We conducted a registries-based cohort study of long-term care facility residents >65 years of age offered vaccination against severe acute respiratory syndrome coronavirus 2 before March 10, 2021, ...in Spain. Risk for infection in vaccinated and nonvaccinated persons was compared with risk in the same persons in a period before the vaccination campaign, adjusted by daily-varying incidence and reproduction number. We selected 299,209 persons; 99.0% had >1 dose, 92.6% had 2 doses, and 99.8% of vaccines were Pfizer/BioNTech (BNT162b2). For vaccinated persons with no previous infection, vaccine effectiveness was 81.8% (95% CI 81.0%-82.7%), and 11.6 (95% CI 11.3-11.9) cases were prevented per 10,000 vaccinated/day. In those with previous infection, effectiveness was 56.8% (95% CI 47.1%-67.7%). In nonvaccinated residents with no previous infection, risk decreased by up to 81.4% (95% CI 73.3%-90.3%). Our results confirm vaccine effectiveness in this population and suggest indirect protection in nonvaccinated persons.
By employing a common protocol and data from electronic health registries in Denmark, Navarre (Spain), Norway and Portugal, we estimated vaccine effectiveness (VE) against hospitalisation due to ...COVID-19 in individuals aged ≥ 65 years old, without previous documented infection, between October 2021 and March 2022. VE was higher in 65-79-year-olds compared with ≥ 80-year-olds and in those who received a booster compared with those who were primary vaccinated. VE remained high (ca 80%) between ≥ 12 and < 24 weeks after the first booster administration, and after Omicron became dominant.
Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown.
A prospective cohort of human immunodeficiency virus (HIV)-infected participants with ...suppressed virological replication was recruited to compare whole-blood telomere length (measured by quantitative multiplex polymerase chain reaction analysis) in participants with current exposure to tenofovir disoproxil fumarate (TDF) to that in participants never exposed to TDF.
A total of 172 participants were included: 67 were in the TDF group, and 105 were in the non-TDF group (75 were receiving 2 nucleosides of whom 69 were receiving abacavir, 25 were receiving a nucleostide reverse transcriptase inhibitor N{t}RTI-sparing regimen, and 5 were receiving lamivudine as the only nucleoside). After 2 years, the mean blood telomere length increased significantly in the whole cohort. The TDF group had significantly smaller gains in telomere length than the non-TDF group. In the analysis restricted to participants receiving N(t)RTIs, TDF exposure was not associated with an independent negative effect. In the non-TDF group, participants treated with 2 nucleosides also had significantly smaller gains in telomere length than those receiving N(t)RTI-sparing regimens or lamivudine as the only nucleoside.
In HIV-infected adults with prolonged virological suppression, treatment with TDF or abacavir was associated with smaller gains in blood telomere length after 2 years of follow-up.
Ambulance dispatches for respiratory syndromes reflect incidence of influenza-like illness in primary care. Associations are highest in children (15%-34% of respiratory calls attributable to ...influenza), out-of-office hours (9%), and highest urgency-level calls (9%-11%). Ambulance dispatches might be an additional source of data for severe influenza surveillance.
Burden of disease (BoD) estimations are increasingly used to prioritize public health interventions. Previous Cryptosporidium BoD models accounted only for acute episodes, while there is increasing ...evidence of long-term manifestations. Our objective was to update Cryptosporidium BoD and cost-of-illness (COI) models and to estimate BoD and COI for the Netherlands in years 2013-2017.
We performed a scoping literature review and drew an outcome tree including long-term manifestations for which sufficient evidence was found, such as recurrent diarrhea and joint pain. We chose the Disability-Adjusted Life Year (DALY) metric to synthesize years of life lost due mortality (YLLs) and years lived with disability due to non-fatal outcomes (YLDs). For the costs, we adopted a societal perspective accounting for direct healthcare costs, patient costs and productivity losses. Uncertainty was managed using Latin Hypercube sampling (30,000 iterations).
In the Netherlands in 2017, we estimated 50,000 Cryptosporidium cases (95% uncertainty interval (UI): 15,000-102,000), 7,000 GP visits, 300 hospitalizations and 3 deaths, resulting in 137 DALYs (95%UI: 54-255) and €19.2 million COI (95%UI: €7.2 million- €36.2 million). Estimates were highest for 2016 (218 DALYs and €31.1 million in COI), and lowest in 2013 (100 DALYs and €13.8 million in COI). Most of the BoD was attributable to YLD (≈80% of DALYs). The most important cost was productivity losses (≈90% of total COI). Long-term manifestations, including recurring diarrhea and joint pain, accounted for 9% of the total DALYs and 7% of the total COI.
