Vitamin D and Insulin-Dependent Diabetes: A Systematic Review of Clinical Trials.

(1) Background: Vitamin D supplementation after type 1 diabetes mellitus (T1DM) onset has led to conflicting results on beta-cell preservation. Aim: This paper presents a systematic review to verify whether randomized prospective controlled trials (RCTs) demonstrate that improved vitamin D status confers protection on T1DM. (2) Methods: A systematic review was conducted up until 18 January 2024 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching MEDLINE, MEDLINE In-Process, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, using keywords "vitamin D", "type 1 diabetes", and "children". (3) Results: Following the above-mentioned search process, 408 articles in PubMed and 791 in Embase met inclusion criteria. After removing duplicates, 471 articles remained. After exclusion criteria, 11 RCTs remained. Because of major heterogeneity in design and outcomes, no meta-analyses were conducted, allowing only for qualitative analyses. There was no strong evidence that vitamin D supplementation has lasting effects on beta-cell preservation or glycemic control in new-onset T1DM. (4) Conclusions: More rigorous, larger studies are needed to demonstrate whether vitamin D improves beta-cell preservation or glycemic control in new-onset T1DM. Because T1DM may cause osteopenia, it is advisable that patients with new onset T1DM have adequate vitamin D stores.

A Statistical Approach to the High Mortality Rate of Israeli Citizens Held Hostage in Gaza.

BACKGROUND: According to Hamas sources, many Israeli hostages in Gaza were killed by indiscriminate Israeli airstrikes, together with a large number of Palestinian citizens. OBJECTIVES: To verify whether the estimated death rate of Israeli hostages was similar to the estimated death rate of Gaza citizens from these acts of war. METHODS: We used two estimates of hostage death rates, one obtained from Israeli intelligence sources, and one published by a Hamas spokesperson. We used the Palestinian casualty rates published by the Palestinian Ministry of Health. We compared death rates using Fisher's exact test. RESULTS: By 30 December 2023, the rate of Israeli hostage death was 23/238 (9.7%) according to Israeli intelligence sources, and 60/238 (25.2%) according to Hamas. Both figures are strikingly and significantly higher than the death rate among Palestinians, estimated to be 19,667/2.2 million (0.89%) by 19 December 2023 (P < 0.0001). CONCLUSIONS: Israeli airstrikes as the cause of death of Israeli hostages are implausible unless they were specifically exposed to these strikes more than Palestinian citizens.

Hepatitis C Virus Elimination Program among Prison Inmates, Israel.

The Israeli Prison Services implemented a hepatitis C virus (HCV) elimination program in 2020. Inmates considered high risk for HCV were offered serology; HCV-seropositive participants were offered HCV RNA testing. Among participants, 7.0% had detectable HCV RNA and were offered antiviral drug therapy. This program reduced HCV burden among incarcerated persons.

Securing wider EU commitment to the elimination of hepatitis C virus.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

CONCERTO: A randomized, placebo-controlled trial of oral laquinimod in relapsing-remitting multiple sclerosis.

BACKGROUND: Interventions targeting the adaptive immune response are needed in multiple sclerosis (MS). OBJECTIVE: Evaluate laquinimod's efficacy, safety, and tolerability in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: CONCERTO was a randomized, double-blind, placebo-controlled, phase-3 study. RRMS patients were randomized 1:1:1 to receive once-daily oral laquinimod 0.6 or 1.2 mg or placebo for ⩽24 months (n = 727, n = 732, and n = 740, respectively). Primary endpoint was time to 3-month confirmed disability progression (CDP). The laquinimod 1.2-mg dose arm was discontinued (1 January 2016) due to cardiovascular events at high doses. Safety was monitored throughout the study. RESULTS: CONCERTO did not meet the primary endpoint of significant effect with laquinimod 0.6-mg versus placebo on 3-month CDP (hazard ratio: 0.94; 95% confidence interval: 0.67-1.31; p = 0.706). Secondary endpoint p values were nominal and non-inferential. Laquinimod 0.6 mg demonstrated 40% reduction in percent brain volume change from baseline to Month 15 versus placebo (p < 0.0001). The other secondary endpoint, time to first relapse, and annualized relapse rate (an exploratory endpoint) were numerically lower (both, p = 0.0001). No unexpected safety findings were reported with laquinimod 0.6 mg. CONCLUSION: Laquinimod 0.6 mg demonstrated only nominally significant effects on clinical relapses and magnetic resonance imaging (MRI) outcomes and was generally well tolerated. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT01707992).

