Reduced risk for Omicron SARS-CoV-2 infection observed in older adults with hybrid immunity.

BACKGROUND: Hybrid SARS-CoV-2 immunity may provide longer duration protection against severe SARS-CoV-2 infection and hospitalisation than purely vaccine-derived immunity. Older adults represent a high-risk group for severe disease, yet available data is skewed towards younger adults. METHODS: A prospective longitudinal study at a large London long-term care facility (LTCF) was conducted from March 2020 to April 2022 to assess the effect of hybrid versus vaccine-only immunity on SARS-CoV-2 infection in older adults during Omicron variant dominance. Hybrid immunity was assessed by a combination of SARS-CoV-2 polymerase chain reaction testing weekly (asymptomatic screening) and as required (symptomatic testing), as well as serial SARS-CoV-2 serology. RESULTS: 280 participants (median age 82 yrs, IQR 76-88 yrs; 95.4% male) were followed up. 168/280 (60%) had evidence of hybrid immunity prior to the Omicron variant wave. Participants with hybrid immunity had substantially lower odds of acquiring COVID-19 infection during the Omicron wave compared to those with vaccine-only immunity (unadjusted odds ratio 0.26, 95% CI 0.14-0.47, chi-squared P < .0001). Participants with hybrid immunity had an odds ratio of 0.40 (0.19-0.79) for asymptomatic infection and 0.15 (0.06-0.34) for symptomatic infection (Likelihood ratio test, P < .0001). DISCUSSION: Our data highlight potential opportunities to target ongoing booster vaccination campaigns for those most at risk of severe infection. Reporting of data in older adults will be of particular value to examine the effect of hybrid immunity as new variants continue to emerge and vaccination strategies evolve.

Remote assessment of the Penn computerised neurocognitive battery in individuals with 22q11.2 deletion syndrome.

BACKGROUND: Neurocognitive functioning is an integral phenotype of 22q11.2 deletion syndrome relating to severity of psychopathology and outcomes. A neurocognitive battery that could be administered remotely to assess multiple cognitive domains would be especially beneficial to research on rare genetic variants, where in-person assessment can be unavailable or burdensome. The current study compares in-person and remote assessments of the Penn computerised neurocognitive battery (CNB). METHODS: Participants (mean age = 17.82, SD = 6.94 years; 48% female) completed the CNB either in-person at a laboratory (n = 222) or remotely (n = 162). RESULTS: Results show that accuracy of CNB performance was equivalent across the two testing locations, while slight differences in speed were detected in 3 of the 11 tasks. CONCLUSIONS: These findings suggest that the CNB can be used in remote settings to assess multiple neurocognitive domains.

Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey.

BACKGROUND: Accurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients. For use in community testing, evaluation of finger-prick self-tests, in non-hospitalised individuals, is required. METHODS: Sensitivity analysis was conducted on 276 non-hospitalised participants. All had tested positive for SARS-CoV-2 by reverse transcription PCR and were ≥21 days from symptom onset. In phase I, we evaluated five LFIAs in clinic (with finger prick) and laboratory (with blood and sera) in comparison to (1) PCR-confirmed infection and (2) presence of SARS-CoV-2 antibodies on two 'in-house' ELISAs. Specificity analysis was performed on 500 prepandemic sera. In phase II, six additional LFIAs were assessed with serum. FINDINGS: 95% (95% CI 92.2% to 97.3%) of the infected cohort had detectable antibodies on at least one ELISA. LFIA sensitivity was variable, but significantly inferior to ELISA in 8 out of 11 assessed. Of LFIAs assessed in both clinic and laboratory, finger-prick self-test sensitivity varied from 21% to 92% versus PCR-confirmed cases and from 22% to 96% versus composite ELISA positives. Concordance between finger-prick and serum testing was at best moderate (kappa 0.56) and, at worst, slight (kappa 0.13). All LFIAs had high specificity (97.2%-99.8%). INTERPRETATION: LFIA sensitivity and sample concordance is variable, highlighting the importance of evaluations in setting of intended use. This rigorous approach to LFIA evaluation identified a test with high specificity (98.6% (95%CI 97.1% to 99.4%)), moderate sensitivity (84.4% with finger prick (95% CI 70.5% to 93.5%)) and moderate concordance, suitable for seroprevalence surveys.

