Wellbeing After Finalization of a Workers' Compensation Claim: A Systematic Scoping Review.

OBJECTIVE: A workers' compensation claim may have significant negative impacts on an injured worker's wellbeing. Wellbeing provides a good global measure of potential effects of a claim on an individual, and is important for contemporary economic modelling. The purpose of this study was to synthesize knowledge about the wellbeing of injured workers after the finalization of a workers' compensation claim and identify gaps in the current literature. METHODS: A systematic scoping review was conducted. RESULTS: 71 full-text articles were screened for inclusion, with 32 articles eligible for this review. None of the included articles evaluated overall wellbeing. Included articles did evaluate a variety of constructs inherent in wellbeing. Injured workers were generally disadvantaged in some manner following claim finalization. The literature recommends a focus on reducing negative impacts on injured workers after finalization of a compensation claim, with a need for regulatory bodies to review policy in this area. CONCLUSION: There appears to be potential for ongoing burden for individuals, employers, and society after finalization of a workers' compensation claim. A gap in knowledge exists regarding the specific evaluation of wellbeing of injured workers following finalization of a workers' compensation claim.

Exploration of the Usual Care Pathway for Rotator Cuff Related Shoulder Pain in the Western Australian Workers' Compensation System.

PURPOSE: Investigate components of care for rotator cuff related shoulder pain in workers' compensation in relation to claim outcomes (claim duration, total medical spend, total claim cost, return to work outcome). METHODS: Engagement with (had care, time to care) four components of care (prescribed exercise, imaging, injections, surgery) were obtained from auditing 189 closed workers' compensation files. Associations were analysed between components of care and claim outcomes. RESULTS: 80% received prescribed exercise, 81% imaging, 42% injection and 35% surgery. Median time to imaging (11 days) was shorter than the prescribed exercise (27 days), with injection at 38 days and surgery 118.5 days. With univariable regression analysis higher age, the involvement of legal representation and the presence of rotator cuff pathology from diagnostic imaging (partial thickness tear or full thickness tear) were all associated with increased claim duration, total medical spend, total claim cost and less successful return to work outcomes. After adjusting for these three associations, having an injection or surgery were both positively associated with longer claim duration and greater medical spend, and surgery with greater total claim costs. In general, longer time to receiving components of care was associated with increased claim duration and reduced odds of returning to full duties at work. CONCLUSION: Early management was not consistent with clinical guidelines for managing workers' compensation rotator cuff related shoulder pain. This may negatively affect claims outcomes.

Prediction of Electron Beam Welding Penetration Depth Using Machine Learning-Enhanced Computational Fluid Dynamics Modelling.

The necessity for precise prediction of penetration depth in the context of electron beam welding (EBW) cannot be overstated. Traditional statistical methodologies, including regression analysis and neural networks, often necessitate a considerable investment of both time and financial resources to produce results that meet acceptable standards. To address these challenges, this study introduces a novel approach for predicting EBW penetration depth that synergistically combines computational fluid dynamics (CFD) modelling with artificial neural networks (ANN). The CFD modelling technique was proven to be highly effective, yielding predictions with an average absolute percentage deviation of around 8%. This level of accuracy is consistent across a linear electron beam (EB) power range spanning from 86 J/mm to 324 J/mm. One of the most compelling advantages of this integrated approach is its efficiency. By leveraging the capabilities of CFD and ANN, the need for extensive and costly preliminary testing is effectively eliminated, thereby reducing both the time and financial outlay typically associated with such predictive modelling. Furthermore, the versatility of this approach is demonstrated by its adaptability to other types of EB machines, made possible through the application of the beam characterisation method outlined in the research. With the implementation of the models introduced in this study, practitioners can exert effective control over the quality of EBW welds. This is achieved by fine-tuning key variables, including but not limited to the beam power, beam radius, and the speed of travel during the welding process.

