Protocol for iSISTAQUIT: Implementation phase of the supporting indigenous smokers to assist quitting project.

INTRODUCTION: About 44% of Aboriginal and/or Torres Strait Islander women smoke during pregnancy compared to 12% of their general population counterparts. Evidence-based quit smoking advice received from health care professionals (HCPs) can increase smoking cessation rates. However, HCPs lack culturally appropriate smoking cessation training, which is a major barrier to provision of smoking cessation care for this population. METHODS AND ANALYSIS: iSISTAQUIT is a multicentre, single arm study aiming to implement and evaluate the evidence-based, culturally competent iSISTAQUIT smoking cessation training among health practitioners who provide support and assistance to pregnant, Aboriginal and Torres Strait Islander women in Australia. This project will implement the iSISTAQUIT intervention in Aboriginal Medical Services and Mainstream Health Services. The proposed sample size is 10 of each of these services (total N = 20), however if the demand is higher, we will aim to accommodate up to 30 services for the training. Participating sites and their HCPs will have the option to choose one of the two iSISTAQUIT packages available: a) Evaluation- research package b) Training package (with or without continued professional development points). Training will be provided via an online eLearning platform that includes videos, text, interactive elements and a treatment manual. A social media campaign will be conducted from December 2021 to September 2022 to raise brand and issue awareness about smoking cessation for Aboriginal and Torres Strait Islander women in pregnancy. This national campaign will consist of systematic advertising and promotion of iSISTAQUIT and video messages through various social media platforms. ANALYSIS: We will use the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation and Maintenance) to plan, evaluate and report the intervention impact of iSISTAQUIT. Effectiveness of social media campaign will be assessed via social media metrics, cross-sectional surveys, and interviews. DISCUSSION: This innovative research, using a multi-component intervention, aims to practically apply and integrate a highly translatable smoking cessation intervention in real-world primary care settings in Aboriginal Medical Services and Mainstream services. The research benefits Aboriginal women, babies and their family and community members through improved support for smoking cessation during pregnancy. The intervention is based on accepted Australian and international smoking cessation guidelines, developed and delivered in a culturally appropriate approach for Aboriginal communities.

SISTAQUIT: training health care providers to help pregnant Aboriginal and Torres Strait Islander women quit smoking. A cluster randomised controlled trial.

BACKGROUND: About 44% of Indigenous Australian women smoke during pregnancy, compared with 12% of pregnant non-Indigenous women. Health care providers can assist smoking cessation, but they are not typically trained in culturally appropriate methods. OBJECTIVES: To determine whether a health care worker training intervention increases smoking cessation rates among Indigenous pregnant smokers compared with usual care. METHODS AND ANALYSIS: Supporting Indigenous Smokers to Assist Quitting (SISTAQUIT) study is a multicentre, hybrid type 1, pragmatic, cluster randomised controlled trial that compares the effects of an intervention for improving smoking cessation by pregnant Indigenous women (16 years or older, 32 weeks' gestation or less) with usual care. Twenty-one health services caring for Indigenous people in five Australian jurisdictions were randomised to the intervention (ten sites) or control groups (eleven sites). Health care providers at intervention sites received smoking cessation care training based on the ABCD (ask/assess; brief advice; cessation; discuss psychosocial context) approach to smoking cessation for Indigenous women, an educational resource package, free oral nicotine replacement therapy for participating women, implementation support, and trial implementation training. Health care providers in control group services provided usual care. PRIMARY OUTCOME: abstinence from smoking (self-reported abstinence via survey, validated by carbon monoxide breath testing when possible) four weeks after enrolment in the study. SECONDARY OUTCOMES: health service process evaluations; knowledge, attitudes, and practices of health care providers; and longer term abstinence, perinatal outcomes, and respiratory outcomes for babies (to six months). Ethics approval: The human research ethics committees of the University of Newcastle (H-2015-0438) and the Aboriginal Health and Medical Research Council of NSW (1140/15) provided the primary ethics approval. Dissemination of results: Findings will be disseminated in peer-reviewed publications, at local and overseas conferences, and via public and social media, and to participating health services in art-based formats and reports. Policy briefs will be communicated to relevant government organisations. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry, ACTRN12618000972224 (prospective).

