasingly intense therapeutic regimens. Hence, more children are also surviving new second and third line treatments for relapsed disease. This has increased the number of children with cancer who are susceptible to nutritional problems associated with their disease treatment and survivorship. It is important that health professionals are aware of predisposing factors which can lead to inadequate nutrition. Understanding can help alleviate them and prompt recognition and treatment can help prevent nutrition becoming a problem for these children. This article provides an overview of the particular problems faced by children with cancer obtaining adequate nutrition, nutritional risk factors and highlights why good nutrition status is essential for any child undergoing cancer therapy. The aims of nutritional therapy, a guide to nutritional assessment/interventions and long-term nutritional considerations are discussed. [ABSTRACT FROM AUTHOR]

Apremilast is approved for treatment of psoriasis and psoriatic arthritis (PsA). Real-world evidence on apremilast effectiveness in clinical practice is limited. Observational study enrolling adult patients, across 21 Spanish centres, who had initiated apremilast in the prior 6 (±1) months and were biologic naive. Data were collected at routine follow-up visits 6 and 12 months after apremilast initiation. Primary outcome was 6 and 12-month persistence to apremilast. Secondary outcomes included Disease Activity for PsA (DAPSA), joint erosions, enthesitis, dactylitis, and patient-reported quality of life (QoL, measured using the PsA impact of disease [PsAID] questionnaire). We included 59 patients. Most had oligoarticular PsA, moderate disease activity, and high comorbidity burden. Three-quarters were continuing apremilast at 6 months and two-thirds at 12 months; mean (SD) apremilast treatment duration was 9.43 (1.75) months. DAPSA scores showed improved disease activity: one-third of patients in remission or low activity at apremilast initiation versus 62% and 78% at 6 and 12 months, respectively. Eleven of 46 patients with radiographic assessments had joint erosions at apremilast initiation and none at month 12. Median (Q 1, Q 3) number of swollen joints was 4.0 (2.0, 6.0) at apremilast initiation versus 0.0 (0.0, 2.0) at 12 months. Incidence of dactylitis and enthesitis decreased between apremilast initiation (35.6% and 28.8%, respectively) and month 12 (11.6% and 2.4%, respectively). Over two-thirds of patients had a PSAID-9 score <4 (cut-off for patient-acceptable symptom state) at month 12. In Spanish clinical practice, two-thirds of PsA patients continued apremilast at 12 months, with clinical benefits at the joint level, no radiographic progression of erosions, and a positive impact on patient-reported QoL. Trial registration number Clinicaltrials.gov: NCT03828045. [ABSTRACT FROM AUTHOR]

To present the preliminary results on the clinical utilisation of an online daily adaptive magnetic resonance-guided radiation therapy (MRgRT) for various gynaecological cancers. Twelve patients treated between September 2018 and June 2022 were included. Six patients (50%) were treated with pelvic radiation therapy followed by MRgRT boost as brachytherapy boost was ineligible or unavailable, three patients (25%) were treated with pelvic MRgRT followed by high dose rate brachytherapy, two patients (16.7%) were treated with only MRgRT, one patient (8.3%) was treated with linear accelerator-based radiation therapy followed by MRgRT boost for bulky iliac lymph nodes. The median age was 56.5 years (range 31–86 years). Eight patients (66.7%) had a complete response, three patients (25%) had a partial response and one patient (8.3%) died due to acute renal failure. The mean follow-up time was 11.2 months (range 3.1–42.6 months). The estimated 1-year overall survival was 88.9%. The median treatment time was 47 days (range 10–87 days). During external beam radiation therapy, 10 (83.3%) patients had concomitant chemoradiotherapy. Pelvic external beam radiation therapy doses for all cohorts were 45–50.4 Gy with a fraction dose of 1.8 Gy. The median magnetic resonance-guided boost dose was 32 Gy (range 20–50 Gy) and fraction doses ranged between 4 and 10 Gy. Three patients were treated with intracavitary high dose rate brachytherapy (26–28 Gy in four to five fractions). None of the patients had grade >3 late genitourinary toxicities. MRgRT is reliable and clinically feasible for treating patients with gynaecological cancers alone or in combination with brachytherapy with an acceptable toxicity and outcome. MRgRT boost could be an option when brachytherapy is not available or ineligible. • MRgRT represents a new method for delivering radiotherapy for gynaecological cancers. • MRgRT is a markerless method providing online adaptive planning and real-time tracking. • MRgRT boost could be an option when brachytherapy is not available or is ineligible. [ABSTRACT FROM AUTHOR]

