How is postoperative pain after hip and knee replacement managed? An analysis of two large hospitals in Australia.

BACKGROUND: Multimodal analgesia regimens are recommended for the postoperative period after hip and knee replacement surgeries. However, there are no data on practice patterns for analgesic use in the immediate postoperative period after hip and knee replacements in Australia. OBJECTIVES: To describe analgesic prescribing patterns in the inpatient postoperative phase for patients undergoing hip and knee replacement. METHODS: Retrospective study of electronic medical record data from two major hospitals in Sydney, Australia. We identified analgesic medication prescriptions for all patients aged 18 years and older who underwent hip or knee replacement surgery in 2019. We extracted data on pain medications prescribed while in the ward up until discharge. These were grouped into distinct categories based on the Anatomical Therapeutic Chemical classification. We described the frequency (%) of pain medications used by category and computed the average oral morphine equivalent daily dose (OMEDD) during hospitalisation. RESULTS: We identified 1282 surgeries in 1225 patients. Patients had a mean (SD) age of 69 (11.8) years; most (57.1%) were female. Over 99% of patients were prescribed opioid analgesics and paracetamol during their hospital stay. Most patients (61.4%) were managed with paracetamol and opioids only. The most common prescribed opioid was oxycodone (87.3% of patients). Only 19% of patients were prescribed nonsteroidal anti-inflammatories (NSAIDs). The median (IQR) average daily OMEDD was 50.2 mg (30.3-77.9). CONCLUSION: We identified high use of opioids analgesics as the main strategies for pain control after hip and knee replacement in hospital. Other analgesics were much less frequently used, such as NSAIDs, and always in combination with opioids and paracetamol.

Compliance with Australian Orthopaedic Association guidelines does not reduce the risk of venous thromboembolism after total hip and knee arthroplasty.

Preventing avoidable venous-thrombo-embolism (VTE) is a priority to improve patient and service outcomes after total hip and total knee arthroplasty (THA, TKA), but compliance with relevant clinical guidelines varies. This study aims to determine the degree to which prophylaxis was compliant with Australian Orthopaedic Association (AOA) VTE prophylaxis guidelines and whether non-compliance is associated with increased risk of VTE. A prospective multi-centre cohort study of adults with osteoarthritis undergoing primary TKA/THA was completed at 19 high-volume public and private hospitals. Data were collected prior to surgery and for one-year post-surgery. Logistic regression was undertaken to explore associations between non-compliance with AOA VTE prophylaxis guidelines and symptomatic 90-day VTE outcomes. Data were analysed for 1838 participants from 19 sites. The rate of non-compliance with all clinical guideline recommendations was 20.1% (N = 369), with 14.1% (N = 259) non-compliance for risk-stratified prophylaxis, 35.8% (N = 658) for duration, and 67.8% (N = 1246) for other general recommendations. Symptomatic VTE was experienced up to 90-days post-surgery by 48 people (2.6%). Overall guideline non-compliance (AOR = 0.93, 95%CI = 0.4 to 1.3, p = 0.86) was not associated with a lower risk of symptomatic 90-day VTE. Results were consistent when people with high bleeding risk were excluded (AOR = 0.94, 95%CI = 0.44 to 2.34, p = 0.89). Non-compliance with the AOA VTE prophylaxis guidelines was not associated with risk of 90-day VTE after arthroplasty. This counterintuitive finding is concerning and necessitates a rigorous review of the AOA VTE prevention clinical guideline.

Screening for lipid nanoparticles that modulate the immune activity of helper T cells towards enhanced antitumour activity.