A tale of two reef systems: Local conditions, disturbances, coral life histories, and the climate catastrophe.

Coral reefs have evolved over millennia to survive disturbances. Yet, in just a few decades chronic local pressures and the climate catastrophe have accelerated so quickly that most coral reefs are now threatened. Rising ocean temperatures and recurrent bleaching pose the biggest threat, affecting even remote and well-managed reefs on global scales. We illustrate how coral bleaching is altering reefs by contrasting the dynamics of adjacent reef systems over more than two decades. Both reef systems sit near the edge of northwest Australia's continental shelf, have escaped chronic local pressures and are regularly affected by tropical storms and cyclones. The Scott reef system has experienced multiple bleaching events, including mass bleaching in 1998 and 2016, from which it is unlikely to fully recover. The Rowley Shoals has maintained a high cover and diversity of corals and has not yet been impacted by mass bleaching. We show how the dynamics of both reef systems were driven by a combination of local environment, exposure to disturbances and coral life history traits, and consider future shifts in community structure with ongoing climate change. We then demonstrate how applying knowledge of community dynamics at local scales can aid management strategies to slow the degradation of coral reefs until carbon emissions and other human impacts are properly managed.

Codeveloping a multibehavioural mobile phone app to enhance social and emotional well-being and reduce health risks among Aboriginal and Torres Strait Islander women during preconception and pregnancy: a three-phased mixed-methods study.

OBJECTIVE: Describe the development and pretest of a prototype multibehavioural change app MAMA-EMPOWER. DESIGN: Mixed-methods study reporting three phases: (1) contextual enquiry included stakeholder engagement and qualitative interviews with Aboriginal women, (2) value specification included user-workshop with an Aboriginal researcher, community members and experts, (3) codesign with Aboriginal researchers and community members, followed by a pretest of the app with Aboriginal women, and feedback from qualitative interviews and the user-Mobile Application Rating Scale (U-MARS) survey tool. SETTINGS: Aboriginal women and communities in urban and regional New South Wales, Australia. PARTICIPANTS: Phase 1: interviews, 8 Aboriginal women. Phase 2: workshop, 6 Aboriginal women. Phase 3: app trial, 16 Aboriginal women. U-MARS, 5 Aboriginal women. RESULTS: Phase 1 interviews revealed three themes: current app use, desired app characteristics and implementation. Phase 2 workshop provided guidance for the user experience. Phase 3 app trial assessed all content areas. The highest ratings were for information (mean score of 3.80 out of 5, SD=0.77) and aesthetics (mean score of 3.87 with SD of 0.74), while functionality, engagement and subjective quality had lower scores. Qualitative interviews revealed the acceptability of the app, however, functionality was problematic. CONCLUSIONS: Developing a mobile phone app, particularly in an Aboriginal community setting, requires extensive consultation, negotiation and design work. Using a strong theoretical foundation of behavioural change technique's coupled with the consultative approach has added rigour to this process. Using phone apps to implement behavioural interventions in Aboriginal community settings remains a new area for investigation. In the next iteration of the app, we aim to find better ways to personalise the content to women's needs, then ensure full functionality before conducting a larger trial. We predict the process of development will be of interest to other health researchers and practitioners.

Smoking Cessation Messages for Pregnant Aboriginal and Torres Strait Islander Women: A Rapid Review of Peer-Reviewed Literature and Assessment of Research Translation of Media Content.

This review summarized literature about knowledge, attitudes, and beliefs of Aboriginal and Torres Strait Islander women from Australia who smoke during pregnancy, then examined the extent that existing health promotion materials and media messages aligned with evidence on smoking cessation for pregnant Aboriginal and Torres Strait Islander women. Knowledge, attitudes, and beliefs of pregnant Aboriginal women who smoke tobacco were identified in the literature. Health promotion campaigns were retrieved from a grey literature search with keywords and social and professional networks. Key themes from peer-reviewed papers were compared against the content of health promotion campaigns using the Aboriginal Social and Emotional Wellbeing Model, the Behavior Change Wheel and thematic analysis. Eleven empirical studies and 17 campaigns were included. Empirical studies highlighted women sought holistic care that incorporated nicotine replacement therapy, engaged with their family and community and the potential for education about smoking cessation to empower a woman. Health promotion campaigns had a strong focus on 'engagement with family and community', 'knowledge of risks of smoking,' 'giving up vs cutting down' and 'culture in language and arts'. There were similarities and variances in the key themes in the research evidence and promotion materials. Topics highly aligned included risks from smoking and quitting related issues.