Current evidence supports the inclusion of long-term manifestations in Cryptosporidium models, which contribute close to 10% of the total DALYs and costs. This may be an underestimation, as we were conservative in our assumptions. Cryptosporidium should be considered a priority organism with respect to public health surveillance, even in industrialized countries with high hygiene standards.
BackgroundIn the Netherlands, echovirus type 6 (E6) is identified through clinical and environmental enterovirus surveillance (CEVS and EEVS). AimWe aimed to identify E6 transmission clusters and to ...assess the role of EEVS in surveillance and early warning of E6. MethodsWe included all E6 strains from CEVS and EEVS from 2007 through 2016. CEVS samples were from patients with enterovirus illness. EEVS samples came from sewage water at pre-specified sampling points. E6 strains were defined by partial VP1 sequence, month and 4-digit postcode. Phylogenetic E6 clusters were detected using pairwise genetic distances. We identified transmission clusters using a combined pairwise distance in time, place and phylogeny dimensions. ResultsE6 was identified in 157 of 3,506 CEVS clinical episodes and 92 of 1,067 EEVS samples. Increased E6 circulation was observed in 2009 and from 2014 onwards. Eight phylogenetic clusters were identified; five included both CEVS and EEVS strains. Among these, identification in EEVS did not consistently precede CEVS. One phylogenetic cluster was dominant until 2014, but genetic diversity increased thereafter. Of 14 identified transmission clusters, six included both EEVS and CEVS; in two of them, EEVS identification preceded CEVS identification. Transmission clusters were consistent with phylogenetic clusters, and with previous outbreak reports. ConclusionAlgorithms using combined time-place-phylogeny data allowed identification of clusters not detected by any of these variables alone. EEVS identified strains circulating in the population, but EEVS samples did not systematically precede clinical case surveillance, limiting EEVS usefulness for early warning in a context where E6 is endemic.
We estimated the association between the level of restriction in nine different fields of activity and SARS-CoV-2 transmissibility in Spain, from 15 September 2020 to 9 May 2021.
A stringency index ...(0-1) was created for each Spanish province (
= 50) daily. A hierarchical multiplicative model was fitted. The median of coefficients across provinces (95% bootstrap confidence intervals) quantified the effect of increasing one standard deviation in the stringency index over the logarithmic return of the weekly percentage variation of the 7-days SARS-CoV-2 cumulative incidence, lagged 12 days.
Overall, increasing restrictions reduced SARS-CoV-2 transmission by 22% (RR = 0.78; one-sided 95%CI: 0, 0.82) in 1 week, with highest effects for culture and leisure 14% (0.86; 0, 0.98), social distancing 13% (0.87; 0, 0.95), indoor restaurants 10% (0.90; 0, 0.95) and indoor sports 6% (0.94; 0, 0.98). In a reduced model with seven fields, culture and leisure no longer had a significant effect while ceremonies decreased transmission by 5% (0.95; 0, 0.96). Models
was around 70%.
Increased restrictions decreased COVID-19 transmission. Limitations include remaining collinearity between fields, and somewhat artificial quantification of qualitative restrictions, so the exact attribution of the effect to specific areas must be done with caution.
The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted ...Drug Resistance (TDR) defined by the 2009 update of the WHO SDRM list.
We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain) between 2007-2011. Using the Stanford algorithm "Low-level resistance", "Intermediate resistance" and "High-level resistance" categories were considered as "Resistant".
70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs 6.8% (95%Confidence Interval: 5.8-7.7), and 221 harbored TDR using the WHO list 7.9% (6.9-9.0). Differences were due to a lower prevalence in clinically relevant resistance for NRTIs 2.3% (1.8-2.9) vs. 3.6% (2.9-4.3) by the WHO list and PIs 0.8% (0.4-1.1) vs. 1.7% (1.2-2.2), while it was higher for NNRTIs 4.6% (3.8-5.3) vs. 3.7% (3.0-4.7). While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02).
Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations.
In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease ...inhibitor monotherapy is associated to a higher rate of neurocognitive impairment.
In this observational, cross-sectional study we included patients with plasma virological suppression (≥ 1 year) without concomitant major neurocognitive confounders, currently receiving for ≥ 1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed.
Of the 191 included patients--triple therapy: 96, 1-2 years of monotherapy: 40 and >2 years of monotherapy: 55--proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9-33.6); triple therapy, 31.6% (22.1-41.0); short-term monotherapy, 25.0% (11.3-38.7); long-term monotherapy: 21.4% (10.5-32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29-2.50) and for long-term monotherapy 0.40 (0.14-1.15).
Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.
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