Using the Behaviour Change Wheel and modified Delphi method to identify behavioural change techniques for improving adherence to smoking cessation medications.

BACKGROUND: Medication adherence is a crucial component of the pharmacological treatment of smoking. Previous interventions targeted to improve adherence to smoking cessation medications (SCMs) were designed using pragmatic approaches. This study aims to develop a comprehensive intervention strategy to improve adherence to SCMs using the Behaviour Change Wheel (BCW) and a modified Delphi method. METHODS: Recommendations for the design of intervention strategies were based on the BCW guide and six studies conducted by the research team. Factors related to healthcare providers and consumers (person making a quit attempt) that showed associations with adherence were mapped into the Capability, Opportunity, Motivation, Behaviour (COM-B) model, and corresponding intervention functions and policy categories. Interventions were then represented using the Behaviour Change Technique Taxonomy. Finally, a modified Delphi study using 17 experts was conducted to evaluate the nominated strategies using the Acceptability, Practicability, Effectiveness, Affordability, Side-effects, and Equity (APEASE) criteria. RESULTS: Following a stepped approach, an adherence support wheel was designed to guide implementation strategies and programmes. Thirteen intervention strategies were selected. The selected interventions include providing detailed instructions on how to use SCMs; establishing realistic expectations from SCMs; and providing training for healthcare providers regarding comprehensive smoking cessation care with specifics on the provision of adherence support. CONCLUSION: The BCW guide and a modified Delphi were applied successfully to design interventions tailored to improve adherence to SCMs. Improving adherence to SCMs requires a comprehensive intervention approach involving various stakeholders. Future research is needed to assess the effectiveness of the nominated intervention strategies.

Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol.

BACKGROUND: The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches. METHODS/DESIGN: A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures. DISCUSSION: This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with this population and more generally on other agonist replacement treatments (e.g. nicotine, opioids). TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12616000103460 (Registered 1st February 2016).

A High Rate of Alternative Diagnoses in Patients Referred for Presumed Clostridium difficile Infection.

GOALS: We evaluated a cohort of patients referred to our center for presumed recurrent Clostridium difficile infection (CDI) to determine final diagnoses and outcomes. BACKGROUND: As rates of CDI have increased, more patients are diagnosed with recurrent CDI and other sequelae of the infection. Distinguishing symptomatic patients with CDI from those who are colonized with an alternative etiology of diarrheal symptoms may be challenging. MATERIALS AND METHODS: We performed a retrospective review of 117 patients referred to our center for recurrent CDI between January 2013 and June 2014. Data collected included demographics, the referring provider, previous anti-CDI treatment, and significant medical conditions. In addition, we gathered data on atypical features of CDI and investigations obtained to investigate the etiology of symptoms. Outcomes included rates of alternative diagnoses and the accuracy of CDI diagnosis by the referral source. RESULTS: The mean age was 61 years, and 70% were female. About 29 patients (25%) were determined to have a non-CDI diagnosis. Most common alternative diagnoses included irritable bowel syndrome (18 patients: 62%) and inflammatory bowel disease (3 patients:10%). The age was inversely correlated with the rate of non-CDI diagnosis (P=0.016). Of the remaining 88 (75%) patients with a confirmed diagnosis of CDI, 25 (28%) received medical therapy alone and 63 (72%) underwent fecal microbiota transplantation. CONCLUSIONS: Among patients referred to our center for recurrent CDI, a considerable percentage did not have CDI, but rather an alternative diagnosis, most commonly irritable bowel syndrome. The rate of alternative diagnosis correlated inversely with age. Providers should consider other etiologies of diarrhea in patients presenting with features atypical of recurrent CDI.

Dissecting New Medicare Physician Pay.

A summary of key aspects of the new Medicare physician payment system and the implications for hospitals.

Lockdown Drills and Young Children with Autism Spectrum Disorder: Practitioner Confidence, Experiences, and Perceptions.