Challenges of Remote Medical Care in South Sudan: Centipede Bites.

Centipede bites are a constant risk throughout tropical regions and have the rare potential for systemic side effects. We report a case of multiple centipede bites in South Sudan that was complicated by severe pain refractory to opioid analgesia and an unusual association with acute involuntary muscle contractions. Treatment with local anesthetic, antihistamines, and corticosteroids was effective. This report aims to add to the local literature; because of decades of internal conflict and poor infrastructure, reporting of health data from South Sudan is severely lacking. Further investigation into the pharmacological variation and activity of toxic peptides in centipede venom is recommended. As it stands, this case provides additional information on potential effects of centipede envenomation that should be useful to any healthcare providers preparing for the delivery of remote medical care throughout the Great Upper Nile region.

Feasibility and Acceptability of Ecological Momentary Assessment of Daily Functioning Among Older Adults with HIV.

OBJECTIVE: This study aimed to examine the feasibility, acceptability, and initial validity of using smartphone-based ecological momentary assessment (EMA) to assess daily functioning and other behavioral factors among older HIV+ adults. METHODS: Twenty older HIV+ adults (mean age: 59 years) completed laboratory-based neurobehavioral and functional assessments then completed EMA surveys via smartphones five times per day for one week. RESULTS: Excellent EMA adherence (86.4%) was found, and participants rated their experience with EMA methods positively. Time-use data indicated participants were spending 74% of their waking-sampled time at home, 63% of their time alone, and 32% of their time engaged in passive leisure activities (e.g., watching TV). Better neurocognitive and functional capacity abilities were correlated with less time spent in passive leisure activities. Lastly, mood and cognitive symptom data collected via EMA were significantly associated with scores from laboratory-based assessments of these same constructs. CONCLUSIONS: EMA via smartphones is a feasible and acceptable data collection method among older HIV+ adults and appears to be a promising mobile tool to assess daily functioning behaviors in HIV. These preliminary findings indicate older HIV+ adults are spending a considerable amount of time at home, alone, and engaged in passive leisure activities, primarily watching TV. EMA may contribute to future research examining functional disability among the growing population of older HIV+ adults.

Characterizing social environment's association with neurocognition using census and crime data linked to the Philadelphia Neurodevelopmental Cohort.

BACKGROUND: The contribution of 'environment' has been investigated across diverse and multiple domains related to health. However, in the context of large-scale genomic studies the focus has been on obtaining individual-level endophenotypes with environment left for future decomposition. Geo-social research has indicated that environment-level variables can be reduced, and these composites can then be used with other variables as intuitive, precise representations of environment in research. METHOD: Using a large community sample (N = 9498) from the Philadelphia area, participant addresses were linked to 2010 census and crime data. These were then factor analyzed (exploratory factor analysis; EFA) to arrive at social and criminal dimensions of participants' environments. These were used to calculate environment-level scores, which were merged with individual-level variables. We estimated an exploratory multilevel structural equation model (MSEM) exploring associations among environment- and individual-level variables in diverse communities. RESULTS: The EFAs revealed that census data was best represented by two factors, one socioeconomic status and one household/language. Crime data was best represented by a single crime factor. The MSEM variables had good fit (e.g. comparative fit index = 0.98), and revealed that environment had the largest association with neurocognitive performance (ß = 0.41, p < 0.0005), followed by parent education (ß = 0.23, p < 0.0005). CONCLUSIONS: Environment-level variables can be combined to create factor scores or composites for use in larger statistical models. Our results are consistent with literature indicating that individual-level socio-demographic characteristics (e.g. race and gender) and aspects of familial social capital (e.g. parental education) have statistical relationships with neurocognitive performance.

