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Background : Despite the fact that thiocolchicoside has been widely used in the treatment of musculoskeletal pain, its efficacy has never been systematically evaluated. We carried out a systematic review and meta-analysis of randomized clinical trials (RCTs) to appraise the existing evidence on the efficacy of thiocolchicoside for musculoskeletal pain management. Methods : The literature search was performed on multiple databases, extracting reports of RCTs evaluating the efficacy of thiocolchicoside compared to placebo or no exposure. The reduction in pain intensity was evaluated through between-groups mean differences (MDs) in Visual Analogue Scale (VAS) scores after the intervention. The pooled effect estimates were compared to a minimally important difference (MID) of 1 point on a scale from 0 to 10. Results : We retrieved eight RCTs, including a total of 1397 patients. All the included studies were determined as being at high risk of bias. Seven trials evaluated patients with acute low back pain. After 2-3 days of treatment, the pooled MD in VAS score was -0.49 (95%CI = -0.90; -0.09) compared to controls. After 5-7 days of treatment, the summary MD was -0.82 (95%CI = -1.46; -0.18). Conclusions : Although thiocolchicoside was found to significantly reduce patient-reported low back pain, the clinical impact was very small, as the pooled effect estimates were below the MID, and the overall certainty of evidence was very low. In light of the safety concerns raised by the European Medicine Agency, an in-depth analysis on the risk-benefit balance of thiocolchicoside is required.

Background: An increasing number of individuals use online Artificial Intelligence (AI) - based chatbots to retrieve information on health-related topics. This study aims to evaluate the accuracy in answering vaccine-related answers of the currently most commonly used, advanced chatbots - ChatGPT-4.0 and Google Gemini Advanced., Methods: We compared the answers provided by the World Health Organization (WHO) to 38 open questions on vaccination myths and misconception, with the answers created by ChatGPT-4.0 and Gemini Advanced. Responses were considered as "appropriate", if the information provided was coherent and not in contrast to current WHO recommendations or to drug regulatory indications., Results and Conclusions: The rate of agreement between WHO answers and Chat-GPT-4.0 or Gemini Advanced was very high, as both provided 36 (94.7%) appropriate responses. The few discrepancies between WHO and AI-chatbots answers could not be considered "harmful", and both chatbots often invited the user to check reliable sources, such as CDC or the WHO websites, or to contact a local healthcare professional. In their current versions, both AI-chatbots may already be powerful instrument to support the traditional communication tools in primary prevention, with the potential to improve health literacy, medication adherence, and vaccine hesitancy and concerns. Given the rapid evolution of AI-based systems, further studies are strongly needed to monitor their accuracy and reliability over time.

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., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

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.

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.

The risk of SARS-CoV-2 reinfections changes as new variants emerge, but the follow-up time for most of the available evidence is shorter than two years. This study evaluated SARS-CoV-2 reinfection rates in the total population of an Italian province up to three years since the pandemic's start. This retrospective cohort study used official National Healthcare System data on SARS-CoV-2 testing and vaccinations, demographics, and hospitalizations in the Province of Pescara, Italy, from 2 March 2020 to 31 December 2022. A total of 6541 (5.4%) reinfections and 33 severe and 18 lethal COVID-19 cases were recorded among the 121,412 subjects who recovered from a primary infection. There were no severe events following reinfection in the young population, whereas 1.1% of reinfected elderly died. A significantly higher reinfection risk was observed among females; unvaccinated individuals; adults (30-59 y); and subjects with hypertension, COPD, and kidney disease. Up to three years after a primary SARS-CoV-2 infection, the majority of the population did not experience a reinfection. The risk of severe COVID-19 following a reinfection was very low for young and adult individuals but still high for the elderly. The subjects with hybrid immunity showed a lower reinfection risk than the unvaccinated.