A quantitative comparison of towed-camera and diver-camera transects for monitoring coral reefs.

Novel tools and methods for monitoring marine environments can improve efficiency but must not compromise long-term data records. Quantitative comparisons between new and existing methods are therefore required to assess their compatibility for monitoring. Monitoring of shallow water coral reefs is typically conducted using diver-based collection of benthic images along transects. Diverless systems for obtaining underwater images (e.g. towed-cameras, remotely operated vehicles, autonomous underwater vehicles) are increasingly used for mapping coral reefs. Of these imaging platforms, towed-cameras offer a practical, low cost and efficient method for surveys but their utility for repeated measures in monitoring studies has not been tested. We quantitatively compare a towed-camera approach to repeated surveys of shallow water coral reef benthic assemblages on fixed transects, relative to benchmark data from diver photo-transects. Differences in the percent cover detected by the two methods was partly explained by differences in the morphology of benthic groups. The reef habitat and physical descriptors of the site-slope, depth and structural complexity-also influenced the comparability of data, with differences between the tow-camera and the diver data increasing with structural complexity and slope. Differences between the methods decreased when a greater number of images were collected per tow-camera transect. We attribute lower image quality (variable perspective, exposure and focal distance) and lower spatial accuracy and precision of the towed-camera transects as the key reasons for differences in the data from the two methods and suggest changes to the sampling design to improve the application of tow-cameras to monitoring.

Early recovery dynamics of turbid coral reefs after recurring bleaching events.

The worlds' coral reefs are declining due to the combined effects of natural disturbances and anthropogenic pressures including thermal coral bleaching associated with global climate change. Nearshore corals are receiving increased anthropogenic stress from coastal development and nutrient run-off. Considering forecast increases in global temperatures, greater understanding of drivers of recovery on nearshore coral reefs following widespread bleaching events is required to inform management of local stressors. The west Pilbara coral reefs, with cross-shelf turbidity gradients coupled with a large nearby dredging program and recent history of repeated coral bleaching due to heat stress, represent an opportune location to study recovery from multiple disturbances. Mean coral cover at west Pilbara reefs was monitored from 2009 to 2018 and declined from 45% in 2009 to 5% in 2014 following three heat waves. Recruitment and juvenile abundance of corals were monitored from 2014 to 2018 and were combined with biological and physical data to identify which variables enhanced or hindered early-stage coral recovery of all hard corals and separately for the acroporids, the genera principally responsible for recovery in the short-term (<7 years). From 2014 to 2018, coral cover increased from 5 to 10% but recovery varied widely among sites (0-13%). Hard coral cover typically recovered most at shallower sites that had higher abundance of herbivorous fish, less macroalgae, and lower turbidity. Similarly, acroporid corals recovered most at sites with lower turbidity and macroalgal cover. Juvenile acroporid densities were a good indicator of recovery at least two years after they were recorded. However, recruitment to settlement tiles was not a good predictor of total coral or acroporid recovery. This study shows that coral recovery can be slower in areas of high turbidity and the rate may be reduced by local pressures, such as dredging. Management should focus on improving or maintaining local water quality to increase the likelihood of coral recovery under climate stress. Further, in turbid environments, juvenile coral density predicts early coral recovery better than recruits on tiles and may be a more cost-effective technique for monitoring recovery potential.

Low-dose ketamine provides poor analgesia for pain in redback spider envenoming.

Redback spider envenoming causes severe pain lasting several days. A recent clinical trial found that antivenom is not effective. We investigated ketamine for pain in redback spider envenoming. Ten adult patients with severe pain from redback spider envenoming were administered 15 mg intravenous ketamine after standard analgesia, then up to 4 oral doses of ketamine 25- 50 mg. Three patients had a clinically significant improvement in pain compared to baseline after intravenous ketamine. Five patients had a minimal decrease in pain and 2 had no improvement. Eight patients received oral ketamine: 4 doses in 5 and 2 doses in 3. At 24 h, 3/6 patients assessed had clinically significant improvement in pain and 4/5 patients assessed at 48 h, had clinically significant improvement in pain. Six patients reported side effects, including dissociation (4) and hallucinations (2). Five patients required rescue opioids and 2 were readmitted to hospital. We found that ketamine provided no additional pain relief in redback spider envenoming, compared to standard analgesia, and resulted in unacceptable adverse effects.