People with HIV (PHW) are at greater risk of depression than the general population. Insight into the time-to-treatment-response and predictors of response to psychotherapy may improve implementation in primary care. We assessed depression treatment response among 80 participants in a trial of cognitive-behavioral therapy for adherence and depression (CBT-AD) for PWH with MDD and suboptimal antiretroviral therapy (ART) adherence. Participants self-reported depressive symptoms (CES D) at each therapy session. Clinicians assessed participants' depression (HAM D), along with potential predictors of response, every four months for one year. Latent class analyses examined classes of responders for the active and the post-treatment phases. Regression analyses identified predictors of class membership for each phase. During the active treatment phase (CES D) we identified an early response (at session 2 and with continued trajectory of improvement) and a non-response group. There were also two classes during post-treatment (HAM-D): early responders (4-month) and late responders (12-month). Distress aversion was associated with lower likelihood of early response to CBT-AD (aOR = 0.74, 95%CI[0.56–0.90], p =.009), and social support was associated with increased likelihood of early response (aOR = 2.24, 95%CI[1.07–5.46], p =.045). Self-reported depression during the treatment phase may have resulted from social desirability bias. Most participants responded to CBT-AD early during treatment (89 %) and had sustained improvements in depression by 4 months (80 %). Distress aversion was a risk factor for late response, and social support was protective. Future research is needed to assess the optimal dose of CBT-AD in resource limited settings. • Cognitive Behavioural Therapy effectively treats depression and adherence in Persons with HIV. It therefore improves rates of viral suppression, more than treatment as usual. • Early self-reported improvements in depression most likely are the result of being in a trial. Improvement continued to occur throughout the acute treatment phase. • Clinician-rated depression over 4, 8 and 12 months also occurred, with steep improvement seen at 4 months. • Whether or not shorter durations of therapy, delivered by nurses, is effective remains to be explored. [ABSTRACT FROM AUTHOR]

To compare the efficacy of McLaughlin Bennett Trevisi (MBT) appliance and Clear Aligner Therapy (CAT) among nonextraction Class I crowding cases. The study sample (60 patients) was allotted into two equal groups (30 patients each) using block randomization wherein Group 1: treated with 0.018" MBT appliance and Group 2: treated with CAT for correction of malocclusion. At the end of treatment (T1), treatment duration, chairside time, laboratory time, number, and type of appointments were noted from treatment record cards. For comparing the acceptability among patients treated with both modalities at T1, the patients were interviewed regarding the comfort and ease of using an appliance with a questionnaire-based survey. The median number of nonscheduled/emergency and finishing stage appointments was significantly higher in Group 1 compared to Group 2 (P-value <0.001). The median duration of treatment at the scheduled, finishing, and overall appointments, was significantly higher in Group 1 compared to Group 2 (P-value <0.001). The median chairside time of all appointments was significantly higher in Group 1 compared to Group 2 (P-value <0.001). The experience with treatment and overall acceptability was significantly higher in Group 2 compared to Group 1 (P-value <0.001). However, mean laboratory time per aligner fabrication in Group 2 was 30.26 ± 3.45 min against no laboratory time consumed in Group 1. CAT significantly reduces treatment duration, chairside time, number of nonscheduled/emergency, and finishing stage appointments in nonextraction Class I crowding cases. Prospective studies with 3D aligner systems are recommended to add further evidence in this regard. CTRI/2018/04/013301. [ABSTRACT FROM AUTHOR]

The outcomes and management of bloodstream infection (BSI) in patients on temporary mechanical circulatory support (TMCS) awaiting heart transplant (HT) are poorly understood. We present outcomes of patients on TMCS with BSI (TMCS-I) relative to matched uninfected patients (TMCS-U) and discuss their management. Between January 1, 2013, and April 30, 2023, N = 136 patients were bridged to transplant with TMCS at Emory Transplant Center. Twenty-one (15.4%) patients were TMCS-I. Two (9.5%) had infective endocarditis. Median duration of antimicrobial treatment was 24 days (interquartile range 28.3). All TMCS-I were reactivated for transplant within 48 to 72 hours of negative blood cultures. None developed recurrent BSI. Post-transplant survival did not differ between TMCS-I and TMCS-U (p = 0.38). HT for TMCS-I may be safe as soon as blood cultures clear. Duration of antimicrobial therapy is individualized and depends on the organism, duration of bacteremia, presence of endocarditis, and timing of HT. Additional research is needed to determine optimal duration of treatment. [ABSTRACT FROM AUTHOR]

