Real-world effectiveness of sodium-glucose cotransporter-2 inhibitors on the progression of chronic kidney disease in patients without diabetes, with and without albuminuria.

AIM: To examine the renal effects of sodium-glucose cotransporter-2 (SGLT2) inhibition among non-diabetic individuals with chronic kidney disease (CKD) in a real-world setting. METHODS: We collected de-identified data on adults without diabetes and with an estimated glomerular filtration rate (eGFR) of 25-60 mL/min/1.73 m2, who initiated the SGLT2 inhibitors dapagliflozin or empagliflozin between September 2020 and November 2022 at Maccabi Healthcare Services, an Israeli health maintenance organization. We assessed the effects of SGLT2 inhibitors on renal function (changes in eGFR slope/time). Index date was defined as the date of the first dispensing of SGLT2 inhibitors. Annual baseline slope was calculated using all eGFR measurements during the 2 years prior to index date (median = 7 measurements), while annual follow-up slope was calculated from all evaluations during 90-900 days post index date, along with baseline measurement at index date (median = 6 measurements). Paired t tests were used to compare differences between baseline and follow-up annual slopes. RESULTS: Of a total of 354 participants with CKD, without diabetes, who received SGLT2 inhibitors and were followed for a median of 527 days, the mean age was 72.8 ± 11.8 years, 26% were female, and 91% used renin-angiotensin system blockade. The mean eGFR was 45.4 ± 9.5 mL/min/1.73 m2. The mean body mass index was 29.1 ± 5.4 kg/m2. During the year before index date, 146 participants (41%) had a urinary albumin to creatinine ratio (UACR) <30 mg/g, 81 (23%) had a UACR of 30-300 mg/g, 74 (21%) had a UACR >300 mg/g, and 53 (15%) had no UACR evaluation. The mean eGFR slope over time was -5.6 ± 7.7 mL/min/1.73 m2 per year at baseline, which improved to -1.7 ± 6.8 mL/min/1.73 m2 per year after SGLT2 inhibitor administration (p <0.001). This effect was independent of UACR. CONCLUSION: In a real-world study of primarily older non-diabetic adults with CKD, SGLT2 inhibition was associated with a slower rate of kidney function decline, regardless of baseline UACR level.

Revealing misattributed parentage through the integration of genetic information into the electronic health record.

The integration of genetic information (GI) into the electronic health record (EHR) seems inevitable as the mainstreaming of genomics continues. Such newly provided accessibility to GI could be beneficial for improving health care, as well as for supporting clinical decision-making and health management. Notwithstanding these promising benefits, the automatic integration of GI into the EHR, allowing unrestricted access to one's GI through patient portals, carries various knowledge-related risks for patients. This article is focused on the potential case of inadvertently revealing misattributed parentage through such practice. The article aims to identify key clinical and ethical implications of such revelation for adult patients. Clinical implications include, for example, altering the physician-patient interaction and the need to enhance physician's genetic literacy to improve genetic-information-specific communication skills. Ethical implications yield arguments supporting disclosure of MP, such as autonomy, individuals' right to know medical information pertaining to them, and the right to know one's genetic origins. Arguments opposing disclosure of MP centre on the right not to know GI and concerns for post-disclosure family relationships. Following the clinical and ethical analyses of these respective implications, we consider how such integration of GI into the EHR ought to be carried out, ethically. We therefore suggest a solution, featuring an autonomy-based approach, built around EHR users' right not to know. Our solution of nuanced consent options (including a 'genetic ignorance option') is designed to enable patients' informed exposure to GI through the EHR, allowing them some control over their self- and familial narrative.

Waning Effectiveness of the BNT162b2 Vaccine Against Infection in Adolescents in Israel.