An update and systematic review on drug therapies for the treatment of refractory chronic cough.

INTRODUCTION: Chronic Cough (CC) is common and often associated with significant comorbidity and decreased quality of life. In up to 50% of cases, the cough is refractory despite extensive investigation and treatment trials. It is likely that the key abnormality in refractory CC is dysfunctional, hypersensitive sensory nerves, similar to conditions such as laryngeal hypersensitivity and neuropathic pain. AREAS COVERED: The aim of this systematic review is to assess drug therapies for refractory CC. The authors review the current management of CC and provide discussion of the similarities between neuropathic pain and refractory CC. They review repurposed and new pharmacological treatments. Several meta-analyses were performed to compare the efficacy of treatments where possible. EXPERT OPINION: Repurposed pain medications such as gabapentin and pregabalin reduce the frequency of cough and improve quality of life. Along with speech pathology, they are important and alternate treatments for refractory CC. However, more treatments are needed and the P2X3 ion channel receptor antagonists show the most promise. With a better understanding of neuronal activation and sensitisation and their signal processing in the brain, improved animal models of cough, and the use of validated cough measurement tools, more effective treatments will develop.

The safety of high-dose insulin euglycaemia therapy in toxin-induced cardiac toxicity.

CONTEXT: High-dose insulin euglycaemia (HIE) is recommended in the management of toxin-induced cardiac toxicity, with increasing insulin doses now being used. We aimed to investigate the safety of HIE in toxin-induced cardiac toxicity. METHODS: This was a retrospective review of cases from two clinical toxicology units. Demographics, toxin(s) ingested, clinical effects, investigations (serum glucose, electrolytes), treatments (insulin, glucose, electrolyte replacement), length of stay (LOS) and outcomes were extracted from the patients' medical records. Associations between insulin and glucose/electrolyte homeostasis were explored by comparing insulin administration and glucose or electrolyte concentrations and replacement. RESULTS: There were 22 patients (12 females), median age 57 years (15-88 years) treated with HIE. There were 12 beta-blocker, six calcium channel blocker and three combined beta-blocker and calcium channel blocker ingestions. A total of 19 patients had a systolic blood pressure <80mmHg and 18 patients required inotropes in addition to HIE. There were three deaths. Despite glucose and electrolyte replacement, 16 patients (73%) developed hypoglycaemia (Reference range [RR] < 3.5 mmol/L or <63 mg/dl). In 7 patients, hypoglycaemia was mild (2.5-3.4 mmol/L or 45-62 mg/dl) and in nine was severe (<2.5 mmol/L or <45 mg/dl). There were no neurological effects from hypoglycaemia. A total of 18 patients (82%) developed hypokalaemia (<3.5 mEq/L). In 16 patients, this was mild (2.5-3.4 mEq/L). There were no cardiac arrhythmias associated with this hypokalaemia. There was no apparent association between insulin dosing and severity of hypoglycaemia or hypokalaemia, or in glucose or potassium replacement. Median insulin loading dose was 80U (range 50-125 U) and the median maximum insulin infusion rate was 150 U/h (range 38-1500 U/h). Median glucose infusions rates were 37.5g/h (range 4-75g/h). There was no apparent association between insulin and glucose administration. Glucose was administered for a median of 18h after ceasing insulin. The duration of glucose administration after ceasing insulin increased with the rate and total insulin administered during HIE. DISCUSSION: Despite the benefits of HIE in toxin-induced cardiac toxicity, it caused significant disruption to glucose and electrolyte homeostasis, although there were no apparent complications from this. There was no association by comparing the amount of insulin administered on adverse effects or glucose administered, suggesting higher doses of insulin are associated with no more adverse effects.

The Australian Snakebite Project, 2005-2015 (ASP-20).