In this cohort study, the general population of an Italian Province was followed for three years after the start of the pandemic, in order to identify the predictors of SARS-CoV-2 infection and severe or lethal COVID-19. All the National Healthcare System information on biographical records, vaccinations, SARS-CoV-2 swabs, COVID-19 cases, hospitalizations and co-pay exemptions were extracted from 25 February 2020 to 15 February 2023. Cox proportional hazard analysis was used to compute the relative hazards of infection and severe or lethal COVID-19, adjusting for age, gender, vaccine status, hypertension, diabetes, major cardiovascular diseases (CVD), chronic obstructive pulmonary disease (COPD), kidney disease or cancer. Among the 300,079 residents or domiciled citizens, 41.5% had ≥1 positive swabs during the follow-up (which lasted a mean of 932 days). A total of 3.67% of the infected individuals experienced severe COVID-19 ( n = 4574) and 1.76% died ( n = 2190). Females, the elderly and subjects with diabetes, CVD, COPD, kidney disease and cancer showed a significantly higher risk of SARS-CoV-2 infection. The likelihood of severe or lethal COVID-19 was >90% lower among the youngest, and all comorbidities were independently associated with a higher risk (ranging from +28% to +214%) of both outcomes. Two years after the start of the immunization campaign, the individuals who received ≥2 doses of COVID-19 vaccines still showed a significantly lower likelihood of severe or lethal disease, with the lowest risk observed among subjects who received at least one booster dose.

We carried out a cohort study on the overall population of the province of Pescara, Italy, to assess the real-world effectiveness of SARS-CoV-2 vaccination against infection, severe, or lethal COVID-19, two years after the start of the vaccination campaign. We included all the resident or domiciled subjects, and extracted the official demographic, vaccination, COVID-19, hospital and co-pay exemption datasets from 1 January 2021, up to 15 February 2023. Cox proportional hazards analyses were adjusted for gender, age, diabetes, hypertension, COPD, major cardio- and cerebrovascular events, cancer, and kidney diseases. Throughout the follow-up (466 days on average), 186,676 subjects received greater than or equal to three vaccine doses (of ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, NVX-CoV2373, or JNJ-78436735), 47,610 two doses, 11,452 one dose, and 44,989 none. Overall, 40.4% of subjects were infected with SARS-CoV-2. Of them, 2.74% had severe or lethal (1.30%) COVID-19. As compared to the unvaccinated, the individuals who received greater than or equal to one booster dose showed a ≥85% lower risk of severe or lethal COVID-19. A massive impact of vaccination was found among the elderly: 22.0% of the unvaccinated, infected individuals died, as opposed to less than 3% of those who received greater than or equal to three vaccine doses. No protection against infection was observed, although this finding was certainly influenced by the Italian restriction policies to control the pandemic. Importantly, during the Omicron predominance period, only the group who received at least a booster dose showed a reduced risk of COVID-19-related death.

