Safety of e-cigarettes and nicotine patches as stop-smoking aids in pregnancy: Secondary analysis of the Pregnancy Trial of E-cigarettes and Patches (PREP) randomized controlled trial.

AIMS: The aim of this study was to examine the safety of e-cigarettes (EC) and nicotine patches (NRT) when used to help pregnant smokers quit. DESIGN: A recent trial of EC versus NRT reported safety outcomes in the randomized arms. We conducted a further analysis based on product use. SETTING: Twenty-three hospitals in England and a stop-smoking service in Scotland took part. PARTICIPANTS: The participants comprised 1140 pregnant smokers. INTERVENTIONS: We compared women using and not using EC and NRT regularly during pregnancy. MEASUREMENTS: Measurements included nicotine intake compared with baseline, birth weight, other pregnancy outcomes, adverse events, maternal respiratory symptoms and relapse in early abstainers. FINDINGS: Use of EC was more common than use of NRT (47.3% vs 21.6%, P < 0.001). Women who stopped smoking (abstainers) and used EC at the end-of-pregnancy (EOP) reduced their salivary cotinine by 45% [49.3 ng/ml, 95% confidence interval (CI) = -79.8 to -10]. Only one abstainer used NRT at EOP. In dual users, cotinine increased by 19% (24 ng/ml, 95% CI = 3.5-68). In women reporting a reduction of at least 50% in cigarette consumption, cotinine levels increased by 10% in those using nicotine products and by 9% in those who did not. Birth weights in dual users and exclusive smokers were the same (3.1 kg). Birth weight in abstainers using either nicotine product was higher than in smokers [3.3 kg, standard deviation (SD) = 0.7] versus 3.1 kg, SD = 0.6; difference = 0.15 kg, 95% CI = 0.05-0.25) and not different from abstainers not using nicotine products (3.1 kg, SD = 0.8). Abstainers and smokers using nicotine products had no worse pregnancy outcomes or more adverse events than abstainers and smokers not using them. EC users reported more improvements than non-users in cough [adjusted relative risk (aRR) = 0.59, 95% CI = 0.37-0.93] and phlegm (aRR = 0.53, 95% CI = 0.31-0.92), controlling for smoking status. EC or NRT use had no association with relapse. CONCLUSIONS: Regular use of e-cigarettes or nicotine patches by pregnant smokers does not appear to be associated with any adverse outcomes.

Helping pregnant smokers quit: a multi-centre randomised controlled trial of electronic cigarettes versus nicotine replacement therapy.