OBJECTIVE: To describe the epidemiology, treatment and adverse events after snakebite in Australia. DESIGN: Prospective, multicentre study of data on patients with snakebites recruited to the Australian Snakebite Project (2005-2015) and data from the National Coronial Information System. Setting, participants: Patients presenting to Australian hospitals with suspected or confirmed snakebites from July 2005 to June 2015 and consenting to participation. MAIN OUTCOME MEASURES: Demographic data, circumstances of bites, clinical effects of envenoming, results of laboratory investigations and snake venom detection kit (SVDK) testing, antivenom treatment and adverse reactions, time to discharge, deaths. RESULTS: 1548 patients with suspected snakebites were enrolled, including 835 envenomed patients (median, 87 per year), for 718 of which the snake type was definitively established, most frequently brown snakes (41%), tiger snakes (17%) and red-bellied black snakes (16%). Clinical effects included venom-induced consumption coagulopathy (73%), myotoxicity (17%), and acute kidney injury (12%); severe complications included cardiac arrest (25 cases; 2.9%) and major haemorrhage (13 cases; 1.6%). There were 23 deaths (median, two per year), attributed to brown (17), tiger (four) and unknown (two) snakes; ten followed out-of-hospital cardiac arrests and six followed intracranial haemorrhages. Of 597 SVDK test results for envenomed patients with confirmed snake type, 29 (4.9%) were incorrect; 133 of 364 SVDK test results for non-envenomed patients (36%) were false positives. 755 patients received antivenom, including 49 non-envenomed patients; 178 (24%), including ten non-envenomed patients, had systemic hypersensitivity reactions, of which 45 (6%) were severe (hypotension, hypoxaemia). Median total antivenom dose declined from four vials to one, but median time to first antivenom was unchanged (4.3 hours; IQR, 2.7-6.3 hours). CONCLUSIONS: Snake envenoming is uncommon in Australia, but is often severe. SVDKs were unreliable for determining snake type. The median antivenom dose has declined without harming patients. Improved early diagnostic strategies are needed to reduce the frequently long delays before antivenom administration.

Treatments for Latrodectism-A Systematic Review on Their Clinical Effectiveness.

Latrodectism or envenomation by widow-spiders is common and clinically significant worldwide. Alpha-latrotoxin is the mammalian-specific toxin in the venom that results in toxic effects observed in humans. Symptoms may be incapacitating and include severe pain that can persist for days. The management of mild to moderate latrodectism is primarily supportive while severe cases have variously been treated with intravenous calcium, muscle relaxants, widow-spider antivenom and analgesic opioids. The object of this systematic review is to examine the literature on the clinical effectiveness of past and current treatments for latrodectism. MEDLINE, EMBASE and Google Scholar were searched from 1946 to December 2016 to identify clinical studies on the treatment of latrodectism. Studies older than 40 years and not in English were not reviewed. There were only two full-publications and one abstract of placebo-controlled randomised trials on antivenom use for latrodectism. Another two randomised comparative trials compared the route of administration of antivenom for latrodectism. There were fourteen case series (including two abstracts), fourteen case reports and one letter investigating drug treatments for latrodectism with the majority of these also including antivenom for severe latrodectism. Antivenom with opioid analgesia is often the major treatment reported for latrodectism however; recent high quality evidence has cast doubt on the clinical effectiveness of this combination and suggests that other treatments need to be investigated.

Adult clonidine overdose: prolonged bradycardia and central nervous system depression, but not severe toxicity.