Lipid nanoparticles (LNPs) can be designed to potentiate cancer immunotherapy by promoting their uptake by antigen-presenting cells, stimulating the maturation of these cells and modulating the activity of adjuvants. Here we report an LNP-screening method for the optimization of the type of helper lipid and of lipid-component ratios to enhance the delivery of tumour-antigen-encoding mRNA to dendritic cells and their immune-activation profile towards enhanced antitumour activity. The method involves screening for LNPs that enhance the maturation of bone-marrow-derived dendritic cells and antigen presentation in vitro, followed by assessing immune activation and tumour-growth suppression in a mouse model of melanoma after subcutaneous or intramuscular delivery of the LNPs. We found that the most potent antitumour activity, especially when combined with immune checkpoint inhibitors, resulted from a coordinated attack by T cells and NK cells, triggered by LNPs that elicited strong immune activity in both type-1 and type-2 T helper cells. Our findings highlight the importance of optimizing the LNP composition of mRNA-based cancer vaccines to tailor antigen-specific immune-activation profiles.

Identification of the pore-forming and binding domains of the Sneathia vaginalis cytopathogenic toxin A.

The association between Sneathia vaginalis and preterm birth is emerging. The Gram-negative anaerobe produces a large exotoxin, the cytopathogenic toxin A (CptA), that forms pores in human epithelial cells and red blood cells. The structure of the toxin has not been determined, but in silico analysis predicts that a large amino-terminal region of the protein is globular and separated from the carboxy-terminal tandem repeats by a disordered region. We found that a recombinant protein consisting of the predicted structured amino-terminal portion of CptA and devoid of the repeat region was sufficient to permeabilize epithelial cells and red blood cells. The repeat region was capable of binding to epithelial cells but did not permeabilize them or lyse red blood cells. CptA is the only S. vaginalis virulence factor that has been examined mechanistically to date, and this analysis sets the foundation for an understanding of how this novel pore-forming toxin exerts its activity.

Surgical versus non-surgical treatment for sciatica: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To investigate the effectiveness and safety of surgery compared with non-surgical treatment for sciatica. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organisation International Clinical Trials Registry Platform from database inception to June 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing any surgical treatment with non-surgical treatment, epidural steroid injections, or placebo or sham surgery, in people with sciatica of any duration due to lumbar disc herniation (diagnosed by radiological imaging). DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data. Leg pain and disability were the primary outcomes. Adverse events, back pain, quality of life, and satisfaction with treatment were the secondary outcomes. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst pain or disability). Data were pooled using a random effects model. Risk of bias was assessed with the Cochrane Collaboration's tool and certainty of evidence with the grading of recommendations assessment, development, and evaluation (GRADE) framework. Follow-up times were into immediate term (≤six weeks), short term (>six weeks and ≤three months), medium term (>three and <12 months), and long term (at 12 months). RESULTS: 24 trials were included, half of these investigated the effectiveness of discectomy compared with non-surgical treatment or epidural steroid injections (1711 participants). Very low to low certainty evidence showed that discectomy, compared with non-surgical treatment, reduced leg pain: the effect size was moderate at immediate term (mean difference -12.1 (95% confidence interval -23.6 to -0.5)) and short term (-11.7 (-18.6 to -4.7)), and small at medium term (-6.5 (-11.0 to -2.1)). Negligible effects were noted at long term (-2.3 (-4.5 to -0.2)). For disability, small, negligible, or no effects were found. A similar effect on leg pain was found when comparing discectomy with epidural steroid injections. For disability, a moderate effect was found at short term, but no effect was observed at medium and long term. The risk of any adverse events was similar between discectomy and non-surgical treatment (risk ratio 1.34 (95% confidence interval 0.91 to 1.98)). CONCLUSION: Very low to low certainty evidence suggests that discectomy was superior to non-surgical treatment or epidural steroid injections in reducing leg pain and disability in people with sciatica with a surgical indication, but the benefits declined over time. Discectomy might be an option for people with sciatica who feel that the rapid relief offered by discectomy outweighs the risks and costs associated with surgery. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021269997.

A Low-Cost Modular Imaging System for Rapid, Multiplexed Immunofluorescence Detection in Clinical Tissues.

