Superinfection exclusion: A viral strategy with short-term benefits and long-term drawbacks.

Viral superinfection occurs when multiple viral particles subsequently infect the same host. In nature, several viral species are found to have evolved diverse mechanisms to prevent superinfection (superinfection exclusion) but how this strategic choice impacts the fate of mutations in the viral population remains unclear. Using stochastic simulations, we find that genetic drift is suppressed when superinfection occurs, thus facilitating the fixation of beneficial mutations and the removal of deleterious ones. Interestingly, we also find that the competitive (dis)advantage associated with variations in life history parameters is not necessarily captured by the viral growth rate for either infection strategy. Putting these together, we then show that a mutant with superinfection exclusion will easily overtake a superinfecting population even if the latter has a much higher growth rate. Our findings suggest that while superinfection exclusion can negatively impact the long-term adaptation of a viral population, in the short-term it is ultimately a winning strategy.

Simulated nonlinear genetic and environmental dynamics of complex traits.

Genetic studies of complex traits often show disparities in estimated heritability depending on the method used, whether by genomic associations or twin and family studies. We present a simulation of individual genomes with dynamic environmental conditions to consider how linear and nonlinear effects, gene-by-environment interactions, and gene-by-environment correlations may work together to govern the long-term development of complex traits and affect estimates of heritability from common methods. Our simulation studies demonstrate that the genetic effects estimated by genome wide association studies in unrelated individuals are inadequate to characterize gene-by-environment interaction, while including related individuals in genome-wide complex trait analysis (GCTA) allows gene-by-environment interactions to be recovered in the heritability. These theoretical findings provide an explanation for the "missing heritability" problem and bridge the conceptual gap between the most common findings of GCTA and twin studies. Future studies may use the simulation model to test hypotheses about phenotypic complexity either in an exploratory way or by replicating well-established observations of specific phenotypes.

Help-seeker satisfaction with diagnosis and treatment of tinnitus.

OBJECTIVE: To examine help-seeker satisfaction with the first communication of a tinnitus diagnosis by a healthcare provider, whether help-seekers undertook treatment and how they rated this treatment. DESIGN: A survey design assessed tinnitus characteristics and distress, health status, help-seeking, diagnosis communication, treatment and patient satisfaction. STUDY SAMPLE: A self-selected cohort and a population-based cohort. RESULTS: Satisfaction scores were examined against demographic, clinical factors, and type of healthcare provider. A total of 281 adults participated (median age 61.6, IQR = 10.8 years), 52.3% sought help for tinnitus and 22.4% received treatment. The most frequently seen healthcare providers were general practitioners (34.0%), audiologists (29.3%) and ear, nose and throat specialists (25.9%). About two-thirds (64.1%) of help-seekers were unsatisfied with the first communication of a tinnitus diagnosis they received, and 56.5% rated their first tinnitus treatment as poor. Help-seekers were significantly more satisfied with audiologists than other providers regarding the communication of the first tinnitus diagnosis. Higher tinnitus distress scores were significantly associated with lower patient satisfaction with communication of first tinnitus diagnosis. No other factors were associated with patient satisfaction. CONCLUSION: There are significant communication barriers along the tinnitus clinical pathway. Identifying and addressing these barriers could improve patient satisfaction.

Conversion Total Hip Arthroplasty in the Era of Bundled Care Payments: Impacts on Costs of Care.