CONTEXT: There are limited reports of adult clonidine overdose. We aimed to describe the clinical effects and treatment of clonidine overdose in adults. METHODS: This was a retrospective review of a prospective cohort of poisoned patients who took clonidine overdoses (>200 µg). Demographic information, clinical effects, treatment, complications (central nervous system and cardiovascular effects) and length of stay (LOS) were extracted from a clinical database or medical records. RESULTS: From 133 admissions for clonidine poisoning (1988-2015), no medical record was available in 14 and 11 took staggered ingestions. Of 108 acute clonidine overdoses (median age 27 years; 14-65 years; 68 females), 40 were clonidine alone ingestions and 68 were clonidine with co-ingestants. Median dose taken was 2100 µg (interquartile range [IQR]: 400-15,000 µg). Median LOS was 21h (IQR: 14-35 h) and there were no deaths. Glasgow coma score [GCS] <15 occurred in 73/108 (68%), and more patients taking co-ingestants (8/68; 12%) had coma (GCS <9) compared to clonidine alone (2/40; 5%). Miosis occurred in 31/108 (29%) cases. Median minimum HR was 48 bpm (IQR: 40-57 bpm), similar between clonidine alone and co-ingestant overdoses. There was a significant association between dose and minimum HR for clonidine alone overdoses (p = 0.02). 82/108 (76%) had bradycardia, median onset 2.5 h post-ingestion (IQR: 1.7-5.5 h) and median duration 20 h (2.5-83 h), similar for clonidine alone and co-ingestant overdoses. There were no arrhythmias. Three patients ingesting 8000-12,000 µg developed early hypertension. Median minimum systolic BP was 96 mmHg (IQR: 90-105 mmHg) and hypotension occurred in 26/108 (24%). 12/108 patients were intubated, but only 2 were clonidine alone cases. Treatments included activated charcoal (24), atropine (8) and naloxone (23). The median total naloxone dose was 2 mg (IQR: 1.2-2.4 mg), but only one patient given naloxone was documented to respond with partial improvement in GCS. DISCUSSION: Clonidine causes persistent but not life-threatening clinical effects. Most patients develop mild central nervous system depression and bradycardia. Naloxone was not associated with improved outcomes.

Australian taipan (Oxyuranus spp.) envenoming: clinical effects and potential benefits of early antivenom therapy - Australian Snakebite Project (ASP-25).

CONTEXT: Taipans (Oxyuranus spp.) are medically important venomous snakes from Australia and Papua New Guinea. The objective of this study was to describe taipan envenoming in Australian and its response to antivenom. METHODS: Confirmed taipan bites were recruited from the Australian Snakebite Project. Data were collected prospectively on all snakebites, including patient demographics, bite circumstances, clinical effects, laboratory results, complications and treatment. Blood samples were taken and analysed by venom specific immunoassay to confirm snake species and measure venom concentration pre- and post-antivenom. RESULTS: There were 40 confirmed taipan bites: median age 41 years (2-85 years), 34 were males and 21 were snake handlers. Systemic envenoming occurred in 33 patients with neurotoxicity (26), complete venom induced consumption coagulopathy (VICC) (16), partial VICC (15), acute kidney injury (13), myotoxicity (11) and thrombocytopenia (7). Venom allergy occurred in seven patients, three of which had no evidence of envenoming and one died. Antivenom was given to 34 patients with a median initial dose of one vial (range 1-4), and a median total dose of two vials (range 1-9). A greater total antivenom dose was associated with VICC, neurotoxicity and acute kidney injury. Early antivenom administration was associated with a decreased frequency of neurotoxicity, acute kidney injury, myotoxicity and intubation. There was a shorter median time to discharge of 51 h (19-432 h) in patients given antivenom <4 h post-bite, compared to 175 h (27-1104 h) in those given antivenom >4 h. Median peak venom concentration in 25 patients with systemic envenoming and a sample available was 8.4 ng/L (1-3212 ng/L). No venom was detected in post-antivenom samples, including 20 patients given one vial initially and five patients bitten by inland taipans. DISCUSSION: Australian taipan envenoming is characterised by neurotoxicity, myotoxicity, coagulopathy, acute kidney injury and thrombocytopenia. One vial of antivenom binds all measurable venom and early antivenom was associated with a favourable outcome.

Adverse reactions to snake antivenom, and their prevention and treatment.

Antivenom is the mainstay of treatment of snakebite envenoming. However, adverse reactions to snake antivenom that is available are common in many parts of the world where snakebite is prevalent. Both acute (anaphylactic or pyrogenic) and delayed (serum sickness type) reactions occur. Acute reactions are usually mild but severe systemic anaphylaxis may develop, often within an hour or so of exposure to antivenom. Serum sickness after antivenom has a delayed onset between 5 and 14 days after its administration. Ultimately, the prevention reactions will depend mainly on improving the quality of antivenom. Until these overdue improvements take place, doctors will have to depend on pharmacological prophylaxis, where the search for the best prophylactic agent is still on-going, as well as careful observation of patients receiving antivenom in preparation for prompt management of acute as well as delayed reactions when they occur.

