Strengthening Australia's Chemical Regulation.

Humans are exposed to a myriad of chemicals every day, some of which have been established to have deleterious effects on human health. Regulatory frameworks play a vital role in safeguarding human health through the management of chemicals and their risks. For this review, we focused on agricultural and veterinary (Agvet) chemicals and industrial chemicals, which are regulated, respectively, by the Australian Pesticides and Veterinary Medicines Authority (APVMA), and the Australian Industrial Chemicals Introduction Scheme (AICIS). The current frameworks have been considered fragmented, inefficient, and most importantly, unsafe in prioritizing human health. We evaluated these frameworks, identified gaps, and suggested improvements that would help bring chemical regulation in Australia in line with comparative regulations in the EU, US, and Canada. Several weaknesses in the Australian frameworks include the lack of a national program to monitor chemical residues, slow pace in conducting chemical reviews, inconsistent risk management across states and territories, a paucity of research efforts on human health impacts, and inadequate framework assessment systems. Recommendations for Australia include establishing a national surveillance and chemical residue monitoring system, harmonizing risk assessment and management across jurisdictions, improving chemical review efficiency, and developing regular performance review mechanisms to ensure that human health is protected.

In spontaneous pneumothorax, initial needle aspiration and large- and narrow-bore chest tubes do not differ for success.

SOURCE CITATION: Mummadi SR, de Longpre' J, Hahn PY. Comparative effectiveness of interventions in initial management of spontaneous pneumothorax: a systematic review and a Bayesian network meta-analysis. Ann Emerg Med. 2020;76:88-102. 32115203.

Long-term quality-adjusted survival following therapeutic bronchoscopy for malignant central airway obstruction.

BACKGROUND: While therapeutic bronchoscopy has been used to treat malignant central (CAO) airway obstruction for >25 years, there are no studies quantifying the impact of therapeutic bronchoscopy on long-term quality-adjusted survival. METHODS: We conducted a prospective observational study of consecutive patients undergoing therapeutic bronchoscopy for CAO. Patients had follow-up at 1 week and monthly thereafter until death. Outcomes included technical success (ie, relief of anatomic obstruction), dyspnoea, health-related quality of life (HRQOL) and quality-adjusted survival. RESULTS: Therapeutic bronchoscopy was performed on 102 patients with malignant CAO. Partial or complete technical success was achieved in 90% of patients. At 7 days postbronchoscopy, dyspnoea improved (mean ∆Borg-day-7=-1.8, 95% CI -2.2 to -1.3, p<0.0001) and HRQOL improved (median prebronchoscopy 0.618 utiles, 25%-75% IQR 0.569 to 0.699, mean ∆utility-day-7+0.047 utiles, 95% CI +0.023 to 0.071, p=0.0002). Improvements in dyspnoea and HRQOL were maintained long-term. Compared with the prebronchoscopy baseline, HRQOL per day of life postbronchoscopy improved (mean ∆utility-long-term+0.036 utiles, 95% CI +0.014 to 0.057, p=0.002). Median quality-adjusted survival was 109 quality-adjusted life-days (QALDs) (95% CI 74 to 201 QALDs). Factors associated with longer quality-adjusted survival included better functional status, treatment-naïve tumour, endobronchial disease, less dyspnoea, shorter time from diagnosis to bronchoscopy, absence of cardiac disease, bronchoscopic dilation and receiving chemotherapy. CONCLUSIONS: Therapeutic bronchoscopy improves HRQOL as compared with baseline, resulting in approximately a 5.8% improvement in HRQOL per day of life. The risk-benefit profile in these carefully selected patients was very favourable. TRIAL REGISTRATION NUMBER: Results; NCT03326570.

Bronchoscopic Laser Interstitial Thermal Therapy: An Experimental Study in Normal Porcine Lung Parenchyma.

