Clinical Considerations for Routine Auditory and Vestibular Monitoring in Patients with Cystic Fibrosis

Purpose Specific classes of antibiotics, such as aminoglycosides, have well-established adverse events producing permanent hearing loss, tinnitus, and balance and/or vestibular problems (i.e., ototoxicity). Although these antibiotics are frequently used to treat pseudomonas and other bacterial infections in patients with cystic fibrosis (CF), there are no formalized recommendations describing approaches to implementation of guideline adherent ototoxicity monitoring as part of CF clinical care. Method This consensus statement was developed by the International Ototoxicity Management Working Group (IOMG) Ad Hoc Committee on Aminoglycoside Antibiotics to address the clinical need for ototoxicity management in CF patients treated with known ototoxic medications. These clinical protocol considerations were created using consensus opinion from a community of international experts and available evidence specific to patients with CF, as well as published national and international guidelines on ototoxicity monitoring. Results The IOMG advocates four clinical recommendations for implementing routine and guideline adherent ototoxicity management in patients with CF. These are (a) including questions about hearing, tinnitus, and balance/vestibular problems as part of the routine CF case history for all patients; (b) utilizing timely point-of-care measures; (c) establishing a baseline and conducting posttreatment evaluations for each course of intravenous ototoxic drug treatment; and (d) repeating annual hearing and vestibular evaluations for all patients with a history of ototoxic antibiotic exposure. Conclusion Increased efforts for implementation of an ototoxicity management program in the CF care team model will improve identification of ototoxicity signs and symptoms, allow for timely therapeutic follow-up, and provide the clinician and patient an opportunity to make an informed decision about potential treatment modifications to minimize adverse events

Estimating the health effects of COVID-19-related immunisation disruptions in 112 countries during 2020-30: a modelling study.

BACKGROUND: There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered. METHODS: For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up. FINDINGS: We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073]). INTERPRETATION: Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption. FUNDING: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation. TRANSLATIONS: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

The effects of repeated low-level blast exposure on hearing in marines

Background: The study evaluates a group of Military Service Members specialized in blast explosive training called “Breachers” who are routinely exposed to multiple low-level blasts while teaching breaching at the U.S. Marine Corps in Quantico Virginia. The objective of this study was to determine if there are any acute or long-term auditory changes due to repeated low-level blast exposures used in training. The performance of the instructor group “Breachers” was compared to a control group, “Engineers”. Methods: A total of 11 Breachers and four engineers were evaluated in the study. The participants received comprehensive auditory tests, including pure-tone testing, speech-in-noise (SIN) measures, and central auditory behavioral and objective tests using early and late (P300) auditory evoked potentials over a period of 17 months. They also received shorter assessments immediately following the blast-exposure onsite at Quantico. Results: No acute or longitudinal effects were identified. However, there were some interesting baseline effects found in both groups. Contrary to the expected, the onsite hearing thresholds and distortion product otoacoustic emissions were slightly better at a few frequencies immediately after blast-exposure than measurements obtained with the same equipment weeks to months after each blast-exposure. Conclusions: To date, the current study is the most comprehensive study that evaluates the long-term effects of blast-exposure on hearing. Despite extensive testing to assess changes, the findings of this study suggest that the levels of current exposures used in this military training environment do not seem to have an obvious deleterious effect on hearing

A multi-year assessment of blacklegged tick (Ixodes scapularis) population establishment and Lyme disease risk areas in Ottawa, Canada, 2017-2019.