To image 4-plex immunofluorescence-stained tissue samples at a low cost with cellular level resolution and sensitivity and dynamic range required to detect lowly and highly abundant targets, here we describe a robust, inexpensive (<$9000), 3D printable portable imaging device (Tissue Imager). The Tissue Imager can immediately be deployed on benchtops for in situ protein detection in tissue samples. Applications for this device are broad, ranging from answering basic biological questions to clinical pathology, where immunofluorescence can detect a larger number of markers than the standard H&E or chromogenic immunohistochemistry (CIH) staining, while the low cost also allows usage in classrooms. After characterizing our platform's specificity and sensitivity, we demonstrate imaging of a 4-plex immunology panel in human cutaneous T-cell lymphoma (CTCL) formalin-fixed paraffin-embedded (FFPE) tissue samples. From those images, positive cells were detected using CellProfiler, a popular open-source software package, for tumor marker profiling. We achieved a performance on par with commercial epifluorescence microscopes that are >10 times more expensive than our Tissue Imager. This device enables rapid immunofluorescence detection in tissue sections at a low cost for scientists and clinicians and can provide students with a hands-on experience to understand engineering and instrumentation. We note that for using the Tissue Imager as a medical device in clinical settings, a comprehensive review and approval processes would be required.

Barriers and enablers to monitoring and deprescribing opioid analgesics for chronic non-cancer pain: a systematic review with qualitative evidence synthesis using the Theoretical Domains Framework.

BACKGROUND: Understanding barriers and enablers to monitoring and deprescribing opioids will enable the development of tailored interventions to improve both practices. OBJECTIVE: To perform a qualitative evidence synthesis of the barriers and enablers to monitoring ongoing appropriateness and deprescribing of opioids for chronic non-cancer pain (CNCP) and to map the findings to the Theoretical Domains Framework (TDF). METHODS: We included English-language qualitative studies that explored healthcare professional (HCP), patient, carer and the general public's perceptions regarding monitoring and deprescribing opioids for CNCP. We searched MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED) and PsycINFO from inception to August 2020. Two authors independently selected the studies, extracted the data, assessed the methodological quality using the Critical Appraisal Skills Programme, and assessed the confidence in the findings using GRADE CERQual (Grading of Recommendations Assessment, Development, and Evaluation Confidence in the Evidence from Reviews of Qualitative Research). We used an inductive approach to synthesis of qualitative data and mapped identified themes to TDF domains. RESULTS: From 6948 records identified we included 21 studies, involving 209 HCPs and 330 patients. No studies involved carers or the general public. Five barrier themes were identified: limited alternatives to opioids, management of pain is top priority, patient understanding, expectations and experiences, prescriber pressures, and reluctance to change. Four enabler themes were identified: negative effects of opioids and benefits of deprescribing, clear communication and expectations for deprescribing, support for patients, and support for prescribers. 16 barrier and 12 enabler subthemes were identified; most were graded as high (n=15) or moderate (n=9) confidence. The TDF domains 'beliefs about consequences', 'environmental context and resources', 'social influences' and 'emotion' were salient for patients and HCPs. The domains 'skills' and 'beliefs about capabilities' were more salient for HCPs. CONCLUSION: Future implementation interventions aimed at monitoring and deprescribing opioids should target the patient and HCP barriers and enablers identified in this synthesis. PROSPERO REGISTRATION NUMBER: CRD42019140784.

Efficacy and safety of antidepressants for the treatment of back pain and osteoarthritis: systematic review and meta-analysis.

