COPD in Never-Smokers: BOLD Australia Study.

Purpose: Tobacco smoking is the major risk factor for COPD, and it is common for other risk factors in never-smokers to be overlooked. We examined the prevalence of COPD among never-smokers in Australia and identified associated risk factors. Methods: We used data from the Australia Burden of Obstructive Lung Disease (BOLD) study, a cross-section of people aged ≥40 years from six sites. Participants completed interviews and post-bronchodilator spirometry. COPD was primarily defined as an FEV1/FVC ratio <0.70 and secondarily as the ratio less than the lower limit of normal (LLN). Results: The prevalence of COPD in the 1656 never-smokers who completed the study was 10.5% (95% CI: 9.1-12.1%) [ratio

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.

Acute disseminated actinomycosis presenting as pneumonia with bilateral pulmonary nodules and pelvic osteomyelitis in an immunocompetent patient.

Actinomycosis is an indolent human infectious disease caused by gram-positive anaerobic filamentous bacteria Actinomyces. Despite its sluggish growth, clinical manifestations can be acute or chronic. Over the last five decades, a significant incidence decline in the western world is due to the discovery of effective antimicrobials and improved oral hygiene. Actinomycosis is now rarely encountered and often misdiagnosed as its manifestations mimic malignancy and other infectious diseases. Due to prior use of antimicrobials, laboratory diagnostic processes often fail to isolate the organism making it arduous to establish the diagnosis. Clinical classification is based on the geographical distribution of the disease as oro-cervicofacial, thoracic, abdominopelvic, neurologic, musculoskeletal, and disseminated. Disseminated and pulmonary actinomycosis in an immunocompetent individual is extremely rare. Here we present a 53-year-old healthy male presenting with acute disseminated actinomycosis with bilateral pulmonary nodules, right upper lobe pneumonia, and pelvic osteomyelitis from Actinomyces odontolyticus infection.

Tuberculosis Aortitis and Mycotic Pseudo-aneurysm of the Infra-renal Aorta after Intravesicular BCG Therapy.

We report a patient who presented with a rapidly expanding symptomatic tuberculous aortitis and mycotic pseudo-aneurysm of the infra-renal aorta, after intra-vesical BCG chemotherapy for bladder cancer, treated by required emergency open aneurysm repair. His case highlights this rare complication of intravesical BCG treatment, haematological seeding causing tuberculous aortitis and mycotic pseudo-aneurysm formation of the infra-renal aorta. It also illustrates successful treatment with emergency open surgery, local debridement of mycotic pseudoaneurysm, in-situ surgical reconstruction using a custom bovine-wrap interposition graft to create a neo-aorta and multi-agent anti-tuberculous chemotherapy.

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.

Normal limits for oscillometric bronchodilator responses and relationships with clinical factors.

INTRODUCTION: We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide clinical interpretation. We also examined relationships between bronchodilator responses and respiratory symptoms, asthma diagnosis, smoking and baseline lung function. METHODS: Subjects recruited from Sydney, Melbourne and Busselton, Australia, underwent measurements of spirometry, resistance (R rs6 ) and reactance (X rs6 ) at 6 Hz, before and after inhalation of salbutamol 200 µg. Respiratory symptoms and/or medication use, asthma diagnosis, and smoking were recorded. Threshold bronchodilator responses were defined as the fifth percentile of decrease in R rs6 and 95th percentile increase in X rs6 in a healthy subgroup. RESULTS: Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for ΔR rs6 was -1.38 cmH2O·s·L-1 (-30.0% or -1.42 Z-scores) and upper threshold for ΔX rs6 was 0.57 cmH2O·s·L-1 (1.36 Z-scores). Respiratory symptoms and/or medication use, asthma diagnosis, and smoking all predicted bronchodilator response, as did baseline oscillometry and spirometry. When categorised into clinically relevant groups according to those predictors, ΔX rs6 was more sensitive than spirometry in smokers without current asthma or chronic obstructive pulmonary disease (COPD), ∼20% having a positive response. Using absolute or Z-score change provided similar prevalences of responsiveness, except in COPD, in which responsiveness measured by absolute change was twice that for Z-score. DISCUSSION: This study describes normative thresholds for bronchodilator responses in oscillometry parameters, including intra-breath parameters, as determined by absolute, relative and Z-score changes. Positive bronchodilator response by oscillometry correlated with clinical factors and baseline function, which may inform the clinical interpretation of oscillometry.

A Dispatch Screening Tool to Identify Patients at High Risk for COVID-19 in the Prehospital Setting.