Decreased Physical Working Capacity in Adolescents With Nonalcoholic Fatty Liver Disease Associates With Reduced Iron Availability.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is common and related to obesity and insulin resistance. Iron metabolism is impaired in obese individuals and iron deficiency has been associated with physical inactivity. We investigated whether iron bioavailability is reduced in patients with NAFLD and contributes to reduced cardiorespiratory fitness. METHODS: We collected information on weight-adjusted, submaximal physical work capacity (PWC), ultrasound-determined hepatic steatosis, iron indices, and hematologic and metabolic parameters from 390 female and 458 male participants of the Raine Study-a longitudinal study of disease development in 2868 children in Western Australia. X2 and linear regression analyses were used to compare characteristics of study participants according to NAFLD status at age 17 years. RESULTS: Fourteen percent of the cohort had NAFLD. PWC was significantly reduced in adolescents with NAFLD compared to adolescents without NAFLD (reduction of 0.17 W/kg, P = .0003, adjusted for sex and body mass index [BMI]). Iron bioavailability (assessed by mean corpuscular volume [MCV], mean corpuscular haemoglobin [MCH], transferrin saturation, and serum levels of iron) was inversely correlated with BMI in adolescents with NAFLD (P ≤ .01 for all, adjusted for sex) but not in adolescents without NAFLD (P > .30). MCV and MCH correlated with PWC (MCV, P = .002 for female and P = .0003 male participants; MCH, P = .004 for female and P = .01 for male participants), irrespective of NAFLD status. Reduced PWC was associated with lower transferrin saturation in adolescents with NAFLD (reduction of 0.012 W/kg per unit decrease in transferrin saturation, P = .007) but not in adolescents without NAFLD (reduction of 0.001 W/kg, P = .40), adjusted for sex. This association was independent of MCV or MCH. CONCLUSIONS: In a well-defined cohort of adolescents, we found NAFLD to be associated with decreased cardiorespiratory fitness, independent of BMI. The relationship between transferrin saturation and PWC in adolescents with NAFLD indicates that functional iron deficiency might contribute to reductions in cardiorespiratory fitness.

IL-17 can be protective or deleterious in murine pneumococcal pneumonia.

Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains.

Structure-Guided Identification of a Nonhuman Morbillivirus with Zoonotic Potential.

Morbilliviruses infect a broad range of mammalian hosts, including ruminants, carnivores, and humans. The recent eradication of rinderpest virus (RPV) and the active campaigns for eradication of the human-specific measles virus (MeV) have raised significant concerns that the remaining morbilliviruses may emerge in so-called vacated ecological niches. Seeking to assess the zoonotic potential of nonhuman morbilliviruses within human populations, we found that peste des petits ruminants virus (PPRV)-the small-ruminant morbillivirus-is restricted at the point of entry into human cells due to deficient interactions with human SLAMF1-the immune cell receptor for morbilliviruses. Using a structure-guided approach, we characterized a single amino acid change, mapping to the receptor-binding domain in the PPRV hemagglutinin (H) protein, which overcomes this restriction. The same mutation allowed escape from some cross-protective, human patient, anti-MeV antibodies, raising concerns that PPRV is a pathogen with zoonotic potential. Analysis of natural variation within human and ovine SLAMF1 also identified polymorphisms that could correlate with disease resistance. Finally, the mechanistic nature of the PPRV restriction was also investigated, identifying charge incompatibility and steric hindrance between PPRV H and human SLAMF1 proteins. Importantly, this research was performed entirely using surrogate virus entry assays, negating the requirement for in situ derivation of a human-tropic PPRV and illustrating alternative strategies for identifying gain-of-function mutations in viral pathogens.IMPORTANCE A significant proportion of viral pandemics occur following zoonotic transmission events, where animal-associated viruses jump species into human populations. In order to provide forewarnings of the emergence of these viruses, it is necessary to develop a better understanding of what determines virus host range, often at the genetic and structural levels. In this study, we demonstrated that the small-ruminant morbillivirus, a close relative of measles, is unable to use human receptors to enter cells; however, a change of a single amino acid in the virus is sufficient to overcome this restriction. This information will be important for monitoring this virus's evolution in the field. Of note, this study was undertaken in vitro, without generation of a fully infectious virus with this phenotype.

Implementation of Questionnaire-Based Risk Profiling for Clients in a Workers' Compensation Environment: An Example in Australian Physiotherapy Practice.

