How strong is the evidence supporting the WHO guidelines on physical activity, sedentary behaviour and sleep in early childhood?

BACKGROUND: The WHO issued recommendations about the ideal amount of physical activity, sedentary behaviour and sleep in infants, toddlers and preschool children. To facilitate their interpretation and translation into public health policies, we analysed the quantity and quality of the evidence that supported the development of each WHO recommendation. METHODS: All data for each exposure-outcome pair analysed in the studies informing WHO guidelines were extracted, and predefined criteria, based upon GRADE methodology, were used to classify each outcome and study result. RESULTS: Among the 237 studies that could be included, 37 were experimental and 200 were observational, yielding 920 analyses of exposure-outcome associations. Sixty-two analyses used a relevant outcome, with or without significant results. Five of the 10 WHO recommendations were based upon zero analyses with significant results on relevant health outcomes. The remaining recommendations were mostly based upon analyses evaluating obesity-related outcomes. Eight of the 10 GLs thresholds were not supported by any significant analysis on clinically relevant outcomes. CONCLUSION: While these findings should not be interpreted as an attempt to disprove the benefits of healthy lifestyle habits in early childhood, neither to minimize the work of the experts in this complex research field, very limited evidence currently supports the adoption of recommended thresholds as behavioural surveillance and public health interventions targets. Therefore, until further data are available, public health interventions should be developed balancing whether to focus on the achievement of specific targets that are still not supported by high-quality evidence or on the general promotion of healthy behaviours.

Searching for a "Window of Opportunity" in the Treatment of Vulvar Lichen Sclerosus: Evidence for Therapeutic Benefits of an Early Corticosteroid Treatment.

INTRODUCTION: Vulvar lichen sclerosus (VLS) is characterized by progressive anatomical changes which become increasingly severe and irreversible. The objective of this study was to investigate if a "window of opportunity" exists in VLS, i.e., to assess if an early treatment may prevent disease progression and facilitate clearance of symptoms and/or signs. METHODS: This retrospective, cohort study included VLS patients treated for the first time with a topical corticosteroid, namely with mometasone furoate 0.1% ointment, for 12 weeks (2016-2021). Scoring of subjective symptoms (global subjective score, GSS, and dyspareunia) and clinical features (global objective score [GOS] and sclerosis-scarring-atrophy) was performed at baseline (T0) and at the control visit (T1). We assessed if the achievement of clearance in GSS, GOS, sclerosis-scarring-atrophy, or dyspareunia depended on the time elapsed between VLS onset and treatment initiation. RESULTS: Among the 168 patients (59.2 ± 13.2 years) included, the median time between VLS onset and first treatment was 14.0 months. At T1, 48.8% of patients achieved clearance of GSS, 28% of GOS and 11.9% of both GSS and GOS, 57.9% of dyspareunia, and 19.2% of sclerosis-scarring-atrophy. The logistic regression model showed that each 10-month increase in treatment initiation adversely affected the clearance of GSS while starting treatment within 6 months of disease onset was significantly associated with clearance of GOS and sclerosis-scarring-atrophy. CONCLUSION: Early treatment is crucial in determining a complete healing of VLS-related symptoms and signs, especially of tissue sclerosis-scarring-atrophy, which appear poorly responsive, or even unresponsive, after the earliest stages of the disease. Thus our findings provide evidence for a "window of opportunity" in VLS treatment.

Ultrasound prediction of fetal macrosomia in pregnancies complicated by diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVES: To report the diagnostic accuracy of ultrasound in identifying fetuses with macrosomia in pregnancies complicated by gestational or pregestational diabetes. METHODS: Medline, Embase and Cochrane databases were searched. Inclusion criteria were singleton pregnancies complicated by diabetes undergoing third-trimester ultrasound evaluation. The index test was represented by ultrasound estimation of fetal macrosomia (estimated fetal weight EFW or abdominal circumference AC >90th or 95th percentile). Subgroup analyses were also performed. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were computed using the hierarchical summary receiver-operating characteristics model. RESULTS: Twenty studies were included in the systematic review including 8,530 pregnancies complicated by diabetes. Ultrasound showed an overall moderate accuracy in identifying fetuses with macrosomia with a sensitivity of 71.2 % (95 % CI 63.1-78.2), a specificity of 88.6 % (95 % CI 83.9-92.0). The interval between ultrasound and birth of two weeks showed the highest sensitivity and specificity (71.6 %, 95 % CI 47.9-87.3 and 91.7, 95 % CI 86.2-95.5). EFW sensitivity and specificity were 76.6 % (95 % CI 70.1-82.3) and 82.9 % (95 % CI 80.9-84.8), while AC 84.8 % (95 % CI 78.2-90.0) and 73.7 % (95 % CI 71.0-76.4). CONCLUSIONS: Ultrasound demonstrates an overall good diagnostic accuracy in detecting fetal macrosomia in pregnancies with diabetes.