INTRODUCTION: Emergency medical services (EMS) dispatchers have made efforts to determine whether patients are high risk for coronavirus disease 2019 (COVID-19) so that appropriate personal protective equipment (PPE) can be donned. A screening tool is valuable as the healthcare community balances protection of medical personnel and conservation of PPE. There is little existing literature on the efficacy of prehospital COVID-19 screening tools. The objective of this study was to determine the positive and negative predictive value of an emergency infectious disease surveillance tool for detecting COVID-19 patients and the impact of positive screening on PPE usage. METHODS: This study was a retrospective chart review of prehospital care reports and hospital electronic health records. We abstracted records for all 911 calls to an urban EMS from March 1-July 31, 2020 that had a documented positive screen for COVID-19 and/or had a positive COVID-19 test. The dispatch screen solicited information regarding travel, sick contacts, and high-risk symptoms. We reviewed charts to determine dispatch-screening results, the outcome of patients' COVID-19 testing, and documentation of crew fidelity to PPE guidelines. RESULTS: The sample size was 263. The rate of positive COVID-19 tests for all-comers in the state of Massachusetts was 2.0%. The dispatch screen had a sensitivity of 74.9% (confidence interval [CI], 69.21-80.03) and a specificity of 67.7% (CI, 66.91-68.50). The positive predictive value was 4.5% (CI, 4.17-4.80), and the negative predictive value was 99.3% (CI, 99.09-99.40). The most common symptom that triggered a positive screen was shortness of breath (51.5% of calls). The most common high-risk population identified was skilled nursing facility patients (19.5%), but most positive tests did not belong to a high-risk population (58.1%). The EMS personnel were documented as wearing full PPE for the patient in 55.7% of encounters, not wearing PPE in 8.0% of encounters, and not documented in 27.9% of encounters. CONCLUSION: This dispatch-screening questionnaire has a high negative predictive value but moderate sensitivity and therefore should be used with some caution to guide EMS crews in their PPE usage. Clinical judgment is still essential and may supersede screening status.

The prevalence and comorbidities of obstructive sleep apnea in middle-aged men and women: the Busselton Healthy Ageing Study.

STUDY OBJECTIVES: Population surveys suggest the prevalence of obstructive sleep apnea (OSA) is high and increasing and that risk factors and outcomes differ between sexes. To explore these relationships we assessed current OSA prevalence, potential risk factors and comorbidities, and their changes relative to previous estimates in the same community. METHODS: All adults on the Busselton, Australia, electoral roll born 1946-1964 were invited to participate in a general health survey. Of the 5,037 (62% response rate) respondents, 3,686 successfully completed overnight 2-channel (oximetry, airflow) sleep studies. These were scored and categorized as nil, mild, moderate, or severe OSA based on apnea-hypopnea index (< 5, ≥ 5 to < 15, ≥ 15 to < 30, and ≥ 30 events/h, respectively). Sleep scores were related to participant characteristics and health profiles. OSA prevalence was compared with previous surveys in the community. RESULTS: Prevalences of any and moderate-severe OSA were 57.7% and 20.2% in males and 41.7% and 10.0% in females. Matched for age group, the prevalence of moderate-severe OSA was similar to that in 2007 (males 24.6%, females 9.8%) and was higher than in 1995 (males 4.7%). OSA was associated with age, body mass index, and alcohol intake in males and age and body mass index in females. Conditions associated with OSA included hypertension and current depression in males and hypertension, skin cancer, and diabetes in females. CONCLUSIONS: Prevalence of OSA in a middle-aged, predominantly White population in 2010-2015 was high, has increased since 1995, and has remained stable since 2007. Sex differences exist in associated features, including potential risk factors and comorbidities. CITATION: Cunningham J, Hunter M, Budgeon C, et al. The prevalence and comorbidities of obstructive sleep apnea in middle-aged men and women: the Busselton Healthy Ageing Study. J Clin Sleep Med. 2021;17(10):2029-2039.

Airway microbial communities, smoking and asthma in a general population sample.