Background: Some pregnant smokers try e-cigarettes, but effectiveness and safety of such use are unknown. Objectives: To compare effectiveness and safety of nicotine patches and e-cigarettes in pregnancy. Design: A pragmatic multi-centre randomised controlled trial. Setting: Twenty-three hospitals across England, and a Stop Smoking Service in Scotland. Participants: One thousand one hundred and forty pregnant daily smokers (12-24 weeks' gestation) motivated to stop smoking, with no strong preference for using nicotine patches or e-cigarettes. Interventions: Participants in the e-cigarette arm were posted a refillable e-cigarette device with two 10 ml bottles of tobacco-flavoured e-liquid (18 mg nicotine). Participants in the nicotine patches arm were posted a 2-week supply of 15 mg/16-hour nicotine patches. Supplies were provided for up to 8 weeks. Participants sourced further supplies themselves as needed. Participants in both arms received support calls prior to their target quit date, on the quit date, and weekly for the next 4 weeks. Outcome measures: The primary outcome was validated prolonged abstinence at the end of pregnancy. Participants lost to follow-up or not providing biochemical validation were included as non-abstainers. Secondary outcomes included self-reported abstinence at different time points, treatment adherence and safety outcomes. Results: Only 55% of self-reported abstainers mailed back useable saliva samples. Due to this, validated sustained abstinence rates were low (6.8% vs. 4.4% in the e-cigarettes and nicotine patches arms, respectively, risk ratio = 1.55, 95% confidence interval 0.95 to 2.53; Bayes factor = 2.7). In a pre-specified sensitivity analysis that excluded abstainers using non-allocated products, the difference became significant (6.8% vs. 3.6%, risk ratio = 1.93, 95% confidence interval 1.14 to 3.26; Bayes factor = 10). Almost a third of the sample did not set a target quit date and the uptake of support calls was low, as was the initial product use. At end of pregnancy, 33.8% versus 5.6% of participants were using their allocated product in the e-cigarettes versus nicotine patches arm (risk ratio = 6.01, 95% confidence interval 4.21 to 8.58). Regular use of e-cigarettes in the nicotine patches arm was more common than use of nicotine replacement products in the e-cigarette arm (17.8% vs. 2.8%). Rates of adverse events and adverse birth outcomes were similar in the two study arms, apart from participants in the e-cigarette arm having fewer infants with low birthweight (<2500 g) (9.6% vs. 14.8%, risk ratio = 0.65, 95% confidence interval 0.47 to 0.90; Bayes factor = 10.3). Limitations: Low rates of validation reduced the study power. A substantial proportion of participants did not use the support on offer sufficiently to test its benefits. Sample size may have been too small to detect differences in less frequent adverse effects. Conclusions: E-cigarettes were not significantly more effective than nicotine patches in the primary analysis, but when e-cigarettes use in the nicotine patches arm was accounted for, e-cigarettes were almost twice as effective as patches in all abstinence outcomes. In pregnant smokers seeking help, compared to nicotine patches, e-cigarettes are probably more effective, do not pose more risks to birth outcomes assessed in this study and may reduce the incidence of low birthweight. Future work: Routine monitoring of smoking cessation and birth outcomes in pregnant women using nicotine patches and e-cigarettes and further studies are needed to confirm these results. Trial registration: This trial is registered as ISRCTN62025374 and Eudract 2017-001237-65. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 13. See the NIHR Journals Library website for further project information.

Like many other smokers in the UK, some pregnant smokers try to limit or stop smoking with the help of e-cigarettes. It is not known whether this helps with stopping smoking and whether using e-cigarettes has any bad effects on the baby. We recruited 1140 pregnant smokers who wanted to quit. A random half were given nicotine patches, which are commonly used to help smokers quit. The other half were given an e-cigarette. They also received six weekly phone calls to support them in stopping smoking. We then looked at how many in each group stopped smoking by the end of pregnancy. More women stopped smoking in the group that was given an e-cigarette, but the difference was small and could be due to chance. However, some of the women in the nicotine patch group who had successfully stopped smoking were using e-cigarettes rather than patches. When these (and women in the e-cigarette group who used patches) were not counted, e-cigarettes helped almost twice as many women stop smoking than patches. E-cigarettes were better than patches in preventing low birthweight (having babies who weigh less than 2.5 kg). Otherwise, women given patches and those given e-cigarettes (and their babies) had similar numbers of medical complications. For pregnant women who smoke and need help to quit, e-cigarettes are probably more helpful than nicotine patches, and do not pose any additional risks to women or their babies.

Microsurgical Reconstruction of the Columella.

BACKGROUND: Traditionally, the columella can be difficult to reconstruct because of its unique contours, paucity of adjacent soft tissues, and tenuous vascularity. When local or regional tissues are unavailable, microsurgical transfer can provide a means for reconstruction. In this retrospective review, the authors report their experience with microsurgical reconstruction of the columella. METHODS: Seventeen patients were enrolled in this study and divided into two groups: group 1, isolated columella defects; and group 2, defects of the columella and portions of adjacent soft tissues. RESULTS: There were 10 patients in group 1. Their average age was 41.2 years. Average follow-up was 10.1 years. Causes of the columellar defects included trauma, complication of nasal reconstruction, and complication of rhinoplasty. The first dorsal metacarpal artery flap was used in seven cases, and the radial forearm flap was used in five. Two flap losses were salvaged with a second free flap. The average number of surgical revisions was 1.5. In group 2, there were seven patients with an average follow-up of 10.1 years. Causes of the columella defects included cocaine injury, carcinoma, and complication of rhinoplasty. The average number of surgical revisions was 3.3. The radial forearm flap was used in all cases. There were no flap losses. All 17 cases in this series were brought to a successful conclusion. CONCLUSIONS: The authors' experience shows that microsurgical reconstruction of the columella provides a reliable and aesthetic means for reconstruction. This technique avoids the facial disfigurement and visible scarring that often accompany use of local flaps. In addition, microsurgical flaps can be preformed "off site," which may provide certain advantages in selected cases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Acellular Dermal Matrix Mimicking a New Retroareolar Mass After Central Pillar Neonipple Reconstruction.