Objective: This study aimed to investigate the potential role of aspirin in reducing the risk of preeclampsia and adverse maternal and perinatal outcomes in twin pregnancies., Data Sources: Medline, Embase, Google Scholar, Cochrane, and ClinicalTrial.gov databases were searched., Study Eligibility Criteria: The search and selection criteria were restricted to the English language., Methods: The primary outcome was the incidence of preeclampsia. The secondary outcomes included gestational hypertension; fetal growth restriction; preterm birth, either spontaneous or iatrogenic, before 34 weeks of gestation; gestational age at birth; neonatal birthweight; and adverse events secondary to the administration of aspirin, including antepartum and postpartum hemorrhage. In addition, subgroup analyses according to chorionicity (dichorionic vs monochorionic), aspirin dose, and gestational age at administration of aspirin (<16 vs ≥16 weeks of gestation) and considering only studies with a daily aspirin dose of ≥100 mg/d were performed. Head-to-head meta-analyses reporting results as summary odds ratios and mean differences were used to analyze categorical and continuous variables, respectively. Quality assessment for randomized controlled trials was independently performed by 2 researchers based on the risk of bias that was assessed using the revised Cochrane risk-of-bias tool for randomized trials. The conclusion of the meta-analysis on the primary outcome was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation., Results: Overall, 9 studies (2273 twin pregnancies) were included. When considering all studies, the risk of preeclampsia was lower in twin pregnancies treated with aspirin than in those not treated with aspirin (odds ratio, 0.64; 95% confidence interval, 0.48-0.85; P=.003), although there was no significant difference in the risk of gestational hypertension (P=.987), fetal growth restriction (P=.9), or adverse maternal and perinatal events (P=.9) in twin pregnancies treated with aspirin compared with those not treated with aspirin. There was no significant difference in the gestational age at birth (P=.2) and neonatal birthweight (P=.06) between women receiving aspirin and those not receiving aspirin. When considering only studies with an aspirin dose of >100 mg/d, the risk of preeclampsia (odds ratio, 0.45; 95% confidence interval, 0.23-0.86; P=.02) was significantly lower in pregnancies receiving aspirin than in those not receiving aspirin, Conversely, there was no significant difference in the risk of gestational hypertension (P=.20), fetal growth restriction (P=.1), gestational age at birth (P=.06), and neonatal weight (P=.05) between the 2 groups. Furthermore, there was no significant difference in the risk of preeclampsia when considering only studies with an aspirin dose of >80 mg/d (P=.611). The association between the administration of aspirin and preeclampsia persisted when considering an aspirin dose of >100 mg/day or when the medication was started before 16 weeks of gestation. The overall quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation assessment was low., Conclusion: The administration of aspirin in women with twin pregnancies reduced the risk of preeclampsia. The findings from this study highlighted the need for randomized controlled trials elucidating the actual role of aspirin in affecting maternal and perinatal outcomes in twin pregnancies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This cohort study on the entire population of an Italian Province assessed the incidence of potentially vaccine-related serious adverse events (PVR-SAEs) by COVID-19 vaccination status. From January 2021 to July 2022, we extracted all deaths and hospitalizations due to several cardiovascular diseases, pulmonary embolism, and deep vein thrombosis from National Healthcare System official data. During the follow-up, 5743 individuals died, and 2097 were hospitalized for PVR-SAEs. Vaccinated subjects (n = 259,821) did not show an increased risk of all-cause death, non-COVID death, or any PVR-SAEs, as compared to the unvaccinated (n = 56,494). These results were consistent across genders, age-classes, vaccine types, and SARS-CoV-2 infection status and did not vary in Cox models adjusting for age, gender, SARS-CoV-2 infection, and selected comorbidities. In the infected population, any dose of vaccine was associated with a lower likelihood of death and PVR-SAE. In the uninfected population, subjects who received one or two doses showed a significantly higher incidence of most outcomes, likely due to a large selection bias introduced by the Italian restriction policies targeting uninfected subjects who received less than three doses. In conclusion, COVID-19 vaccination was not associated with an increase of mortality or selected PVR-SAEs incidence. Further research is warranted to evaluate the long-term safety of COVID-19 vaccines.