BACKGROUND: Normal airway microbial communities play a central role in respiratory health but are poorly characterized. Cigarette smoking is the dominant global environmental influence on lung function, and asthma has become the most prevalent chronic respiratory disease worldwide. Both conditions have major microbial components that are incompletely defined. METHODS: We investigated airway bacterial communities in a general population sample of 529 Australian adults. Posterior oropharyngeal swabs were analyzed by sequencing of the 16S rRNA gene. The microbiota were characterized according to their prevalence, abundance and network memberships. FINDINGS: The microbiota were similar across the general population, and were strongly organized into co-abundance networks. Smoking was associated with diversity loss, negative effects on abundant taxa, profound alterations to network structure and expansion of Streptococcus spp. By contrast, the asthmatic microbiota were selectively affected by an increase in Neisseria spp. and by reduced numbers of low abundance but prevalent organisms. INTERPRETATION: Our study shows that the healthy airway microbiota in this population were contained within a highly structured ecosystem, suggesting balanced relationships between the microbiome and human host factors. The marked abnormalities in smokers may contribute to chronic obstructive pulmonary disease (COPD) and lung cancer. The narrow spectrum of abnormalities in asthmatics encourages investigation of damaging and protective effects of specific bacteria. FUNDING: The study was funded by the Asmarley Trust and a Wellcome Joint Senior Investigator Award to WOCC and MFM (WT096964MA and WT097117MA). The Busselton Healthy Ageing Study is supported by the Government of Western Australia (Office of Science, Department of Health) the City of Busselton, and private donations.

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.

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.

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report.

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.

Cytomegalovirus pneumonitis-induced secondary hemophagocytic lymphohistiocytosis and SIADH in an immunocompetent elderly male literature review.

Hemophagocytic lymphohistiocytosis (HLH) is also known as hemophagocytic syndrome. It is a lethal hematologic condition due to a dysregulated immune response which results in inappropriately activated macrophages damaging host tissues. Based on the etiology, HLH can be primary (genetic) or secondary (acquired). The most common cause of a secondary HLH is an infection. Viral infections are the most common cause of secondary HLH. Among the viral causes of secondary HLH, Epstein-Barr virus is the most common etiologic agent. Cytomegalovirus (CMV) is a common causative pathogen in the immunocompromised host but is rare in an immunocompetent adult. In infection- associated secondary HLH, treatment includes antimicrobial therapy. HLH carries a high mortality and morbidity rate as it is an underdiagnosed clinical condition. Successful early diagnosis allows for adequate time for curative therapy. Treatment for HLH includes chemotherapy, immunomodulators, and a hematopoietic stem-cell transplant. The 2004 diagnostic criteria set by the Histiocyte Society serves as a guide to make an earlier clinical diagnosis. A review of PubMed literature revealed only five reported cases of CMV-induced HLH. We describe the sixth case of CMV pneumonitis-induced HLH and syndrome of inappropriate antidiuretic hormone secretion in a 72-year-old White male. He was treated successfully with oral valganciclovir and corticosteroids.

Conjugation of a peptide to an antibody engineered with free cysteines dramatically improves half-life and activity.

The long circulating half-life and inherently bivalent architecture of IgGs provide an ideal vehicle for presenting otherwise short-lived G-protein-coupled receptor agonists in a format that enables avidity-driven enhancement of potency. Here, we describe the site-specific conjugation of a dual agonist peptide (an oxyntomodulin variant engineered for potency and in vivo stability) to the complementarity-determining regions (CDRs) of an immunologically silent IgG4. A cysteine-containing heavy chain CDR3 variant was identified that provided clean conjugation to a bromoacetylated peptide without interference from any of the endogenous mAb cysteine residues. The resulting mAb-peptide homodimer has high potency at both target receptors (glucagon receptor, GCGR, and glucagon-like peptide 1 receptor, GLP-1R) driven by an increase in receptor avidity provided by the spatially defined presentation of the peptides. Interestingly, the avidity effects are different at the two target receptors. A single dose of the long-acting peptide conjugate robustly inhibited food intake and decreased body weight in insulin resistant diet-induced obese mice, in addition to ameliorating glucose intolerance. Inhibition of food intake and decrease in body weight was also seen in overweight cynomolgus monkeys. The weight loss resulting from dosing with the bivalently conjugated dual agonist was significantly greater than for the monomeric analog, clearly demonstrating translation of the measured in vitro avidity to in vivo pharmacology.

Intramedullary Nail Fixation for the Treatment of Pathologic Humeral Shaft Fractures.