BACKGROUND: Conversion hip arthroplasty is defined as a patient who has had prior open or arthroscopic hip surgery with or without retained hardware that is removed and replaced with arthroplasty components. Currently, it is classified under the same diagnosis-related group as primary total hip arthroplasty (THA); however, it frequently requires a higher cost of care. METHODS: A retrospective study of 228 conversion THA procedures in an orthopaedic specialty hospital was performed. Propensity score matching was used to compare the study group to a cohort of 510 primary THA patients by age, body mass index, sex, and American Society of Anesthesiologists score. These matched groups were compared based on total costs, implants used, operative times, length of stay (LOS), readmissions, and complications. RESULTS: Conversion THA incurred 25% more mean total costs compared to primary THA (P < .05), longer lengths of surgery (154 versus 122 minutes), and hospital LOS (2.1 versus 1.56 days). A subgroup analysis showed a 57% increased cost for cephalomedullary nail conversion, 34% increased cost for sliding hip screw, 33% for acetabular open reduction and internal fixation conversion, and 10% increased costs in closed reduction and percutaneous pinning conversions (all P < .05). There were 5 intraoperative complications in the conversion group versus none in the primary THA group (P < .01), with no statistically significant difference in readmissions. CONCLUSION: Conversion THA is significantly more costly than primary THA and has longer surgical times and greater LOS. Specifically, conversion THA with retained implants had the greatest impact on cost.

State Space Mixture Modeling: Finding People with Similar Patterns of Change.

Increasingly, behavioral scientists encounter data where several individuals were measured on multiple variables over numerous occasions. Many current methods combine these data, assuming all individuals are randomly equivalent. An extreme alternative assumes no one is randomly equivalent. We propose state space mixture modeling as one possible compromise. State space mixture modeling assumes that unknown groups of people exist who share the same parameters of a state space model, and simultaneously estimates both the state space parameters and group membership. The goal is to find people that are undergoing similar change processes over time. The present work demonstrates state space mixture modeling on a simulated data set, and summarizes the results from a large simulation study. The illustration shows how the analysis is conducted, whereas the simulation provides evidence of its general validity and applicability. In the simulation study, sample size had the greatest influence on parameter estimation and the dimension of the change process had the greatest impact on correctly grouping people together, likely due to the distinctiveness of their patterns of change. State space mixture modeling offers one of the best-performing methods for simultaneously drawing conclusions about individual change processes while also analyzing multiple people.

Treatment of chronic or relapsing COVID-19 in immunodeficiency.

BACKGROUND: Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown. OBJECTIVE: Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response. METHODS: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting ≥21 days) or relapsing (≥2 episodes) of COVID-19. RESULTS: We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of ≤20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). Patients receiving no therapy did not clear SARS-CoV-2. CONCLUSIONS: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise.

Establishing a Total Hip T-Score Threshold to Measure Contralateral Hip Bone Mineral Density: Avoiding Missed Diagnosis of Osteoporosis.

Bone mineral density (BMD) of the hip is routinely measured unilaterally, but can differ between left and right. This study aimed to establish total hip T-score thresholds for measuring contralateral hip BMD, to avoid missing the diagnosis of osteoporosis. In 4914 participants (2709 females) in the Busselton Healthy Ageing Study, BMD of both hips and lumbar spine (L1-L4) was measured by dual-energy x-ray absorptiometry (DXA) using a GE Lunar Prodigy Pro densitometer. Least significant change (LSC) was calculated according to International Society for Clinical Densitometry recommendations. For participants whose left-right total hip BMD difference exceeded LSC, the 95th percentile of the difference in T-score was calculated, then added to -2.5 (the cut-off for osteoporosis) to derive T-score thresholds for measuring contralateral hip to avoid a missed diagnosis in 95% of individuals. Participant mean age (±SD) was 57.4 ± 5.8 years; total hip T-score was 0.7 ± 0.1 in males and -0.2 ± 1.1 in females. Left and right total hip BMD were highly correlated (r = 0.943 for males, 0.959 for females), but in 56.2% of males and 50.0% of females, the left-right difference exceeded the LSC of 0.026 g/cm2. In these participants, the 95th percentile of difference in T-score between two hips was 0.872 in males and 0.742 in females. This gave T-score thresholds for measuring contralateral total hip BMD of -1.6 (males) and -1.8 (females). When total hip T-score is between -1.6 and -2.5 (males), or between -1.8 and -2.5 (females), measuring contralateral hip BMD could avoid a missed diagnosis of osteoporosis.

DXA-Derived vs Standard Anthropometric Measures for Predicting Cardiometabolic Risk in Middle-Aged Australian Men and Women.