BACKGROUND: The short-term effectiveness of a 2-dose regimen of the BioNTech/Pfizer BNT162b2 vaccine for adolescents has been demonstrated. However, little is known about the long-term effectiveness in this age group. It is known, however, that waning of vaccine-induced immunity against infection in adult populations is evident within a few months. METHODS: Leveraging the database of Maccabi Healthcare Services (MHS), we conducted a matched case-control design for evaluating the association between time since vaccination and the incidence of infections, where 2 outcomes were evaluated: documented SARS-CoV-2 infection (regardless of symptoms) and symptomatic infection (COVID-19). Cases were defined as individuals aged 12-16 with a positive polymerase chain reaction (PCR) test occurring between 15 June and 8 December 2021, when the Delta variant was dominant in Israel. Controls were adolescents who had not tested positive previously. RESULTS: We estimated a peak vaccine effectiveness between 2 weeks and 3 months following receipt of the second dose, with 85% (95% confidence interval [CI]: 84-86%) and 90% (95% CI: 89-91%) effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19), respectively. However, in line with findings for adults, waning effectiveness was evident. Long-term protection was reduced to 73% (95% CI: 68-77%) against infection and 79% (95% CI: 73-83%) against COVID-19 3-5 months after the second dose and waned to 53% (95% CI: 46-60%) against infection and 66% (95% CI: 59-72%) against COVID-19 after 5 months. CONCLUSIONS: Although vaccine-induced protection against both infection and COVID-19 continues over time in adolescents, the protection wanes with time since vaccination, starting 3 months after inoculation and continuing for more than 5 months.

Dynamics of Naturally Acquired Immunity Against Severe Acute Respiratory Syndrome Coronavirus 2 in Children and Adolescents.

OBJECTIVE: To evaluate the duration of protection against reinfection conferred by a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. STUDY DESIGN: We applied 2 complementary approaches: a matched test-negative, case-control design and a retrospective cohort design. A total of 458 959 unvaccinated individuals aged 5-18 years were included. The analyses focused on the period July 1, 2021, to December 13, 2021, a period of Delta variant dominance in Israel. We evaluated 3 SARS-CoV-2-related outcomes: documented polymerase chain reaction-confirmed infection or reinfection, symptomatic infection or reinfection, and SARS-CoV-2-related hospitalization or death. RESULTS: Overall, children and adolescents who were previously infected acquired durable protection against reinfection with SARS-CoV-2 for at least 18 months. Importantly, no SARS-CoV-2-related deaths were recorded in either the SARS-CoV-2-naïve group or the previously infected group. The effectiveness of naturally acquired immunity against a recurrent infection reached 89.2% (95% CI, 84.7%-92.4%) at 3-6 months after the first infection and declined slightly to 82.5% (95% CI, 79.1%-85.3%) by 9-12 months after infection, with a slight nonsignificant waning trend seen up to 18 months after infection. Additionally, children aged 5-11 years exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in those aged 12-18 years was more prominent but still mild. CONCLUSIONS: Children and adolescents who were previously infected with SARS-CoV-2 remain protected to a high degree for 18 months. Further research is needed to examine naturally acquired immunity against Omicron and newer emerging variants.

Pregnancy Course of 10 Women Diagnosed with Chronic Lymphocytic Leukemia.

Pregnancies following diagnosis of chronic lymphocytic leukemia (CLL) are rare events, mainly because the disease is typically diagnosed in the elderly. Literature on the topic is based only on case reports, and limited data are available on the influence of pregnancy on CLL course. In this retrospective study, we aimed to summarize the clinical and laboratory course of 10 women with CLL who became pregnant. None of the patients had significant changes in blood count during or after pregnancy or had complications such as infection, autoimmune phenomenon, or preeclampsia. Four out of 10 pregnancies were terminated with an early miscarriage. Following labor, 1 patient started anti-CLL treatment due to preexisting anemia, but none of the women required therapy during CLL progression during the first 2 years of follow-up. We conclude that based on our serial, pregnancy does not negatively impact on CLL course.

Clinical Outcomes of COVID-19 in Mycosis Fungoides and Sezary Syndrome.