ABSTRACT: Acellular dermal matrix (ADM) is an increasingly popular alloplastic cadaveric dermis used to enhance postmastectomy reconstruction. Acellular dermal matrix can be used as a nipple-shaped cylinder in central pillar nipple reconstruction to help maintain long-term projection. We report a unique presentation of ADM mimicking a retroareolar mass after central pillar neonipple reconstruction. A 49-year-old woman with a history of invasive ductal carcinoma underwent delayed nipple reconstruction after lumpectomy and oncoplastic closure using an inframammary V-Y advancement flap.The nipple reconstruction was performed using pretattoo and articulated tab flaps. A rolled tube of acellular dermal matrix was placed in the central aspect of the neonipple reconstruction for projection. At 4 months postoperative, a screening mammogram and ultrasound noted a new retroareolar mass classified as BIRADS 4 necessitating a breast biopsy. Biopsy revealed portions of fibrous connective tissue consistent with partially incorporated acellular dermal matrix allograft. There was no evidence of malignancy. To mitigate the risk of future radiographic or clinical misinterpretation of ADM in nipple reconstruction, the placement of radiopaque markers such as microclips on the ADM implant could be a useful adjunct. Radiologists and surgeons should include ADM artifact in their differential diagnosis of radiologic imaging when evaluating a new mass in the proximity of prior ADM placement in neonipple reconstruction of the breast.

STOP- a training intervention to optimise treatment for smoking cessation in community pharmacies: cluster randomised controlled trial.

BACKGROUND: Community pharmacies serve people with high levels of tobacco-related illness, but throughput in NHS Stop Smoking Services in pharmacies remains relatively low. We investigated the effectiveness of a complex intervention to increase service uptake and retention. METHODS: We randomised 60 pharmacies in England and Wales to the STOP intervention or usual practice in a pragmatic, parallel-group, controlled trial over 11 months. Smokers were blind to the allocation. The intervention was theory-based consultation skills training for pharmacy staff with environmental prompts (badges, calendars and behavioural cues). The primary outcome was the number of smokers attending an initial consultation and setting a quit date. RESULTS: The intervention made no significant difference in setting a quit date, retention or quit rate. A total of 631 adult smokers (service users) enrolled and set a quit date in intervention pharmacies compared to 641 in usual practice pharmacies, a rate ratio of 0.75 (95% CI 0.46 to 1.23) adjusted for site and number of prescriptions. A total of 432 (68%) service users were retained at 4 weeks in intervention and 500 (78%) in usual practice pharmacies (odds ratio 0.80, 0.41 to 1.55). A total of 265 (42%) service users quit smoking at 4 weeks in intervention and 276 (43%) in usual practice pharmacies (0.96, 0.65 to 1.43). The pharmacy staff were positive about the intervention with 90% (56/62) stating that it had improved their skills. Sixty-eight per cent would strongly recommend the training to others although there was no difference in self-efficacy for service delivery between arms. Seventy of 131 (53%) service users did not complete the 6-month follow-up assessment. However, 55/61 (90%) service users who completed follow-up were satisfied or very satisfied with the service. All usual practice arm service users (n = 33) and all but one in the intervention arm (n = 27) would recommend the service to smokers. CONCLUSIONS: We found high levels of retention and acceptable quit rates in the NHS pharmacy stop smoking service. Despite pharmacy staff providing positive feedback on the STOP intervention, it made no difference to service throughput. Thus, other factors may currently limit service capacity to help smokers to quit. TRIAL REGISTRATION: ISRCTN, ISRCTN16351033 . Retrospectively registered.