Purpose This study investigated the implementation of a risk profiling process for physiotherapy clients with a compensable musculoskeletal problem. Implementation targeted personal (clinician) and external (organisational) factors to facilitate behavioural change with regard to the use of formal, questionnaire-based risk profiling. Methods A theoretical construct was developed for formal questionnaire-based screening to be implemented across 12 private, metropolitan physiotherapy clinics. To target personal (clinician) factors, a multimodal educational procedure was developed focused on use of the ten-item Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ-10). To target external (organisational) factors, an administrative process was enacted to ensure routine completion of the OMPSQ-10 by compensable clients. Global practice behaviour with regard to the use of formal risk profiling was complete pre- and post-implementation. Results Pre-implementation physiotherapists understood the potential usefulness of formal risk profiling, but the large majority did not routinely have clients complete these types of questionnaires. Post-implementation there was a significant positive shift in behaviour to more frequent use the OMPSQ-10 for new compensable clients. Conclusions The results provide initial support for the use of a framework to develop an implementation strategy to increase physiotherapist adherence to the use of guideline recommended risk profiling questionnaires in clinical practice.

Type and Pattern of Alcohol Consumption is Associated With Liver Fibrosis in Patients With Non-alcoholic Fatty Liver Disease.

INTRODUCTION: It is unclear whether low levels of alcohol are harmful in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to determine whether quantity, binge pattern consumption, or type of alcohol was associated with liver fibrosis in patients with NAFLD. METHODS: Previous and current alcohol consumption was assessed in NAFLD patients undergoing liver biopsy. All subjects currently consumed <210 g per week (male) or <140 g per week (female). Binge consumption was defined as ≥4 standard drinks (female) or ≥5 standard drinks (male) in one sitting. Liver biopsies were scored according to the NASH CRN system with F3/4 fibrosis defined as advanced. RESULTS: Among 187 patients (24% with advanced fibrosis), the median weekly alcohol consumption was 20 (2.3-60) g over an average of 18 years. Modest consumption (1-70 g per week) was associated with lower mean fibrosis stage compared to lifetime abstainers (p < 0.05) and a decreased risk of advanced fibrosis (OR 0.33, 95% CI 0.14-0.78, p = 0.01). The association with reduced fibrosis was not seen in subjects drinking in a binge-type fashion. Exclusive wine drinkers but not exclusive beer drinkers, had lower mean fibrosis stage and lower odds of advanced fibrosis (OR 0.20, 95% CI 0.06-0.69, p = 0.01), compared to lifetime abstinent subjects. No interaction between gender and alcohol quantity, type, or binge consumption on fibrosis was observed. DISCUSSION: Modest (1-70 g per week) alcohol consumption, particularly wine in a non-binge pattern, is associated with lower fibrosis in patients with NAFLD. Prospective longitudinal studies into fibrosis progression, cardiovascular outcomes, and mortality are required before clinical recommendations can be made.

Are Psychologic Factors Associated With Shoulder Scores After Rotator Cuff Surgery?