It is not clear if dual-energy X-ray absorptiometry (DXA) adiposity measures are superior to standard anthropometric measures for predicting cardiometabolic (CM) risk factors in a middle-aged general population. In the Busselton Healthy Ageing Study, we assessed a range of standard anthropometric and DXA-derived adiposity measures to predict metabolic syndrome (MetS) and CM risk factors in 4831 "baby boomers" aged 45-69 yr. Anthropometric and whole body DXA (GE Lunar Prodigy) measures were collected. Cross-sectional relationships of overall adiposity (BMI; DXA fat mass index, body fat %), central adiposity (waist circumference (WC); DXA trunk fat, android fat, abdominal visceral adipose tissue (VAT)) and ratio index (waist-to-hip ratio; DXA trunk/legs fat, android/gynoid ratio, VAT/total fat) with MetS and its components (as both continuous and binary outcomes) were evaluated using linear and logistic regression adjusting for age and lifestyle factors. Youden's Index was used to determine the optimal cut-points for predicting MetS. In linear regression analyses, central adiposity measures showed stronger associations with MetS score and CM risk factors than overall adiposity measures and fat ratio index, and DXA-VAT provided stronger associations than WC. Logistic regression models showed similar findings. For MetS diagnosis present in 35.9% of males and 24.4% of females, the highest odds ratio (95% CI) per SD change was observed for DXA-VAT (males: 5.02 [4.28, 5.88]; females: 3.91 [3.40, 4.49]), which remained significant (all p < 0.001) after further adjustment for BMI (males: 3.27 [2.65, 4.02]; females: 3.37 [2.79, 4.06]) or WC (males: 2.46 [1.95, 3.10]; females: 2.75 [2.21, 3.43]). The optimal DXA-VAT mass cut-point for predicting MetS was 1608 grams in males and 893 grams in females. DXA-VAT was superior to standard anthropometric and other DXA-derived adiposity measures for prediction of cardiometabolic risk factors, and has clinical utility for identifying middle-aged individuals at increased risk of MetS.

Periarticular screws: what's in and what's out of the joint?

Periarticular hardware placement can be challenging and a source of angst for orthopaedic surgeons due to fear of penetrating the articular surface and causing undue harm to the joint. In recent years, many surgeons have turned to computed tomography (CT) and other intraoperative or postoperative modalities to determine whether hardware is truly extraarticular in areas of complex anatomy. Yet, these adjuncts are expensive, time consuming, and often unnecessary given the advancement in understanding of intraoperative fluoroscopy. We present a review article with the goal of empowering surgeons to leave the operating room, with fluoroscopy alone, assured that all hardware is beneath the articular surface that is being worked on. By understanding a simple concept, surgeons can extrapolate the information in this article to any joint and bony surface in the body. While targeted at both residents and surgeons who may not have completed a trauma fellowship, this review can benefit all orthopaedic surgeons alike.

Association between dietary niacin and retinal nerve fibre layer thickness in healthy eyes of different ages.

BACKGROUND: To investigate the relationship between dietary intake of niacin (water-soluble form of vitamin B3 ) and retinal nerve fibre layer (RNFL) thickness in healthy eyes. METHODS: This cross-sectional study examined the association between daily niacin intake and RNFL thickness in three large population-based cohorts with varied age differences. RNFL thickness was extracted from optical coherence tomography data; energy-adjusted niacin intake was estimated from food frequency questionnaires. Linear mixed-effects models were utilised to examine the association between RNFL thickness and energy-adjusted niacin intake. Three separate analyses were conducted, with niacin treated as a continuous, a categorical (quartiles) or a dichotomous (above/below Australian recommended daily intake) variable. RESULTS: In total, 4937 subjects were included in the study [Raine Study Gen2, n = 1204, median age 20; Busselton Healthy Ageing Study (BHAS), n = 1791, median age 64; TwinsUK, n = 1942, median age 64). When analysed as a continuous variable, there was no association between RNFL thickness and niacin intake in any of the three cohorts (95% CI ß: Raine Study Gen 2, -0.174 to 0.074; BHAS, -0.066 to 0.078; TwinsUK -0.435 to 0.350). Similar findings were observed with quartiles of niacin intake and for niacin intakes above or below Australian recommended daily intake levels in all three cohorts. CONCLUSIONS: Dietary intake of niacin from a standard diet does not appear to be associated with age-related RNFL thinning in healthy eyes. Supraphysiological doses of niacin may be required for therapeutic effect in the retina.