Lockdown drill practice is part of the "new normal" in schools for young children with autism spectrum disorder (ASD) and educational practitioners in K-12 schools across the United States. These drills place a tremendous amount of responsibility on practitioners (i.e., teachers, paraprofessionals) that is beyond the scope of their training and typical requirements of their position in the classroom. Lockdown drills also require young children with ASD to engage in actions that are inherently hard for most young children but could be especially difficult for children with ASD who need individualized support to develop the executive function and self-regulation skills to participate in drills successfully. This study investigates practitioners' training experiences and perceptions of perceived confidence in teaching young children with ASD lockdown drills. Practitioner's self-efficacy was measured through survey analysis and their perceptions and experiences were investigated through individual interviews. Results indicated low rates of confidence to teach lockdown drills to young children with ASD and higher rates of confidence were correlated with more drill practice. Themes gleaned from interview data revealed varied training and practice experiences for children and practitioners, general characteristics of ASD that help or hinder children's participation, connections between these characteristics and aspects of lockdown drills that make them difficult to teach, and identification of practitioner responsibilities beyond following protocols.

Combination eravacycline therapy for ventilator-associated pneumonia due to carbapenem-resistant Acinetobacter baumannii in patients with COVID-19: A case series.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia is associated with poor clinical outcomes and increased mortality. Clinical data regarding the optimal treatment of CRAB is limited, and combination therapy is often preferred. Eravacycline has demonstrated in-vitro activity against A. baumannii and has been considered for the treatment of pulmonary infections caused by CRAB. OBJECTIVE: The objective of this case series was to describe clinical outcomes associated with eravacycline when utilized as part of a combination regimen for the treatment of CRAB pneumonia at a county hospital. METHODS: A retrospective chart review was conducted from April 1, 2020, to October 1, 2020, which included hospitalized patients ≥18 years of age, diagnosed with coronavirus disease 2019 (COVID-19), with a sputum culture positive for CRAB, and receipt of at least one dose of eravacycline. The primary outcome studied was clinical resolution of CRAB pneumonia. A key secondary outcome was microbiological resolution. RESULTS: A total of 24 patients received combination eravacycline therapy for a median of 10.5 days. Overall, 17 (71%) patients demonstrated clinical resolution of CRAB pneumonia. Repeat sputum cultures post-treatment were collected in 17 (71%) patients, of which 12 (71%) achieved microbiological resolution. No adverse events attributable to eravacycline were identified. CONCLUSION: With limited viable salvage treatment options, combination eravacycline therapy showed favorable microbiological and clinical outcomes in patients with CRAB pneumonia. In light of this, eravacycline could be considered as a potential treatment option when designing CRAB pneumonia salvage therapy regimens.

Pilot study with randomised control of dual site theta burst transcranial magnetic stimulation (TMS) for methamphetamine use disorder: a protocol for the TARTAN study.

BACKGROUND: Transcranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting. METHODS: Thirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition). DISCUSSION: This study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks). TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023.

Between-female variation in house sparrow yolk testosterone concentration is negatively associated with CYP19A1 (aromatase) mRNA expression in ovarian follicles.

Maternally-derived yolk androgens influence the development and long-term phenotype of offspring in oviparous species. Between-female variation in the amounts of these yolk androgens has been associated with a number of social and environmental factors, suggesting that the variation is adaptive, but the mechanisms behind it are unknown. Using two different approaches, we tested the hypothesis that variation in yolk androgen levels across individuals is associated with variation in their capacity to synthesize androgens. First, we injected female house sparrows with exogenous gonadotropin-releasing hormone (GnRH) to maximally stimulate ovarian steroidogenesis. Second, we collected pre-ovulatory follicle tissue and quantified the mRNA expression of four key enzymes of the steroid synthesis pathway: steroidogenic acute regulatory protein (StAR), cytochrome P450-side chain cleavage enzyme (CYP11A1), 17ß-hydroxysteroid dehydrogenase (HSD17B1), and aromatase (CYP19A1). Thirty minutes after GnRH injection, androgen concentrations in both the plasma and in the yolks of pre-ovulatory follicles were significantly elevated compared to controls. However, this measure of steroidogenic capacity did not explain variation in yolk testosterone levels, although physiological differences between house sparrows and more widely studied poultry models were revealed by this approach. Steroidogenic enzyme mRNA levels were detectable in all samples and were significantly lower in the most mature pre-ovulatory follicles. Of the four measured genes, CYP19A1 expression exhibited a significant negative relationship with yolk testosterone concentrations in laid eggs, revealing a key mechanism for between-female variation in yolk testosterone. Furthermore, this suggests that any factors which alter the expression of CYP19A1 within an individual female could have dramatic effects on offspring phenotype.