OBJECTIVE: To investigate the efficacy and safety of antidepressants for back and osteoarthritis pain compared with placebo. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, International Pharmaceutical Abstracts, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to 15 November and updated on 12 May 2020. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials comparing the efficacy or safety, or both of any antidepressant drug with placebo (active or inert) in participants with low back or neck pain, sciatica, or hip or knee osteoarthritis. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data. Pain and disability were primary outcomes. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst pain or disability). A random effects model was used to calculate weighted mean differences and 95% confidence intervals. Safety (any adverse event, serious adverse events, and proportion of participants who withdrew from trials owing to adverse events) was a secondary outcome. Risk of bias was assessed with the Cochrane Collaboration's tool and certainty of evidence with the grading of recommendations assessment, development and evaluation (GRADE) framework. RESULTS: 33 trials (5318 participants) were included. Moderate certainty evidence showed that serotonin-noradrenaline reuptake inhibitors (SNRIs) reduced back pain (mean difference -5.30, 95% confidence interval -7.31 to -3.30) at 3-13 weeks and low certainty evidence that SNRIs reduced osteoarthritis pain (-9.72, -12.75 to -6.69) at 3-13 weeks. Very low certainty evidence showed that SNRIs reduced sciatica at two weeks or less (-18.60, -31.87 to -5.33) but not at 3-13 weeks (-17.50, -42.90 to 7.89). Low to very low certainty evidence showed that tricyclic antidepressants (TCAs) did not reduce sciatica at two weeks or less (-7.55, -18.25 to 3.15) but did at 3-13 weeks (-15.95, -31.52 to -0.39) and 3-12 months (-27.0, -36.11 to -17.89). Moderate certainty evidence showed that SNRIs reduced disability from back pain at 3-13 weeks (-3.55, -5.22 to -1.88) and disability due to osteoarthritis at two weeks or less (-5.10, -7.31 to -2.89), with low certainty evidence at 3-13 weeks (-6.07, -8.13 to -4.02). TCAs and other antidepressants did not reduce pain or disability from back pain. CONCLUSION: Moderate certainty evidence shows that the effect of SNRIs on pain and disability scores is small and not clinically important for back pain, but a clinically important effect cannot be excluded for osteoarthritis. TCAs and SNRIs might be effective for sciatica, but the certainty of evidence ranged from low to very low. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020158521.

Correction to: Deprescribing Opioids in Chronic Non­cancer Pain: Systematic Review of Randomised Trials.

Page 9, Fig. 2, which originally appeared as.

Deprescribing Opioids in Chronic Non-cancer Pain: Systematic Review of Randomised Trials.

BACKGROUND: Deprescribing, the process of reducing or discontinuing unnecessary or harmful medicines is an essential part of clinical practice. OBJECTIVE: To evaluate the efficacy of interventions designed to deprescribe opioid analgesics for pain relief in patients with chronic non-cancer pain. METHODS: We searched electronic databases, including clinical trial registries, from database inception to 13th January 2020 without restrictions, and conducted citation tracking. Our systematic review included randomised controlled trials (RCTs) evaluating interventions reducing the prescription, or use of opioid analgesics in patients with chronic pain versus control. Inventions could be aimed at the patient, clinician, or both. We excluded trials enrolling patients with cancer or illicit drug use. Two authors independently screened and extracted data. Outcome follow-up timepoints were short (≤ 3 months), intermediate (> 3 but < 12 months) or long (≥ 12 months) term. Primary outcome was the reduction in opioid dose [morphine milligram equivalent (MME) mg/day]. Methodological quality was assessed using the Cochrane Risk of Bias Tool. RESULTS: We included ten patient-focused RCT interventions (n = 835; median 37 participants) and 2 testing clinician-focused interventions (n = 291 clinicians); none at low risk of bias. Patient-focused interventions did not reduce opioid dose in the intermediate term [e.g. dose reduction protocol, mean difference (MD) - 19.9 MME, 95% CI - 107.5 to 67.7], nor did they increase the number of participants who ceased their dose, or increase the risk of serious adverse events or adverse events. One clinician intervention of education plus decision tools versus decision tools alone reduced the number of opioid prescriptions (risk difference (RD) - 0.1, 95% CI - 0.2 to - 0.1), dose (MD - 5.3 MME, 95% CI - 6.2 to - 4.5) and use (RD - 0.1, 95% CI - 0.1 to - 0.0) in the long term. LIMITATIONS: Study heterogeneity prevented meta-analysis. CONCLUSION: The small number of studies and heterogeneity prevented firm conclusions to recommend any one opioid-analgesic-deprescribing strategy in patients with chronic pain. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42017068422.

Vaginal wellness: whose turf is it?

Dermatologists were the pioneers in the development of laser technology and have the most experience using these lasers to treat the external genitalia for many cutaneous disorders. Dermatologists who have experience and expertise using lasers and devices, are already using them to treat the external genitalia, and are comfortable performing female gynecologic exams may want to explore the wide range of options that are available to treat the functional and aesthetic needs of the female population. Dermatologists should work with obstetricians and gynecologists to ensure that patients are proper candidates for the procedures.