An analysis of existing national action plans for antimicrobial resistance-gaps and opportunities in strategies optimising antibiotic use in human populations.

At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs. Although there have been regional and global analyses of NAPs from a One Health and policy perspective, a global assessment of the NAP objectives targeting antimicrobial use in human populations is needed. In this Health Policy, we report a systematic evidence synthesis of existing NAPs that are aimed at tackling AMR in human populations. We find marked gaps and variability in maturity of NAP development and operationalisation across the domains of: (1) policy and strategic planning; (2) medicines management and prescribing systems; (3) technology for optimised antimicrobial prescribing; (4) context, culture, and behaviours; (5) operational delivery and monitoring; and (6) patient and public engagement and involvement. The gaps identified in these domains highlight opportunities to facilitate sustainable delivery and operationalisation of NAPs. The findings from this analysis can be used at country, regional, and global levels to identify AMR-related priorities that are relevant to infrastructure needs and contexts.

Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation.

BACKGROUND: Older adults, particularly in long-term care facilities (LTCF), remain at considerable risk from SARS-CoV-2. Data on the protective effect and mechanisms of hybrid immunity are skewed towards young adults precluding targeted vaccination strategies. METHODS: A single-centre longitudinal seroprevalence vaccine response study was conducted with 280 LCTF participants (median 82 yrs, IQR 76-88 yrs; 95.4% male). Screening by SARS-CoV-2 polymerase chain reaction with weekly asymptomatic/symptomatic testing (March 2020-October 2021) and serology pre-/post-two-dose Pfizer-BioNTech BNT162b2 vaccination for (i) anti-nucleocapsid, (ii) quantified anti-receptor binding domain (RBD) antibodies at three time-intervals, (iii) pseudovirus neutralisation, and (iv) inhibition by anti-RBD competitive ELISA were conducted. Neutralisation activity: antibody titre relationship was assessed via beta linear-log regression and RBD antibody-binding inhibition: post-vaccine infection relationship by Wilcoxon rank sum test. RESULTS: Here we show neutralising antibody titres are 9.2-fold (95% CI 5.8-14.5) higher associated with hybrid immunity (p < 0.00001); +7.5-fold (95% CI 4.6-12.1) with asymptomatic infection; +20.3-fold, 95% (CI 9.7-42.5) with symptomatic infection. A strong association is observed between antibody titre: neutralising activity (p < 0.00001) and rising anti-RBD antibody titre: RBD antibody-binding inhibition (p < 0.001), although 18/169 (10.7%) participants with high anti-RBD titre (>100BAU/ml), show inhibition <75%. Higher RBD antibody-binding inhibition values are associated with hybrid immunity and reduced likelihood of infection (p = 0.003). CONCLUSIONS: Hybrid immunity in older adults was associated with considerably higher antibody titres, neutralisation and inhibition capacity. Instances of high anti-RBD titre with lower inhibition suggests antibody quantity and quality as independent potential correlates of protection, highlighting added value of measuring inhibition over antibody titre alone to inform vaccine strategy.

Older adults continue to be at risk of COVID-19, particularly in residential care home settings. We investigated the effect of infection and vaccination on antibody development and subsequent SARS-CoV-2 infection in older adults. Antibodies are proteins that the immune system produces on infection or vaccination that can help respond to subsequent infection with SARS-CoV-2. We found that older adults produce antibodies to SARS-CoV-2 after 2-doses of Pfizer BioNTech BNT162b2 vaccine. The strongest immune responses were seen among those older adults who also had prior history of infection. The results highlight the importance of both antibody quality and quantity when considering possible indicators of protection against COVID-19 and supports the need for a third, booster, vaccination in this age group..

Squeaking in third- and fourth-generation ceramic-on-ceramic total hip arthroplasty: meta-analysis and systematic review.