INTRODUCTION: Haemato-oncologic patients are more susceptible to severe infections with SARS-CoV-2. We aimed to assess the clinical outcomes of SARS-CoV-2 infection among patients with Mycosis Fungoides and Sezary Syndrome (MF/SS). METHODS: The data were retrieved from anonymized electronic medical records of Maccabi Healthcare Services (MHS), the second-largest healthcare organization in Israel. Patients diagnosed with MF/SS were included in the study. COVID-19 PCR test results together with sociodemographic and clinical data were extracted and analyzed to evaluate the association of COVID-19 with clinical outcomes. RESULTS: In the period of 2020-2022, 1,472 MF/SS patients were included in the study. Among them, 768 (52%) had SARS-CoV-2 infection. The hospitalization rate was 2.9% and infection by the Delta variant was associated with the highest hospitalization rate (7.7%). The hospitalization rate was lower among fully vaccinated patients (p = 0.032) but higher for patients older than 65 (p < 0.001) and patients with SS (vs. MF) (p < 0.001) or COPD (p = 0.024) diagnosis. There was a tendency for decreased hospitalization among patients treated with nirmatrelvir + ritonavir within 5 days of infection, with a 79% risk reduction, although it was not statistically significant (p = 0.164). CONCLUSION: Patients with MF/SS do not necessarily have worse COVID-19 outcomes compared to the general population.

The Incidence of SARS-CoV-2 Reinfection in Persons With Naturally Acquired Immunity With and Without Subsequent Receipt of a Single Dose of BNT162b2 Vaccine : A Retrospective Cohort Study.

BACKGROUND: There is insufficient evidence regarding the magnitude and durability of protection conferred by a combined effect of naturally acquired immunity after SARS-CoV-2 infection and vaccine-induced immunity. OBJECTIVE: To compare the incidence rate of SARS-CoV-2 reinfection in previously infected persons to that of previously infected persons who subsequently received a single dose of BNT162b2 messenger RNA vaccine. DESIGN: A retrospective cohort study emulating a randomized controlled target trial through a series of nested trials. SETTING: Nationally centralized database of Maccabi Healthcare Services, Israel. PARTICIPANTS: Persons with documented SARS-CoV-2 infection who did not receive subsequent SARS-CoV-2 vaccination were compared with persons with documented SARS-CoV-2 infection who received a single dose of the BNT162b2 vaccine at least 3 months after infection. INTERVENTION: Forty-one randomized controlled trials were emulated, in which 107 413 Maccabi Healthcare Services' members aged 16 years and older were eligible for at least 1 trial. MEASUREMENTS: SARS-CoV-2-related outcomes of infection, symptomatic disease, hospitalization, and death, between 2 March and 13 December 2021. RESULTS: A statistically significant decreased risk (hazard ratio, 0.18 [95% CI, 0.15 to 0.20]) for reinfection was found among persons who were previously infected and then vaccinated versus those who were previously infected but remained unvaccinated. In addition, there was a decreased risk for symptomatic disease (hazard ratio, 0.24 [CI, 0.20 to 0.29]) among previously infected and vaccinated persons compared with those who were not vaccinated after infection. No COVID-19-related mortality cases were found. LIMITATION: Hybrid protection against non-Delta variants could not be inferred. CONCLUSION: Persons previously infected with SARS-CoV-2 gained additional protection against reinfection and COVID-19 from a subsequent single dose of the BNT162b2 vaccine. Nonetheless, even without a subsequent vaccination, reinfection appeared relatively rare. PRIMARY FUNDING SOURCE: None.

The Effectiveness of the Two-Dose BNT162b2 Vaccine: Analysis of Real-World Data.

BACKGROUND: Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were shown to be highly efficacious in preventing the disease in randomized controlled trials; nonetheless, evidence on the real-world effectiveness of this vaccine is limited. Study objective was to evaluate the effectiveness of BNT162b2 vaccine in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and mortality. METHODS: This historical cohort study included members of a large health provider in Israel that were vaccinated with at least 1 dose of BNT162b2. The primary outcome was incidence rate of a SARS-CoV-2 infection confirmed with real-time polymerase chain reaction (rt-PCR), between 7 and 27 days after second dose (protection-period), as compared to days 1-7 after the first dose, where no protection by the vaccine is assumed (reference-period). RESULTS: Data of 1 178 597 individuals vaccinated with BNT162b2 were analyzed (mean age 47.7 years [SD = 18.1], 48.4% males) of whom 872 454 (74.0%) reached the protection period. Overall, 4514 infections occurred during the reference period compared to 728 during the protection period, yielding a weighted mean daily incidence of 54.8 per 100 000 (95% confidence interval [CI]: 26.1-115.0 per 100 000) and 5.4 per 100 000 (95% CI: 3.5-8.4 per 100 000), respectively. The vaccine effectiveness in preventing infection was 90% (95% CI: 79%-95%) and 94% (95% CI: 88%-97%) against COVID-19. Among immunosuppressed patients, vaccine effectiveness against infection was 71% (95% CI: 37%-87%). The adjusted hazard ratios for hospitalization in those infected were 0.82 (95% CI: .36-1.88), 0.45 (95% CI: .23-.90), and 0.56 (95% CI: .36-.89) in the age groups 16-44, 45-64. and ≥75 years, respectively. CONCLUSIONS: The effectiveness of the BNT162b2 vaccine is comparable to the one reported in the phase III clinical trial.