The goal of this study was to report the clinical outcomes of pathologic humeral shaft fractures treated with reamed or unreamed intramedullary nail fixation in an era of longer patient survival. A retrospective review was conducted of all patients who underwent intramedullary nail fixation performed by a single surgeon for pathologic humeral shaft fractures at a Level I trauma center from 2009 to 2017. Of the 25 patients who were identified, 9 were excluded. Groups were categorized according to whether they underwent reamed or unreamed fixation, and they were evaluated for evidence of union, complications, and reoperation. Of the patients, 11 underwent an unreamed procedure and 5 underwent a reamed procedure. Mean length of follow-up was 51.5 weeks. Of the patients who participated, 12 (75%) showed evidence of union and 2 patients (12.5%) showed evidence of nonunion, with no statistical difference between the groups. Five patients (31.3%) had complications. One nonunion occurred in the reamed group and did not require reoperation. In the unreamed group, complications consisted of 1 delayed union, 1 nonunion treated with revision intramedullary nail fixation, and 2 cases of disease progression that required reoperation. Intramedullary nail fixation of pathologic humeral shaft fractures achieves rates of union parallel to those seen with fixation in a healthy population. The length of follow-up in the current study was longer than the life expectancy reported by previous authors, which can be attributed to improvements in the treatment of cancer. The current authors argue that unreamed fixation is the optimal technique because it yields similar outcomes to a reamed approach and is faster and potentially safer. [Orthopedics. 2020;43(5):e389-e398.].

Periprosthetic proximal femoral fractures in cemented and uncemented stems according to Vancouver classification: observation of a new fracture pattern.

BACKGROUND: Periprosthetic fractures are increasingly encountered in hip arthroplasty. The Vancouver classification system is widely used. Little knowledge exists regarding the association of the Vancouver classification with either cemented or uncemented stems. The aim was to analyse a series of fractures and determine associations. METHODS: A series of consecutive patients over 8 years was identified including only post-operative fractures of primary hip arthroplasties. Baseline and radiographic characteristics were recorded including the type of stem fixation (cemented or uncemented) and Vancouver classification. Statistical analysis was performed to determine the association of the Vancouver classification between cemented and uncemented stems. RESULTS: A total of 172 patients were identified (84 cemented stems, 88 uncemented stems). There were 30 Vancouver A fractures (12 cemented vs.18 uncemented, p > 0.05), 125 Vancouver B fractures (63 cemented vs. 62 uncemented, p > 0.05) and 17 Vancouver C fractures (9 cemented vs. 8 uncemented, p > 0.05). The Vancouver B2 fracture occurred most frequently (N = 95; 44 cemented vs. 51 uncemented, p > 0.05) and consists of four distinct fracture patterns: the previously described comminuted 'burst', clamshell and spiral patterns and the newly observed 'reverse' clamshell. The burst and spiral fracture patterns are significantly associated with cemented stems, and the clamshell pattern is significantly associated with uncemented stems. CONCLUSIONS: Vancouver A, B and C fractures occur equally in cemented and uncemented stems. Awareness of four distinct Vancouver B2 fracture patterns, including the newly observed reverse clamshell, will aid surgeons in predicting stem instability.

The influence of linkages between 1-hydroxy-2(1H)-pyridinone coordinating groups and a tris(2-aminoethyl)amine core in a novel series of synthetic hexadentate iron(III) chelators on antimicrobial activity.

Resistance of pathogens to antimicrobials is a major current healthcare concern. In a series of linked studies, we have investigated synthetic iron chelators based on hydroxy-pyridinone ligands as novel bacteriostatic agents. Herein we describe our synthesis of several useful building blocks based on the 1-hydroxy-2(1H)-pyridinone moiety, including a novel formyl derivative, which were combined with a tris(2-aminoethyl)amine core to obtain a series of new high-affinity hexadentate Fe(III) chelators. The design principle examined by this series is the size and flexibility of the linker between the core and the metal ligands. Measurement of the pKa and stability constants (Fe3+ and Cu2+) of representative coordinating groups was performed to help rationalise the biological activity of the chelators. The novel chelators were tested on a panel of representative microorganisms with some effectively inhibiting microbial growth. We demonstrate that the nature and position of the linker between the hydroxypyridinone and the tris(2-aminoethyl)amine core has considerable impact upon microbial growth inhibition and that both amide or amine linkages can give efficacious chelators.

Comparison of outcomes and analysis of risk factors for non-union in locked plating of closed periprosthetic and non-periprosthetic distal femoral fractures in a retrospective cohort study.