Comprehensive engineering of the tarantula venom peptide huwentoxin-IV to inhibit the human voltage-gated sodium channel hNav1.7.

Pain is a significant public health burden in the United States, and current treatment approaches rely heavily on opioids, which often have limited efficacy and can lead to addiction. In humans, functional loss of the voltage-gated sodium channel Nav1.7 leads to pain insensitivity without deficits in the central nervous system. Accordingly, discovery of a selective Nav1.7 antagonist should provide an analgesic without abuse liability and an improved side-effect profile. Huwentoxin-IV, a component of tarantula venom, potently blocks sodium channels and is an attractive scaffold for engineering a Nav1.7-selective molecule. To define the functional impact of alterations in huwentoxin-IV sequence, we produced a library of 373 point mutants and tested them for Nav1.7 and Nav1.2 activity. We then combined favorable individual changes to produce combinatorial mutants that showed further improvements in Nav1.7 potency (E1N, E4D, Y33W, Q34S-Nav1.7 pIC50 = 8.1 ± 0.08) and increased selectivity over other Nav isoforms (E1N, R26K, Q34S, G36I, Nav1.7 pIC50 = 7.2 ± 0.1, Nav1.2 pIC50 = 6.1 ± 0.18, Nav1.3 pIC50 = 6.4 ± 1.0), Nav1.4 is inactive at 3 µm, and Nav1.5 is inactive at 10 µm We also substituted noncoded amino acids at select positions in huwentoxin-IV. Based on these results, we identify key determinants of huwentoxin's Nav1.7 inhibition and propose a model for huwentoxin-IV's interaction with Nav1.7. These findings uncover fundamental features of huwentoxin involved in Nav1.7 blockade, provide a foundation for additional optimization of this molecule, and offer a basis for the development of a safe and effective analgesic.

Multilevel Modeling in Classical Twin and Modern Molecular Behavior Genetics.

For more than a decade, it has been known that many common behavior genetics models for a single phenotype can be estimated as multilevel models (e.g., van den Oord 2001; Guo and Wang 2002; McArdle and Prescott 2005; Rabe-Hesketh et al. 2007). This paper extends the current knowledge to (1) multiple phenotypes such that the method is completely general to the variance structure hypothesized, and (2) both higher and lower levels of nesting. The multi-phenotype method also allows extended relationships to be considered (see also, Bard et al. 2012; Hadfield and Nakagawa 2010). The extended relationship model can then be continuously expanded to merge with the case typically seen in the molecular genetics analyses of unrelated individuals (e.g., Yang et al. 2011). We use the multilevel form of behavior genetics models to fit a multivariate three level model that allows for (1) child level variation from unique environments and additive genetics, (2) family level variation from additive genetics and common environments, and (3) neighborhood level variation from broader geographic contexts. Finally, we provide R (R Development Core Team 2020) functions and code for multilevel specification of several common behavior genetics models using OpenMx (Neale et al. 2016).

Combining Structural-Equation Modeling with Genomic-Relatedness-Matrix Restricted Maximum Likelihood in OpenMx.