Postoperative squeaking in ceramic-on-ceramic total hip arthroplasty is a recently emerging phenomenon. We performed a meta-analysis of published data to examine patient and procedural risk factors. Twelve studies (6137 patients, total) were analyzed, with 150 patients (2.4%) complaining of squeaking. The only significant patient risk factor was increasing body mass index (P = .03, n = 2957). There was no significance found with patient age, sex, height, weight, or procedural laterality for squeak incidence. For implant type, the presence of a Stryker Accolade femoral stem (beta-titanium; Stryker Orthopedics, Mahwah, NJ) was significantly found to increase squeak (P < .0001, n = 4654). The presence of a raised metallic lip on the acetabular component was not found to be associated with squeak. Acetabular cup position was also not found to have a significant bearing on the incidence of squeaking.

Early identification of high-risk individuals for monoclonal antibody therapy and prophylaxis is feasible by SARS-CoV-2 anti-spike antibody specific lateral flow assay.

Monoclonal antibody therapy has been approved for prophylaxis and treatment of severe COVID-19 infection. Greatest benefit appears limited to those yet to mount an effective immune response from natural infection or vaccination, but concern exists around ability to make timely assessment of immune status of community-based patients where laboratory-based serodiagnostics predominate. Participants were invited to undergo paired laboratory-based (Abbott Architect SARS-CoV-2 IgG Quant II chemiluminescent microparticle immunoassay) and lateral flow assays (LFA; a split SARS-CoV-2 IgM/IgG and total antibody test) able to detect SARS-CoV-2 anti-spike antibodies. LFA band strength was compared with CMIA titer by log-linear regression. Two hundred individuals (median age 43.5 years, IQR 30-59; 60.5% female) underwent testing, with a further 100 control sera tested. Both LFA band strengths correlated strongly with CMIA antibody titers (P < 0.001). LFAs have the potential to assist in early identification of seronegative patients who may demonstrate the greatest benefit from monoclonal antibody treatment.

Catastrophic polyethylene failure diagnosed with magnetic resonance imaging in a painful total knee arthroplasty.

Determining the etiology of a painful knee after arthroplasty can be extremely challenging. Traditionally, orthopedists relied mainly on physical examination, laboratory results, serial radiographs, and 3-phase bone or indium-labeled white blood cell scans; however, recent advances in magnetic resonance imaging (MRI) software have given orthopedists another powerful tool in their diagnostic armamentarium. We provide the MRI software modification technique for metallic artifact reduction as well as present a novel case in which MRI was used to diagnose catastrophic polyethylene postfailure in a posterior cruciate ligament substituting knee. Although the role for MRI in the postarthroplasty knee has yet to be clearly defined, its utility in working up a painful arthroplasty when history, physical examination, and other diagnostic utilities fail to provide answers is clearly demonstrated in this case.

Targeting location relates to treatment response in active but not sham rTMS stimulation.

BACKGROUND: Precise targeting of brain functional networks is believed critical for treatment efficacy of rTMS (repetitive pulse transcranial magnetic stimulation) in treatment resistant major depression. OBJECTIVE: To use imaging data from a "failed" clinical trial of rTMS in Veterans to test whether treatment response was associated with rTMS coil location in active but not sham stimulation, and compare fMRI functional connectivity between those stimulation locations. METHODS: An imaging substudy of 49 Veterans (mean age, 56 years; range, 27-78 years; 39 male) from a randomized, sham-controlled, double-blinded clinical trial of rTMS treatment, grouping participants by clinical response, followed by group comparisons of treatment locations identified by individualized fiducial markers on structural MRI and resting state fMRI derived networks. RESULTS: The average stimulation location for responders versus nonresponders differed in the active but not in the sham condition (P = .02). The average responder location derived from the active condition showed significant negative functional connectivity with the subgenual cingulate (P < .001) while the nonresponder location did not (P = .17), a finding replicated in independent cohorts of 84 depressed and 35 neurotypical participants. The responder and nonresponder stimulation locations evoked different seed based networks (FDR corrected clusters, all P < .03), revealing additional brain regions related to rTMS treatment outcome. CONCLUSION: These results provide evidence from a randomized controlled trial that clinical response to rTMS is related to accuracy in targeting the region within DLPFC that is negatively correlated with subgenual cingulate. These results support the validity of a neuro-functionally informed rTMS therapy target in Veterans.