There is limited literature examining the effect of early electroconvulsive therapy(ECT) on the length of stay(LOS), especially for psychotic disorders. This study aimed to evaluate the association between early ECT and LOS in three main groups of patients with bipolar, depressive and primary psychotic disorders. A retrospective descriptive analysis of 464 patients who received inpatient ECT from May 2017 to March 2021 in a large tertiary psychiatric institution was conducted. Early ECT was defined as ECT done before the mean number of days from admission to initiation of ECT by diagnosis. The main outcome measure was LOS, which was examined by diagnosis between the early and late ECT groups, using a linear regression model with adjustment factors chosen based on univariate analysis. A strong, significant association was found between early ECT and a shorter LOS (β −28.3, 95 % CI −33.6 to −23.0, p < 0.001), even after accounting for adjustment factors. This association was consistent in all three diagnosis groups: bipolar disorders (β −14.5, 95 % CI −20.1 to −9.0, p < 0.001), major depressive disorder (β −18.2, 95 % CI −27.1 to −9.3, p < 0.001) and psychotic disorders (β −39.0, 95 % CI −46.8 to −31.2, p < 0.001). There was no significant difference in the 30-day readmission rates between the early and late ECT groups trans-diagnostically. Early ECT is strongly associated with a shorter LOS across a range of diagnostic indications including major depressive disorder, bipolar disorder and schizophrenia. ECT can be considered earlier in treatment-decision algorithms and may offer a reduction in LOS. [ABSTRACT FROM AUTHOR]

Based on multiple randomized-controlled clinical trials, shorter antibiotic courses are equally effective as traditional longer courses for many types of infections. However, longer courses are still being used widely in the clinical practice. To describe four components involved in the successful implementation of shorter antibiotic courses in our health care institutions, including an academic, public hospital and a community hospital staffed primarily by private practitioners. Clinical trials and peer-reviewed publications. We provide practical advice on how to support the change in clinical practice to shorten antibiotic duration. Specifically, we list the steps that we have successfully used to develop and implement an institutional practice change regarding the duration of antibiotic therapy: (a) establishing consensus documents outlining a data-driven expected practice for using antibiotics, (b) antibiotic stewardship programme support, (c) provider education, and (d) reinforcing behaviour through psychological and other tools. The implementation of these processes has successfully led to shorter antibiotic courses and decreased antibiotic use in our diverse practice settings. Intentional improvement in decreasing the duration of antibiotic therapy can be achieved by a specific antibiotic stewardship programme strategy and tactics. The implementation of shorter antibiotic courses has effects at individual and societal levels in an era of increasing antibacterial resistance and health care costs. [ABSTRACT FROM AUTHOR]

We investigated the impacts of the standard treatment durations of and adherence to standard anti-tuberculous therapy (ATT) on recurrence after the successful completion of tuberculosis (TB) treatment. We recruited patients with TB who had received treatment for six or nine months from the 2008–2017 databases of the Taiwanese National Health Insurance Research Database. Treatment duration and adherence to standard ATT were analyzed for their impacts on recurrence within two years. Complete adherence to standard ATT was defined as daily use of ethambutol, isoniazid, pyrazinamide, and rifampin for the first two months, and daily use of isoniazid and rifampin for the first six months. A total of 33,298 TB patients with new-onset TB were identified and classified into two groups by treatment duration: six months (n = 25,849, 77.63%) and nine months (n = 7449). Sex and age distributions varied between the groups. Treatment duration did not affect TB recurrence within two years (adjusted hazard ratio (AHR): 1.18, 95% confidence interval (C.I.) [0.96–1.44], p = 0.1156). Multivariable logistic regression showed that incomplete adherence to standard anti-tuberculous therapy (80–89% and 90–99% standard anti-TB therapy, AHR: 1.57, 95% C.I. [1.26–1.95], and 1.63, 95% C.I. [1.26–2.06], respectively, p < 0.0001) increased TB recurrence. In addition, male sex, older age, and comorbidity with diabetes mellitus or chronic obstructive pulmonary disease were independent risk factors for TB recurrence within two years. TB recurrence was 1.54% within two years under a DOT era. TB treatment durations of six or nine months did not affect TB recurrence within two years after completion of TB treatment, but incomplete adherence to standard anti-tuberculous therapy might increase the TB recurrence rate. [ABSTRACT FROM AUTHOR]