Electronic cigarettes versus nicotine patches for smoking cessation in pregnancy: a randomized controlled trial.

Nicotine replacement therapy, in the form of nicotine patches, is commonly offered to pregnant women who smoke to help them to stop smoking, but this approach has limited efficacy in this population. Electronic cigarettes (e-cigarettes) are also used by pregnant women who smoke but their safety and efficacy in pregnancy are unknown. Here, we report the results of a randomized controlled trial in 1,140 participants comparing refillable e-cigarettes with nicotine patches. Pregnant women who smoked were randomized to e-cigarettes (n = 569) or nicotine patches (n = 571). In the unadjusted analysis of the primary outcome, validated prolonged quit rates at the end of pregnancy in the two study arms were not significantly different (6.8% versus 4.4% in the e-cigarette and patch arms, respectively; relative risk (RR) = 1.55, 95%CI: 0.95-2.53, P = 0.08). However, some participants in the nicotine patch group also used e-cigarettes during the study. In a pre-specified sensitivity analysis excluding abstinent participants who used non-allocated products, e-cigarettes were more effective than patches (6.8% versus 3.6%; RR = 1.93, 95%CI: 1.14-3.26, P = 0.02). Safety outcomes included adverse events and maternal and birth outcomes. The safety profile was found to be similar for both study products, however, low birthweight (<2,500 g) was less frequent in the e-cigarette arm (14.8% versus 9.6%; RR = 0.65, 95%CI: 0.47-0.90, P = 0.01). Other adverse events and birth outcomes were similar in the two study arms. E-cigarettes might help women who are pregnant to stop smoking, and their safety for use in pregnancy is similar to that of nicotine patches. ISRCTN62025374.

A Qualitative Study of Factors Influencing Adherence among Pregnant Women Taking Part in a Trial of E-Cigarettes for Smoking Cessation.

Use of e-cigarettes (vaping) has potential to help pregnant women stop smoking. This study explored factors influencing adherence among participants in the vaping arm of the first trial of vaping for smoking cessation in pregnancy. We conducted semi-structured telephone interviews (n = 28) with women at three-months postpartum. Interviews were analysed using thematic analysis, informed by the Theoretical-Domains Framework, Necessity-Concerns Framework and Perceptions and Practicalities Approach. Interviewees generally reported high levels of vaping. We found that: (1) intervention adherence was driven by four necessity beliefs-stopping smoking for the baby, and vaping for harm reduction, smoking cessation or as a last resort; (2) necessity beliefs outweighed vaping concerns, such as dependence and safety; (3) adherence was linked to four practicalities themes, acting as barriers and facilitators to vaping-device and e-liquid perceptions, resources and support, whether vaping became habitual, and social and environmental factors; and (4) intentional non-adherence was rare; unintentional non-adherence was due to device failures, forgetting to vape, and personal circumstances and stress. Pregnant smokers provided with e-cigarettes, and with generally high levels of vaping, had positive beliefs about the necessity of vaping for smoking cessation which outweighed concerns about vaping. Non-adherence was mainly due to unintentional factors.

The First Dorsal Metacarpal Artery Free Flap for Salvage of Nasal Reconstructions.

ABSTRACT: The first dorsal metacarpal artery free flap is widely known for its use as a pedicled flap in thumb and hand reconstruction; however, its potential for use as a free flap is less well known. We previously described successful use of the first dorsal metacarpal artery free flap for salvage of a subtotal nasal reconstruction. In this retrospective study, we have expanded our experience to 7 consecutive cases in which a FDMFF was utilized to salvage a nasal reconstruction. Single island flaps were used in 6 of 7 cases, in one case a double island configuration was utilized. Sites restored included the columella (5 patients), membranous septum (1 patient), and nasal sidewall (1 patient). Vascular repairs were to the angular artery and vein (2 patients) or the vascular pedicle of a prior free flap (5 patients). There were no flap failures or major complications. The dorsal hand donor sites were uniformly closed using full-thickness skin grafts. All of the salvage nasal reconstructions were brought to a successful completion. Donor site morbidity was minimal with no compromise in hand function noted. Owing to its thinness, consistent anatomy, ease of harvest, and minimal donor site morbidity, the FDMFF has proved to be a very useful flap for restoration of small, but critical, nasal defects arising during the course of nasal reconstruction.