BNT162b2 mRNA Vaccine Effectiveness Given Confirmed Exposure: Analysis of Household Members of Coronavirus Disease 2019 Patients.

BACKGROUND: Although BNT162b2 vaccine-efficacy analyses have been published, the effectiveness of the vaccine in preventing coronavirus disease 2019 given confirmed exposure has not been previously demonstrated, even though it has policy implications, such as the need for self-quarantine when exposure has occurred. METHODS: In a retrospective cohort study, we used data collected between 20 December 2020 and 17 March 2021 from the second largest healthcare provider in Israel to analyze the probability of an additional household infection occurring within 10 days after an index infection. In model 1, vaccine effectiveness was described for Fully Vaccinated individuals (7 or more days from second dose) vs either Unvaccinated individuals or those Recently Vaccinated Once (0-7 days from the first dose, presumably still unprotected). Secondary analyses included correction for differing testing rates. In model 2, we conducted a separate analysis of households comprised of only adults with the same vaccination status. RESULTS: A total of 173 569 households were included, of which 6351 had an index infection (mean [standard deviation] age, 58.9 [13.5] years); 50% were women. Adjusted vaccine effectiveness of Fully Vaccinated compared with Unvaccinated participants was 80.3% (95% confidence interval [CI], 73.5-85.4) and 82.0% (95% CI, 75.6-86.8) compared with those Recently Vaccinated Once. CONCLUSIONS: The BNT162b2 vaccine is effective in high-risk real-life exposure scenarios, but the protection afforded in these settings is lower than that previously described. Individuals with a confirmed significant exposure to severe acute respiratory syndrome are still at risk of being infected even if fully vaccinated.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Naturally Acquired Immunity versus Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: A Retrospective Cohort Study.

BACKGROUND: Waning of protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) conferred by 2 doses of the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within 4 months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity. METHODS: A retrospective observational study of 124 500 persons, compared 2 groups: (1) SARS-CoV-2-naive individuals who received a 2-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes-infection, symptomatic disease (coronavirus disease 2019 [COVID-19]), hospitalization, and death-between 1 June and 14 August 2021, when the Delta variant was dominant in Israel. RESULTS: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% confidence interval [CI], 8.08-21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 and February 2021, evidence of waning naturally acquired immunity was demonstrated, although SARS-CoV-2 naive vaccinees still had a 5.96-fold (95% CI: 4.85-7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI: 5.51-9.21) increased risk for symptomatic disease. CONCLUSIONS: Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 2-dose vaccine-indued immunity.

Self-Reported and Physiologic Reactions to Third BNT162b2 mRNA COVID-19 (Booster) Vaccine Dose.

Despite extensive technological advances in recent years, objective and continuous assessment of physiologic measures after vaccination is rarely performed. We conducted a prospective observational study to evaluate short-term self-reported and physiologic reactions to the booster BNT162b2 mRNA (Pfizer-BioNTech, https://www.pfizer.com) vaccine dose. A total of 1,609 participants were equipped with smartwatches and completed daily questionnaires through a dedicated mobile application. The extent of systemic reactions reported after the booster dose was similar to that of the second dose and considerably greater than that of the first dose. Analyses of objective heart rate and heart rate variability measures recorded by smartwatches further supported this finding. Subjective and objective reactions after the booster dose were more apparent in younger participants and in participants who did not have underlying medical conditions. Our findings further support the safety of the booster dose from subjective and objective perspectives and underscore the need for integrating wearables in clinical trials.