BACKGROUND: Population aging and lung cancer screening strategies may lead to an increase in detection of early-stage lung cancer in medical inoperable patients. Recent advances in peripheral bronchoscopy have made it a suitable platform for ablation of small peripheral tumors. METHODS: We investigated the tissue-ablative effect of a diode laser bronchoscopically applied by a laser delivery fiber (LDF) with wide aperture on porcine lung parenchyma. Laser was tested ex vivo and in vivo to identify the most effective power settings and LDF. Chest computed tomography (CT) were obtained immediately after ablation and after 3 days of observation. At day 3, necropsy was performed. RESULTS: On the basis of our ex vivo and in vivo experiments, we selected the round-tip LDF to be activated at 25 W for 20 seconds. Ten ablations were performed in 5 pigs. One ablation resulted in a pneumothorax requiring aspiration. All animals remained stable for 72 hours. CT findings at days 1 and 3 showed an area of cavitation surrounded by consolidation and ground glass. Median size of CT findings (long axis) was 26 mm (range, 24 to 38) at day 1, and 34 mm (range, 30 to 44) at day 3. Necropsy showed an area of central char measuring from 0.8×0.7×0.9 cm to 2.4×3.5×1.2 cm, surrounded by a gray-brown to dark red area. On histology, variable degrees of necrosis were evident around the charred areas. CONCLUSION: Bronchoscopic laser interstitial thermal therapy can achieve relatively large areas of ablation of normal lung parenchyma with a low rate of periprocedural complications.

Recent advances in diagnostic bronchoscopy.

The field of diagnostic bronchoscopy has been revolutionized in the last decade primarily with the advent of endobronchial ultrasound (EBUS) but also with the addition of multiple different techniques for "guided-bronchoscopy". These advances have had a substantial impact in the management of lung cancer with bronchoscopy now providing both diagnosis and mediastinal staging in a single procedure. EBUS has, in fact, become the first choice for staging of the mediastinum over cervical mediastinoscopy (CM). Although EBUS is now a well-established technique, there are continuous efforts from the scientific community to improve its diagnostic performance, and these will be reviewed in this manuscript. The term "guided-bronchoscopy" was recently coined to describe a myriad of techniques that guide our bronchoscopes or bronchoscopic tools into the periphery of the lungs in addition to our conventional fluoroscopy. Electromagnetic and non-electromagnetic navigation, thin and ultrathin scopes, as well as radial-probe EBUS have collectively increased our yield for smaller peripheral lung lesions and continue to evolve. Despite this improved diagnostic yield, there is still ample room for improvement and newer techniques are under way. With new therapies available for patients with interstitial lung disease, achieving a specific histologic diagnosis is now of paramount importance. Given the high morbidity and mortality of surgical biopsies, bronchoscopic cryobiopsy is being rapidly adopted as a safer and effective alternative, and it is likely going to play a major role in the management of these diseases in the near future. This manuscript we will focus on recent advances in EBUS, guided-bronchoscopy, and the use of cryobiopsy.

Endobronchial ultrasound-guided transbronchial needle aspiration for systematic nodal staging of lung cancer in patients with N0 disease by computed tomography and integrated positron emission tomography-computed tomography.

RATIONALE: Data regarding the sensitivity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging of lung cancer in patients with radiographic N0 disease is scant and inconsistent. With increasing use of nonoperative ablative therapies, studies focusing on the performance characteristics of EBUS-TBNA in this population are important. OBJECTIVES: To evaluate the sensitivity and negative predictive value (NPV) of EBUS-TBNA in patients with non-small cell lung cancer and radiographic N0 disease both by computed tomography (CT) and positron emission tomography (PET)-CT. METHODS: This was a retrospective review of EBUS-TBNA performed for lung cancer staging at two major academic centers from 2009 to 2014. Patients with radiographic N0 disease (lymph nodes [LN]≤1 cm in the short axis and maximum standardized uptake value≤2.5 by PET-CT) were included. Primary outcome was sensitivity and NPV of EBUS-TBNA. MEASUREMENTS AND MAIN RESULTS: Two hundred twenty patients with radiographic N0 disease underwent EBUS-TBNA, and 734 LN were sampled (median 3, range 1-6). Median LN diameter was 0.72 cm. One hundred patients (45.5%) underwent surgery, and 120 patients (54.5%) had nonsurgical therapy. N status was up-staged in 49 patients (22.3%): 18 by EBUS-TBNA (N1=11, N2=6, N3=1), 27 by surgery (N1 intralobar=16, N1 extralobar=3, N2=8 [5 LN in stations 4 and 7, and 3 LN in stations 5-6), and 4 by imaging follow-up (N1=2, N2=2). Overall false-negative rate of EBUS was 14.1% (sensitivity, 36.7%; specificity, 100%; and NPV, 84.7%). False-negative rate was 27 and 3.3% in surgical and nonsurgical populations, respectively. Excluding patients with occult disease "outside" the reach of EBUS, the overall false-negative rate of EBUS-TBNA was 5.5% (sensitivity, 60%; specificity, 100%; and NPV, 93.4%). CONCLUSIONS: This is the largest report of EBUS-TBNA in patients with N0 disease by "integrated" PET-CT. The majority of false-negative EBUS results were in LN stations outside its reach. In our study, both sensitivity and NPV of EBUS-TBNA were lower than early reports despite more extensive LN sampling. Given the high false-negative rate of imaging modalities, EBUS-TBNA may still play an important role in patients with radiographic N0 disease, particularly when nonsurgical ablative therapies are planned. Prospective studies are needed to corroborate our findings in the nonsurgical population.