Canadians face an emerging threat of Lyme disease due to the northward expansion of the tick vector, Ixodes scapularis. We evaluated the degree of I. scapularis population establishment and Borrelia burgdorferi occurrence in the city of Ottawa, Ontario, Canada from 2017-2019 using active surveillance at 28 sites. We used a field indicator tool developed by Clow et al. to determine the risk of I. scapularis establishment for each tick cohort at each site using the results of drag sampling. Based on results obtained with the field indicator tool, we assigned each site an ecological classification describing the pattern of tick colonization over two successive cohorts (cohort 1 was comprised of ticks collected in fall 2017 and spring 2018, and cohort 2 was collected in fall 2018 and spring 2019). Total annual site-specific I. scapularis density ranged from 0 to 16.3 ticks per person-hour. Sites with the highest density were located within the Greenbelt zone, in the suburban/rural areas in the western portion of the city of Ottawa, and along the Ottawa River; the lowest densities occurred at sites in the suburban/urban core. B. burgdorferi infection rates exhibited a similar spatial distribution pattern. Of the 23 sites for which data for two tick cohorts were available, 11 sites were classified as "high-stable", 4 were classified as "emerging", 2 were classified as "low-stable", and 6 were classified as "non-zero". B. burgdorferi-infected ticks were found at all high-stable sites, and at one emerging site. These findings suggest that high-stable sites pose a risk of Lyme disease exposure to the community as they have reproducing tick populations with consistent levels of B. burgdorferi infection. Continued surveillance for I. scapularis, B. burgdorferi, and range expansion of other tick species and emerging tick-borne pathogens is important to identify areas posing a high risk for human exposure to tick-borne pathogens in the face of ongoing climate change and urban expansion

Abstract P313: Association of Positive Emotion and Cardiovascular Health in Hispanics/Latinos With Chronic Kidney Disease: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Introduction: Mounting evidence exists, linking positive emotion (e.g., joy) to favorable health outcomes. Little is known of the relationship between positive emotion and the American Heart Association defined concept of cardiovascular health ( CVH ), particularly in Hispanics/Latinos with chronic kidney disease ( CKD ), a group at high risk of cardiovascular mortality. Hypothesis: In Hispanics/Latinos with CKD, those with greater positive emotion will display more favorable CVH profiles. Methods: We analyzed data from adults ages 18-74 with stage 1-5 non-dialysis dependent CKD enrolled in the Hispanic Community Health Study/Study of Latinos in 2008-11. Positively worded items of the Center for Epidemiologic Studies Depression Scale were used to create a composite positive emotion score (range, 0-6; higher scores indicative of greater positive emotion). A composite overall CVH score was calculated using metrics of diet, body mass index, physical activity, cholesterol, blood pressure, fasting glucose, and smoking status. Each metric was defined as ideal, intermediate, or poor to compute an additive score ranging from 0-14; ideal metrics were also enumerated to compute an ideal CVH score, ranging from 0-7. Linear and logistic regression analyses were used to examine associations of positive emotion with CVH, after adjusting for relevant covariates. Results: Overall, 1,716 participants screened positive for CKD † . In multivariable-adjusted models, a higher positive emotion score was associated with higher overall and ideal CVH scores when modeling CVH as a continuous outcome, (overall CVH: β=0.11, 95% CI=0.01, 0.20; ideal CVH: β=0.06, 95% CI=0.01, 0.11) ( Table 1 ). A 1-unit increase in positive emotion was associated with 1.14 times higher odds of having > 4 (vs. <4) ideal CVH indicators. Conclusions: These findings provide preliminary evidence for an association between positive emotion and CVH in Hispanics/Latinos with CKD. Future studies should explore the mechanism through which emotion influence heart health

The association of positive affect and cardiovascular health in Hispanics/Latinos with chronic kidney disease: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

The beneficial influence of positive affect (e.g., joy) remains unexplored in relation to heart health in adults with chronic kidney disease (CKD)—a population at increased risk for poor cardiovascular health (CVH). Therefore, we evaluated the association of positive affect and CVH in a diverse U.S. population of Hispanics/Latinos with CKD. We analyzed cross-sectional data of adults ages 18–74 enrolled between 2008 and 2011 in the Hispanic Community Health Study/Study of Latinos with prevalent CKD (N = 1712). Positively worded items from the Center for Epidemiologic Studies Depression Scale were used to create a composite positive affect score (0–6; higher scores indicate greater positive affect). Prevalent CKD was defined as estimated glomerular filtration 4 (vs. <4) ideal CVH indicators. Positive affect is associated with favorable CVH profiles in Hispanics/Latinos with CKD. Replication and prospective studies are needed to elucidate whether emotional well-being is a potential therapeutic target for intervention. •Positive affect is unexplored in relation to heart health in adults with chronic kidney disease.•Positive affect is associated with favorable cardiovascular health profiles in Hispanics/Latinos with chronic kidney disease.•No effect modification by age, sex, or heritage background in the relationship of positive affect and cardiovascular health.•Replication studies are needed to elucidate whether emotional wellbeing is a potential therapeutic target for intervention