Background: Current data suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections are rare, but no information are available on minors and after 12 months of follow-up., Methods: This retrospective cohort study included all the population of an Italian Province, diagnosed with a SARS-CoV-2 infection from March 2020 to May 2021. The primary outcome was the incidence of a reinfection, defined as a new positive polymerase chain reaction (PCR) test occurring ≥90 days after complete resolution of the first infection, and data were retrieved from the official datasets (coronavirus disease 2019 [COVID-19], demographic, hospital and co-pay exemption) of the Local Health Unit (LHU) of Pescara., Results: After an average of 201 days of follow-up (max. 414), we recorded 24 reinfections ≥90 days after the resolution of the first 7173 infections (0.33%). Four reinfections required hospitalization, one was lethal. Most of the reinfections (n = 13) occurred 6-9 months after the resolution of the first infection; no new infection was detected 12 or more months later and among the 832 minors., Conclusions: This study confirms previous findings on a low risk of SARS-CoV-2 reinfection. If confirmed, these findings suggest that more targeted restriction policies can be applied to the subjects that recovered after a first infection., (© The Author(s) 2021. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: A precise estimate of the frequency and severity of SARS-CoV-2 reinfections would be critical to optimize restriction and vaccination policies for the hundreds of millions previously infected subjects. We performed a meta-analysis to evaluate the risk of reinfection and COVID-19 following primary infection., Methods: We searched MedLine, Scopus and preprint repositories for cohort studies evaluating the onset of new infections among baseline SARS-CoV-2-positive subjects. Random-effect meta-analyses of proportions were stratified by gender, exposure risk, vaccination status, viral strain, time between episodes, and reinfection definition., Results: Ninety-one studies, enrolling 15,034,624 subjects, were included. Overall, 158,478 reinfections were recorded, corresponding to a pooled rate of 0.97% (95% CI: 0.71%-1.27%), with no substantial differences by definition criteria, exposure risk or gender. Reinfection rates were still 0.66% after ≥12 months from first infection, and the risk was substantially lower among vaccinated subjects (0.32% vs. 0.74% for unvaccinated individuals). During the first 3 months of Omicron wave, the reinfection rates reached 3.31%. Overall rates of severe/lethal COVID-19 were very low (2-7 per 10,000 subjects according to definition criteria) and were not affected by strain predominance., Conclusions: A strong natural immunity follows the primary infection and may last for more than one year, suggesting that the risk and health care needs of recovered subjects might be limited. Although the reinfection rates considerably increased during the Omicron wave, the risk of a secondary severe or lethal disease remained very low. The risk-benefit profile of multiple vaccine doses for this subset of population needs to be carefully evaluated., (© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This systematic review and meta-analysis aimed to provide a comprehensive estimate of HPV genotype prevalence for Japan., Methods: English and Japanese databases were searched to March 2021 for research reporting HPV genotypes in cytology and histology samples from Japanese women. Summary estimates were calculated by disease stage from cytology only assessment - Normal, ASCUS, LSIL, HSIL and from histological assessment - CIN1, CIN2, CIN3/AIS, ICC (ICC-SCC, and ICC-ADC), and other. A random-effects meta-analysis was used to calculate summary prevalence estimates of any-HPV, high-risk (HR) and low-risk (LR) vaccine types, and vaccine genotypes (bivalent, quadrivalent, or nonavalent). This study was registered with PROSPERO: CRD42018117596., Results: A total of 57759 women with normal cytology, 1766 ASCUS, 3764 LSIL, 2017 HSIL, 3130 CIN1, 1219 CIN2, 869 CIN3/AIS, and 4306 ICC (which included 1032 ICC-SCC, and 638 ICC-ADC) were tested for HPV. The summary estimate of any-HPV genotype in women with normal cytology was 15·6% (95% CI: 12·3-19·4) and in invasive cervical cancer (ICC) was 85·6% (80·7-89·8). The prevalence of HR-HPV was 86·0% (95% CI: 73·9-94·9) for cytological cases of HSIL, 76·9% (52·1-94·7) for histological cases of CIN3/AIS, and 75·7% (68·0-82·6) for ICC. In women with ICC, the summary prevalence of bivalent vaccine genotypes was 58·5% (95% CI: 52·1-64·9), for quadrivalent genotypes was 58·6% (52·2-64·9) and for nonavalent genotypes was 71·5% (64·9-77·6), and of ICC cases that were HPV positive over 90% of infections are nonavalent vaccine preventable. There was considerable heterogeneity in all HPV summary estimates and for ICC, this heterogeneity was not explained by variability in study design, sample type, HPV assay type, or HPV DNA detection method, although studies published in the 1990s had lower prevalence estimates of any-HPV and HR HPV genotypes., Interpretations: HPV prevalence is high among Japanese women. The nonavalent vaccine is likely to have the greatest impact on reducing cervical cancer incidence and mortality in Japan., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: [Kota Katanoda reports financial support and article publishing charges were provided by Grants–in–Aid for Scientific Research from Japan Society for the Promotion of Science (17H03589), and The Grant of the National Cancer Center, Japan (Gan Kenkyu Kaihatsuhi 31-A-20)]., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Face masks are recommended based on the assumption that they protect against SARS-CoV-2 transmission, however studies on their potential side effects are still lacking. We aimed to evaluate the inhaled air carbon dioxide (CO 2 ) concentration, when wearing masks., Methods: We measured end-tidal CO 2 using professional side-stream capnography, with water-removing tubing, (1) without masks, (2) wearing a surgical mask, and (3) wearing a FFP2 respirator (for 5 minutes each while seated after 10 minutes of rest), in 146 healthy volunteers aged 10 to 90 years, from the general population of Ferrara, Italy. The inhaled air CO 2 concentration was computed as: ([mask volume × end-tidal CO 2 ] + [tidal volume - mask volume] × ambient air CO 2 )/tidal volume., Results: With surgical masks, the mean CO 2 concentration was 7091 ± 2491 ppm in children, 4835 ± 869 in adults, and 4379 ± 978 in the elderly. With FFP2 respirators, this concentration was 13 665 ± 3655 in children, 8502 ± 1859 in adults, and 9027 ± 1882 in the elderly. The proportion showing a CO 2 concentration higher than the 5000 ppm (8-hour average) acceptable threshold for workers was 41.1% with surgical masks, and 99.3% with FFP2 respirators. Adjusting for age, gender, BMI, and smoking, the inhaled air CO 2 concentration significantly increased with increasing respiratory rate (mean 10 837 ±3712 ppm among participants ⩾18 breaths/minute, with FFP2 respirators), and among the minors., Conclusion: If these results are confirmed, the current guidelines on mask-wearing should be reevaluated., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Cocaine use disorder (CUD) is a chronic and relapsing brain disorder with no approved treatments. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in open label and single-blind studies, reducing cocaine craving and consumption. Although, large randomized, double-blind, controlled trials are still missing., Objective: This multi-center, randomized, double-blind, sham-controlled study was designed to evaluate the safety and efficacy of multiple sessions of active rTMS compared to sham stimulation in patients with CUD., Methods: rTMS (15 Hz, 2 daily sessions for 5 days/week,for a total of 20 stimulation sessions) was delivered over the left DLPFC for two weeks of continuous treatment followed by 12 weeks of maintenance (1 day/week, twice a day), in a double-blind, randomized sham-controlled design. Our primary outcomes included self-reported cue-induced craving and cocaine consumption, as measured by percentage of negative urine tests. Our secondary outcomes included: 1) changes in depressive symptoms; 2) changes in cocaine withdrawal symptoms; and 3) changes in self-reported days of cocaine use., Results: Forty-two outpatients with CUD were enrolled in the active rTMS group and 38 patients in the sham group. We observed a significant decrease in self-reported cue-induced cocaine craving and consumption in both the active rTMS and sham, whereas no main effect of treatment was found. However, the active rTMS group showed greater changes in depressive symptoms. The improvement on depressive symptomatology was particularly marked among patients receiving a total number of rTMS sessions greater than 40 and those reporting more severe depressive symptoms at baseline., Conclusions: A significant improvement of CUD symptoms during active rTMS treatment was observed. However, we did not observe significant differences in cocaine craving and consumption between treatment groups, highlighting the complexity of factors contributing to CUD maintenance. A significant improvement in depressive symptoms was observed in favour of the active group. Clinical trial registration details:clinicaltrials.govidentifierNCT03333460., (Copyright © 2022. Published by Elsevier Inc.)