There is a long history of fitting biometrical structural-equation models (SEMs) in the pregenomic behavioral-genetics literature of twin, family, and adoption studies. Recently, a method has emerged for estimating biometrical variance-covariance components based not upon the expected degree of genetic resemblance among relatives, but upon the observed degree of genetic resemblance among unrelated individuals for whom genome-wide genotypes are available-genomic-relatedness-matrix restricted maximum-likelihood (GREML). However, most existing GREML software is concerned with quickly and efficiently estimating heritability coefficients, genetic correlations, and so on, rather than with allowing the user to fit SEMs to multitrait samples of genotyped participants. We therefore introduce a feature in the OpenMx package, "mxGREML", designed to fit the biometrical SEMs from the pregenomic era in present-day genomic study designs. We explain the additional functionality this new feature has brought to OpenMx, and how the new functionality works. We provide an illustrative example of its use. We discuss the feature's current limitations, and our plans for its further development.

The Analytic Identification of Variance Component Models Common to Behavior Genetics.

Many behavior genetics models follow the same general structure. We describe this general structure and analytically derive simple criteria for its identification. In particular, we find that variance components can be uniquely estimated whenever the relatedness matrices that define the components are linearly independent (i.e., not confounded). Thus, we emphasize determining which variance components can be identified given a set of genetic and environmental relationships, rather than the estimation procedures. We validate the identification criteria with several well-known models, and further apply them to several less common models. The first model distinguishes child-rearing environment from extended family environment. The second model adds a gene-by-common-environment interaction term in sets of twins reared apart and together. The third model separates measured-genomic relatedness from the scanner site variation in a hypothetical functional magnetic resonance imaging study. The computationally easy analytic identification criteria allow researchers to quickly address model identification issues and define novel variance components, facilitating the development of new research questions.

The Spinal Muscular Atrophy Health Index: A novel outcome for measuring how a patient feels and functions.

INTRODUCTION: The Spinal Muscular Atrophy Health Index (SMA-HI) is a multifaceted, disease-specific, patient-reported outcome to measure an SMA patient's perception of their disease burden. In preparation for upcoming therapeutic trials, we examine the validity, reliability, and usability of the SMA-HI in adults, teenagers, and children with SMA. METHODS: Using data from a cross-sectional study of 359 international adult patients with SMA, we identified the most relevant symptoms to include in the SMA-HI. We utilized factor analysis, patient interviews with adults and minors (age 8-15 years), known-group validity testing, and test-retest reliability assessments to evaluate and refine the SMA-HI. RESULTS: The SMA-HI measures overall disease burden and 15 areas of SMA health. Fifteen adult patients and five patients, age 8 to 15 years, participated in semistructured qualitative interviews and found the SMA-HI to be comprehensive, easily completed, and to have clear meaning. The final SMA-HI and its subscales demonstrated good internal consistency (Cronbach α = 0.77-0.96), high test-retest reliability (intraclass correlation coefficient = 0.60-0.96), and an ability to differentiate between SMA groups with different disease severities affecting areas such as employment and ambulation (P < .0001 for both). DISCUSSION: This research provides evidence that the SMA-HI is a valid, relevant, and reliable outcome measure to assess multifaceted patient-reported disease burden in older children, teenagers, and adults with SMA. The SMA-HI provides an opportunity for researchers and clinicians to measure a SMA patient's perception of their health and determine relevant changes in response to therapeutic intervention or disease progression.

Emotional and interpersonal mechanisms in community SSRI treatment of social anxiety disorder.

BACKGROUND: Affective and interpersonal behavioural patterns characteristic of social anxiety disorder show improvement during treatment with serotonin agonists (e.g., selective serotonin reuptake inhibitors), commonly used in the treatment of social anxiety disorder. The present study sought to establish whether, during community psychopharmacological treatment of social anxiety disorder, changes in positive or negative affect and agreeable or quarrelsome behaviour mediate improvement in social anxiety symptom severity or follow from it. METHODS: Adults diagnosed with social anxiety disorder (n = 48) recorded their interpersonal behaviour and affect naturalistically in an event-contingent recording procedure for 1-week periods before and during the first 4 months of treatment with paroxetine. Participants and treating psychiatrists assessed the severity of social anxiety symptoms monthly. A multivariate latent change score framework examined temporally lagged associations of change in affect and interpersonal behaviour with change in social anxiety symptom severity. RESULTS: Elevated agreeable behaviour and positive affect predicted greater subsequent reduction in social anxiety symptom severity over the following month of treatment. Elevated negative affect, but not quarrelsome behaviour, predicted less subsequent reduction in symptom severity. LIMITATIONS: Limitations included limited assessment of extreme behaviour (e.g., violence) that may have precluded examining the efficacy of paroxetine because of the lack of a placebo control group. CONCLUSION: The present study suggests that interpersonal behaviour and affect may be putative mechanisms of action for serotonergic treatment of social anxiety disorder. Prosocial behaviour and positive affect increase during serotonergic treatment of social anxiety disorder. Specifically, modulating agreeable behaviour, positive affect and negative affect in individuals' daily lives may partially explain and refine clinical intervention.

