Trajectories of Alcohol Use and Related Harms for Managed Alcohol Program Participants over 12 Months Compared with Local Controls: A Quasi-Experimental Study.

AIM: Investigate changes in alcohol use and related harm using the first multisite, controlled, longitudinal study of Managed Alcohol Programs (MAPs). MAPs provide regular doses of alcohol, accommodation, social supports and healthcare to unstably housed people with alcohol dependence. METHODS: A multisite, quasi-experimental, longitudinal study was conducted in day centres, shelters and residential programs for unstably housed people. There were 59 MAP participants from six Canadian cities and 116 local controls. Self-reported alcohol consumption and harms were assessed at 0-2, 6 and 12 months. Liver function test results were accessed for MAP participants. RESULTS: Both groups had similar reductions in mean drinks per day (MAP: -8.11; controls: -8.54 controls, P < 0.001) and days drinking per month (MAP: -2.51 days, P < 0.05; control: -4.81 days, P = 0.0001) over 6--12 months. Both reduced non-beverage alcohol consumption. MAP participants reported significantly fewer harms at both 0-2 and 6 months than controls. MAP participants had similar total consumption to controls, but spread out over more days (25.41 versus 19.64 days per month, P = 0.001). After leaving a MAP, participants' liver status deteriorated, with increases in both aspartate transaminase and bilirubin levels. MAP sites with effective policies on outside drinking drank less and had fewer harms. CONCLUSION: MAP participants drank less hazardously than controls, especially with effective management of non-MAP drinking. Reductions in alcohol use and harms occurred for both groups, although MAP participants reported fewer harms at 0-6 months. Departing an MAP was associated with deterioration in liver status. Although providing stable housing, MAPs did not worsen health or increase alcohol use.

Heavy Drinkers and the Potential Impact of Minimum Unit Pricing-No Single or Simple Effect?

AIMS: To explore the potential impact of a minimum unit price (MUP: 50 pence per UK unit) on the alcohol consumption of ill Scottish heavy drinkers. METHODS: Participants were 639 patients attending alcohol treatment services or admitted to hospital with an alcohol-related condition. From their reported expenditure on alcohol in their index week, and assuming this remained unchanged, we estimated the impact of a MUP (50 ppu) on future consumption. (Around 15% purchased from both the more expensive on-sale outlets (hotels, pubs, bars) and from off-sales (shops and supermarkets). For them we estimated the change in consumption that might follow MUP if (i) they continued this proportion of 'on-sales' purchasing or (ii) their reported expenditure was moved entirely to off-sale purchasing (to maintain consumption levels)). RESULTS: Around 69% of drinkers purchased exclusively off-sale alcohol at <50 ppu. Their drinking, post MUP, may reduce by a mean of 33%. For this group, from a population of very heavy, ill consumers, we were unable to show a differential effect across multiple deprivation quintiles. For other drinkers there might be no reduction, especially if after MUP there were many products priced close to 50 ppu. Moving away from on-sales purchases could support, for some, an increase in consumption. CONCLUSIONS: While a proportion of our harmed, heavy drinkers might be able to mitigate the impact of MUP by changing purchasing habits, the majority are predicted to reduce purchasing. This analysis, focusing specifically on harmed drinkers, adds a unique dimension to the evidence base informing current pricing policy. SHORT SUMMARY: From drink purchasing data of heavy drinkers, we estimated the impact of legislating £0.50 minimum unit price. Over two thirds of drinkers, representing all multiple deprivation quintiles, were predicted to decrease alcohol purchasing; remainder, hypothetically, could maintain consumption. Our data address an important gap within the evidence base informing policy.

Alcohol purchasing by ill heavy drinkers; cheap alcohol is no single commodity.

OBJECTIVES: Potential strategies to address alcohol misuse remain contentious. We aim to characterise the drink purchases of one population group: heavy drinkers in contact with Scottish health services. We contrast our findings with national sales data and explore the impact of socio-economic status on purchasing behaviour. STUDY DESIGN: Cross-sectional study comparing alcohol purchasing and consumption by heavy drinkers in Edinburgh and Glasgow during 2012. METHODS: 639 patients with serious health problems linked to alcohol (recruited within NHS hospital clinics (in- and out-patient settings) 345 in Glasgow, 294 in Edinburgh) responded to a questionnaire documenting demographic data and last week's or a 'typical' weekly consumption (type, brand, volume, price, place of purchase). Scottish Index of Multiple Deprivation quintile was derived as proxy of sociodemographic status. RESULTS: Median consumption was 184.8 (IQR = 162.2) UK units/week paying a mean of 39.7 pence per alcohol unit (£0.397). Off-sales accounted for 95% of purchases with 85% of those <50 pence (£0.5 UK) per alcohol unit. Corresponding figures for the Scottish population are 69% and 60%. The most popular low-priced drinks were white cider, beer and vodka with the most common off-sales outlet being the corner shop, despite supermarkets offering cheaper options. Consumption levels of the cheapest drink (white cider) were similar across all quintiles apart from the least deprived. CONCLUSIONS: Heavy drinkers from all quintiles purchase the majority of their drinks from off-sale settings seeking the cheapest drinks, often favouring local suppliers. While beer was popular, recent legislation impacting on the sale of multibuys may prevent the heaviest drinkers benefiting from the lower beer prices available in supermarkets. Non-etheless, drinkers were able to offset higher unit prices with cheaper drink types and maintain high levels of consumption. Whilst price is key, heavy drinkers are influenced by other factors and adapt their purchasing as necessary.