Current data suggest that SARS-CoV-2 reinfections are rare. Uncertainties remain, however, on the duration of the natural immunity, its protection against Omicron variant, and on the impact of vaccination to reduce reinfection rates. In this retrospective cohort analysis of the entire population of an Italian region, we followed 1,293,941 subjects from the beginning of the pandemic to the current scenario of Omicron predominance (up to mid-February 2022). After an average of 277 days, we recorded 729 reinfections among 119,266 previously infected subjects (overall rate: 6.1‰), eight COVID-19-related hospitalizations (7/100,000), and two deaths. Importantly, the incidence of reinfection did not vary substantially over time: after 18-22 months from the primary infection, the reinfection rate was still 6.7‰, suggesting that protection conferred by natural immunity may last beyond 12 months. The risk of reinfection was significantly higher among females, unvaccinated subjects, and during the Omicron wave., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Flacco, Soldato, Acuti Martellucci, Di Martino, Carota, Caponetti and Manzoli.)

Purpose: To assess the blood flow and vascular visibility of irises in relation to pigmentation and pupil size, using an anterior segment optical coherence tomography angiography (OCTA)., Materials and Methods: This is a cross-sectional study. OCTA images were acquired in the nasal and temporal quadrants from a cohort of 30 healthy subjects in photopic (miosis) and scotopic (mydriasis) conditions. Patients were divided according to iris color (less pigmented: group L vs more pigmented: group D). Vascular parameters (vessel density (VD), vessel length density (VLD), fractal dimension (FD)) were applied and compared among groups L and D, location and different pupil status. A novel vascular index called Luminance Index (LI) was developed and applied in order to quantify vascular flow and evaluate its variation in photopic and scotopic conditions. Multivariable analyses were performed to evaluate possible predictors of VD and LI., Results: No differences were found for all vascular measurements (VD, VDL, FD, LI) between nasal and temporal quadrants. All vascular measurements were higher in group L than in group D ( p  < 0.05), except for LI and FD in photopic condition. In group L, all vascular parameters increased ( p  < 0.001) after dark adaptation. In group D, only LI increased after dark adaptation ( p  < 0.001). Pigmentation and iris thickness were significantly associated with VD in scotopic and photopic conditions, and with LI only in scotopic condition., Conclusions: Pigmentation still remains a major issue for vascular visibility. Quantitative and qualitative vascular changes follow pupil size variation. LI could be a new surrogate to quantify blood flow.