The timing of the switch from intravenous (i.v.) to oral antibiotic therapy for orthopaedic bone and joint infections (BJIs) is debated. In this narrative article, we discuss the evidence for and against an early switch in BJIs. We performed a PubMed and internet search investigating the association between the duration of i.v. treatment for BJI and remission of infection among adult orthopaedic patients. Among eight randomized controlled trials and multiple retrospective studies, we failed to find any minimal duration of postsurgical i.v. therapy associated with clinical outcomes. We did not find scientific data to support the prolonged use of i.v. therapy or to inform a minimal duration of i.v. therapy. Growing evidence supports the safety of an early switch to oral medications once the patient is clinically stable. After surgery for BJI, a switch to oral antibiotics within a few days is reasonable in most cases. We recommend making the decision on the time point based on clinical criteria and in an interdisciplinary team at the bedside. [ABSTRACT FROM AUTHOR]

Patients with acute pancreatitis (AP) are at increased risk of developing post pancreatitis diabetes mellitus (PPDM). The aim of this study was to explore the incidence, risk factors and sequelae of developing PPDM in a UK tertiary referral centre. A prospectively collected single centre database was analysed. Patients were grouped according to whether they had DM or not. Patients with DM were further sub-grouped into pre-existing DM or PPDM. Outcomes measured included incidence of PPDM, mortality, ITU admission, overall length of stay (LOS) and local pancreatitis specific complications. 401 patients with AP between 2018 and 2021 were identified. Sixty-four (16%) of patients had pre-existing DM. Thirty-eight patients (11%) developed PPDM [mild (n = 4, 8.2%), moderate (n = 19, 10.1%), severe (n = 15, 15.2%), p = 0.326]. 71% required insulin therapy for the duration of follow-up or until death. The development of PPDM was strongly associated with the presence (p < 0.001) and extent of necrosis (p < 0.0001). On multi-variate analysis, the development of PPDM was not an independent predictor for increased LOS, ITU admission or overall mortality. The incidence of PPDM was 11%. There was a strong correlation with extent of necrosis and the development of PPDM. PPDM did not adversely affect morbidity or mortality. [ABSTRACT FROM AUTHOR]

The number of sessions in an acute TMS course for major depressive disorder (MDD) is greater than in the earlier randomized controlled trials. To compare clinical outcomes in groups that received differing numbers of TMS sessions. From a registry sample (N = 13,732), data were extracted for 7215 patients treated for MDD with PHQ-9 assessments before and after their TMS course. Groups were defined by number of acute course treatment sessions: 1–19 (N = 658), 20–29 (N = 616), 30–35 (N = 1375), 36 (N = 3591), 37–41 (N = 626), or >41 (N = 349) and compared in clinical outcomes at endpoint and at fixed intervals (after 10, 20, 30, and 36 sessions). The impact of additional treatments beyond 36 sessions was also examined. Groups that received fewer than 30 sessions had inferior endpoint outcomes than all other groups. PHQ-9 symptom reduction was greatest in the group that ended treatment at 36 sessions. The extended treatment groups (>36 sessions) differed from all other groups by manifesting less antidepressant response early in the course and had a slower but steady rate of improvement over time. Extending treatment beyond 36 sessions was associated with further improvement without evidence of a plateau. In real-world practice, there are strong relations between the number of TMS sessions in a course and the magnitude of symptom reduction. Courses with less than 30 sessions are associated with diminished benefit. Patients with longer than standard courses typically show less initial improvement and a more gradual trajectory, but meaningful benefit accrues with treatment beyond 36 sessions. • In a study of 7215 MDD patients, there were powerful associations between number of TMS sessions and effectiveness. • The average trajectory was rapid improvement over the first 10 sessions then a markedly slower but steady rate. • Patients with long TMS courses had reduced benefit after 10 sessions but steady improvement thereafter. • There was no evidence in group data that the antidepressant effects of TMS plateau with additional treatment. • The additional treatments given to patients with long TMS courses were associated with substantial clinical improvement. [ABSTRACT FROM AUTHOR]

The aim is to evaluate the functions of the overjet in mediating, aggravating, and enabling the expression of jaw growth in growing patients with Class II division 1 and Class III malocclusions. Beside malocclusion severity and treatment timing, treatment duration warrants special consideration, contrasting shorter-term (2-3 years) and longer-term (5-7 years) responders to treatment, both encompassing the contribution of the adolescent growth spurt. Analysis of the genetic and environmental components affecting the development of malocclusion and growth modification indicates that varying critical periods of growth among the craniofacial components account for the variable individual responses to treatment. Clinical implications include keeping the overjet off the path of mandibular horizontal movement during orthopedic treatment, recognizing gender differences in the potential response to treatment, and assessing the value of longer treatment in slow responders. [ABSTRACT FROM AUTHOR]

