Effectiveness of septoplasty compared to medical management in adults with obstruction associated with a deviated nasal septum: the NAIROS RCT.

Background: The indications for septoplasty are practice-based, rather than evidence-based. In addition, internationally accepted guidelines for the management of nasal obstruction associated with nasal septal deviation are lacking. Objective: The objective was to determine the clinical effectiveness and cost-effectiveness of septoplasty, with or without turbinate reduction, compared with medical management, in the management of nasal obstruction associated with a deviated nasal septum. Design: This was a multicentre randomised controlled trial comparing septoplasty, with or without turbinate reduction, with defined medical management; it incorporated a mixed-methods process evaluation and an economic evaluation. Setting: The trial was set in 17 NHS secondary care hospitals in the UK. Participants: A total of 378 eligible participants aged > 18 years were recruited. Interventions: Participants were randomised on a 1: 1 basis and stratified by baseline severity and gender to either (1) septoplasty, with or without turbinate surgery (n = 188) or (2) medical management with intranasal steroid spray and saline spray (n = 190). Main outcome measures: The primary outcome was the Sino-nasal Outcome Test-22 items score at 6 months (patient-reported outcome). The secondary outcomes were as follows: patient-reported outcomes - Nasal Obstruction Symptom Evaluation score at 6 and 12 months, Sino-nasal Outcome Test-22 items subscales at 12 months, Double Ordinal Airway Subjective Scale at 6 and 12 months, the Short Form questionnaire-36 items and costs; objective measurements - peak nasal inspiratory flow and rhinospirometry. The number of adverse events experienced was also recorded. A within-trial economic evaluation from an NHS and Personal Social Services perspective estimated the incremental cost per (1) improvement (of ≥ 9 points) in Sino-nasal Outcome Test-22 items score, (2) adverse event avoided and (3) quality-adjusted life-year gained at 12 months. An economic model estimated the incremental cost per quality-adjusted life-year gained at 24 and 36 months. A mixed-methods process evaluation was undertaken to understand/address recruitment issues and examine the acceptability of trial processes and treatment arms. Results: At the 6-month time point, 307 participants provided primary outcome data (septoplasty, n = 152; medical management, n = 155). An intention-to-treat analysis revealed a greater and more sustained improvement in the primary outcome measure in the surgical arm. The 6-month mean Sino-nasal Outcome Test-22 items scores were -20.0 points lower (better) for participants randomised to septoplasty than for those randomised to medical management [the score for the septoplasty arm was 19.9 and the score for the medical management arm was 39.5 (95% confidence interval -23.6 to -16.4; p < 0.0001)]. This was confirmed by sensitivity analyses and through the analysis of secondary outcomes. Outcomes were statistically significantly related to baseline severity, but not to gender or turbinate reduction. In the surgical and medical management arms, 132 and 95 adverse events occurred, respectively; 14 serious adverse events occurred in the surgical arm and nine in the medical management arm. On average, septoplasty was more costly and more effective in improving Sino-nasal Outcome Test-22 items scores and quality-adjusted life-years than medical management, but incurred a larger number of adverse events. Septoplasty had a 15% probability of being considered cost-effective at 12 months at a £20,000 willingness-to-pay threshold for an additional quality-adjusted life-year. This probability increased to 99% and 100% at 24 and 36 months, respectively. Limitations: COVID-19 had an impact on participant-facing data collection from March 2020. Conclusions: Septoplasty, with or without turbinate reduction, is more effective than medical management with a nasal steroid and saline spray. Baseline severity predicts the degree of improvement in symptoms. Septoplasty has a low probability of cost-effectiveness at 12 months, but may be considered cost-effective at 24 months. Future work should focus on developing a septoplasty patient decision aid. Trial registration: This trial is registered as ISRCTN16168569 and EudraCT 2017-000893-12. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/226/07) and is published in full in Health Technology Assessment; Vol. 28, No. 10. See the NIHR Funding and Awards website for further award information.