We performed a cohort analysis of the entire population of Abruzzo, Italy, to evaluate the real-world effectiveness of SARS-CoV-2 vaccines against infection, COVID-19 hospitalization or death, over time and during the Omicron wave. All resident or domiciled subjects were included, and official vaccination, COVID-19, demographic, hospital and co-pay exemption datasets were extracted up to 18 February 2022. Multivariable analyses were adjusted for age, gender, hypertension, diabetes, major cardio- and cerebrovascular events, COPD, kidney diseases, and cancer. During the follow-up (average 244 days), 252,365 subjects received three vaccine doses (of BNT162b2, ChAdOx1 nCoV-19, mRNA-1273 or JNJ-78436735), 684,860 two doses, 29,401 one dose, and 313,068 no dose. Overall, 13.4% of the individuals were infected with SARS-CoV-2 ( n = 170,761); 1.1% of them had severe COVID-19, and 0.6% died. Compared with the unvaccinated, those receiving two or three vaccine doses showed an 80% to 90% lower risk of COVID-19 hospitalization or death. Protection decreased during the Omicron wave and six months after the last dose, but it remained substantial. Lethal disease was uncommon during the Omicron wave and in the young population, even among the unvaccinated. Some of the current policies may need a re-evaluation in light of these findings. The results from the Omicron wave will inevitably require confirmation.

Competing Interests: Competing of interests: Akihiko Ozaki receives personal fees from MNES Inc., and Tetsuya Tanimoto receives personal fees from MNES Inc. and Bionics Co. Ltd, outside the submitted work. The authors completed the ICMJE Declaration of Interest Form (available upon request from the corresponding author), and declare no other competing interests.

Objectives: The present study aimed to investigate the potential delays in healthcare seeking and diagnosis of women with cervical cancer (CC) in Afghanistan. Methods: Clinical records of three hospitals in Kabul were searched for CC cases, and the women identified were interviewed by a trained physician using a semi-structured questionnaire. The main outcomes were the prevalence of potential delays over 90 days (1) from symptoms onset to healthcare seeking (patient delay), and (2) from first healthcare visit to CC diagnosis (healthcare delay). Information was also collected on: type and stage of CC, diagnostic test utilized, familiarity for CC, signs and symptoms, treatment type, and potential reasons for delaying healthcare seeking. Results: 31 women with CC were identified, however only 11 continued their treatment in the study hospitals or were reachable by telephone, and accepted the interview. The mean age was 51 ± 14 years, and only 18.2% had a previous history of seeking medical care. Patient delay was seen in 90.9% of the women (95% CI: 58.7-99.8), with a median of 304 ± 183 days. Instead, healthcare delay was found in 45.4% (95% CI: 16.7-76.6), with a median of 61 ± 152 days. The main reasons for patient delays were unawareness of the seriousness of the symptoms (70.0%) and unwillingness to consult a healthcare professional (30.0%). None of the women ever underwent cervical screening or heard of the HPV vaccination. Conclusions: Given the global effort to provide quality health care to all CC patients, Afghanistan needs interventions to reduce the delays in the diagnosis of this cancer, for instance by improving all women's awareness of gynecological signs and symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Acuti Martellucci, Delsoz, Qaderi, Madadi, Bhandari, Ozaki and Mousavi.)

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography., Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (

Purpose: To quantify the severity and location of corneal neovascularization (cNV) and its impact on the visual acuity and corneal sensitivity in a cohort of the patients referred to a specialist cornea clinic and also to describe the etiology of cNV in the cohort. Methods: We retrospectively evaluated the charts of 13,493 subjects referred to the San Raffaele Cornea Unit between January 2004 and December 2018 to search for cNV diagnosis. The corneal neovascularization severity was measured in the quadrants (range: 1-4) and location was defined as superficial, deep, or both. Best spectacle corrected visual acuity (BSCVA) was measured in logMar. We used the multiple regression analysis to identify the independent predictors of logMAR, after adjusting for age, gender, keratoconus, herpes keratitis, penetrating keratoplasty, trauma, and cataract surgery. Results: Corneal neovascularization was diagnosed in 10.4% of the patients analyzed. The most prevalent etiology of cNV in our population was non-infectious corneal dystrophies/degenerations followed by herpes simplex virus infection. cNV affected OD, OS, or both eyes in 35.6, 40.2, and 24.2 of cases, respectively. Mean BSCVA (SD) was 0.59 (0.76), 0.74 (0.94), and 1.24 (1.08) in cNV one, two, and three or four of the quadrant groups. Superficial, deep, or mixed cNV occurred in 1,029, 348, and 205 eyes. Severe cNV (three or four of the quadrants) was a significant predictor of low visual acuity ( p < 0.001) and reduced corneal sensitivity ( p < 0.05). cNV location and its severity were associated ( p < 0.05). In addition, corneal anesthesia was associated with lower BSCVA ( p < 0.001). Conclusion: Severe and deep cNV are associated with the reduced visual acuity and corneal sensitivity. Our data strongly support the relevance of appropriate follow-up as cNV is a major risk factor for graft rejection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lasagni Vitar, Triolo, Fonteyne, Acuti Martellucci, Manzoli, Rama and Ferrari.)

Competing Interests: Competing interests: None declared.

Objective:  To elucidate the role of Doppler ultrasound in predicting perinatal outcome in appropriate for gestational age (AGA) fetuses at term., Material and Methods:  Prospective study carried out in a dedicated research ultrasound clinic. The inclusion criterion was AGA fetuses, defined as those with an estimated fetal weight between the 10 th and 90 th percentile, at 36 + 0-37 + 6 weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome including either adverse intrapartum events or abnormal acid-base status at birth. Secondary outcomes were the individual components of the primary outcome. The Doppler parameters explored were umbilical artery (UA) PI, middle cerebral artery (MCA) PI, uterine arteries (UtA) PI and cerebroplacental ratio (CPR). Attending clinicians were blinded to Doppler findings. Logistic regression and ROC curve analyses were used to analyze the data., Results:  553 AGA fetuses were included. There was no difference in mean UA PI (p = 0.486), MCA PI (p = 0.621), CPR (p = 0.832) and UtA PI (p = 0.611) between pregnancies complicated by composite perinatal morbidity compared to those not complicated by composite perinatal morbidity. In pregnancies complicated by adverse intrapartum outcome, the mean MCA PI (1.47 ± 0.4 vs 1.61 ± 0.4, p = 0.0039) was lower compared to the control group, while there was no difference in UA PI (p = 0.758), CPR (p = 0.108), and UtA PI (p = 0.177). Finally, there was no difference in any of the Doppler parameters explored between AGA fetuses with abnormal acid-base status at birth compared to those without abnormal acid-base status at birth. In the logistic regression analysis, UA PI, MCA PI, CPR, UtA PI, EFW and AC percentiles were not independently associated with composite adverse outcome, adverse intrapartum outcome or abnormal acid-base status at birth in non-SGA fetuses. The diagnostic performance of all of these Doppler parameters for predicting composite adverse outcome, adverse intrapartum outcome and abnormal acid-base status was poor., Conclusion:  Cerebroplacental and maternal Doppler is not associated with or predictive of adverse pregnancy outcome in AGA fetuses close to term., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

This retrospective cohort study compared the rates of virologically-confirmed SARS-CoV-2 infections, symptomatic or lethal COVID-19 among the residents of the Italian province of Pescara who received one or two doses of COVID-19 vaccines, versus the unvaccinated. The official data of the National Health System were used, and a total of 69,539 vaccinated adults were compared with 175,687 unvaccinated. Among the subjects who received at least one vaccine dose, 85 infections (0.12%), 18 severe and 3 lethal COVID-19 cases were recorded after an average follow-up of 38 days. Among the unvaccinated, the numbers were 6948 (4.00%), 933 (0.53%) and 241 (0.14%), respectively. The serious adverse event reports-yet unconfirmed-were 24 out of 102,394 administered doses. In a Cox model, adjusting for age, gender, and selected comorbidities, the effectiveness of either BNT162b2, ChAdOx1 nCoV-19 or mRNA-1273 vaccines was higher than 95% in preventing infections (mostly due to B.1.1.7 variant), symptomatic or lethal COVID-19. No differences were observed across genders, and among the 691 subjects who received the second dose of vaccine later than the recommended date. Although preliminary, these findings support current immunization policies and may help reducing vaccine hesitancy.