BACKGROUND: Psychologic factors are associated with pain and disability in patients with chronic shoulder pain. Recent research regarding the association of affective psychologic factors (emotions) with patients' pain and disability outcome after surgery disagrees; and the relationship between cognitive psychologic factors (thoughts and beliefs) and outcome after surgery is unknown. QUESTIONS/PURPOSES: (1) Are there identifiable clusters (based on psychologic functioning measures) in patients undergoing shoulder surgery? (2) Is poorer psychologic functioning associated with worse outcome (American Shoulder and Elbow Surgeons [ASES] score) after shoulder surgery? METHODS: This prospective cohort study investigated patients undergoing shoulder surgery for rotator cuff-related shoulder pain or rotator cuff tear by one of six surgeons between January 2014 and July 2015. Inclusion criteria were patients undergoing surgery for rotator cuff repair with or without subacromial decompression and arthroscopic subacromial decompression only. Of 153 patients who were recruited and consented to participate in the study, 16 withdrew before data collection, leaving 137 who underwent surgery and were included in analyses. Of these, 124 (46 of 124 [37%] female; median age, 54 years [range, 21-79 years]) had a complete set of four psychologic measures before surgery: Depression, Anxiety and Stress Scale; Pain Catastrophizing Scale; Pain Self-Efficacy Questionnaire; and Tampa Scale for Kinesiophobia. The existence of clusters of people with different profiles of affective and cognitive factors was investigated using latent class analysis, which grouped people according to their pattern of scores on the four psychologic measures. Resultant clusters were profiled on potential confounding variables. The ASES score was measured before surgery and 3 and 12 months after surgery. Linear mixed models assessed the association between psychologic cluster membership before surgery and trajectories of ASES score over time adjusting for potential confounding variables. RESULTS: Two clusters were identified: one cluster (84 of 124 [68%]) had lower scores indicating better psychologic functioning and a second cluster (40 of 124 [32%]) had higher scores indicating poorer psychologic functioning. Accounting for all variables, the cluster with poorer psychologic functioning was found to be independently associated with worse ASES score at all time points (regression coefficient for ASES: before surgery -9 [95% confidence interval {CI}, -16 to -2], p = 0.011); 3 months after surgery -15 [95% CI, -23 to -8], p < 0.001); and 12 months after surgery -9 [95% CI, -17 to -1], p = 0.023). However, both clusters showed improvement in ASES score from before to 12 months after surgery, and there was no difference in the amount of improvement between clusters (regression coefficient for ASES: cluster with poorer psychologic function 31 [95% CI, 26-36], p < 0.001); cluster with better psychologic function 31 [95% CI, 23-39], p < 0.001). CONCLUSIONS: Patients who scored poorly on a range of psychologic measures before shoulder surgery displayed worse ASES scores at 3 and 12 months after surgery. Screening of psychologic factors before surgery is recommended to identify patients with poor psychologic function. Such patients may warrant additional behavioral or psychologic management before proceeding to surgery. However, further research is needed to determine the optimal management for patients with poorer psychologic function to improve pain and disability levels before and after surgery. LEVEL OF EVIDENCE: Level II, therapeutic study.

Red Blood Cell Susceptibility to Pneumolysin: CORRELATION WITH MEMBRANE BIOCHEMICAL AND PHYSICAL PROPERTIES.

This study investigated the effect of the biochemical and biophysical properties of the plasma membrane as well as membrane morphology on the susceptibility of human red blood cells to the cholesterol-dependent cytolysin pneumolysin, a key virulence factor of Streptococcus pneumoniae, using single cell studies. We show a correlation between the physical properties of the membrane (bending rigidity and surface and dipole electrostatic potentials) and the susceptibility of red blood cells to pneumolysin-induced hemolysis. We demonstrate that biochemical modifications of the membrane induced by oxidative stress, lipid scrambling, and artificial cell aging modulate the cell response to the toxin. We provide evidence that the diversity of response to pneumolysin in diabetic red blood cells correlates with levels of glycated hemoglobin and that the mechanical properties of the red blood cell plasma membrane are altered in diabetes. Finally, we show that diabetic red blood cells are more resistant to pneumolysin and the related toxin perfringolysin O relative to healthy red blood cells. Taken together, these studies indicate that the diversity of cell response to pneumolysin within a population of human red blood cells is influenced by the biophysical and biochemical status of the plasma membrane and the chemical and/or oxidative stress pre-history of the cell.

Transition to adult care for pediatric liver transplant recipients: the Western Australian experience.

Transition to adult care is a vulnerable period for pediatric transplant recipients and is associated with reduced medication compliance, graft loss, and increased mortality. Psychosocial outcomes in young adults differ between pediatric transplant recipients and their healthy peers. We conducted a single-center, retrospective cohort study of all pediatric liver transplant recipients who were transitioned through our center. This study aimed to assess the outcomes of transitioned pediatric liver transplant recipients at an Australian center, including mortality, adherence, and psychosocial morbidity. The 1- and 5-year survival rates following transition were 100% and 92%, respectively. There were no episodes of late rejection. In total, 66.7% of patients were compliant with immunosuppression and 61.1% of patients were compliant with clinic attendance. There was a significant relationship between medication compliance and clinic attendance, as well as presence of psychological issues with clinic non-attendance. Psychosocial outcomes were in keeping with age-matched data from the general population. All patients were employed or studying following transition. This is the first study of its kind in the Australian population, and outcomes were superior to published international data. Despite the demonstrated good outcomes, transition programs may improve healthcare engagement in this cohort.