Tobacco treatment incorporating contingency management, nicotine replacement therapy, and behavioral counseling for pregnant women who use substances: a feasibility trial.

Introduction: Most pregnant women with substance use problems smoke, and few will quit during their pregnancy. Tobacco treatment is often overlooked, with the focus usually placed on other substance use. Additionally, few targeted effective treatments for this group exist. To address this, the feasibility of an intensive tobacco treatment incorporating contingency management (CM) that featured non-face-to-face delivery was examined. Methods: A single-arm pre-post design feasibility trial was conducted in three antenatal services that support women who use substances in metropolitan Australia. Participants were over the age of 15, had <33-week gestation, and smoked tobacco daily. They received financial incentives for daily carbon monoxide-verified smoking abstinence or reduction through an internet-based CM programme, nicotine replacement therapy (NRT) posted to women and partners or household members who smoked and telephone-delivered behavioral counseling from study enrolment to birth. Results: Of the 101 referrals, 46 women (46%) consented. The mean (SD) age was 31(±6) years, and the gestation period was 22(±6) weeks. Nineteen (41%) of those enrolled were retained for 12-week postpartum. Of 46 women, 32 (70%) utilized CM; 32 (70%) used NRT for ≥2 weeks; 23 (50%) attended ≥1 counseling session; and 15 (22%) received NRT for partners/household members. Fifteen (33%) were verified abstinent from tobacco at delivery after a median (IQR) period of abstinence of 65(36-128) days. All non-smokers at birth utilized NRT and financial incentives, and 9/15 (60%) utilized counseling. Four (9%) were abstinent at 12-week postpartum. Median cigarettes smoked/day reduced from baseline to delivery (10(6-20) to 1(0-6) p =< 0.001). Women who quit smoking had more education (72% vs. 33% p =< 0.02), completed more CO samples (median (IQR) 101(59-157) vs. 2(0-20) p =< 0.001), and received more incentives (median (IQR) $909($225-$1980) vs. $34($3-$64) p =< 0.001). Intervention acceptability was rated favorably by participants (9 items rated 0-10 with scores >5 considered favorable). Discussion: This study demonstrated the feasibility and acceptability of a consumer-informed, non-face-to-face intensive tobacco treatment, highlighting the potential of remotely delivered technology-based CM to reduce the health impact of tobacco smoking in high-priority populations. The intervention demonstrates scale-up potential. Future studies should extend treatment into the postpartum period, utilizing new technologies to enhance CM delivery and improve counseling provision and partner support. Clinical trial registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374196, ACTRN1261800056224.

The salmonid myostatin gene family: a novel model for investigating mechanisms that influence duplicate gene fate.

BACKGROUND: Most fishes possess two paralogs for myostatin, a muscle growth inhibitor, while salmonids are presumed to have four: mstn1a, mstn1b, mstn2a and mstn2b, a pseudogene. The mechanisms responsible for preserving these duplicates as well as the depth of mstn2b nonfunctionalization within the family remain unknown. We therefore characterized several genomic clones in order to better define species and gene phylogenies. RESULTS: Gene organization and sequence conservation was particularly evident among paralog groupings and within salmonid subfamilies. All mstn2b sequences included in-frame stop codons, confirming its nonfunctionalization across taxa, although the indels and polymorphisms responsible often differed. For example, the specific indels within the Onchorhynchus tshawytscha and O. nerka genes were remarkably similar and differed equally from other mstn2b orthologs. A phylogenetic analysis weakly established a mstn2b clade including only these species, which coupled with a shared 51 base pair deletion might suggest a history involving hybridization or a shared phylogenetic history. Furthermore, mstn2 introns all lacked conserved splice site motifs, suggesting that the tissue-specific processing of mstn2a transcripts, but not those of mstn2b, is due to alternative cis regulation and is likely a common feature in salmonids. It also suggests that limited transcript processing may have contributed to mstn2b nonfunctionalization. CONCLUSIONS: Previous studies revealed divergence within gene promoters while the current studies provide evidence for relaxed or positive selection in some coding sequence lineages. These results together suggest that the salmonid myostatin gene family is a novel resource for investigating mechanisms that regulate duplicate gene fate as paralog specific differences in gene expression, transcript processing and protein structure are all suggestive of active divergence.

Mood, sleep and pain comorbidity outcomes in cannabis dependent patients: Findings from a nabiximols versus placebo randomised controlled trial.