The management of high-risk primary and locoregionally metastatic melanoma has changed in recent years with improvements in systemic therapy and evolving surgical recommendations. Data regarding the use of adjuvant radiotherapy (RT) in the contemporary era for patients at high risk of local recurrence is sparse. Herein we present a cohort of patients with cutaneous melanoma who received adjuvant primary site RT at a high-volume center in the immunotherapy era. 123 patients with melanoma who received adjuvant primary site RT between 12/1/2017 (FDA approval of adjuvant anti-PD–1 for Stage III melanoma) and 12/31/2021 were identified. All patients received 30 Gy in 5 fractions over 2–2.5 weeks. For electrons, the plan was normalized to a Dmax of 30 Gy. Correspondingly, photon plans were normalized such that the PTV V95% ≥ 27 Gy and D30 Gy < 1 cc. The median age at diagnosis was 67 (interquartile range [IQR]: 59–76). 46 patients (37%) had nodal disease (41 with sentinel lymph node biopsy positive [SLNB+] disease and 5 with clinically involved nodes [cN+]). 55 patients (45%) received adjuvant systemic therapy: 29 with SLNB+ (71%), 5 with cN+ (100%) and 21 with stage II disease (27%). Of these, most (93%) received single-agent anti-PD–1 therapy and the median duration of systemic therapy was 7.5 months (IQR: 3–11 months). At our institution, indications for adjuvant primary site RT included microsatellitosis (n=46, 37%), prior local recurrence (n=23, 19%), pure desmoplasia (n=5, 4%), and positive margins (n=5, 4%). Additional risk factors for local recurrence whose cumulative effect we used to gauge the appropriateness of adjuvant primary site RT included a primary site in the head and neck (n=72, 59%), perineural invasion (n=60, 49%) and Breslow thickness ≥ 4 mm (n=70, 57%). Radiotherapy techniques included electron RT (n=84, 68%), 3D photons (n=16, 13%) and IMRT/VMAT (n=23, 19%). With a median follow-up of 25 months, 2-year local recurrence-free survival was 92%. The crude in-field local recurrence rate was 8%. For lymph node negative patients, the 2-year progression-free survival and overall survival were 61% and 88%. Most RT-associated acute toxicities were grade 1–2; however, 14 patients (11%) had grade 3 radiation dermatitis. Late toxicities occurred in 7 patients (6%), of which a majority were grade 1 (n=2 fibrosis; n=1 lymphedema; n=1 dry eye). 3 patients had late surgical site complications (2 scalp graft failures of 31 total grafts radiated [6%] and 1 pretibial nonhealing wound). Five-fraction adjuvant primary site RT for melanoma is well tolerated with low rates of toxicity. Local control rates are favorable at > 90%, which is similar to historical rates with this regimen. Given the low risks and track-record of efficacy, our data suggests adjuvant primary site radiotherapy should continue to be considered for high-risk melanoma patients in the modern era. [ABSTRACT FROM AUTHOR]

Deep inspiration breath-hold (DIBH) can reduce heart dose in patients undergoing breast radiotherapy. Therefore, stable and relatively long times of breath-holding are necessary. This study is to assess the clinical benefits of regular breathing training for treatment requiring DIBH. Twenty-five patients with cancer of the left breast received regular breathing training and twenty-five controls did not. Data on breath-holding time, set-up time for radiotherapy in training group and treatment time of two groups, were collated. Breath-holding time data are presented as mean values. Treatment time and setup error were presented as median and percentile. Breath-holding stability and repeatability was analyzed by comparison of 6DoF real-time deltas (RTD) of a motion tracking system at the set-up, X-Ray Volume Imaging (XVI) and treatment stages. Differences in each direction were evaluated by nonparametric Wilcoxon rank test with a two-tailed p-value＜0.05 was considered statistically significant. A gradual increase in the duration of breath-holding was seen with regular training and set-up time decreased from > 5 minutes for the first time to about 3 minutes for the fifth time. The median (quartile) treatment duration of the trained group was 229 (196.5-260) seconds compared with 298 (249-363) seconds for controls (p ＜0.05). Median (maximum quartile) for 3DoF results of a motion tracking system and XVI were 0.02 (0.085)/0.02 (0.115) in the vertical (VRT), 0.04 (0.13)/0 (0.1) in the longitudinal (LNG) and 0.04 (0.04)/0.04 (0.15) in the latitudinal (LAT) directions with no significant differences found. Median (maximum quartile) values for setup, XVI and treatment were 0.02 (0.085)/0.04 (0.15)/0.01 (0.1) in the VRT, 0.04 (0.13)/0.02 (0.11)/0.01 (0.14) in the LNG, 0.04 (0.15)/0.03 (0.12)/0.05 (0.14) in the LAT, 0.3 (1)/0.06 (0.85)/0.1 (1.3) in the Yaw, 0.3 (1)/0.1 (0.58)/0.3 (1) in the Roll and 0.05 (1)/0.3 (0.98)/0.2 (0.9) in the Pitch directions with no significant differences. Motion tracking system and XVI give similar results in response to setup errors which may inform clinical use of XVI. Regular training improves patients' breath-holding stability and repeatability, increases cooperation, enhances doctor-patient relationships and reduces treatment time. The performance of 3 breath-holds to ensure breath-holding stability during setup is recommended for fine-tuning and verification. [ABSTRACT FROM AUTHOR]