Dynamics in COVID-19 symptoms during different waves of the pandemic among children infected with SARS-CoV-2 in the ambulatory setting.

The aim of this real-life, big data population-based study was to evaluate differences in symptomatic presentation of children infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) between the third and fourth waves of the pandemic in Israel, dominated by the Alpha and Delta variants, respectively. Our cohort included all children and adolescents, members of the second-largest Health Maintenance Organization in Israel that had positive real-time polymerase chain reaction (RT-PCR) test during the third and fourth waves of the pandemic (December 1, 2020, to April 30, 2021, and June 1, 2021, to October 10, 2021, respectively). A total of 32,485 and 44,130 children and adolescents in the third and fourth waves were included in the final analysis. The rate of children with symptomatic disease among patients with documented SARS-CoV-2 infection was higher in the fourth wave compared to the third wave (49.9% vs. 37.5%). The most commonly reported symptom and the only symptom that substantially differed between waves was fever, with 33% of SARS-CoV-2 infected children in the fourth wave vs. 13.6% in the third wave. Preschool children had the lowest prevalence of febrile illness compared to other age groups. CONCLUSION: Children and adolescents infected during the fourth wave of the pandemic in Israel, a Delta-dominant period, had a significantly higher rate of symptomatic febrile illness than the Alpha-dominant period. This phenomenon occurred across all age groups. WHAT IS KNOWN: • There are differences in COVID-19 severity among adults and children during different waves of the pandemic. • There is a paucity of data regarding symptomatic characteristics in children in large-scale cohorts aside from hospital settings. WHAT IS NEW: • In a time period dominated by the Delta variant, there were substantially more children with symptomatic disease and febrile illness compared to a period dominated by the alpha variant. • Preschool children had the lowest rate of febrile illness among all age groups.

Long-COVID in patients with a history of mild or asymptomatic SARS-CoV-2 infection: a Nationwide Cohort Study.

OBJECTIVE: Evaluating the prevalence of long-COVID symptoms in patients with a history of mild or asymptomatic infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the factors associated with developing long-COVID. DESIGN: A nationwide cohort study. Using a centralized database, we have identified patients with and without a history of SARS-CoV-2 infection 1-6 months before data collection. Patients were asked to fill out an online questionnaire through text messages. SETTING: Israeli general practice. SUBJECTS: 2755 persons participated in the study in September 2021 (a response rate of 7.5%): 819 with and, 936 without a history of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: We asked patients to provide details about their demographic status, medical history, COVID-related variables and the presence of long-COVID symptoms. RESULTS: Most prevalent long-COVID symptoms were decreased smell sensation (35.1% vs. 4.3%, p < 0.001), decreased taste sensation (25.2% vs. 3.2%, p < 0.001), memory disturbances (36.9% vs. 14.4%, p < 0.001), dyspnea (24.2% vs. 10.7%, p < 0.001) and arthralgia (33% vs. 16.3%, p < 0.001). Risk factors associated with long-COVID included female gender, symptomatic COVID-19, overweight or obesity and the presence of dyslipidemia. About 34.6% of participants reported not returning to their baseline health condition after the acute illness. CONCLUSION: Long-COVID is frequently seen following a mild symptomatic COVID-19 infection and, to a lesser extent, following an asymptomatic SARS-CoV-2 infection. Primary care physicians should be aware of these symptoms and consider this option in their differential diagnosis. Health policymakers should expect a significant impact of this syndrome on public health.Key PointsLong-COVID has emerged as a significant health problem with a serious impact on normal daily function• Long-COVID symptoms were evident in patients with mild symptomatic disease and in asymptomatic patients to a lesser extent.• Risk factors for having Long-COVID symptoms include female gender, symptomatic disease, increased BMI, and the presence of dyslipidemia.• Fatigue, dyspnea, weakness, decreased libido, weight changes, memory, and sleep disturbances were associated with not returning to the baseline health state.

SARS-CoV-2 spike IgG titres up to 137 days following Comirnaty mRNA COVID-19 vaccination, Israel, February to May 2021.