Worsening trends in analgesics recommended for spinal pain in primary care.

PURPOSE: Limited evidence exists on secular trends of analgesics for spinal pain. We investigated general practitioner's (GP) recommendations of analgesic medicines for spinal pain and investigated characteristics associated with their recommendation. METHODS: We accessed data on spinal pain consultations from the Bettering the Evaluation and Care of Health (BEACH) database, a nationally representative database on GP activity in Australia. Data extracted included consultation details and management provided. Medicines recommended were grouped as simple analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), opioid analgesics or neuropathic pain medicines. Multivariate logistic regression determined if patient characteristics and GP characteristics were associated with medication recommendations. RESULTS: We analysed BEACH data for 9100 GPs who managed 39,303 patients with spinal pain between 2004 and 2014. Over the decade, analgesic recommendations increased. After accounting for patient and GP characteristics, there was a significant increase in the rate single-ingredient opioid analgesics [annual relative increase of 6% (RR 1.06 (95% CI 1.05-1.07), P < 0.001)] and neuropathic pain medicines [annual relative increase of 19% (RR 1.19 (95% CI 1.16-1.22), P < 0.001)] were recommended; and a significant decrease in the rate NSAIDs were recommended [annual relative decrease of 4% (RR 0.96 (95% CI 0.95-0.97), P < 0.001)]. Logistic regression identified several patient and GP characteristics associated with medicine recommendations, e.g. stronger opioids were less likely recommended for Indigenous patients [odds ratio 0.15 (95% CI 0.04-0.56)]. CONCLUSIONS: GP's analgesic recommendations for spinal pain have become increasingly divergent from guideline recommendations over time.

Neuropathic pain screening questionnaires have limited measurement properties. A systematic review.

OBJECTIVES: The Douleur Neuropathique 4 (DN4), ID Pain, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), PainDETECT, and Neuropathic Pain Questionnaire have been recommended as screening questionnaires for neuropathic pain. This systematic review aimed to evaluate the measurement properties (eg, criterion validity and reliability) of these questionnaires. STUDY DESIGN AND SETTING: Online database searches were conducted and two independent reviewers screened studies and extracted data. Methodological quality of included studies and the measurement properties were assessed against established criteria. A modified Grading of Recommendations Assessment, Development and Evaluation approach was used to summarize the level of evidence. RESULTS: Thirty-seven studies were included. Most studies recruited participants from pain clinics. The original version of the DN4 (French) and Neuropathic Pain Questionnaire (English) had the most number of satisfactory measurement properties. The ID Pain (English) demonstrated satisfactory hypothesis testing and reliability, but all other properties tested were unsatisfactory. The LANSS (English) was unsatisfactory for all properties, except specificity. The PainDETECT (English) demonstrated satisfactory hypothesis testing and criterion validity. In general, the cross-cultural adaptations had less evidence than the original versions. CONCLUSION: Overall, the DN4 and Neuropathic Pain Questionnaire were most suitable for clinical use. These screening questionnaires should not replace a thorough clinical assessment.

Surgical versus conservative treatment for high-risk stress fractures of the lower leg (anterior tibial cortex, navicular and fifth metatarsal base): a systematic review.