Prevalence and patterns of multimorbidity in Australian baby boomers: the Busselton healthy ageing study.

BACKGROUND AND OBJECTIVE: Chronic medical conditions accumulate within individuals with age. However, knowledge concerning the trends, patterns and determinants of multimorbidity remains limited. This study assessed the prevalence and patterns of multimorbidity using extensive individual phenotyping in a general population of Australian middle-aged adults. METHODS: Participants (n = 5029, 55% female), born between 1946 and 1964 and attending the cross-sectional phase of the Busselton Healthy Ageing Study (BHAS) between 2010 and 2015, were studied. Prevalence of 21 chronic conditions was estimated using clinical measurement, validated instrument scores and/or self-reported doctor-diagnosis. Non-random patterns of multimorbidity were explored using observed/expected (O/E) prevalence ratios and latent class analysis (LCA). Variables associated with numbers of conditions and class of multimorbidity were investigated. RESULTS: The individual prevalence of 21 chronic conditions ranged from 2 to 54% and multimorbidity was common with 73% of the cohort having 2 or more chronic conditions. (mean ± SD 2.75 ± 1.84, median = 2.00, range 0-13). The prevalence of multimorbidity increased with age, obesity, physical inactivity, tobacco smoking and family history of asthma, diabetes, myocardial infarct or cancer. There were 13 pairs and 27 triplets of conditions identified with a prevalence > 1.5% and O/E > 1.5. Of the triplets, arthritis (> 50%), bowel disease (> 33%) and depression-anxiety (> 33%) were observed most commonly. LCA modelling identified 4 statistically and clinically distinct classes of multimorbidity labelled as: 1) "Healthy" (70%) with average of 1.95 conditions; 2) "Respiratory and Atopy" (11%, 3.65 conditions); 3) "Non-cardiometabolic" (14%, 4.77 conditions), and 4) "Cardiometabolic" (5%, 6.32 conditions). Predictors of multimorbidity class membership differed between classes and differed from predictors of number of co-occurring conditions. CONCLUSION: Multimorbidity is common among middle-aged adults from a general population. Some conditions associated with ageing such as arthritis, bowel disease and depression-anxiety co-occur in clinically distinct patterns and at higher prevalence than expected by chance. These findings may inform further studies into shared biological and environmental causes of co-occurring conditions of ageing. Recognition of distinct patterns of multimorbidity may aid in a holistic approach to care management in individuals presenting with multiple chronic conditions, while also guiding health resource allocation in ageing populations.

Change in the prevalence of myopia in Australian middle-aged adults across 20 years.