Topical Corticosteroid Phobia Among Women Affected With Vulvar Lichen Sclerosus: Results From a Cross-sectional Survey.

OBJECTIVE: Topical corticosteroid (TC) phobia (TCP) is common in subjects affected with chronic inflammatory skin diseases who need prolonged corticosteroid treatments. The aim of this study was to assess TCP in women affected with vulvar lichen sclerosus (VLS). MATERIALS AND METHODS: This observational, cross-sectional study included adult patients with VLS who either started or were undergoing a TC treatment at our vulva unit between May 2022 and May 2023. All patients completed the self-administered TOPICOP questionnaire, which is validated for measuring concerns, worries, and beliefs about TC use. The scores obtained were analyzed in relation to demographic, history, and clinical data. RESULTS: The majority of the 165 (92.1%, 66.5 ± 11.9 years) included patients who had previously undergone TC treatments, mostly for VLS; 81.8% of them had received information about TCs, mainly from dermatologists (86.7%). The median global TOPICOP score was 16.7% (interquartile range. 8.3-30.6), corresponding to a raw median value of 6.0 (interquartile range, 3.0-11.0). The median subscores for the 2 TOPICOP domains, namely, mistaken beliefs and worries about TCs, were equal to each other. At multivariate analysis, none of the collected variables showed a significant association with the degree of TCP. CONCLUSIONS: In our VLS patients, TCP resulted rather low, probably because of the small skin area being treated and the high percentage of women who had already used TCs and who had received information about them from a dermatologist. This latter point suggests that adequate counseling could be a strong basis for greater awareness and serenity in the long-term use of TCs.

Effects of a sphenopalatine ganglion block on postcraniotomy pain management: a randomized, double-blind, clinical trial.

OBJECTIVE: Postcraniotomy pain (PCP) is a common finding after neurosurgical procedures, occurring in as many 87% of patients. The sphenopalatine ganglion (SPG) has a pivotal role in several headache syndromes, and its anesthetic block is currently used in different clinical conditions with benefit. The aim of this study was to evaluate the efficacy of an SPG block (SPGB) via a transnasal approach as adjunctive therapy in reducing pain scores during the postcraniotomy period. METHODS: In this single-center, double-blind, randomized controlled trial, patients undergoing elective surgery with a supratentorial craniotomy were randomly assigned to a scalp block, local anesthetic infiltration of the wound, and systemic analgesia during the first 48 postoperative hours (standard therapy), or to standard therapy as well as an SPGB (experimental therapy). According to the available evidence, assuming a 50% reduction in the incidence of the main outcome in patients with an SPGB (vs standard treatment), 82 patients were needed to achieve 80% statistical power in an intent-to-treat analysis. Pain intensity was recorded during the first 180 postoperative days at selective time points (5 times in the hospital, 3 times by telephone interview) with different pain rating systems (a visual analog scale [VAS], numeric rating scale [NRS], and pain assessment in advanced dementia [PAINAD] scale), together with demographic, clinical, and surgical variables and complications. Heart rate and blood pressure were recorded during surgery. Differences in all variables were evaluated using a paired t-test and confirmed through Wilcoxon matched-pairs signed-rank and Kruskal-Wallis tests. RESULTS: No complications occurred among the 83 patients enrolled. Statistically significant differences were found in the mean VAS score at postoperative days 0 (p = 0.05), 2 (p = 0.03), and 3 (p = 0.03). The PAINAD scale score showed significant differences between groups at postoperative days 1 (p = 0.006), 2 (p = 0.001), 3 (p = 0.03), and 4 (p = 0.05). The proportion of patients reporting a VAS score ≥ 3 in the first day after surgery was lower in the SPGB group than in the standard treatment group (71.9% vs 89.5%), although this difference did not reach statistical significance. At postoperative day 180, 5 patients (2 in the control group, 3 in the treatment group) had developed chronic PCP (NRS score ≥ 3). CONCLUSIONS: SPGB is a safe and effective procedure as an adjunctive treatment for PCP management in elective supratentorial craniotomy during the first 4 postoperative days compared with standard therapy. Further studies are needed to better define the clinical impact of SPGB use and its indications. Clinical trial registration no.: NCT05136625 (ClinicalTrials.gov).

Oral Budesonide and low serum albumin levels at surgery are associated with a higher risk of postoperative intra-abdominal septic complications after primary ileocaecal resection for Crohn's disease: A retrospective analysis of 853 consecutive patients.