Acute kidney injury is under-recognised and under-reported in hospitalised patients in Australia.

Acute kidney injury (AKI) in hospitalised patients is associated with adverse outcomes; however, it remains unrecognised and under-reported. A total of 48 045 serum creatinine results from 8129 tertiary hospital inpatients were reviewed. The prevalence of AKI was 4.33%. Mortality was significantly higher in patients with AKI (16.76%) compared to those without AKI (1.88%, P < 0.001). Documentation of AKI in discharge summaries was poor.

Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis.

Psoriasis is a chronic autoimmune disease affecting the skin and characterized by aberrant keratinocyte proliferation and function. Immune cells infiltrate the skin and release proinflammatory cytokines that play important roles in psoriasis. The Th17 network, including IL-23 and IL-22, has recently emerged as a critical component in the pathogenesis of psoriasis. IL-22 and IL-23 signaling is dependent on the JAK family of protein tyrosine kinases, making JAK inhibition an appealing strategy for the treatment of psoriasis. In this study, we report the activity of SAR-20347, a small molecule inhibitor with specificity for JAK1 and tyrosine kinase 2 (TYK2) over other JAK family members. In cellular assays, SAR-20347 dose dependently (1 nM-10 µM) inhibited JAK1- and/or TYK2-dependent signaling from the IL-12/IL-23, IL-22, and IFN-α receptors. In vivo, TYK2 mutant mice or treatment of wild-type mice with SAR-20347 significantly reduced IL-12-induced IFN-γ production and IL-22-dependent serum amyloid A to similar extents, indicating that, in these models, SAR-20347 is probably acting through inhibition of TYK2. In an imiquimod-induced psoriasis model, the administration of SAR-20347 led to a striking decrease in disease pathology, including reduced activation of keratinocytes and proinflammatory cytokine levels compared with both TYK2 mutant mice and wild-type controls. Taken together, these data indicate that targeting both JAK1- and TYK2-mediated cytokine signaling is more effective than TYK2 inhibition alone in reducing psoriasis pathogenesis.

Dominant role of nucleotide substitution in the diversification of serotype 3 pneumococci over decades and during a single infection.

Streptococcus pneumoniae of serotype 3 possess a mucoid capsule and cause disease associated with high mortality rates relative to other pneumococci. Phylogenetic analysis of a complete reference genome and 81 draft sequences from clonal complex 180, the predominant serotype 3 clone in much of the world, found most sampled isolates belonged to a clade affected by few diversifying recombinations. However, other isolates indicate significant genetic variation has accumulated over the clonal complex's entire history. Two closely related genomes, one from the blood and another from the cerebrospinal fluid, were obtained from a patient with meningitis. The pair differed in their behaviour in a mouse model of disease and in their susceptibility to antimicrobials, with at least some of these changes attributable to a mutation that up-regulated the patAB efflux pump. This indicates clinically important phenotypic variation can accumulate rapidly through small alterations to the genotype.

Resolving Salmonella infection reveals dynamic and persisting changes in murine bone marrow progenitor cell phenotype and function.

The generation of immune cells from BM precursors is a carefully regulated process. This is essential to limit the potential for oncogenesis and autoimmunity yet protect against infection. How infection modulates this is unclear. Salmonella can colonize systemic sites including the BM and spleen. This resolving infection has multiple IFN-γ-mediated acute and chronic effects on BM progenitors, and during the first week of infection IFN-γ is produced by myeloid, NK, NKT, CD4(+) T cells, and some lineage-negative cells. After infection, the phenotype of BM progenitors rapidly but reversibly alters, with a peak ∼ 30-fold increase in Sca-1(hi) progenitors and a corresponding loss of Sca-1(lo/int) subsets. Most strikingly, the capacity of donor Sca-1(hi) cells to reconstitute an irradiated host is reduced; the longer donor mice are exposed to infection, and Sca-1(hi) c-kit(int) cells have an increased potential to generate B1a-like cells. Thus, Salmonella can have a prolonged influence on BM progenitor functionality not directly related to bacterial persistence. These results reflect changes observed in leucopoiesis during aging and suggest that BM functionality can be modulated by life-long, periodic exposure to infection. Better understanding of this process could offer novel therapeutic opportunities to modulate BM functionality and promote healthy aging.