BACKGROUND: The prevalence of myopia is increasing globally including in Europe and parts of Asia but Australian data are lacking. This study aim described the change in myopia prevalence in middle-aged Australian adults over approximately a 20-year period. METHODS: Two contemporary Western Australian studies (conducted in mid-late 2010s): the coastal-regional Busselton Healthy Ageing Study (BHAS) and the urban Gen1 of the Raine Study (G1RS) were compared to two earlier studies (early-mid 1990s) in Australia: the urban Blue Mountains Eye Study (BMES) and urban/regional Melbourne Visual Impairment Project (MVIP). Refractive error was measured by autorefraction, vertometry, or subjective refraction. Participants (49-70 years) of European descent without self-reported/diagnosed cataract, corneal disease, or refractive or corneal surgery were included. RESULTS: After exclusions, data were available from 2217, 1760, 700, 2987 and 756 participants from BMES, urban MVIP, regional MVIP, BHAS, and G1RS, respectively. The mean age ranged from 57.1 ± 4.6 years in the G1RS to 60.1 ± 6.0 years in the BMES; 44-48% of participants were male. When stratified by location, the contemporary urban G1RS cohort had a higher age-standardised myopia prevalence than the urban MVIP and BMES cohorts (29.2%, 16.4%, and 23.9%, p < 0.001). The contemporary coastal-regional BHAS had a higher age-standardised myopia prevalence than the regional MVIP cohort (19.4% vs. 13.8%, p = 0.001). CONCLUSIONS: We report an increase in myopia prevalence in older adults in Australia born after World War ll compared to cohorts born before, accounting for urban/regional location. The prevalence of myopia remains relatively low in middle-aged Australian adults.

The utility of 16S rRNA gene sequencing on intraoperative specimens from intracranial infections: an 8-year study in a regional UK neurosurgical unit.

Background: Optimal management of intracranial infections relies on microbiological diagnosis and antimicrobial choice, but conventional culture-based testing is limited by pathogen viability and pre-sampling antimicrobial exposure. Broad-range 16S rRNA gene sequencing has been reported in the management of culture-negative infections but its utility in intracranial infection is not well-described. We studied the efficacy of 16S rRNA gene sequencing to inform microbiological diagnosis and antimicrobial choice in intracranial infections.Methods: This was a retrospective study of all intraoperative neurosurgical specimens sent for 16S rRNA gene sequencing over an 8-year period at a regional neurosurgical centre in the UK. Specimen selection was performed using multidisciplinary approach, combining neurosurgical and infection specialist discussion.Results: Twenty-five intraoperative specimens taken during neurosurgery from 24 patients were included in the study period. The most common reason for referral was pre-sampling antimicrobial exposure (68%). Bacterial rDNA was detected in 60% of specimens. 16S rRNA gene sequencing contributed to microbiological diagnosis in 15 patients and informed antimicrobial management in 10 of 24 patients with intracranial infection. These included targeted antibiotics after detection of a clinically-significant pathogen that had not been identified through other microbiological testing (3 cases), detection of commensal organisms in neurosurgical infection which justified continued broad cover (2 cases) and negative results from intracranial lesions with low clinical suspicion of bacterial infection which justified avoidance or cessation of antibiotics (5 cases).Conclusion: Overall, 16S rRNA gene sequencing represented an incremental improvement in diagnostic testing and was most appropriately used to complement, rather than replace, conventional culture-based testing for intracranial infection.

A brief report: The National Adult Reading Test (NART) is a stable assessment of premorbid intelligence across disease severity in obstructive sleep apnea (OSA).

Obstructive sleep apnea (OSA) is a widely prevalent disorder that can affect cognitive function. The relationship between cognitive function and OSA is known to be affected by an individual's premorbid cognitive ability. Tools to measure premorbid intelligence across OSA disease severity have not been validated. This brief report aims to establish if the National Adult Reading Test (NART) provides a stable estimate of premorbid intelligence across levels of OSA disease severity. We examined if NART scores varied systematically across levels of untreated OSA severity (defined according to the apnea-hypopnea index [AHI]) and mean oxygen saturation in sleep clinic (n = 121) and community samples (n = 398) using regression analysis. Simple linear regression was used to predict NART scores based on the AHI. NART-estimated premorbid IQ scores without demographics did not vary systematically with AHI (F < 1; ß = 0.01) or mean SpO2 (F < 1; ß = 0.12). NART-estimated premorbid IQ scores with added demographic information also did not vary systematically with AHI (F < 1; ß = -0.01) or mean SpO2 (F < 1; ß = 0.15). This preliminary examination shows that the NART provides a stable estimate of premorbid intelligence across untreated OSA disease severity, as demarcated by AHI or mean nocturnal SpO2 .