BACKGROUND: The primary aim was to compare the outcomes of locked plating of closed distal femur periprosthetic and non-periprosthetic fractures by testing the hypothesis that outcomes would be worse in the periprosthetic group. The secondary aim of this study was to identify risk factors for non-union. METHODS: A single-center study over an 8-year period utilizing a retrospective cohort design was performed. Sixty-eight patients with periprosthetic fractures and 57 patients with non-periprosthetic fractures met inclusion criteria for the study. There was a significant difference between groups in mean age (80.1 years periprosthetic vs. 70.9 years non-periprosthetic (p < 0.001)). Statistical analysis between groups was used to assess the outcomes of time to union, incidence of non-union, post-operative functionality, incidence of complications, progression to revision surgery, and mortality. A secondary multivariable analysis was used to assess risk factors for non-union and factors positively associated with union. RESULTS: There were no significant differences in outcomes between groups. Union rates were 83.8% (57/68) in the periprosthetic group and 78.9% (45/57) in the non-periprosthetic group (p = 0.648). Comminution was identified as a significant risk factor for non-union (p = 0.005). Use of a submuscular technique had a significant positive association with union (p = 0.006). CONCLUSIONS: Outcomes of surgical treatment for periprosthetic and non-periprosthetic distal femur fractures are similar. There is a significant risk of non-union in locked plating of both groups.

Production of IgG2 Antibodies to Pneumococcal Polysaccharides After Vaccination of Treated HIV Patients May Be Augmented by IL-7Rα Signaling in ICOS+ Circulating T Follicular-Helper Cells.

Greater understanding of factors influencing the maturation of antibody responses against pneumococcal polysaccharides (PcPs) may improve pneumococcal vaccination strategies. Although PcPs are type 2 T cell-independent antigens thought not to induce follicular immune responses, we have previously shown that IgG2 antibody responses against antigens in the 23-valent unconjugated PcP vaccine (PPV23) are associated with expansion of ICOS+ circulating T follicular helper (cTFH) cells in HIV seronegative subjects but not HIV patients. As IL-7Rα signaling in CD4+ T cells may affect TFH cell function and is adversely affected by HIV-1 infection, we have examined the relationship of IL-7Rα expression on ICOS+ cTFH cells with PcP-specific IgG2 antibody responses. PPV23 vaccination was undertaken in HIV patients receiving antiretroviral therapy (n = 25) and HIV seronegative subjects (n = 20). IL-7Rα expression on ICOS+ and ICOS- cTFH cells was assessed at day(D) 0, 7, and 28. Fold increase between D0 and D28 in serum IgG1 and IgG2 antibodies to PcP serotypes 4, 6B, 9V, and 14 and the frequency of IgG1+ and IgG2+ antibody secreting cells (ASCs) at D7 were also assessed. Decline in IL-7Rα expression on ICOS+ cTFH cells between D0 and D7 occurred in 75% of HIV seronegative subjects and 60% of HIV patients (Group A), with changes in IL-7Rα expression being more pronounced in HIV patients. Group A patients exhibited abnormally high IL-7Rα expression pre-vaccination, an association of serum IgG2, but not IgG1, antibody responses with a decline of IL-7Rα expression on ICOS+ cTFH cells between D0 and D7, and an association of higher IgG2+ ASCs with lower IL-7Rα expression on ICOS+ cTFH cells at D7. As decline of IL-7Rα expression on CD4+ T cells is an indicator of IL-7Rα signaling, our findings suggest that utilization of IL-7 by cTFH cells affects production of IgG2 antibodies to PPV23 antigens in some HIV patients.

Healthcare-seeking behaviour and utilization of treatment in a community-based screening study for obstructive sleep apnoea in Busselton, Western Australia.

OBJECTIVES: To investigate whether in-home screening for obstructive sleep apnoea (OSA) promotes healthcare-seeking or lifestyle modification behaviour. We also examined the uptake and adherence rates to different treatment options, the factors affecting adherence, and the impact of treatment on health-related quality of life. DESIGN: Follow-up survey of adults at high risk of OSA. SETTING: Community-based sample. PARTICIPANTS: Adults who completed an in-home sleep study in the 2005-07 or 2010-15 Busselton surveys of adults with apnoea-hypopnoea index (AHI) > 15 (n = 192). MEASUREMENTS: The follow-up questionnaire was administered in 2016 and assessed healthcare-seeking and lifestyle modification behaviour, treatment utilization and adherence, and health-related quality of life. RESULTS: Of the 159 that recalled receiving a result from their in-home sleep study, 65% (n = 103) sought help and/or made lifestyle changes, 49% (n = 78) discussed the results with their GP, 21% (n = 33) underwent a confirmatory study and 33% (n = 53) started treatment. The most common treatment used was continuous positive airway pressure (CPAP) (72%) and adherence rates were high (84%). Self-reported snoring, breathing pauses, daytime tiredness and AHI were identified as predictors of whether people displayed healthcare-seeking behaviour. CONCLUSIONS: This study provides promising evidence that in-home screening for OSA could contribute towards relieving the associated morbidity, especially if health promotion strategies including education are implemented.