BACKGROUND: Mood, sleep and pain problems are common comorbidities among treatment-seeking cannabis-dependent patients. There is limited evidence suggesting treatment for cannabis dependence is associated with their improvement. This study explored the impact of cannabis dependence treatment on these comorbidities. METHODS: This is a secondary analysis from a 12-week double-blind placebo-controlled trial testing the efficacy of a cannabis agonist (nabiximols) against placebo in reducing illicit cannabis use in 128 cannabis-dependent participants. Outcome measurements including DASS-21 (Depression, Anxiety, and Stress subscales); Insomnia Severity Index (ISI); and Brief Pain Inventory (BPI), were performed at weeks 0, 4, 8, 12 and 24. Each was analysed as continuous outcomes and as binary cases based on validated clinical cut-offs. RESULTS: Among those whose DASS and ISI scores were in the moderate to severe range at baseline, after controlling for cannabis use, there was a gradual decrease in severity of symptoms over the course of the trial. BPI decreased significantly until week 12 and then rose again in the post-treatment period during weeks 12-24. Neither pharmacotherapy type (nabiximols vs placebo) nor number of counselling sessions contributed significant explanatory power to any of the models and were excluded from the final analyses for both continuous and categorical outcomes. CONCLUSIONS: Participants in this trial who qualified as cases at baseline had elevated comorbidity symptoms. There was no evidence that nabiximols treatment is a barrier to achieving reductions in the comorbid symptoms examined. Cannabis dependence treatment reduced illicit cannabis use and improved comorbidity symptoms, even when complete abstinence was not achieved.

Using mixed methods to establish tobacco treatment acceptability from the perspective of clients and clinicians of antenatal substance use services.

BACKGROUND: Up to 95% of pregnant women with alcohol and other drug (AOD) problems also smoke tobacco. Challenging psychosocial circumstances and a lack of targeted tobacco interventions contribute to low rates of prenatal abstinence and more effective treatment strategies are required. This study explores smoking in pregnant clients of AOD treatment services from a consumer and healthcare provider perspective to examine characteristics of behaviour change and the acceptability of evidence-based tobacco treatment strategies. Outcomes will support the design and implementation of a comprehensive tobacco intervention. METHODS: A mixed methods triangulated design was used. Thirteen women who smoked and attended antenatal AOD services in New South Wales, Australia, were interviewed and 28 clinicians from the same services were surveyed. Domains including experiences of tobacco smoking in pregnancy, motivators and barriers to cessation and evidence-based strategies to assist cessation during pregnancy were explored. Interviews were analysed using Iterative Categorization, with interpretation guided by Qualitative Description. Online surveys were analysed descriptively. A convergent-parallel mixed methods analysis was performed. RESULTS: Women and clinicians agreed that improving baby's health outcomes was the primary motivation to stop smoking. Negative experiences with nicotine replacement therapy (NRT), financial constraints and maternal contraindications restricted its uptake and effectiveness during pregnancy. Both groups agreed that other AOD use, stopping multiple substances concurrently, difficulty coping with stress and the influence of partners who smoke had the biggest impacts on cessation efforts. Clinicians favoured harm-reduction rather than abstinence-based tobacco interventions and women appeared satisfied with reduction efforts. Both views may influence the attainment of prenatal abstinence-based goals. Although previous evidence suggested the contrary, clinicians were willing to encourage simultaneous cessation of tobacco and other substances. Non-judgmental treatment approaches that provide extra support, education and motivation were important for women. Women and clinicians supported use of NRT despite concerns. Financial incentives, counselling, partner support and offering tobacco treatment with antenatal AOD care were considered acceptable treatment options. CONCLUSIONS: NRT, incentives, counselling and partner support could be utilized in a tobacco intervention for pregnant women with substance use concerns. Non-judgmental education, motivation, and provision of NRT including instruction for correct use are important considerations.

Smoking cessation interventions for pregnant women attending treatment for substance use disorders: A systematic review.