Mendelian randomization case-control PheWAS in UK Biobank shows evidence of causality for smoking intensity in 28 distinct clinical conditions.

BACKGROUND: Smoking is one of the greatest threats to public health worldwide. We integrated phenome-wide association study (PheWAS) and Mendelian randomization (MR) approaches to explore causal effects of genetically predicted smoking intensity across the human disease spectrum. METHODS: We conducted PheWAS case-control analyses in 152,483 ever smokers of White-British ancestry, aged 39-73 years. Disease diagnoses were based on hospital inpatient and mortality registrations. Smoking intensity was instrumented by four genetic variants, and disease risks estimated for one cigarette per day heavier intakes. Associations passing the FDR threshold (p<0•0025) were assessed for causality using several complementary MR approaches. FINDINGS: Genetically instrumented smoking intensity was associated with 48 conditions, with MR supporting a possible causal effect for 28 distinct outcomes. Each cigarette smoked per day elevated the odds of respiratory diseases by 5% to 33% (nine distinct diseases, including pneumonia, emphysema, obstructive chronic bronchitis, pleurisy, pulmonary collapse, respiratory failure) and the odds of circulatory disease by 5% to 23% (seven diseases, including atherosclerosis, myocardial infarction, congestive heart failure, arterial embolisms). Further effects were seen for cancer within the respiratory system and other neoplasms, renal failure, septicaemia, and retinal disorders. No associations were observed in sensitivity analyses on 185,002 never smokers. INTERPRETATION: These genetic data demonstrate the substantial adverse health impacts by smoking intensity and suggest notable increases in the risks of several diseases. Public health initiatives should highlight the damage caused by smoking intensity and the potential benefits of reducing or ideally quitting smoking.

Identification of slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour.

To facilitate smoking genetics research we determined whether a screen of mutagenized zebrafish for nicotine preference could predict loci affecting smoking behaviour. From 30 screened F3 sibling groups, where each was derived from an individual ethyl-nitrosurea mutagenized F0 fish, two showed increased or decreased nicotine preference. Out of 25 inactivating mutations carried by the F3 fish, one in the slit3 gene segregated with increased nicotine preference in heterozygous individuals. Focussed SNP analysis of the human SLIT3 locus in cohorts from UK (n=863) and Finland (n=1715) identified two variants associated with cigarette consumption and likelihood of cessation. Characterisation of slit3 mutant larvae and adult fish revealed decreased sensitivity to the dopaminergic and serotonergic antagonist amisulpride, known to affect startle reflex that is correlated with addiction in humans, and increased htr1aa mRNA expression in mutant larvae. No effect on neuronal pathfinding was detected. These findings reveal a role for SLIT3 in development of pathways affecting responses to nicotine in zebrafish and smoking in humans.

Evaluating the effectiveness and cost-effectiveness of the Smoking Treatment Optimisation in Pharmacies (STOP) intervention: protocol for a cluster randomised controlled trial.

BACKGROUND: NHS community pharmacies provide effective smoking cessation services; however, there is scope for increasing throughput and improving quit rates. This trial examines whether the Smoking Treatment Optimisation in Pharmacies (STOP) intervention can improve smoker engagement to increase service throughput, retention and quitting. METHODS: This study is a pragmatic, cluster randomised controlled trial in 60 pharmacies in England and Wales. All workers in intervention pharmacies are offered STOP training while control pharmacies provide usual care. The STOP intervention, based on behavioural and organisational theories, comprises educational sessions for staff and environmental prompts in the pharmacy. Intervention fidelity is assessed by actors visiting pharmacies posing as smokers. The primary outcome is throughput, defined as the number of smokers who join the programme, set a firm quit date and undergo at least one stop smoking treatment session, and is measured using routinely collected data. Secondary outcomes include retention and quit rates at 4 weeks and continuous abstinence at 6 months verified by salivary cotinine. Cost-effectiveness is estimated using quality-adjusted life years and the probability that the intervention is effective at different levels of willingness to pay is calculated. DISCUSSION: The trial will generate evidence to inform the public health smoking cessation strategy in England and Wales, and may help to shape service commissioning decisions. The STOP intervention model may help inform the undertaking of a range of health behaviour change tasks in community pharmacies. TRIAL REGISTRATION: ClinicalTrials.gov, ISRCTN16351033. Retrospectively registered on 21 March 2017.