BACKGROUND AND AIMS: The terminal ileum is the most frequent site of Crohn's Disease (CD) that necessitates surgery. Of the postoperative complications (POCs) associated with ileocaecal resection for CD, intra-abdominal septic complications (IASCs) include anastomotic leak, abscesses, and entero-cutaneous fistula. We aimed to identify predictors of IASCs and severe POCs (Clavien-Dindo ≥3) after primary ileocaecal resection for CD. METHODS: This is a retrospective single-centre cohort study including all consecutive primary ileocaecal resection for CD in a tertiary IBD centre between 2004 and 2021. RESULTS: A total of 853 patients underwent primary ileocaecal resection for CD. 307 (36.6 %) patients were receiving antibiotics, 253 (29.8 %), systemic steroids, and 178 (21.0 %) oral budesonide at surgery. At 90 days, 260 (30.8 %) patients developed POCs, 62 (7.3 %) severe POCs, and 56 (6.6 %) IASCs. At multivariate analysis, severe POCs were associated with lower preoperative albumin levels (OR1.58, 95 %CI 1.02-2.50, p = 0.040) and a history of cardiovascular diseases (OR2.36, 95 %CI 1.08-7.84, p = 0.030). IASCs were associated with lower preoperative albumin levels (OR1.81, 95 %CI 1.15-2.94, p = 0.011) and oral budesonide (OR2.07, 95 %CI 1.12-3.83, p = 0.021) with a dose-dependent effect. CONCLUSIONS: The independent association, dose-dependent effect, and biological plausibility of budesonide and IASCs suggest a robust causal effect. Oral budesonide should be carefully assessed before primary ileocaecal resection for CD.

Impact of the Italian Healthcare Outcomes Program (PNE) on the Care Quality of the Poorest Performing Hospitals.

One of the main aims of the Italian National Healthcare Outcomes Program (Programma Nazionale Esiti, PNE) is the identification of the hospitals with the lowest performance, leading them to improve their quality. In order to evaluate PNE impact for a subset of outcome indicators, we evaluated whether the performance of the hospitals with the lowest scores in 2016 had significantly improved after five years. The eight indicators measured the risk-adjusted likelihood of the death of each patient (adjusted relative risk-RR) 30 days after the admission for acute myocardial infarction, congestive heart failure, stroke, chronic obstructive pulmonary disease, chronic kidney disease, femur fracture or lung and colon cancer. In 2016, the PNE identified 288 hospitals with a very low performance in at least one of the selected indicators. Overall, 51.0% (n = 147) of these hospitals showed some degree of improvement in 2021, and 27.4% of them improved so much that the death risk of their patients fell below the national mean value. In 34.7% of the hospitals, however, the patients still carried a mean risk of death >30% higher than the average Italian patient with the same disease. Only 38.5% of the hospitals in Southern Italy improved the scores of the selected indicators, versus 68.0% in Northern and Central Italy. Multivariate analyses, adjusting for the baseline performance in 2016, confirmed univariate results and showed a significantly lower likelihood of improvement with increasing hospital volume. Despite the overall methodological validity of the PNE system, current Italian policies and actions aimed at translating hospital quality scores into effective organizational changes need to be reinforced with a special focus on larger southern regions.

Chronobiological Variation in Takotsubo Syndrome: an Updated Systematic Review and Meta-analysis.

Takotsubo syndrome (TTS) might exhibit particular chronobiological patterns in its onset, characterized by variations according to time of the day, day of the week, and month of the year. The aim of this study was to fully explore the temporal patterns (circadian, weekly and seasonal) in the onset of TTS. A systematic review and meta-analysis of literature were conducted for studies (2006-2024) reporting the temporal patterns (circadian, weekly and/or seasonal) in the onset of TTS. Among the 4257 studies retrieved, 20 (including 64,567 subjects) fulfilled all eligibility criteria. Data were aggregated used random effects model as pooled risk ratio and the attributable risk (AR). The proportion analysis (including 8 studies; n=853) showed a decreasing pattern of the pooled rates of TTS shifting from the morning to the night (pooled TTS rates: 34.0%; 32.1%; 21.7%; 12.7% in the morning, afternoon, evening and night, respectively). The same pattern was observed stratifying by type of preceding stressful factor or event, considering physical stressors (pooled rates in the morning and night: 37.6% and 9.8%, respectively), and also in case no event could be identified. The pooled rates of TTS onset peaked on Monday and Tuesday (17.3% and 18.4% respectively), then declined during the week, reaching the lowest rates on Friday and Saturday (10.6% and 10.8%, respectively), with no sex differences. TTS onset reached the highest values on summer, and the lowest in winter (27.9% versus 21.7% in summer and winter, respectively). The TTS morning peak based analyses (∼33% of all the registered events) account for a RR of 1.46 (95% CI: 1.38-1.54), the week-based for a RR of 1.26 (1.16-1.35), the season-based for a RR of 1.04 (1.04-1.05). TTS onset exhibits specific chronobiological patterns, characterized by a peak during the morning hours, and on Monday and Tuesday. Differing from other cardiovascular emergencies TTS was more frequent during summer. Further studies are needed to fully understand the underlying pathophysiological mechanisms in order to tailor relative management and preventive strategies.