The biology of pneumolysin.

Cholesterol dependent cytolysins are important in the ability of some bacteria to cause disease in man and animals. Pneumolysin (PLY) plays a key role in the diseases caused by Streptococcus pneumoniae (the pneumococcus). This chapter describes the role of PLY in some of the key process in disease. These include induction of cell death by pore formation and toxin-induced apoptosis as well as more subtle effects on gene expression of host cells including epigenetic effects of the toxin. The use of bacterial mutants that either do not express the toxin or express altered versions in biological systems is described. Use of isolated tissue and whole animal systems to dissect the structure/function relationships of the toxin as well as the role played by different activities in the pathogenesis of infection are described. The role of PLY in meningitis and the associated deafness is discussed as well as the role of the toxin in promoting increased lung permeability and inflammation during pneumococcal pneumonia. Different clinical strains of the pneumococcus produce different forms of PLY and the impact of this on disease caused by these strains is discussed. Finally, the impact of this knowledge on the development of treatment and prevention strategies for pneumococcal disease is discussed.

Impact of routine reporting of estimated glomerular filtration rate using the CKD-EPI formula in a community population: A cross-sectional cohort study.

AIM: Most laboratories are moving to report estimated glomerular filtration rates (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. However, data on the prevalence of chronic kidney disease (CKD) in the population and its economic impact have to date been modelled using data derived from the modification of diet in renal disease (MDRD) equation. Evaluating the impact of CKD-EPI on prevalence has important implications for referral patterns and health expenditure. METHODS: eGFR were calculated from 2 295313 creatinine results from 833334 patients using the MDRD and CKD-EPI formulae. The proportion of patients in each CKD stage was determined and annual rates of change of eGFR in patients assigned to a new CKD stage compared with their previous CKD stage calculated. The effects of age on eGFR were assessed. RESULTS: Reporting of eGFR using the CKD-EPI equation reduced the prevalence of CKD stages III-V from 9.2% to 7.6%. A total of 181126 patients were reclassified using CKD-EPI with 171298 changing to a better CKD stage. Reclassification rates were highest in CKD stages II and III. Patients reclassified from stage III to II tended to be younger or female. eGFR declines rapidly after the age of 60. CONCLUSIONS: Introduction of routine eGFR reporting using the CKD-EPI formula will reduce the population prevalence of CKD. CKD-EPI reporting better identifies patients at risk of further decline in renal function. Improvement in the classification should reduce unnecessary costs related to surveillance and referral. The impact of ageing on renal function should be appreciated.

Effects of cigarette smoke condensate on pneumococcal biofilm formation and pneumolysin.

Although the well-recognised predisposition of cigarette smokers to the development of severe pneumococcal disease may be attributable to impairment of local host defences, less is known about the direct effects of smoke exposure on airway pathogens, or their virulence factors. In the current study, we have investigated the effects of cigarette smoke condensate (CSC) on biofilm formation by Streptococcus pneumoniae, and on the pore-forming activity of its major toxin, pneumolysin. Biofilm formation following exposure of the pneumococcus to CSC (20-160 µg·mL(-1)) was measured using a crystal violet-based spectrophotometric procedure, while the pore-forming activity of recombinant pneumolysin was determined by a fura-2/acetoxymethyl ester-based spectrofluorimetric procedure to monitor the uptake of extracellular Ca(2+) by isolated human neutrophils. Exposure of the pneumococcus or pneumolysin to CSC resulted in significant dose-related augmentation of biofilm formation (p≤0.05 at 80 and 160 µg·mL(-1)) and substantial attenuation of the pore-forming interactions of pneumolysin, respectively. Augmentation of biofilm formation and inactivation of pneumolysin as a consequence of smoking are likely to favour microbial colonisation and persistence, both being essential precursors of pneumococcal disease.