The dose to healthy tissue surrounding the tumor in diffusing alpha-emitters radiation therapy (DaRT) was shown in previous works to amount to negligible levels (< 3 Gy) already at a distance of ~4 mm from the outermost sources, where it is dominated by beta and gamma contributions. The aim of this work was to confirm these predictions using thermoluminescent dosimetry (TLD) detectors in the tumor margins. Twelve subjects from an ongoing clinical trial had a TLD taped to a position approximately 5 mm from a DaRT source following implantation. The TLD was made from crystalline LiF: Mg, Ti, with a 10 uGy detection threshold and a linear dose response to 5 Gy. Following the 15–21-day duration of DaRT treatment, the TLD was removed and sent for dosimetric evaluation. In addition, subjects had a CT performed immediately following the DaRT source implantation, with the location of the TLD indicated with a radiopaque marker. The beta and gamma dose at the marker position was calculated as a superposition of contributions from all sources, based on their coordinates as inferred from the CT. The actual distance of TLD from the nearest DaRT source varied between 3.5 to 8.75 mm. In all cases where the TLD was placed greater than 5.5 mm from the nearest source (10 of 12 subjects), the measured dose was less than 0.18 Gy. TLDs placed 5.5 mm and 3.5 mm from the nearest source measured a dose of 0.5 Gy and 2.3 Gy, respectively. In all cases the measurement and calculation were within error (with the measurement smaller than the calculation in 10 of 12 cases), assuming a relative placement error of <1.8 mm. In 10 of 12 cases the measurement and calculation were within error assuming a relative placement error of <1.3 mm. Given the magnitude of the measured dose at 5 mm distance from the outermost source, there appears to be no safety concern for use of DaRT even in the rare cases where higher doses than predicted are delivered as all measurements are very low and have no clinical significance. [ABSTRACT FROM AUTHOR]

We previously reported an association between PBT and fewer unplanned hospitalizations, lower effective dose to immune circulating cells (EDIC) and less G3+ lymphopenia compared to IMRT among pts with LA-NSCLC treated with concurrent chemoradiation (cCRT) in the era of ICI consolidation. We seek to corroborate these results in a larger cohort. This single-institution, multi-site retrospective study evaluated consecutive pts with unresectable LA-NSCLC treated with cCRT using IMRT or PBT from 01/2011 to 12/2021. The primary endpoint was 90-day unplanned hospitalization from first RT fraction. Secondary endpoints included G3+ lymphopenia, G3+ pneumonitis, G3+ esophagitis, G3+ cardiac events, PFS and OS. Logistic regression was used to evaluate 90-day hospitalization and G3+ lymphopenia. Competing risk regression was used to evaluate G3+ pneumonitis, esophagitis and cardiac events. Kaplan-Meier analysis was used for PFS and OS. Inverse-probability treatment weighting (IPTW) was used to account for imbalances between treatment groups. Of 746 pts included, 295 (39.5%) were treated with PBT and 451 (60.5%) with IMRT. The PBT group was older (median 70.3 vs 65.6 yrs, p<0.0001), had a higher Charlson Comorbidity Index (CCI) (median 4 vs 3, p<0.0001) and received a slightly higher RT dose (median 6664 vs 6660 cGy, p = 0.04). There was no difference in the use of ICI post cCRT (26.8% vs 30.6%, p = 0.26) or duration of therapy (median 32 vs 38 weeks, p = 0.99). The PBT group received a lower mean heart dose (median 6.4 vs 12.4 Gy, p<0.0001), LAD V15Gy (median 0 vs 10.2%, p<0.0001), lung V20Gy (median 26.8 vs 28.5%, p = 0.04) and EDIC (median 4 vs 5.4, p<0.0001) but a higher esophagus V50Gy (median 23.8 vs 18.9%, p = 0.005). After IPTW-analysis adjusting for age, race, COPD, CCI, ECOG performance status, smoking pack years, histology, GTV, N stage, concurrent chemotherapy agent and ICI receipt, PBT was associated with fewer acute hospitalizations (aOR 0.64, 95% CI 0.51-0.80, p = 0.0001) and less G3+ lymphopenia (aOR 0.52, 95% CI 0.40-0.68, p<0.001) compared with IMRT. After IPTW-adjustment, PBT was associated with an improved OS compared to IMRT (median OS 31.2 vs 23.6 mo, p = 0.02) but no difference in PFS (median PFS 14.2 vs 11.5 mo, p = 0.23). Presence of an unplanned hospitalization (median OS 17.8 vs 33.5 mo, p<0.0001) or G3+ lymphopenia (median OS 28.0 vs 37.3 mo, p = 0.03) was associated with worse OS. There was no difference in incidence of G3+ pneumonitis, G3+ esophagitis or G3+ cardiac events. An acute, unplanned hospitalization or G3+ lymphopenia during or immediately after definitive treatment for LA-NSCLC is associated with worse OS. Our data suggests that PBT may be associated with fewer hospitalizations and improved patient outcomes due to lower RT dose to circulating lymphocytes, but prospective data are needed. [ABSTRACT FROM AUTHOR]