Septoplasty is an operation to straighten the septum, which is the partition wall between the nostrils inside the nose. Septoplasty can be used as a treatment for people who have a bent septum and symptoms of a blocked nose, such as difficulty sleeping and exercising. Medical management (a saltwater spray to clear the nose followed by a nose steroid spray) is an alternative treatment to septoplasty. The Nasal AIRway Obstruction Study (NAIROS) aimed to find out whether septoplasty or medical management is a better treatment for people with a bent septum and symptoms of a blocked nose. We recruited 378 patients with at least moderately severe nose symptoms from 17 hospitals in England, Scotland and Wales to take part in the NAIROS. Participants were randomly put into one of two groups: septoplasty or medical management. Participants' nose symptoms were measured both when they joined the study and after 6 months, using a questionnaire called the Sino-nasal Outcome Test-22 items. This questionnaire was chosen because patients reported that it included symptoms that were important to them. Other studies have shown that a 9-point change in the Sino-nasal Outcome Test-22 items score is significant. After 6 months, on average, people in the septoplasty group improved by 25 points, whereas people in the medical management group improved by 5 points. We saw improvement after septoplasty among patients with moderate symptoms, and among those with severe symptoms. Most patients who we spoke to after a septoplasty were happy with their treatment, but some would have liked more information about what to expect after their nose surgery. In the short term, septoplasty is more costly than medical management. However, over the longer term, taking into account all the costs and benefits of treatment, suggests that septoplasty would be considered good value for money for the NHS.

Clinical effectiveness of septoplasty versus medical management for nasal airways obstruction: multicentre, open label, randomised controlled trial.

OBJECTIVE: To assess the clinical effectiveness of septoplasty. DESIGN: Multicentre, randomised controlled trial. SETTING: 17 otolaryngology clinics in the UK's National Health Service. PARTICIPANTS: 378 adults (≥18 years, 67% men) newly referred with symptoms of nasal obstruction associated with septal deviation and at least moderate symptoms of nasal obstruction (score >30 on the Nasal Obstruction and Symptom Evaluation (NOSE) scale). INTERVENTIONS: Participants were randomised 1:1 to receive either septoplasty (n=188) or defined medical management (n=190, nasal steroid and saline spray for six months), stratified by baseline symptom severity and sex. MAIN OUTCOME MEASURES: The primary outcome measure was patient reported score on the Sino-Nasal Outcome Test-22 (SNOT-22) at six months, with 9 points defined as the minimal clinically important difference. Secondary outcomes included quality of life and objective nasal airflow measures. RESULTS: Mean SNOT-22 scores at six months were 19.9 (95% confidence interval 17.0 to 22.7) in the septoplasty arm (n=152, intention-to-treat population) and 39.5 (36.1 to 42.9) in the medical management arm (n=155); an estimated 20.0 points lower (better) for participants randomised to receive septoplasty (95% confidence interval 16.4 to 23.6, P<0.001, adjusted for baseline continuous SNOT-22 score and the stratification variables sex and baseline NOSE severity categories). Greater improvement in SNOT-22 scores was predicted by higher baseline symptom severity scores. Quality of life outcomes and nasal airflow measures (including peak nasal inspiratory flow and absolute inhalational nasal partitioning ratio) improved more in participants in the septoplasty group. Readmission to hospital with bleeding after septoplasty occurred in seven participants (4% of 174 who had septoplasty), and a further 20 participants (12%) required antibiotics for infections. CONCLUSIONS: Septoplasty is a more effective intervention than a defined medical management regimen with a nasal steroid and saline spray in adults with nasal obstruction associated with a deviated nasal septum. TRIAL REGISTRATION: ISRCTN Registry ISRCTN16168569.

The Use of the Antigenically Variable Major Surface Protein 2 in the Establishment of Superinfection during Natural Tick Transmission of Anaplasma marginale in Southern Ghana.