Evaluating NHS Stop Smoking Service engagement in community pharmacies using simulated smokers: fidelity assessment of a theory-based intervention.

OBJECTIVES: Smokers are more likely to quit if they use the National Health Service (NHS) Stop Smoking Service (SSS). However, community pharmacies experience low service uptake. The Smoking Treatment Optimisation in Pharmacies (STOP) programme aims to address this problem by enhancing staff training using a theory-based intervention. In this study, we evaluated intervention fidelity using simulated smokers (actors) to assess smoker engagement and enactment of key intervention components by STOP trained staff. DESIGN: An observational pilot study. SETTINGS: Five community pharmacies in North East London with an NHS SSS. METHODS: Six actors, representative of East London's population, were recruited and trained to complete intervention fidelity assessments. Consenting pharmacy staff from five participating pharmacies received STOP Intervention training. Four weeks after the staff training, the actors visited the participating pharmacies posing as smokers eligible for smoking cessation support. Engagement behaviour by pharmacy staff and enactment of intervention components was assessed using a scoring tool derived from the STOP logic model (scoring range of 0-36), and contemporaneous field notes taken by actors. RESULTS: 18 of 30 completed assessments were with STOP trained staff (10/18 were counter assistants). Mean score for smoker engagement was 24.4 (SD 9.0) points for trained and 16.9 (SD 7.8) for untrained staff, respectively. NHS SSS leaflets (27/30) were the most common smoking cessation materials seen on pharmacy visits. Most trained counter staff engaged with smokers using leaflets and a few proactively offered appointments with their cessation advisors. Appropriate use of body language was reported on 26/30 occasions alongside the use of key phrases from the STOP training session (n=8). Very few pharmacy staff wore STOP promotional badges (4/30). CONCLUSIONS: STOP training may change client engagement behaviour in pharmacy staff and could improve the uptake of the NHS SSS. A cluster randomised controlled trial is currently in progress to evaluate its effectiveness and cost-effectiveness. TRIAL REGISTRATION NUMBER: ISRCTN16351033.

Case finding and therapy for chronic viral hepatitis in primary care (HepFREE): a cluster-randomised controlled trial.