BackgroundData regarding the long-term protection afforded by vaccination for the SARS-CoV-2 infection are essential for allocation of scarce vaccination resources worldwide.MethodsWe conducted a retrospective cohort study aimed at studying the kinetics of IgG antibodies against SARS-CoV-2 in COVID-19-naïve patients fully vaccinated with two doses of Comirnaty mRNA COVID-19 vaccine. Geometric mean concentrations (GMCs) of antibody levels were reported. Linear models were used to assess antibody levels after full vaccination and their decline over time.ResultsThe study included 4,740 patients and 5,719 serological tests. Unadjusted GMCs peaked 28-41 days after the first dose at 10,174 AU/mL (95% CI: 9,211-11,237) and gradually decreased but remained well above the positivity cut-off. After adjusting for baseline characteristics and repeated measurements, the antibodies half-life time was 34.1 days (95% CI: 33.1-35.2), and females aged 16-39 years with no comorbidities had antibody levels of 20,613 AU/mL (95% CI: 18,526-22,934) on day 28 post-first-dose. Antibody levels were lower among males (0.736 of the level measured in females; 95% CI: 0.672-0.806), people aged 40-59 (0.729; 95% CI: 0.649-0.818) and ≥ 60 years (0.452; 95% CI: 0.398-0.513), and patients having haematological (0.241; 95% CI: 0.190-0.306) or solid malignancies (0.757; 95% CI: 0.650-0.881), chronic kidney disease with glomerular filtration rate (GFR) ≥ 30 (0.434; 95% CI: 0.354-0.532) or with GFR < 30 mL/min (0.176; 95% CI: 0.109-0.287), and immunosuppression (0.273; 95% CI: 0.235-0.317). Body mass index, cardiovascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes and inflammatory bowel diseases were not associated with antibody levels.ConclusionsVaccination with two doses resulted in persistently high levels of antibodies (≥ cut-off of 50 AU/mL) up to 137 days post-first-dose. Risk factors for lower antibody levels were identified.

Downwards Vertical Attention Bias in Conversion Disorder vs Controls: A Pilot Study.

BACKGROUND: Conversion disorder (CD) is a largely enigmatic disorder, one that requires a thorough ruling-out process. Prior research suggests that metaphors and conceptualization are rooted in physical experience, and that we interpret our affective world through metaphors. Spatial metaphors (interaction of affect and vertical space) are a prominent example of the grounding of metaphors. This is a relatively unpaved direction of research of CD. OBJECTIVES: The present pilot study sought to explore this view by investigating the "healthy is up, sick is down" spatial metaphors (e.g., "fell ill" and "top shape") in patients with CD, examining the correlation between the processing of bodily-related words, CD, and vertical space. We hypothesized that patients with CD, who experience their bodies as ill, will demonstrate a downwards bias when processing bodily-related words; corresponding to the "healthy is up, sick is down" spatial metaphor. METHODS: A total of 8 female patients (ages M-38.13 SD-10.44) and 42 female controls (ages M-36.4 SD-14.57) performed a visual attention task. Participants were asked to identify a spatial probe at the top or the bottom of a screen, following either a bodily related (e.g., arm) or non-bodily related (e.g., clock) prime word. RESULTS: As predicted, when processing bodily-related words, patients with CD demonstrated a downwards attention bias. Moreover, the higher the patient's level of somatization, the faster the patient detected lower (vs upper) spatial targets. CONCLUSIONS: This study suggests that the changed health paradigm of patients with CD is grounded in sensorimotor perception. Further research could propose new diagnostic and treatment options for CD.

Supplement of Vitamin D for early-stage Chronic Lymphocytic Leukemia Patients is Associated with a Longer Time to first Treatment.