SARS-CoV-2 lateral flow assays for possible use in national covid-19 seroprevalence surveys (React 2): diagnostic accuracy study.

OBJECTIVE: To evaluate the performance of new lateral flow immunoassays (LFIAs) suitable for use in a national coronavirus disease 2019 (covid-19) seroprevalence programme (real time assessment of community transmission 2-React 2). DESIGN: Diagnostic accuracy study. SETTING: Laboratory analyses were performed in the United Kingdom at Imperial College, London and university facilities in London. Research clinics for finger prick sampling were run in two affiliated NHS trusts. PARTICIPANTS: Sensitivity analyses were performed on sera stored from 320 previous participants in the React 2 programme with confirmed previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Specificity analyses were performed on 1000 prepandemic serum samples. 100 new participants with confirmed previous SARS-CoV-2 infection attended study clinics for finger prick testing. INTERVENTIONS: Laboratory sensitivity and specificity analyses were performed for seven LFIAs on a minimum of 200 serum samples from participants with confirmed SARS-CoV-2 infection and 500 prepandemic serum samples, respectively. Three LFIAs were found to have a laboratory sensitivity superior to the finger prick sensitivity of the LFIA currently used in React 2 seroprevalence studies (84%). These LFIAs were then further evaluated through finger prick testing on participants with confirmed previous SARS-CoV-2 infection: two LFIAs (Surescreen, Panbio) were evaluated in clinics in June-July 2020 and the third LFIA (AbC-19) in September 2020. A spike protein enzyme linked immunoassay and hybrid double antigen binding assay were used as laboratory reference standards. MAIN OUTCOME MEASURES: The accuracy of LFIAs in detecting immunoglobulin G (IgG) antibodies to SARS-CoV-2 compared with two reference standards. RESULTS: The sensitivity and specificity of seven new LFIAs that were analysed using sera varied from 69% to 100%, and from 98.6% to 100%, respectively (compared with the two reference standards). Sensitivity on finger prick testing was 77% (95% confidence interval 61.4% to 88.2%) for Panbio, 86% (72.7% to 94.8%) for Surescreen, and 69% (53.8% to 81.3%) for AbC-19 compared with the reference standards. Sensitivity for sera from matched clinical samples performed on AbC-19 was significantly higher with serum than finger prick at 92% (80.0% to 97.7%, P=0.01). Antibody titres varied considerably among cohorts. The numbers of positive samples identified by finger prick in the lowest antibody titre quarter varied among LFIAs. CONCLUSIONS: One new LFIA was identified with clinical performance suitable for potential inclusion in seroprevalence studies. However, none of the LFIAs tested had clearly superior performance to the LFIA currently used in React 2 seroprevalence surveys, and none showed sufficient sensitivity and specificity to be considered for routine clinical use.

Effect of Temperature on Severity of Fusarium Wilt of Lettuce Caused by Fusarium oxysporum f. sp. lactucae.

The effect of temperature on Fusarium wilt of lettuce (Lactuca sativa), caused by Fusarium oxysporum f. sp. lactucae, was examined in a controlled environment. Nine lettuce cultivars planted in infested potting mix (500 or 5,000 CFU/g) were maintained under high/low diurnal temperature regimes of 26/18°C, 28/20°C, or 33/26°C. Three cultivars were resistant to Fusarium wilt under all test conditions, and thus were little affected by differences in inoculum level or temperature. The remaining cultivars were more susceptible and manifested more severe symptoms at the higher inoculum level and when maintained at higher temperatures. The tendency for the disease to be more severe under warmer conditions may be due, in part, to an effect of temperature on growth of the pathogen. Radial growth rates calculated for six isolates of F. oxysporum f. sp. lactucae were observed to increase from 10°C up to an apparent maximum near 25°C. The results of this study suggest that growers can reduce the risk of damage from Fusarium wilt by avoiding susceptible cultivars during the warmest planting periods. Further, isolates of F. oxysporum f. sp. lactucae were shown to have a distinctive colony morphology in culture, which made it possible to distinguish them from nonpathogenic strains.

Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK: a prospective multicentre cohort study.

BACKGROUND: Health-care workers constitute a high-risk population for acquisition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Capacity for acute diagnosis via PCR testing was limited for individuals with mild to moderate SARS-CoV-2 infection in the early phase of the COVID-19 pandemic and a substantial proportion of health-care workers with suspected infection were not tested. We aimed to investigate the performance of point-of-care and laboratory serology assays and their utility in late case identification, and to estimate SARS-CoV-2 seroprevalence. METHODS: We did a prospective multicentre cohort study between April 8 and June 12, 2020, in two phases. Symptomatic health-care workers with mild to moderate symptoms were eligible to participate 14 days after onset of COVID-19 symptoms, as per the Public Health England (PHE) case definition. Health-care workers were recruited to the asymptomatic cohort if they had not developed PHE-defined COVID-19 symptoms since Dec 1, 2019. In phase 1, two point-of-care lateral flow serological assays, the Onsite CTK Biotech COVID-19 split IgG/IgM Rapid Test (CTK Bitotech, Poway, CA, USA) and the Encode SARS-CoV-2 split IgM/IgG One Step Rapid Test Device (Zhuhai Encode Medical Engineering, Zhuhai, China), were evaluated for performance against a laboratory immunoassay (EDI Novel Coronavirus COVID-19 IgG ELISA kit [Epitope Diagnostics, San Diego, CA, USA]) in 300 samples from health-care workers and 100 pre-COVID-19 negative control samples. In phase 2 (n=6440), serosurveillance was done among 1299 (93·4%) of 1391 health-care workers reporting symptoms, and in a subset of asymptomatic health-care workers (405 [8·0%] of 5049). FINDINGS: There was variation in test performance between the lateral flow serological assays; however, the Encode assay displayed reasonable IgG sensitivity (127 of 136; 93·4% [95% CI 87·8-96·9]) and specificity (99 of 100; 99·0% [94·6-100·0]) among PCR-proven cases and good agreement (282 of 300; 94·0% [91·3-96·7]) with the laboratory immunoassay. By contrast, the Onsite assay had reduced sensitivity (120 of 136; 88·2% [95% CI 81·6-93·1]) and specificity (94 of 100; 94·0% [87·4-97·8]) and agreement (254 of 300; 84·7% [80·6-88·7]). Five (7%) of 70 PCR-positive cases were negative across all assays. Late changes in lateral flow serological assay bands were recorded in 74 (9·3%) of 800 cassettes (35 [8·8%] of 400 Encode assays; 39 [9·8%] of 400 Onsite assays), but only seven (all Onsite assays) of these changes were concordant with the laboratory immunoassay. In phase 2, seroprevalence among the workforce was estimated to be 10·6% (95% CI 7·6-13·6) in asymptomatic health-care workers and 44·7% (42·0-47·4) in symptomatic health-care workers. Seroprevalence across the entire workforce was estimated at 18·0% (95% CI 17·0-18·9). INTERPRETATION: Although a good positive predictive value was observed with both lateral flow serological assays and ELISA, this agreement only occurred if the pre-test probability was modified by a strict clinical case definition. Late development of lateral flow serological assay bands would preclude postal strategies and potentially home testing. Identification of false-negative results among health-care workers across all assays suggest caution in interpretation of IgG results at this stage; for now, testing is perhaps best delivered in a clinical setting, supported by government advice about physical distancing. FUNDING: None.