Common femoral arterial access and arteriography in infants: Principles, pearls, and pitfalls.

Infant femoral arterial access is an essential part of interventional procedures, hemodynamic monitoring, and support of critically ill patients. Due to small luminal diameter, superficial location, mobility, and increased risk of vasospasm, dissection, and thrombosis, femoral artery access in the infant is a technically demanding procedure. The purpose of this manuscript is to describe an approach to successful common femoral arterial access and arteriography in infants including common pearls and pitfalls.

Viewing and engaging in an art therapy exhibit by people living with mental illness: implications for empathy and social change.

OBJECTIVE: To determine how healthcare professionals, family members and community members responded to an art exhibit created by people living with mental illness. STUDY DESIGN: Phenomenological study with qualitative analysis. METHODS: Forty-six participants with various relationships with people living with mental illness attended an art therapy exhibit and art making workshop. Surveys, response art, reflective writing and discussion groups were used in this qualitative research study. RESULTS: Responses were categorized into four cluster themes: empathic, self-oriented, other-oriented and world-oriented. CONCLUSIONS: Each response category has strengths and weaknesses, indicating implications for increasing awareness and understanding of the artists and mental illness. They also inform educational interventions that can be utilized when using art exhibits for the purpose of confronting bias and stigma towards people living with mental illness.

Understanding the Benefit of Magnetic Resonance-guided Adaptive Radiotherapy in Rectal Cancer Patients: a Single-centre Study.

AIMS: Neoadjuvant chemoradiotherapy followed by surgery is the mainstay of treatment for patients with rectal cancer. Standard clinical target volume (CTV) to planning target volume (PTV) margins of 10 mm are used to accommodate inter- and intrafraction motion of target. Treating on magnetic resonance-integrated linear accelerators (MR-linacs) allows for online manual recontouring and adaptation (MRgART) enabling the reduction of PTV margins. The aim of this study was to investigate motion of the primary CTV (CTVA; gross tumour volume and macroscopic nodes with 10 mm expansion to cover microscopic disease) in order to develop a simultaneous integrated boost protocol for use on MR-linacs. MATERIALS AND METHODS: Patients suitable for neoadjuvant chemoradiotherapy were recruited for treatment on MR-linac using a two-phase technique; only the five phase 1 fractions on MR-linac were used for analysis. Intrafraction motion of CTVA was measured between pre-treatment and post-treatment MRI scans. In MRgART, isotropically expanded pre-treatment PTV margins from 1 to 10 mm were rigidly propagated to post-treatment MRI to determine overlap with 95% of CTVA. The PTV margin was considered acceptable if overlap was >95% in 90% of fractions. To understand the benefit of MRgART, the same methodology was repeated using a reference computed tomography planning scan for pre-treatment imaging. RESULTS: In total, nine patients were recruited between January 2018 and December 2020 with T3a-T4, N0-N2, M0 disease. Forty-five fractions were analysed in total. The median motion across all planes was 0 mm, demonstrating minimal intrafraction motion. A PTV margin of 3 and 5mm was found to be acceptable in 96 and 98% of fractions, respectively. When comparing to the computed tomography reference scan, the analysis found that PTV margins to 5 and 10 mm only acceptably covered 51 and 76% of fractions, respectively. CONCLUSION: PTV margins can be reduced to 3-5 mm in MRgART for rectal cancer treatment on MR-linac within an simultaneous integrated boost protocol.

Prognostic factors during outpatient treatment for alcohol dependence: cohort study with 6 months of treatment follow-up.