BACKGROUND: The prevalence of viral hepatitis (hepatitis B virus and hepatitis C virus) in migrants is higher than among the general population in many high-income countries. We aimed to determine whether incentivising and supporting primary-care physicians in areas with a high density of migrants increases the numbers of adult migrants screened for viral hepatitis. METHODS: HepFREE was a multicentre, open, cluster-randomised controlled trial in general practices in areas of the UK with a high density of migrants (Bradford, Yorkshire, and northeast and southeast London). Participants were adult patients (aged 18 years or older) in primary care, who had been identified as a first or second generation migrant from a high-risk country. General practices were randomly assigned (1:2:2:2:2) to an opportunistic screening (control) group or to one of four targeted screening (interventional) groups: standard (ie, hospital-based) care and a standard invitation letter; standard care and an enhanced invitation letter; community care and a standard invitation letter; or community care and an enhanced invitation letter. In control screening, general practitioners (GPs) were given a teaching session on viral hepatitis and were asked to test all registered migrants. In the intervention, GPs were paid a nominal sum for setting up searches of records, reimbursed for signed consent forms, and supported by a dedicated clinician. Patients who were eligible for testing and tested positive for viral hepatitis in the intervention groups were eligible to enrol in a second embedded trial of community versus hospital based care. The primary outcomes were the proportion of patients eligible for screening, the proportion of those eligible who were sent an invitation letter in the intervention groups, the uptake of viral hepatitis screening (in the intention-to-treat population), the proportion of patients who tested positive for viral hepatitis, the proportion who complied with treatment, and the cost-effectiveness of the intervention. This trial is registered with ISRCTN, number ISRCTN54828633. FINDINGS: Recruitment and testing ran from Oct 31, 2013, to Feb 4, 2017, and each practice recruited for 18 consecutive calendar months. We approached 70 general practices in three areas with a high density of migrants, of which 63 general practices agreed to participate. Five practices withdrew and 58 practices were randomly assigned: eight to control and 50 to an intervention. In control practices, 26 046 (38·4%) of 67 820 patients who were initially registered were eligible for testing, as were 152 321 (43·3%) of 351 710 patients in the interventional groups in London and Bradford. Of 51 773 randomly selected eligible patients in the intervention groups in London and Bradford, letters were sent to 43 585 (84·2%) patients. In the eight control general practices, screening was taken up by 543 (1·7%) of 31 738 eligible participants, which included 5692 newly registered patients. However, in the 50 general practices that used the intervention, screening was taken up by 11 386 (19·5%) of 58 512 eligible participants (including 6739 newly registered patients; incidence rate ratio 3·70, 95% CI 1·30-10·51; p=0·014) and this intervention was cost-effective. 720 (4·5%) of 15 844 patients who received a standard letter versus 1032 (3·7%) of 28 095 patients who received the enhanced letter were tested (0·70, 0·38-1·31; p=0·26). In the control group, 17 patients tested positive for viral hepatitis, as did 220 patients (one with a co-infection) in the intervention groups. In the embedded study, 220 patients were randomly assigned to either hospital-based care or community care; 80 (87·9%) of 91 patients in the hospital setting complied with treatment versus 105 (81·4%) of 129 patients in the community setting. The intervention was cost-effective at willingness to pay thresholds in excess of £8540. One serious adverse event (thyroiditis) was noted. INTERPRETATION: Screening migrants for viral hepatitis in primary care is effective if doctors are incentivised and supported. Community care is expensive and there is no evidence that this offers benefits in this setting or that bespoke invitation letters add value. We suggest that bespoke invitation letters should not be used, and we suggest that outreach, community-based services for migrants should not be developed. FUNDING: National Institute for Health Research.

Subtotal Nasal Reconstruction Using a Custom 3-Dimensional Porous Polyethylene Construct.

Subtotal loss of the nose is a devastating occurrence. Traditional approaches to reconstruction have employed techniques that sequentially restore the nasal lining, support and external cover using autologous tissues. The results can be quite variable and are heavily weighted on surgical experience and expertise. We report a case of subtotal nasal reconstruction using a computer generated, 3-D printed porous polyethylene (PPE) scaffold. The patient is a 64-year-old man who presented with a sub-total nasal defect following excision of recurrent basal cell carcinoma. The missing parts comprised the distal half of the composite nose including the nasal floor and lining. The replacement nose was constructed on the patient's right radial forearm. A computer generated PPE nasal scaffold was prelaminated with a forearm flap for lining and a free temporal fascial flap and skin graft for external cover. Following healing, nostrils were created and the nasal construct was then microsurgically transferred to the face. At 18 months post-op, the reconstructed nose has remained stable and functional with excellent aesthetic appearance. The implications for use of 3-D scaffolds for composite nasal reconstruction are enormous.

Creating a Theoretically Grounded, Gamified Health App: Lessons From Developing the Cigbreak Smoking Cessation Mobile Phone Game.