Many vector-borne pathogens, including Anaplasma spp., Borrelia spp., Trypanosoma spp., and Plasmodium spp., establish persistent infection in the mammalian host by using antigenic variation. These pathogens are also able to establish strain superinfection, defined as infection of an infected host with additional strains of the same pathogen despite an adaptive immune response. The ability to establish superinfection results in a population of susceptible hosts even with high pathogen prevalence. It is likely that antigenic variation, responsible for persistent infection, also plays a role in the establishment of superinfection. Anaplasma marginale, an antigenically variable, obligate intracellular, tickborne bacterial pathogen of cattle, is well suited for the study of the role of antigenically variant surface proteins in the establishment of superinfection. Anaplasma marginale establishes persistent infection by variation in major surface protein 2 (msp2), which is encoded by approximately six donor alleles that recombine into a single expression site to produce immune escape variants. Nearly all cattle in regions of high prevalence are superinfected. By tracking the acquisition of strains in calves through time, the complement of donor alleles, and how those donor alleles are expressed, we determined that simple variants derived from a single donor allele, rather than multiple donor alleles, were predominant. Additionally, superinfection is associated with the introduction of new donor alleles, but these new donor alleles are not predominantly used to establish superinfection. These findings highlight the potential for competition among multiple strains of a pathogen for resources within the host and the balance between pathogen fitness and antigenic variation.

Both Coinfection and Superinfection Drive Complex Anaplasma marginale Strain Structure in a Natural Transmission Setting.

Vector-borne pathogens commonly establish multistrain infections, also called complex infections. How complex infections are established, either before or after the development of an adaptive immune response, termed coinfection or superinfection, respectively, has broad implications for the maintenance of genetic diversity, pathogen phenotype, epidemiology, and disease control strategies. Anaplasma marginale, a genetically diverse, obligate, intracellular, tick-borne bacterial pathogen of cattle, commonly establishes complex infections, particularly in regions with high transmission rates. Both coinfection and superinfection can be established experimentally; however, it is unknown how complex infections develop in a natural transmission setting. To address this question, we introduced naive animals into a herd in southern Ghana with a high infection prevalence and high transmission pressure and tracked the strain acquisition of A. marginale through time using multilocus sequence typing. As expected, the genetic diversity among strains was high, and 97% of animals in the herd harbored multiple strains. All the introduced naive animals became infected, and three to four strains were typically detected in an individual animal prior to seroconversion, while one to two new strains were detected in an individual animal following seroconversion. On average, the number of strains acquired via superinfection was 16% lower than the number acquired via coinfection. Thus, while complex infections develop via both coinfection and superinfection, coinfection predominates in this setting. These findings have broad implications for the development of control strategies in high-transmission settings.

Correlation Analysis of Perfluoroalkyl Substances in Regional U.S. Precipitation Events.

Per- and polyfluoroalkyl substances (PFAS) are transported in the atmosphere, leading to both wet and dry deposition to the surface. The concentrations of 15 PFAS were measured at six locations in the Ohio-Indiana region of the U.S. during the summer of 2019 and compared to samples collected at a distant site in NW Wyoming. ΣPFAS concentrations ranged from 50-850 ng L-1, with trifluoroacetic acid (TFA) being the dominant compound (~90%). Concentrations of perfluorooctanoic acid (PFOA) and perfluorosulfonic acid (PFOS) were similar to amounts observed over the past 20 years, indicating persistence in the atmosphere despite regulatory action, and the newer species HFPO-DA (GenX) was also widely detected in rainwater. ANOVA modeling and correlation matrices were used to determine association of PFAS concentrations, location, and functional group and chain length. Statistically significant differences (p < 0.05) in PFAS profiles across sites separated by 10-100 km indicate that local point sources strongly contribute to wet deposition. This work introduces correlation plots for PFAS that allow rapid visual comparison of multi-analyte and multi-site data sets.

Assessing safety climate in acute hospital settings: a systematic review of the adequacy of the psychometric properties of survey measurement tools.

BACKGROUND: The perceived importance of safety culture in improving patient safety and its impact on patient outcomes has led to a growing interest in the assessment of safety climate in healthcare organizations; however, the rigour with which safety climate tools were developed and psychometrically tested was shown to be variable. This paper aims to identify and review questionnaire studies designed to measure safety climate in acute hospital settings, in order to assess the adequacy of reported psychometric properties of identified tools. METHODS: A systematic review of published empirical literature was undertaken to examine sample characteristics and instrument details including safety climate dimensions, origin and theoretical basis, and extent of psychometric evaluation (content validity, criterion validity, construct validity and internal reliability). RESULTS: Five questionnaire tools, designed for general evaluation of safety climate in acute hospital settings, were included. Detailed inspection revealed ambiguity around concepts of safety culture and climate, safety climate dimensions and the methodological rigour associated with the design of these measures. Standard reporting of the psychometric properties of developed questionnaires was variable, although evidence of an improving trend in the quality of the reported psychometric properties of studies was noted. Evidence of the theoretical underpinnings of climate tools was limited, while a lack of clarity in the relationship between safety culture and patient outcome measures still exists. CONCLUSIONS: Evidence of the adequacy of the psychometric development of safety climate questionnaire tools is still limited. Research is necessary to resolve the controversies in the definitions and dimensions of safety culture and climate in healthcare and identify related inconsistencies. More importance should be given to the appropriate validation of safety climate questionnaires before extending their usage in healthcare contexts different from those in which they were originally developed. Mixed methods research to understand why psychometric assessment and measurement reporting practices can be inadequate and lacking in a theoretical basis is also necessary.