BACKGROUND AND AIMS: Up to 95% of pregnant women seeking treatment for alcohol and other drug (AOD) use smoke tobacco. Previous reviews indicate few effective smoking cessation treatments for this group. This updated review aimed to identify and measure the efficacy of smoking cessation interventions trialled among pregnant women in AOD treatment settings who smoke tobacco. METHODS: A narrative synthesis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies involving psychological, behavioural or pharmacological interventions used to treat tobacco use, including electronic nicotine delivery systems, for pregnant women of any age, who smoked tobacco and were seeking/receiving treatment, or in post-treatment recovery for AOD concerns, were reviewed. MEDLINE, PsycINFO, CINAHL, EMBASE and ProQuest databases, grey literature and reference lists were searched, and field experts were contacted for unpublished study data. The Effective Public Health Practice Project tool assessed study quality. The review was pre-registered with PROSPERO no. CRD42018108777. RESULTS: Seven interventions (two randomised controlled trials, two single-arm pilot studies, two program evaluations and one causal comparative study) treating 875 women were identified. All were United States (US)-based and targeted women with drug dependence, but not alcohol dependence. Three interventions used contingency management, five provided behavioural counselling, and one offered nicotine replacement therapy. All reported reductions in cigarette consumption; one contingency management-based study demonstrated higher abstinence rates compared with controls at treatment-end that were not maintained at follow-up. Four of six studies were rated as methodologically weak and one unpublished study was not rated. CONCLUSIONS: Conclusions about the efficacy of smoking interventions for pregnant women with alcohol and other drug concerns who also smoke tobacco are hindered by the paucity of available data and poor methodological quality of included studies.

The use and effects of synthetic cannabinoid receptor agonists by New South Wales cannabis treatment clients.

INTRODUCTION: Despite decreasing consumption by general populations, use of synthetic cannabinoid receptor agonists (SCRAs) persists in some marginalised groups, including those who use other substances. This article explores SCRA consumption in an Australian cannabis treatment sample, comparing those who report ever using SCRAs with those who have never used SCRAs. METHODS: A questionnaire orally administered in person to a convenience sample of 154 cannabis treatment service clients from New South Wales, Australia (71% male, median age 35) collected information regarding cannabis and SCRA use including motivations, effects and health-related consequences of use, demographics, other substance use and overall health. Demographic profiles and between-group differences were explored. McNemar tests compared effects of SCRA and cannabis. Logistic regression analysis determined predictors of SCRA use. RESULTS: Half (53%) reported lifetime SCRA use; 20% reported previous-month use. The SCRA + cannabis group displayed greater polysubstance use and psychological distress. Reduced dependence on cannabis but higher levels of other substance use may predict SCRA use. Although curiosity motivated initial SCRA consumption, perceived psychoactive strength drove continued use. SCRAs appear to induce more negative side-effects than cannabis. Of the SCRA + cannabis group, 27% sought medical assistance for SCRA use. Most (90%) preferred cannabis to SCRAs, citing superior safety, effects and consistency of cannabis. CONCLUSIONS: Among clients seeking treatment for cannabis use, SCRA use was relatively common, although not a preferred substance. Hazardous substance use and poor mental health characterised SCRA consumers, highlighting the need for continued monitoring by researchers and treatment providers of SCRA consumption in populations who use substances.

Intensive Behavioural and Pharmacological Treatment for Tobacco Dependence in Pregnant Women with Complex Psychosocial Challenges: A Case Report.

Up to 95% of women who use other substances also smoke tobacco during pregnancy. Challenging psychosocial circumstances and other barriers that contribute to high levels of tobacco dependence result in few quitting successfully. This case report describes the treatment of a highly tobacco dependent 34-year-old pregnant woman with a history of recent substance use, mental illness and trauma, enrolled in the Incentives to Quit Tobacco in Pregnancy program. Heavy smoking, both during the day and overnight, was reported. An extensive history of quit attempts, as well as a strong desire to cease tobacco use during pregnancy, was also noted. Treatment utilising extensive behavioural supports, including financial incentives for carbon monoxide verified abstinence and telephone-based counselling, in combination with nicotine replacement therapy (NRT), was offered to assist cessation. Excellent uptake and adherence to all aspects of treatment saw tobacco cessation achieved and maintained for 24 weeks while on the program. NRT used at doses well above those recommended for pregnancy was required to alleviate strong withdrawal symptoms and maintain abstinence. Daily monitoring of carbon monoxide, financial incentives for continued abstinence and regular phone support were critical to maintaining motivation and preventing relapse to smoking. Post-program relapse to smoking did occur, as is common, and highlights the need for longer-term intensive support for pregnant women with complex behavioural and social problems. Given the prevalence of tobacco smoking in such populations, long-term harm reduction treatment models using extensive behavioural support in combination with NRT should be considered for inclusion in current smoking cessation guidelines.