Low levels of vitamin D are associated with a shorter time to first treatment (TTFT) and inferior overall survival in patients with Chronic Lymphocytic leukemia. But whether vitamin D supplement affects the clinical course of CLL patients, remains an open question. In the current study, we aimed to retrospectively explore the clinical benefit of Vitamin D supplement, or one of its analogues, on TTFT and treatment-free survival (TFS) in a large cohort of patients with asymptomatic CLL, who were under watch and wait approach. Among the 3,474 patients included in the study, 931 patients (26.8%) received either vitamin D supplement or its analogue, for a minimum of 6 months. We found that vitamin D supplement was statistically significant for longer TTFT in the young cohort (age<=65) and was associated with a longer TFS for all ages (p-value=0.004). Among non-vitamin D users, the median TFS was found to be 84 months, while among vitamin D supplement users the median TFS extended to 169 months. In conclusion, our long-term retrospective study demonstrates that the administration of vitamin D to patients with CLL in a watch and wait active surveillance is significantly associated with a longer treatment free survival (in any age) and a longer time to first treatment among young patients (age<=65). A prospective clinical trial is needed to validate results.

Risk for Mortality in High versus Low Antiparkinsonian Therapy Dose During the First Year of Parkinson's Disease: A Real-World Study.

INTRODUCTION: Early, simple predictors for long-term survival in Parkinson's disease (PD) may help identify patients at elevated risk and are crucial for more personalized treatment. METHODS: This large, retrospective study examined whether higher levodopa equivalent daily dose (LEDD) a year after diagnosis predicts long-term survival. RESULTS: Mortality risk was increased among 292 patients receiving ≥ 600 mg LEDD versus 2233 patients receiving < 600 mg LEDD (hazard ratio 1.5; 95% confidence interval 1.3-1.7), particularly among patients aged < 75 years (1.8; 1.4-2.4). CONCLUSION: In PD, higher LEDD can be an early risk marker of increased mortality, probably because it reflects more severe disease.

Immunosuppression as a Hub for SARS-CoV-2 Mutational Drift.

The clinical course of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is largely determined by host factors, with a wide range of outcomes. Despite an extensive vaccination campaign and high rates of infection worldwide, the pandemic persists, adapting to overcome antiviral immunity acquired through prior exposure. The source of many such major adaptations is variants of concern (VOCs), novel SARS-CoV-2 variants produced by extraordinary evolutionary leaps whose origins remain mostly unknown. In this study, we tested the influence of factors on the evolutionary course of SARS-CoV-2. Electronic health records of individuals infected with SARS-CoV-2 were paired to viral whole-genome sequences to assess the effects of host clinical parameters and immunity on the intra-host evolution of SARS-CoV-2. We found slight, albeit significant, differences in SARS-CoV-2 intra-host diversity, which depended on host parameters such as vaccination status and smoking. Only one viral genome had significant alterations as a result of host parameters; it was found in an immunocompromised, chronically infected woman in her 70s. We highlight the unusual viral genome obtained from this woman, which had an accelerated mutational rate and an excess of rare mutations, including near-complete truncating of the accessory protein ORF3a. Our findings suggest that the evolutionary capacity of SARS-CoV-2 during acute infection is limited and mostly unaffected by host characteristics. Significant viral evolution is seemingly exclusive to a small subset of COVID-19 cases, which typically prolong infections in immunocompromised patients. In these rare cases, SARS-CoV-2 genomes accumulate many impactful and potentially adaptive mutations; however, the transmissibility of such viruses remains unclear.

Late diagnosis of autism spectrum disorder-Journey, parents' concerns, and sex influences.

Despite increasing awareness for diagnosing autism spectrum disorder (ASD) and initiating treatments early in life, many children and adolescents continue to be diagnosed at a relatively older age. Focusing on children who first received an ASD diagnosis at age six or older, this study aimed to describe the symptoms that parents reported when ASD was diagnosed, follow the patients' clinical trajectory prior to receiving the diagnosis, and describe differences in symptoms and prior diagnoses between males and females cases. We included 258 children (205 males and 53 females) who were first diagnosed with autism at age 6-18 in 2017-2018. We retrieved demographic information, neurologic and developmental symptoms, diagnoses, and medications dispensing history from the children's electronic medical charts. The data indicated that prior diagnoses of language delays and attention deficit hyperactivity disorder were common among children with a late ASD diagnosis. Two thirds of the children were prescribed one or more medications to treat psychosocial and behavioral conditions before receiving a late ASD diagnosis. Difficulties in social relationships with peers were the leading reported symptoms by parents at the time of ASD diagnosis. Across these different domains, some differences were found between males and females, including a somewhat higher cognitive level in males, who were also more likely to present aggressive behavior.