Pregabalin and Speech Pathology Combination Therapy for Refractory Chronic Cough: A Randomized Controlled Trial.

BACKGROUND: Chronic refractory cough (CRC) is a difficult problem to treat. Speech pathology treatment (SPT) improves symptoms but resolution is incomplete. Centrally acting neuromodulators also improve cough symptoms, but not cough reflex sensitivity, and the effect is short-lived. We hypothesized that combined SPT and centrally acting neuromodulators would have a superior outcome than SPT alone. Our goal was to determine whether combined pregabalin and SPT is more effective than SPT alone. METHODS: Randomized placebo controlled trial. Forty patients with CRC were randomly assigned to receive either combined SPT and pregabalin 300 mg daily or combined SPT and placebo. Outcome measures were collected at baseline, end of treatment, and 4 weeks after the end of treatment. Primary outcome measures were cough frequency using the Leicester Cough Monitor, cough severity using a visual analog scale (coughVAS), and cough-related quality of life (QOL) using the Leicester Cough Questionnaire (LCQ). RESULTS: Cough severity, cough frequency, and cough QOL improved in both groups. The degree of improvement in LCQ and coughVAS was greater with combined SPT and pregabalin than SPT alone; the mean difference in LCQ was 3.5, 95%CI of difference 1.1 to 5.8; the mean difference in coughVAS was 25.1, 95% CI of difference 10.6 to 39.6. There was no significant difference in improvement in cough frequency between groups. There was no deterioration in symptoms once pregabalin was withdrawn. Median capsaicin cough sensitivity improved from 15.7 to 47.5 µM with combined SPT and pregabalin and from 3.92 to 15.7 µM with SPT alone. CONCLUSIONS: Combined SPT and pregabalin reduces symptoms and improves QOL compared with SPT alone in patients with CRC.

Incidence of serum sickness after the administration of Australian snake antivenom (ASP-22).

CONTEXT: Serum sickness is a delayed immune reaction resulting from the injection of foreign protein or serum. Antivenom is known to cause serum sickness but the incidence and characteristics are poorly defined. OBJECTIVE: To investigate the incidence and clinical features of serum sickness following the administration of Australian snake antivenoms. MATERIALS AND METHODS: This was a prospective cohort study of patients recruited to the Australian Snakebite Project who received snake antivenom from November 2012 to March 2014. Demographics, clinical information, laboratory tests and antivenom treatment were recorded prospectively. Patients administered antivenom were followed up at 7-10 days and 6 weeks' post-antivenom. The primary outcome was the proportion with serum sickness, pre-defined as three or more of: fever, erythematous rash/urticaria, myalgia/arthralgia, headache, malaise, nausea/vomiting 5-20 days post-antivenom. RESULTS: During the 16-month period, 138 patients received antivenom. 23 were not followed up (unable to contact, tourist, child, bee sting) and 6 died in hospital. Of 109 patients followed up, the commonest reason for antivenom was venom induced consumption coagulopathy in 77 patients. An acute systemic hypersensitivity reaction occurred post-antivenom in 25 (23%) and 8 (7%) were severe with hypotension. Serum sickness occurred in 32/109 (29%) patients, including 15/37 (41%) given tiger snake, 6/15 (40%) given polyvalent and 4/23 (17%) given brown snake antivenom. There was no association between the volume of antivenom and serum sickness, p = 0.18. The commonest effects were lethargy, headache, muscle/joint aches and fever. DISCUSSION: The incidence of serum sickness after snake antivenom in Australia was higher than earlier investigations which failed to define symptoms or follow-up patients, but similar to more recent studies of antivenoms in the United States. CONCLUSION: Serum sickness is common with Australian snake antivenom but does not appear to be predictable based on the volume of antivenom administered.

Clinical features of serum sickness after Australian snake antivenom.