Interventions for pregnant women who use tobacco and other substances: a systematic review protocol.

INTRODUCTION: The prevalence of tobacco smoking in pregnancy remains elevated in some disadvantaged populations of women. One group is those who use alcohol and/or other psychoactive substances during pregnancy, with tobacco use prevalence estimates ranging from 71% to 95%. Although effective evidence-based cessation treatments exist, few women with co-occurring substance use problems successfully stop smoking during pregnancy. There is limited information about treatments that specifically target this group and a summary of the available research is required to assist and enhance the development of innovative cessation interventions. This article describes a protocol for a comprehensive review of studies that have trialled behavioural and/or pharmacological tobacco cessation interventions in populations of pregnant women who are nicotine dependent and use alcohol and/or other psychoactive substances. METHODS AND ANALYSIS: The review will undertake literature searches in MEDLINE, PsycINFO, CINAHL, EMBASE and ProQuest databases, as well as the grey literature. Studies of any design methodology will be included if they describe changes to tobacco smoking behaviours in quantitative terms. No restriction on year of publication or published language will apply. Participants include pregnant women of any age, who smoke tobacco, who are seeking or having treatment, or in post-treatment recovery for the use of psychoactive substances. Interventions are any psychological, behavioural or pharmacological treatments used to treat tobacco use. Outcome measures are any that quantitatively report abstinence or reductions in participant tobacco consumption. Key details and tobacco-related outcomes from included studies will be extracted and tabulated before being narratively synthesised. The systematic review protocol has been developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. ETHICS AND DISSEMINATION: Ethics approval is not required. Findings will be disseminated via peer-reviewed literature, conference presentations, media and social media. PROSPERO REGISTRATION NUMBER: CRD42018108777.

The Incentives to Quit tobacco in Pregnancy (IQuiP) protocol: piloting a financial incentive-based smoking treatment for women attending substance use in pregnancy antenatal services.

INTRODUCTION: While tobacco smoking prevalence is falling in many western societies, it remains elevated among high-priority cohorts. Rates up to 95% have been reported in women whose pregnancy is complicated by other substance use. In this group, the potential for poor pregnancy outcomes and adverse physical and neurobiological fetal development are elevated by tobacco smoking. Unfortunately, few targeted and effective tobacco dependence treatments exist to assist cessation in this population. The study will trial an evidence-based, multicomponent tobacco smoking treatment tailored to pregnant women who use other substances. The intervention comprises financial incentives for biochemically verified abstinence, psychotherapy delivered by drug and alcohol counsellors, and nicotine replacement therapy. It will be piloted at three government-based, primary healthcare facilities in New South Wales (NSW) and Victoria, Australia. The study will assess the feasibility and acceptability of the treatment when integrated into routine antenatal care offered by substance use in pregnancy antenatal services. METHODS AND ANALYSIS: The study will use a single-arm design with pre-post comparisons. One hundred clients will be recruited from antenatal clinics with a substance use in pregnancy service. Women must be <33 weeks' gestation, ≥16 years old and a current tobacco smoker. The primary outcomes are feasibility, assessed by recruitment and retention and the acceptability of addressing smoking among this population. Secondary outcomes include changes in smoking behaviours, the comparison of adverse maternal outcomes and neonatal characteristics to those of a historical control group, and a cost-consequence analysis of the intervention implementation. ETHICS AND DISSEMINATION: Protocol approval was granted by Hunter New England Human Research Ethics Committee (Reference 17/04/12/4.05), with additional ethical approval sought from the Aboriginal Health and Medical Research Council of NSW (Reference 1249/17). Findings will be disseminated via academic conferences, peer-reviewed publications and social media. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trial Registry (Ref: ACTRN12618000576224).

Increased Calcific Aortic Valve Disease in response to a diabetogenic, procalcific diet in the LDLr-/-ApoB100/100 mouse model.