Radiotherapy for rectal cancer requires an 8-10mm margin around the clinical target volume (CTV) to account for variability in rectal and bladder filling, tumor regression. Online adaptive radiotherapy (oART), with daily re-planning, enables precise dose delivery and potential margin reduction. Although current oART strategies commonly employ CBCT or MRI guidance, the former may offer inferior image quality, whereas the latter can be time consuming. In contrast, CT-Linac-based oART, utilizing diagnostic-quality fan-beam CT (FBCT) guidance, strikes a balance between image quality and treatment efficiency. This study reports on the feasibility and toxicities of oART for rectal cancer with a CT-Linac and analyzes the optimal margins needed. A Phase 2 trial enrolled 13 patients with locally advanced rectal cancer. All patients received long-course neoadjuvant radiotherapy with a 45Gy/25 fractions dose to the CTV. To form the planning target volume (PTV), 5mm margins were added to the CTV. Daily oART was administered using a CT-Linac. Pre-treatment FBCT scans were conducted, and the CTV and OARs were automatically contoured, subject to physician review and confirmation. Treatment plans were then automatically generated. Post-treatment FBCT scans were also obtained. Acute toxicities were graded using CTCAE v5.0. To analyze the margins, CTV contours were drawn on both pre- and post-treatment FBCT. The study employed uniform expansions to PTVpre to estimate the minimum margin necessary to cover CTVpost. Relative distance (RD), target covering rate (TCR), and false coverage rate (FCR) for OARs were used to identify the optimal margin. RD quantifies the distance between PTVpre and CTVpost, where negative values denote overlap and positive values indicate insufficient coverage. TCR and FCR assess target coverage and avoidable OAR irradiation, respectively. All patients successfully completed radiotherapy with an average treatment duration of 18 minutes. The incidences of ≥Grade 2 acute gastrointestinal and genitourinary toxicities were 23.0% and 7.7%, respectively, with no ≥ Grade 3 acute toxicity. Mean RD, TCR and FCR values were shown in the Table. Statistical significance (p<0.01) was observed between all margin comparisons. Most RD values for 1mm and 2mm margins were positive, suggesting incomplete CTV coverage by the PTV. Conversely, results from 3mm to 5mm showed negative RD values, indicating that the majority of the CTV was adequately covered by the PTV. Thus, balancing target coverage and OAR protection, a 3mm margin was deemed sufficient for the CTV when applying daily oART. Daily online adaptive radiotherapy for rectal cancer using a CT-Linac is not only feasible but also associated with a low incidence of acute toxicities. With daily oART, the margin for CTV can be safely reduced to 3mm for rectal cancer. [ABSTRACT FROM AUTHOR]