Incidence of unipolar and bipolar depression, and mania in adults with intellectual disabilities: prospective cohort study.

BACKGROUND: Incidence and determinants of affective disorders among adults with intellectual disabilities are unknown.AimsTo investigate affective disorder incidence, and determinants of unipolar depression, compared with general population reports. METHOD: Prospective cohort study measuring mental ill health of adults with mild to profound intellectual disabilities living within a defined community, over 2 years. RESULTS: There was 70% cohort retention (n = 651). Despite high mood stabiliser use (22.4%), 2-year incident mania at 1.1% is higher than the general population; 0.3% for first episode (standardised incident ratio (SIR) = 41.5, or 52.7 excluding Down syndrome). For any bipolar episode the SIR was 2.0 (or 2.5 excluding Down syndrome). Depression incidence at 7.2% is similar to the general population (SIR = 1.2), suggesting more enduring/undertreatment given the higher prevalence. Problem behaviours (odds ratio (OR) = 2.3) and life events (OR = 1.3) predict incident unipolar depression. CONCLUSIONS: Depression needs improved treatment. Mania has received remarkably little attention in this population, despite high prevalence and incidence (similar to schizophrenia), and given the importance of clinician awareness for accurate differential diagnosis from attention-deficit hyperactivity disorder and problem behaviours.Declaration of interestNone.

Testing the validity of a scenario-based questionnaire to assess the ethical sensitivity of undergraduate medical students.

BACKGROUND: Although medical educators acknowledge the importance of ethics in medical training, there are few validated instruments to assess ethical decision-making. One instrument is the Ethics in Health Care Questionnaire--version 2 (EHCQ-2). The instrument consists of 12 scenarios, each posing an ethical problem in health care, and asking for a decision and rationale. The responses are subjectively scored in four domains: response, issue identification, issue sophistication, and values. GOALS: This study was intended to examine the inter-rater and inter-case reliability of the AHCQ-2 and validity against a national licensing examination of the EHCQ-2 in an international sample. METHODS: A total of 20 final year McMaster students and 45 final year Glasgow students participated in the study. All questionnaires were scored by multiple raters. Generalizability theory was used to examine inter-rater, inter-case and overall test reliability. Validity was assessed by comparing EHCQ-2 scores with scores on the Canadian written licensing examination, both total score and score for the ethics subsection. RESULTS: For both samples, reliability was quite low. Except for the first task, which is multiple choice, inter-rater reliability was 0.08-0.54, and inter-case reliability was 0.14-0.61. Overall test reliability was 0.12-0.54. Correlation between EHCQ-2 task scores and the licensing examination scores ranged from 0.07 to 0.40; there was no evidence that the correlation was higher with the ethics subsection. CONCLUSIONS: The reliability and validity of the measure remains quite low, consistent with other measures of ethical decision-making. However, this does not limit the utility of the instrument as a tool to generate discussion on ethical issues in medicine.

Prevalence of, and factors associated with, problem behaviors in adults with intellectual disabilities.

This study aimed to determine the prevalence of problem behaviors in adults with intellectual disabilities and to investigate which factors are independently associated with problem behaviors. A population-based cohort (n = 1023) had comprehensive individual assessments. Data were examined using multivariate logistic regression. The prevalence of problem behaviors was 22.5% (psychiatrists' opinion) or 18.7% (DC-LD criteria). Factors independently associated with problem behaviors were lower ability level, female gender, living in a congregate care setting or with paid carer support (rather than living with a family carer), having urinary incontinence; visual impairment, not having Down syndrome, and not having severe physical disabilities. Further studies focusing on the etiology, course, and treatment of problem behaviors are required.