OBJECTIVE: Calcific aortic valve disease (CAVD) is a major cause of aortic stenosis (AS) and cardiac insufficiency. Patients with type II diabetes mellitus (T2DM) are at heightened risk for CAVD, and their valves have greater calcification than nondiabetic valves. No drugs to prevent or treat CAVD exist, and animal models that might help identify therapeutic targets are sorely lacking. To develop an animal model mimicking the structural and functional features of CAVD in people with T2DM, we tested a diabetogenic, procalcific diet and its effect on the incidence and severity of CAVD and AS in the, LDLr-/-ApoB100/100 mouse model. RESULTS: LDLr-/-ApoB100/100 mice fed a customized diabetogenic, procalcific diet (DB diet) developed hyperglycemia, hyperlipidemia, increased atherosclerosis, and obesity when compared with normal chow fed LDLr-/-ApoB100/100 mice, indicating the development of T2DM and metabolic syndrome. Transthoracic echocardiography revealed that LDLr-/-ApoB100/100 mice fed the DB diet had 77% incidence of hemodynamically significant AS, and developed thickened aortic valve leaflets and calcification in both valve leaflets and hinge regions. In comparison, normal chow (NC) fed LDLr-/-ApoB100/100 mice had 38% incidence of AS, thinner valve leaflets and very little valve and hinge calcification. Further, the DB diet fed mice with AS showed significantly impaired cardiac function as determined by reduced ejection fraction and fractional shortening. In vitro mineralization experiments demonstrated that elevated glucose in culture medium enhanced valve interstitial cell (VIC) matrix calcium deposition. CONCLUSIONS: By manipulating the diet we developed a new model of CAVD in T2DM, hyperlipidemic LDLr-/-ApoB100/100 that shows several important functional, and structural features similar to CAVD found in people with T2DM and atherosclerosis including AS, cardiac dysfunction, and inflamed and calcified thickened valve cusps. Importantly, the high AS incidence of this diabetic model may be useful for mechanistic and translational studies aimed at development of novel treatments for CAVD.

Osteoclast precursors do not express CD68: results from CD68 promoter-driven RANK transgenic mice.

Macrophages and osteoclasts are thought to derive from CD68 lineage marker-positive common myeloid precursors. We used the CD68 promoter to drive an inducible receptor activator of NF-κB (iRANK) construct that selectively activates RANK signaling in myeloid cells in vivo. The cytoplasmic portion of RANK was fused to a mutant FK506 binding domain, which selectively binds the chemical inducer of dimerization AP20187 and initiates signaling. iRANK mRNA was expressed in macrophages isolated from peritoneal cavity, spleen-, and bone marrow-derived myeloid cells. Unexpectedly, AP20187 did not induce osteoclast formation in spleen- and bone marrow-derived myeloid cells. However, AP20187-dependent RANK signaling induced ERK1/2 phosphorylation and mRNA expression of MMP9 and CathepsinK in peritoneal macrophages. Importantly, CD68 was not expressed until day 3 and day 5 in bone marrow and spleen myeloid cells, respectively. Contrary to dogma, osteoclast precursors do not express the lineage marker CD68.

Temporal and spatial comparisons of the reproductive biology of northern Gulf of Mexico (USA) red snapper (Lutjanus campechanus) collected a decade apart.

In studies done a decade apart, we provide evidence of a recent shift toward a slower progression to sexual maturity as well as reduced egg production, especially among young, small female red snapper, in the Gulf of Mexico (Gulf). Slower maturation rates (among fish ≤6 years old), lower GSI values and decreased spawning frequency were observed, and were especially pronounced in the northwestern Gulf. Furthermore, an Index of Reproductive Importance showed that young fish (ages 2-7) are contributing far less to the spawning stock in recent years, while older fish (>8 years) are contributing more, when compared to fish from the same age groups sampled in the previous decade. Coincident with these changes in reproductive output, fishing pressure has steadily declined gulf-wide, and spawning stock biomass and spawning potential ratio have increased. Thus, it is possible that the age structure of the red snapper stock is becoming less truncated, or that reproductive effort observed is due to the temporary influence of recent strong year classes produced in 2004 and 2006 as they begin to reach full reproductive potential. If the latter is true, careful documentation of the stock's reproductive dynamics during a time of population growth provides new understanding at the meta-population spatial and decadal temporal scales. In contrast, if the former is true, a truncated age structure due to overharvest can limit the productivity of the Gulf red snapper stock. In addition, we have learned that red snapper females in the northwestern Gulf collected on natural reefs and banks have much higher reproductive output than those on artificial reefs in the form of standing and toppled oil and gas platforms, thus making the need to know the relative abundance of females found on these disparate habitats an important next step toward better-understanding factors impacting the reproductive dynamics of this species.