BACKGROUND: Gaming techniques are increasingly recognized as effective methods for changing behavior and increasing user engagement with mobile phone apps. The rapid uptake of mobile phone games provides an unprecedented opportunity to reach large numbers of people and to influence a wide range of health-related behaviors. However, digital interventions are still nascent in the field of health care, and optimum gamified methods of achieving health behavior change are still being investigated. There is currently a lack of worked methodologies that app developers and health care professionals can follow to facilitate theoretically informed design of gamified health apps. OBJECTIVE: This study aimed to present a series of steps undertaken during the development of Cigbreak, a gamified smoking cessation health app. METHODS: A systematic and iterative approach was adopted by (1) forming an expert multidisciplinary design team, (2) defining the problem and establishing user preferences, (3) incorporating the evidence base, (4) integrating gamification, (5) adding behavior change techniques, (6) forming a logic model, and (7) user testing. A total of 10 focus groups were conducted with 73 smokers. RESULTS: Users found the app an engaging and motivating way to gain smoking cessation advice and a helpful distraction from smoking; 84% (62/73) of smokers said they would play again and recommend it to a friend. CONCLUSIONS: A dedicated gamified app to promote smoking cessation has the potential to modify smoking behavior and to deliver effective smoking cessation advice. Iterative, collaborative development using evidence-based behavior change techniques and gamification may help to make the game engaging and potentially effective. Gamified health apps developed in this way may have the potential to provide effective and low-cost health interventions in a wide range of clinical settings.

Evaluating maternal hyperglycemic exposure and fetal placental arterial dysfunction in a dual cotyledon, dual perfusion model.

BACKGROUND: Gestational diabetes affects almost 1 in 10 pregnancies and is associated with adverse outcomes including fetal demise. Pregnancy complications related to diabetes are attributed to placental vascular dysfunction. With diabetes, maternal hyperglycemia is thought to promote placental vasoconstriction. However, it remains poorly understood if and how hyperglycemia leads to placental vascular dysfunction or if humoral factors related to maternal diabetes are responsible. METHODS AND RESULTS: Utilizing a human placenta dual cotyledon, dual perfusion assay we examined the arterial pressure response to the thromboxane mimetic U44619, in cotyledons exposed to normal vs. a hyperglycemic infusion into the intervillous space. Tissues were then analyzed for the activity of key signaling molecules related to vascular tone; eNOS, Akt, PKA and VEGFR2. Results indicate a significant increase in fetal vascular resistance with maternal exposure to hyperglycemia. This response corresponded with a reduction in the phosphorylation of eNOS at Ser1177 and Akt at Thr308. In contrast, VEGFR2 at Tyr1175 and PKA at Thr197 were not different with hyperglycemia. CONCLUSION: Reductions of eNOS and Akt phosphorylation at key residues implicated in nitric oxide production suggest that hyperglycemia alters the vasodilatory signaling of placental vessels. In contrast, acute hyperglycemic exposure may not alter vasoconstriction via VEGF and PKA signaling. Altogether our results link hyperglycemic exposure in human placentas to nitric oxide signaling; a mechanisms that may account for the elevations in vascular resistance commonly observed in diabetic pregnancies.

Current Practices in the Management of Postoperative Arterial Vasospasm in Microsurgery.

BACKGROUND: Postoperative microvascular arterial vasospasm is a rare clinical entity. There are no published management algorithms and also the pathophysiology of this phenomenon has not been elucidated. METHODS: An email survey of American Society for Reconstructive Microsurgery (ASRM) and World Society for Reconstructive Microsurgery (WSRM) members regarding their experiences with postoperative arterial vasospasm was conducted, returning 116 responses. A comprehensive literature search was conducted regarding the current body of knowledge on this entity. RESULTS: Sixty-five percent of respondents encountered cases where postoperative arterial vasospasm was clearly the cause of flap ischemia. The majority (62%) of surgeons believed a damaged segment of the artery was responsible for the spasm, with technical issues cited as the most likely cause. Sixty-two percent and 50% of surgeons used segmental resection of the recipient and donor vessels, respectively.Rated for proclivity to vasospasm, superficial inferior epigastric artery (SIEA) was the flap, superior thyroid artery (STA) the recipient vessel, and the lower limb the anatomic region most frequently mentioned.Most widely used management strategies were: topical vasodilators (91%), adventitial stripping (82%), and dilation of recipient and donor vessels (76%). Over 50% of surgeons used some type of vessel resection technique. CONCLUSIONS: When flap ischemia is encountered without mechanical issues or thrombus, vasospasm can be the root cause. Certain vessels (SIEA, STA) and anatomic regions (lower limb) pose a higher risk for this phenomenon. When a vessel is affected, it is common practice to excise the questionable segment and use a graft as needed. Vessel resection as part of a multimodal approach can result in a reasonable salvage rate.