Short-term femoral vein catheterization rarely causes thrombosis or bacteremia.

BACKGROUND: Experts and national regulatory bodies have deemed femoral vein catheterization (FVC) unsafe, and recommend avoiding it whenever possible. OBJECTIVE: To assess rates of catheter-related bloodstream infections (CRBI) and deep venous thrombosis (DVT) complicating FVC. DESIGN: Prospective observational cohort study. SETTING: Medical intensive care unit (MICU) of a 350-bed community teaching hospital. PATIENTS: Consecutive admissions to the MICU during 7 months. METHODS: Demographic, laboratory and Doppler ultrasound studies were collected on patients receiving large vein catheters (VC) in our MICU. Ultrasound examinations were systematically performed on the day of and 5 to 7 days after removal of FVC. RESULTS: VC were inserted in 238 (35% of) patients. Of that total, 217 catheters were in large veins (49% FVC, 38% internal jugular and 13% subclavian) for an average of 2.7 days for femoral, 5.7 days for internal jugular and 3.6 days for subclavian vein catheters. During 1200 catheter-days, no central VC CRBI was identified. Of 107 FVC, initial and follow-up Doppler studies were performed in 50 patients. A total of 97% of patients received routine thromboprophylaxis and none had a DVT. Of the 57 patients with initial but no Doppler follow-up at 5 to 7 days following removal, no patient developed clinically detected venous thromboembolism (VTE). CONCLUSION: Short-term FVC was used safely in our MICU in the setting of thromboprophylaxis. In light of its favorable safety profile for initial resuscitation of critically ill patients, it may be premature to strongly discourage FVC.

Outcomes of critically ill patients who received cardiopulmonary resuscitation.

RATIONALE: Studies examining survival outcomes after in-hospital cardiopulmonary arrest (CPA) among intensive care unit (ICU) patients requiring medications for hemodynamic support are limited. OBJECTIVES: To examine outcomes of ICU patients who received cardiopulmonary resusitation. METHODS: We identified 49,656 adult patients with a first CPA occurring in an ICU between January 1, 2000 and August 26, 2008 within the National Registry of Cardiopulmonary Resuscitation. Survival outcomes of patients requiring hemodynamic support immediately before CPA were compared with those of patients who did not receive hemodynamic support (pressors), using multivariable logistic regression analyses to adjust for differences in demographics and clinical characteristics. Pressor medications included epinephrine, norepinephrine, phenylephrine, dopamine, dobutamine, and vasopressin. MEASUREMENTS AND MAIN RESULTS: The overall rate of survival to hospital discharge was 15.9%. Patients taking pressors before CPA were less likely to survive to discharge (9.3 vs. 21.2%; P < 0.0001). After multivariable adjustment, patients taking pressors before pulseless CPA were 55% less likely to survive to discharge (adjusted odds ratio [OR], 0.45; 95% confidence interval [CI], 0.42-0.48). Age equal to or greater than 65 years (adjusted OR, 0.77; 95% CI, 0.73-0.82), nonwhite race (adjusted OR, 0.58; 95% CI, 0.54-0.62), and mechanical ventilation (adjusted OR, 0.60; 95% CI, 0.56-0.63) were also variables that could be identified before CPA that were independently associated with lower survival. More than half of survivors were discharged to rehabilitation or extended care facilities. Only 3.9% of patients who had CPA despite pressors were discharged home from the hospital, as compared with 8.5% of patients with a CPA and not taking pressors (adjusted OR, 0.53; 95% CI, 0.49-0.59). CONCLUSIONS: Although overall survival of ICU patients was 15.9%, patients requiring pressors and who experienced a CPA in an ICU were half as likely to survive to discharge and to be discharged home than patients not taking pressors. This study provides robust estimates of CPR outcomes of critically ill patients, and may assist clinicians to inform consent for this procedure.