Early treatment with prednisolone or acyclovir in Bell's palsy.

BACKGROUND: Corticosteroids and antiviral agents are widely used to treat the early stages of idiopathic facial paralysis (i.e., Bell's palsy), but their effectiveness is uncertain. METHODS: We conducted a double-blind, placebo-controlled, randomized, factorial trial involving patients with Bell's palsy who were recruited within 72 hours after the onset of symptoms. Patients were randomly assigned to receive 10 days of treatment with prednisolone, acyclovir, both agents, or placebo. The primary outcome was recovery of facial function, as rated on the House-Brackmann scale. Secondary outcomes included quality of life, appearance, and pain. RESULTS: Final outcomes were assessed for 496 of 551 patients who underwent randomization. At 3 months, the proportions of patients who had recovered facial function were 83.0% in the prednisolone group as compared with 63.6% among patients who did not receive prednisolone (P<0.001) and 71.2% in the acyclovir group as compared with 75.7% among patients who did not receive acyclovir (adjusted P=0.50). After 9 months, these proportions were 94.4% for prednisolone and 81.6% for no prednisolone (P<0.001) and 85.4% for acyclovir and 90.8% for no acyclovir (adjusted P=0.10). For patients treated with both drugs, the proportions were 79.7% at 3 months (P<0.001) and 92.7% at 9 months (P<0.001). There were no clinically significant differences between the treatment groups in secondary outcomes. There were no serious adverse events in any group. CONCLUSIONS: In patients with Bell's palsy, early treatment with prednisolone significantly improves the chances of complete recovery at 3 and 9 months. There is no evidence of a benefit of acyclovir given alone or an additional benefit of acyclovir in combination with prednisolone. (Current Controlled Trials number, ISRCTN71548196 [controlled-trials.com].).

Incidence and predictors of mental ill-health in adults with intellectual disabilities: prospective study.

BACKGROUND: The point prevalence of mental ill-health among adults with intellectual disabilities is 40.9%, but its incidence is unknown. AIMS: To determine the incidence and possible predictors of mental ill-health. METHOD: Prospective cohort study to measure mental ill-health in adults with mild to profound intellectual disabilities. RESULTS: Cohort retention was 70% (n=651). The 2-year incidence of mental ill-health was 16.3% (12.6% excluding problem behaviours, and 4.6% for problem behaviours) and the standardised incidence ratio was 1.87 (95% CI1.51-2.28). Factors related to incident mental ill-health have some similarities with those in the general population, but also important differences. Type of accommodation and support, previous mental ill-health, urinary incontinence, not having impaired mobility, more severe intellectual disabilities, adult abuse, parental divorce in childhood and preceding life events predicted incident ill-health; however, deprivation, other childhood abuse or adversity, daytime occupation, and marital and smoking status did not. CONCLUSIONS: This is a first step towards intervention trials, and identifying subpopulations for more proactive measures. Public health strategy and policy that is appropriate for this population should be developed.

Psychosis and adults with intellectual disabilities. Prevalence, incidence, and related factors.

OBJECTIVE: To determine the point prevalence, incidence, and remission over a 2-year period of psychosis in adults with intellectual disabilities, and to investigate demographic and clinical factors hypothesised to be associated with psychosis. METHOD: A population-based cohort of adults with intellectual disabilities (n = 1,023) was longitudinally studied. Comprehensive face-to-face mental health assessments to detect psychosis, plus review of family physician, psychiatric, and psychology case notes were undertaken at two time points, 2 years apart. RESULTS: Point prevalence is 2.6% (95% CI = 1.8-3.8%) to 4.4% (95% CI = 3.2-5.8%), dependant upon the diagnostic criteria employed. Two-year incidence is 1.4% (95% CI = 0.6-2.6), and for first episode is 0.5% (95% CI = 0.1-1.3). Compared with the general population, the standardised incidence ratio for first episode psychosis is 10.0 (95% CI = 2.1-29.3). Full remission after 2 years is 14.3%. Visual impairment, previous long-stay hospital residence, smoking, and not having epilepsy were independently associated with psychosis, whereas other factors relevant to the general population were not. CONCLUSIONS: The study of psychosis in persons with intellectual disabilities benefits the population with intellectual disabilities, and advances the understanding of psychosis for the general population. Mental health professionals need adequate knowledge in order to address the high rates of psychosis in this population.