AIM: To compare surgical and conservative treatment for high-risk stress fractures of the anterior tibial cortex, navicular and proximal fifth metatarsal. METHODS: Systematic searches of CENTRAL, MEDLINE, EMBASE, CINAHL, SPORTDiscus and PEDro were performed to identify relevant prospective and retrospective studies. Two reviewers independently extracted data and assessed methodological quality. Main outcomes were return to sport and complication rate. RESULTS: 18 studies were included (2 anterior tibia (N=31), 8 navicular (N=200) and 8 fifth metatarsal (N=246)). For anterior tibial fracture, no studies on initial surgery were eligible. Conservative treatment resulted in high complication rates and few cases returned to sport. For navicular fracture, a weighted mean return to sport of 22 for conservative and 16 weeks for surgical treatment was found. Six weeks of non-weightbearing cast was mostly used as conservative treatment. Surgical procedures varied widely. For the fifth metatarsal fracture, weighted mean return to sport was 19 for conservative and 14 weeks for surgical treatment. Surgery consisted of intramedullary screw fixation or tension band wiring. For conservative methods, insufficient details were reported. Overall, there was a high risk of bias; sample sizes were small and GRADE level of evidence was low. CONCLUSIONS: Strong conclusions for surgical or conservative therapy for these high-risk stress fractures cannot be drawn; quality of evidence is low and subjected to a high risk of bias. However, there are unsatisfying outcomes of conservative therapy in the anterior tibia. The role of initial surgery is unknown. For the navicular, surgery provided an earlier return to sport; and when treated conservatively, weightbearing should be avoided. For the fifth metatarsal, surgery provided the best results. Treatment decision-making would greatly benefit from further prospective research. STUDY REGISTRATION NUMBER: PROSPERO database of systematic reviews: CRD42013004201.

Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.

OBJECTIVE: To determine whether tactile acuity is disrupted in people with knee OA and to determine whether tactile acuity, a clinical signature of primary sensory cortex representation, is related to motor imagery performance (MIP; evaluates working body schema) and pain. METHODS: Experiment 1: two-point discrimination (TPD) threshold at the knee was compared between 20 participants with painful knee OA, 20 participants with arm pain and 20 healthy controls. Experiment 2: TPD threshold, MIP (left/right judgements of body parts) and usual pain were assessed in 20 people with painful knee OA, 17 people with back pain and 38 healthy controls (20 knee TPD; 18 back TPD). RESULTS: People with painful knee OA had larger TPD thresholds than those with arm pain and healthy controls (P < 0.05). TPD and MIP were not related in people with knee OA (P = 0.88) but were related in people with back pain and in healthy controls (P < 0.001). Pain did not relate to TPD threshold or to MIP (P > 0.15 for all). CONCLUSION: In painful knee OA, tactile acuity at the knee is decreased, implying disrupted representation of the knee in primary sensory cortex. That TPD and MIP were unrelated in knee OA, but related in back pain, suggests that the relationship between them may vary between chronic pain conditions. That pain was not related to TPD threshold nor MIP suggests against the idea that disrupted cortical representations contribute to the pain of either condition.

Biologic mechanisms of environmental tobacco smoke in children with poorly controlled asthma: results from a multicenter clinical trial.

BACKGROUND: Environmental tobacco smoke (ETS) negatively affects children with asthma. The prevalence of ETS exposure among children with poor asthma control may be changing. Importantly, the mechanisms by which ETS worsens asthma control are poorly understood. OBJECTIVE: We describe how ETS affects gastroesophageal reflux (GER), respiratory infections, and leukotriene production among children with poor asthma control. METHODS: We analyzed data from 306 children between 6 and 17 years of age with poorly controlled asthma enrolled in a 6-month clinical trial. We evaluated prevalence and determinants of ETS exposure by interview, questionnaire, and urinary cotinine and the association of ETS exposure on leukotriene production, respiratory infections, GER, lung function, and asthma control. We used multivariable linear, logistic, and Poisson regressions to assess outcomes. RESULTS: ETS prevalence estimates ranged from 6% to 30%. Children with domestic indoor exposure had worse asthma control (c-Asthma Control Test, 17.8 vs 21.5; P = .04), worse FEV1 % predicted (84.1 vs 90.7; P = .02), and a trend for increased mean urinary leukotriene E4. ETS from any setting was associated with increased symptomatic respiratory infections (adjusted incidence rate ratio: 1.30; P = .02). However, children exposed to ETS did not have symptoms or pH probe results, suggestive of heightened GER. CONCLUSIONS: Domestic smoking exposure was associated with both higher rates of symptomatic respiratory infection and poorer asthma control despite generally intensive controller therapy. ETS exposure is common among asthmatic children with poor control and may worsen asthma control by promoting respiratory infections. Further investigation is required to elucidate ETS mechanisms in poor asthma control.