Treatment of pediatric-onset multiple sclerosis (POMS) is challenging given the lack of safety and efficacy data in the pediatric population for many of the disease-modifying treatments (DMTs) approved for use in adults with MS. Our objective was to describe the demographic features and clinical and radiologic course of patients with POMS treated with the commonly used newer DMTs within the US Network of Pediatric MS Centers (NPMSC). This is an analysis of prospectively collected data from patients who initiated treatment before age 18 with the DMTs listed below at the 12 regional pediatric MS referral centers participating in the NPMSC. One hundred sixty-eight patients on dimethyl fumarate, 96 on fingolimod, 151 on natalizumab, 166 on rituximab, and 37 on ocrelizumab met criteria for analysis. Mean age at DMT initiation ranged from 15.2 to 16.5 years. Disease duration at the time of initiation of index DMT ranged from 1.1 to 1.6 years with treatment duration of 0.9-2.0 years. Mean annualized relapse rate (ARR) in the year prior to initiating index DMT ranged from 0.4 to 1.0. Mean ARR while on index DMT ranged from 0.05 to 0.20. New T2 and enhancing lesions occurred in 75%-88% and 55%-73% of the patients, respectively, during the year prior to initiating index DMT. After initiating index DMT, new T2 and enhancing lesions occurred in 0%-46% and 11%-34% patients, respectively. Rates of NEDA-2 (no evidence of disease activity) ranged from 76% to 91% at 6 months of treatment with index DMTs and 66% to 84% at 12 months of treatment with index DMTs. Though limited by relatively short treatment duration with the index DMTs, our data suggest clinical and MRI benefit, as well as high rates of NEDA-2, in a large number of POMS patients, which can be used to guide future studies in this population. [ABSTRACT FROM AUTHOR]

The optimal treatment following endocrine therapy (ET) plus a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) has not been established. We aimed to investigate treatment patterns and time to treatment failure (TTF) of subsequent therapy after palbociclib in a Japanese real-world setting. This retrospective observational study used de-identified data of patients with advanced breast cancer treated with palbociclib, using a nationwide claims database (April 2008 to June 2021). Measures included the type of subsequent therapies after palbociclib (endocrine-based therapy: ET alone, ET + CDK4/6i, and ET + mammalian target of rapamycin inhibitor [mTORi]; chemotherapy; chemotherapy + ET; and others) and their TTFs. The median TTF and 95% confidence interval (CI) were estimated using the Kaplan-Meier method. Of 1170 patients treated with palbociclib, 224 and 235 received subsequent therapies after first- and second-line palbociclib treatment, respectively. Among them, 60.7% and 52.8% were treated with endocrine-based therapies as first subsequent therapy, including ET + CDK4/6i (31.2% and 29.8%, respectively). The median TTF (95% CI) of ET alone, ET + CDK4/6i, and ET + mTORi as first subsequent therapy after first-line palbociclib were 4.4 (2.8–13.7), 10.9 (6.5–15.6), and 6.1 (5.1–7.2) months, respectively. No apparent relationship between the treatment duration of prior ET + palbociclib and subsequent abemaciclib was observed. This real-world study revealed that one-third of the patients received sequential CDK4/6i after ET + palbociclib, and treatment duration of ET + CDK4/6i following ET + palbociclib was the longest among the treatment options. Further data are awaited to determine whether ET + targeted therapy with CDK4/6i and mTORi provides acceptable treatment options following ET + palbociclib. • No optimal treatments after endocrine therapy (ET) + cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) has been established. • This study investigated treatment patterns and treatment duration after palbociclib in a Japanese real-world setting (n = 1170). • More than 60% were treated with endocrine-based therapies after palbociclib, and one-thirds continued ET + CDK4/6i. • ET + CDK4/6i provided the longest treatment duration among treatment options. • ET + targeted therapy may provide acceptable treatment options after palbociclib. [ABSTRACT FROM AUTHOR]

The main objective was to assess if foods fortified with phytosterols (PS), including plant sterols and plant stanols, reduce low-density lipoprotein cholesterol (LDL-C) concentrations. The secondary objective was to determine the impact of different factors related to PS administration. The search was carried out in MEDLINE, EMBASE, Web of Science, Scopus and The Cochrane Central Register of Controlled Trials (CENTRAL) databases up to March 2023. The meta-analysis was registered in the PROSPERO database (CRD42021236952). From a total of 223 studies, 125 were included. On average, PS lowered LDL-C 0.55 mmol/L [95% confidence interval (CI) = 10.82–12.67], and this decrease was significantly maintained for all analysed subgroups. A greater reduction in LDL-C levels was detected in relation to a higher daily PS dosage. The food format "Bread, biscuits, cereals", conditioned a lower decrease of 0.14 mmol/L (95%CI -8.71 to −2.16) in LDL-C levels, compared to the predominant food format group of "butter, margarine, spreads". No significant differences were detected with the other subgroups (treatment duration, intake pattern, number of daily intakes and concomitant statin treatment). The present meta-analysis supported that the use of PS-fortified foods had a beneficial effect on LDL-C lowering. In addition, it was observed that the factors that influence a decline LDL-C levels were PS dose as well as the food format in which they were consumed. • Use of PS-fortified foods had a beneficial effect on LDL-C reduction, about a 0.55 mmol/L. • The factors that influence LDL-C decreasing levels were the dose of PS and the food format in which they were consumed. [ABSTRACT FROM AUTHOR]