Teaching professionalism in the early years of a medical curriculum: a qualitative study.

CONTEXT: Despite the growing literature on professionalism in undergraduate medical curricula, few studies have examined its delivery. OBJECTIVES: This study investigated tutors' and students' perspectives of the delivery of professionalism in the early years of Glasgow's learner-centred, problem-based learning (PBL), integrated medical curriculum. METHODS: A qualitative approach was adopted involving semistructured interviews, on a 1 in 6 sample of tutors involved in teaching in the early curricular years, and 3 student focus groups. The findings were subjected to between-method triangulation. RESULTS: Involvement in teaching raised students' and tutors' awareness of their professionalism. Learning activities promoting critical reflection were most effective. The integration of professionalism across the domains of Vocational Studies (VS) was important for learning; however, it was not well integrated with the PBL core. Integration was promoted by having the same tutor present throughout all VS sessions. Early patient contact experiences were found to be particularly important. The hidden curriculum provided both opportunities for, and threats to, learning. The small-group format provided a suitable environment for the examination of pre-existing perspectives. The portfolio was an effective learning tool, although its assessment should be formalised. CONCLUSIONS: Reflection is integral to professional development. Early clinical contact is an important part of the process of socialisation, as it allows students to enter the community of practice that is the medical profession. Role models can contribute powerfully to students' learning and identity formation. As students move towards fuller participation, the clinical milieu should be controlled to maximise the influence of role models, and opportunities for guided reflection should be sustained.

An epidemiological investigation of affective disorders with a population-based cohort of 1023 adults with intellectual disabilities.

BACKGROUND: Intellectual disabilities (ID) are common and lifelong. People with ID have health inequalities compared with the general population, but little is known about the epidemiology of affective disorders in this population. This study was undertaken to determine the point prevalence of affective disorders, and to investigate factors associated with depression. METHOD: This population-based study (n=1023) included comprehensive individual assessments with each person. A two-stage process was used for diagnosis of affective disorders. Factors independently associated with depression were investigated through logistic regression analysis. RESULTS: The point prevalence was higher than that reported previously for the general population; DC-LD yielded 3.8% for depression and 0.6% for mania. Additionally, 1.0% had bipolar disorder currently in remission, and 0.1% first episode of mania currently in remission. Similar to general population findings, depression was associated with female gender, smoking, number of preceding family physician appointments, and preceding life events. Important differences were the association of not having a hearing impairment, and the trends for not living in deprived areas, and being married. Unlike general population findings, not having daytime occupation and obesity were not independently associated; nor was previous long-stay hospital residence, severity of ID, or sensory impairments. CONCLUSIONS: This study has found a high point prevalence of affective disorders in adults with ID. The factors associated with depression have differences to general population findings. An understanding of this is important in order to develop appropriate interventions, public strategy and policy, to reduce existing health inequalities.

Mental ill-health in adults with intellectual disabilities: prevalence and associated factors.

BACKGROUND: Reported prevalence of mental ill-health among adults with intellectual disabilities ranges from 7 to 97%, owing to methodological limitations. Little is known about associations. AIMS: To determine the prevalence of mental ill-health in adults with intellectual disabilities and to investigate factors independently associated with it. METHOD: Population-based study (n=1023) with comprehensive individual assessments modelled using regression analyses. RESULTS: Point prevalence of mental ill-health was 40.9% (clinical diagnoses), 35.2% (DC-LD), 16.6% (ICD-10-DCR) and 15.7% (DSM-IV-TR). The most prevalent type was problem behaviours. Mental ill-health was associated with more life events, female gender, type of support, lower ability, more consultations, smoking, incontinence, not having severe physical disabilities and not having immobility; it was not associated with deprived areas, no occupation, communication impairment, epilepsy, hearing impairment or previous institutional residence. CONCLUSIONS: This investigation informs further longitudinal study, and development of appropriate interventions, public health strategy and policy. ICD-10-DCR and DSM-IV-TR undercount mental ill-health in this population compared with DC-LD.