Outbreak of human leptospirosis linked to contaminated water bodies in Northern Israel, June to August 2018.

We report preliminary findings of a large outbreak of human leptospirosis with 36 confirmed/probable and 583 suspected cases from June-August 2018, linked to contaminated water bodies in Northern Israel. There was a travel-associated case in Germany; additional cases are being investigated in other countries. The presumed chain of transmission, implicating wild boar and cattle, raises multiple challenges for risk assessment, risk management and risk communication currently being addressed by a public health response team.

Laquinimod Safety Profile: Pooled Analyses from the ALLEGRO and BRAVO Trials.

BACKGROUND: Laquinimod 0.6 mg is a once-daily, oral, disease-modifying therapy in development for the treatment of multiple sclerosis (MS) that was investigated in two double-blind, placebo-controlled, phase 3 trials: ALLEGRO and BRAVO. METHODS: Data from these studies were pooled to assess the safety profile of laquinimod versus placebo. Adverse events (AEs), laboratory value changes, and potential risks identified in preclinical studies were evaluated in participants in ALLEGRO and BRAVO treated with at least one dose of laquinimod or matching placebo (1:1 random assignment). RESULTS: In total, 1988 patients received at least one dose of study drug (laquinimod: n = 983 [mean ± SD duration, 639 ± 190 days]; placebo: n = 1005 [mean ± SD duration, 627 ± 198 days]). Early terminations due to AEs were infrequent (laquinimod: 6.4%; placebo: 4.7%). Death was reported in four patients (laquinimod: n = 1; placebo: n = 3). Rates of serious AEs (including malignancies, infections, and cardiovascular AEs) were similar between groups. The most common AEs identified with laquinimod use were back and neck pain and appendicitis. Laquinimod was also associated with asymptomatic changes in liver enzyme levels, fibrinogen levels, and hematologic parameters that followed a consistent temporal pattern: mild, nonprogressive, and occurring within 90 days of treatment initiation, then stabilizing or reverting to baseline levels during continued treatment. CONCLUSIONS: Data from these pivotal laquinimod studies demonstrate a safety profile comprising benign or manageable AEs and asymptomatic laboratory findings with a clear temporal pattern. Potential risks noted in preclinical studies were not observed.

Ocular adverse effects of systemic treatment with isotretinoin.

OBJECTIVE: To examine whether isotretinoin therapy could result in deleterious ocular effects, as previously described in case report studies. DESIGN: Retrospective cohort study. SETTING: The study was conducted using the electronic medical databases of a large health maintenance organization in Israel. PATIENTS: The study population consisted of 14 682 adolescents and young adults who were new users of isotretinoin for acne and 2 age- and sex-matched comparison groups (isotretinoin-naive patients with acne and acne-free patients). MAIN OUTCOME MEASURES: Ocular adverse effects (AEs) or purchases of ophthalmic medications within 1 year after the first dispensed isotretinoin prescription. RESULTS: In total, 13.8% of the isotretinoin group experienced ocular AEs vs 9.6% of the isotretinoin-naive group and 7.1% of the acne-free group. During a 1-year follow-up period, the isotretinoin group had significantly higher risk for any ocular AEs (hazard ratio, 1.70; P.001) compared with the acne-free group. No such increased risk was observed for the isotretinoin-naive group. The isotretinoin group had higher relative risks for inflammatory and structural AEs. CONCLUSION: Isotretinoin use may be associated with short-term ocular events, especially conjunctivitis, underscoring the importance of educating patients and caregivers about these potentially important AEs of the therapy.