Serum sickness is a delayed immune reaction in which the immune system responds to a protein in antiserum as a potentially harmful substance and mounts an IgG-mediated antibody response. A 32 year-old female patient had systemic envenoming following a bite by a red-bellied black snake (Pseudechis porphyriacus). She was treated with Tiger snake antivenom and recovered over 24 h and did not develop myotoxicity. She then presented with local pain, itching and swelling, which was partially treated with antihistamines. Eleven days after the bite she presented again with symptoms of worsening serum sickness including rash on the upper legs, joint and muscle pain in arms, ankles and knees, and nausea. The patient was prescribed five days of prednisone 50 mg/day, antihistamine 10 mg/day and analgesia 1000 mg/day and improved over 2 days. She had no further problems on follow up at 4 months. This case highlights that serum sickness can cause significant effects after the treatment of snake envenoming. It develops 5-14 days after antivenom administration and has characteristic clinical and laboratory features. Severe cases of serum sickness can result in morbidity but it appears to respond well to corticosteroid treatment.

Tramadol overdose causes seizures and respiratory depression but serotonin toxicity appears unlikely.

CONTEXT: Tramadol is a commonly used centrally acting analgesic associated with seizures and suspected to cause serotonin toxicity in overdose. OBJECTIVE: This study sought to investigate the effects of tramadol overdose, and included evaluation for serotonin toxicity based on the Hunter Serotonin Toxicity Criteria where the seven clinical features of spontaneous clonus, inducible clonus, ocular clonus, agitation, diaphoresis, tremor and hyperreflexia are examined for in all patients taking serotonergic medications; seizures and central nervous system depression. MATERIALS AND METHODS: This was an observational cases series based on a retrospective review of tramadol overdoses (> 400 mg) admitted to a tertiary toxicology unit from November 2000 to June 2013. Demographic details, information on ingestion (dose and co-ingestants), clinical effects, complications (seizures, serotonin toxicity and cardiovascular effects) and intensive care unit (ICU) admission were extracted from a clinical database. RESULTS: There were 71 cases of tramadol overdose (median age: 41 years, range: 17-69 years; and median ingested dose: 1000 mg, interquartile range [IQR]: 800-2000 mg). Seizures were dose related and occurred in 8 patients, one of them co-ingested a benzodiazepine compared with 16 patients without seizures. There were no cases of serotonin toxicity meeting the Hunter Serotonin Toxicity Criteria. Tachycardia occurred in 27 and mild hypertension occurred in 32. The Glasgow Coma Score was < 15 in 29 and < 9 in 5 patients; three co-ingested tricyclic antidepressants and two tramadol alone (3000 mg and 900 mg). Respiratory depression occurred in 13, median dose: 2500 (IQR: 1600-3000) mg which was significantly different (p = 0.003) to patients without respiratory depression, median dose: 1000 (IQR: 750-1475) mg. Eight patients were admitted to ICU, five due to co-ingestant toxicity and three for respiratory depression. DISCUSSION: Tramadol overdose was associated with a significant risk of seizures and respiratory depression in more severe cases, both which appear to be related to the ingested dose. There were no cases of serotonin toxicity, while opioid-like effects and adrenergic effects were prominent. CONCLUSION: Tramadol overdose is associated with seizures and respiratory depression, but is unlikely to cause serotonin toxicity.

A review on the efficacy and safety of gabapentin in the treatment of chronic cough.

INTRODUCTION: Effective antitussives available to control cough are limited. Consolidation among different afferent branches of the vagus nerve is needed to bring about cough. A general, widely accepted view is that the chronic increase in the sensitivity of the cough reflex is associated with inflammatory hypersensitivity such as from gastro-esophageal reflux disease. There is increasing evidence that an important mechanism is a sensory disorder of the laryngeal branches of the vagus nerve. Neuromodulating drugs are effectively used in the treatment of chronic pain and neuropathic disorders and may have a role in the treatment of refractory chronic cough (CC). AREAS COVERED: Current evidence on the efficacy and safety of gabapentin in the treatment of CC is reviewed. Relevant randomized controlled trials, case reports and reviews were identified through a PubMed search of English-language literature referring to cough, sensory neuropathy and gabapentin over the last 10 years. EXPERT OPINION: Gabapentin appears to be effective and well tolerated in the treatment of CC and in other sensory neuropathic disorders. Relevant clinical trials investigating its efficacy and safety profile in the treatment of cough are limited and further studies are needed. Gabapentin has been shown to cause minimal to no toxicity in overdose.