Factors Influencing COVID-19 Vaccine Hesitancy in Pregnant and Breastfeeding/Puerperium Women: A Cross-Sectional Study.

Vaccination among pregnant and breastfeeding women is critical for protecting this vulnerable population and their children. COVID-19 vaccination is recommended both during pregnancy and breastfeeding; however, we still do not fully understand the determinants that influence hesitancy towards COVID-19 vaccination. This study aimed to identify the determinants of vaccine hesitancy in pregnant and breastfeeding, puerperium women. A multicenter, cross-sectional study, involving 435 pregnant and breastfeeding women, was conducted. Vaccination hesitancy was evaluated by administering the Vaccination Attitudes (VAX) Scale and the Zung Anxiety Self-Assessment Scale (SAS) was adopted to measure anxiety levels. Overall, 14% of the participants reported that they did not receive the COVID-19 vaccine, and 78.3% received their first dose during pregnancy or while breastfeeding. The descriptive statistics for the VAX scale showed a total mean score of 3.35 (±1.6), and 75% of participants reported an anxiety index equal to or lower than the threshold. Vaccine hesitancy increased as "adverse events after vaccination" increased (p < 0.01), while SAS levels positively correlated with the participants' mean age (p < 0.05). Investigating the factors influencing vaccine hesitancy enables the development of targeted health policies and SARS-CoV-2 vaccination programs.

Immunogenicity, Safety and Efficacy of the Dengue Vaccine TAK-003: A Meta-Analysis.

The TAK-003 dengue vaccine was licensed in Europe in December 2022, and the official recommendations from most EU countries are still under formulation. To support policymakers, we performed a meta-analysis to quantify TAK-003's immunogenicity, efficacy and safety among seronegative and seropositive populations after the administration of one or two vaccine doses. We included trials retrieved from MEDLINE, Scopus and ClinicalTrials.gov. The outcomes were the rates of seroconversion, virologically confirmed dengue fever and serious adverse events after each vaccine dose. Data were combined using random-effect proportion or head-to-head meta-analyses. We retrieved a total of 19 datasets, including >20,000 participants. TAK-003 showed an excellent safety profile, and the immunogenicity after two doses against the four DENV serotypes was ≥90% among both adults and children/adolescents who were either seronegative or seropositive at baseline. A single dose was able to elicit a high immunogenic response among adults (≥70%) and children/adolescents (≥90%). The primary two-dose immunization course halved the risk of all types of virologically confirmed dengue fever among seropositive children/adolescents, but seronegative minors were only protected against the diseases caused by DENV-1 and DENV-2. Overall, the results support the use of TAK-003 for the prevention of dengue fever in the pediatric population of endemic countries. Uncertainties remain on the use of a single vaccine dose in non-endemic countries.

Effectiveness of tailored talks between a cancer screening specialist and general practitioners to improve the uptake of colorectal cancer screening in Ancona (Italy) during the pandemic period.

BACKGROUND: Colorectal cancer (CRC) screening uptake in many countries has been low and further impacted by the COVID-19 pandemic. General Practitioners (GPs) are key facilitators, however research on their impact on organised CRC screening is still limited. OBJECTIVES: To evaluate the effectiveness of tailored talks with GPs to increase population uptake of the long-established CRC screening programme in Ancona province, Italy. METHODS: In this prospective cohort study, one-to-one tailored talks were organised in January 2020 between the GPs of one county of the province (with GPs from other counties as controls) and the screening programme physician-in-chief to discuss the deployment and effectiveness of organised screening. Data was extracted from the National Healthcare System datasets and linear regression was used to assess the potential predictors of CRC screening uptake. RESULTS: The mean CRC screening uptake remained stable from 39.9% in 2018-19 to 40.8% in 2020-21 in the 22 GPs of the intervention county, whereas it statistically significantly decreased from 38.7% to 34.7% in the 232 control GPs. In multivariate analyses, belonging to the intervention county was associated with an improved uptake compared to the control counties (+5.1%; 95% Confidence Intervals - CI: 2.0%; 8.1%). CONCLUSION: Persons cared for by GPs who received a tailored talk with a cancer screening specialist avoided a drop in CRC screening adherence, which characterised all other Italian screening programmes during the COVID-19 emergency. If future randomised trials confirm the impact of tailored talks, they may be incorporated into existing strategies to improve population CRC screening uptake.

Tailored talks on CRC screening were conducted between one cancer screening specialist and GPs.Even during the pandemic, CRC screening uptake was stable among persons cared for by GPs targeted by tailored talks.If confirmed by randomised trials, tailored talks may be employed to improve CRC screening uptake.

Panel stacking is a threat to consensus statement validity.

Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.