AIMS: To identify prognostic factors to outpatient alcohol treatment on admission as well as during the treatment period. METHODS: A cohort study of n = 209 alcoholic patients (DSM-IV) during 6 months of outpatient treatment. Eight medical doctors from two hospitals were involved. Co-responsible participation in treatment was a necessary condition. At admission, we documented socio demographic factors, use of other drugs and severity of alcohol consumption. During the 6 months, we observed medication for prevention of alcohol relapse [disulfiram (DIS), acamprosate], number of sessions with the doctor, number of phases of the consultation and medication for depression. Primary outcome variables were time to first heavy relapse and abstinence of heavy alcohol consumption. These were measured with Timeline Followback. Five or more alcohol units of 10 g in one relapse day were considered heavy relapse. RESULTS: The patients were 84% males, with 41 years median age; the median alcohol consumption was 192 g per day with a median duration of 13 years of heavy consumption. The median education was 6 years with 61% of the patients from lower socio-economic levels. The Kaplan-Meier heavy relapse rate at 6 months was 23%. On admission to treatment, female gender, lower socio-economic levels, cocaine use, >20 years of consumption, gamma glutamyl transferase values above normal and five or more alcohol-related problems on the Alcohol-Related Problem Questionnaire predicted worse outcomes. Having a full-time job and shorter abstinence time before treatment (until 7 days) predicted better outcomes. During the 6 months, we found that DIS for <120 days was a prognostic factor of worse outcomes. DIS for at least 120 days, >50% of adherence to consultations and more than two phases on each consultation predicted better outcomes. The combined sensitivity and specificity for DIS for at least 120 days, >50% of adherence to consultations and more than two phases on consultation regarding abstinence from heavy relapse were respectively 100 and 71%. CONCLUSIONS: During 6 months of outpatient treatment, longer adherence to DIS and consultations as well as more phases in a consultation involving necessarily a co-responsible predict a good outcome independently of the patient features at admission.

Feasibility of tumour-focused adaptive radiotherapy for bladder cancer on the MR-linac.

Bladder tumour-focused magnetic resonance image-guided adaptive radiotherapy using a 1.5 Tesla MR-linac is feasible. A full online workflow adapting to anatomy at each fraction is achievable in approximately 30 min. Intra-fraction bladder filling did not compromise target coverage with the class solution employed.

Feasibility of magnetic resonance guided radiotherapy for the treatment of bladder cancer.

Whole bladder magnetic resonance image-guided radiotherapy using the 1.5 Telsa MR-linac is feasible. Full online adaptive planning workflow based on the anatomy seen at each fraction was performed. This was delivered within 45 min. Intra-fraction bladder filling did not compromise target coverage. Patients reported acceptable tolerance of treatment.

Contaminant concentrations in Asian carps, invasive species in the Mississippi and Illinois Rivers.

Populations of invasive fishes quickly reach extremely high biomass. Before control methods can be applied, however, an understanding of the contaminant loads of these invaders carry is needed. We investigated differences in concentrations of selected elements in two invasive carp species as a function of sampling site, fish species, length and trophic differences using stable isotopes (delta (15)N, delta (13)C). Fish were collected from three different sites, the Illinois River near Havana, Illinois, and two sites in the Mississippi River, upstream and downstream of the Illinois River confluence. Five bighead carp (Hypophthalmichthys nobilis) and five silver carp (Hypophthalmichthys molitrix) from each site were collected for muscle tissue analyses. Freshwater mussels (Amblema plicata) previously collected in the same areas were used as an isotopic baseline to standardize fish results among sites. Total fish length, trophic position, and corrected (13)C, were significantly related to concentrations of metals in muscle. Fish length explained the most variation in metal concentrations, with most of that variation related to mercury levels. This result was not unexpected because larger fish are older, giving them a higher probability of exposure and accumulation of contaminants. There was a significant difference in stable isotope profiles between the two species. Bighead carp occupied a higher trophic position and had higher levels of corrected (13)C than silver carp. Additionally bighead carp had significantly lower concentrations of arsenic and selenium than silver carp. Stable isotope ratios of nitrogen in Asian carp were at levels that are more commonly associated with higher-level predators, or from organisms in areas containing high loads of wastewater effluent.

Percutaneous fluoroscopically-guided transcervical retrograde access facilitates successful thoracic duct embolization after failed antegrade transabdominal access.

The purpose of this study was to demonstrate the feasibility of percutaneous fluoroscopically-guided transcervical retrograde access into the thoracic duct following unsuccessful transabdominal cisterna chyli cannulation to perform thoracic duct embolization for the treatment of chylothorax. Five patients, including three (60%) women and two (40%) men, with median age of 62 years, underwent percutaneous transcervical thoracic duct access and embolization after failed transabdominal cisterna chyli cannulation for the treatment of chylothorax. In all patients, fluoroscopically-guided percutaneous transcervical retrograde access into the distal thoracic duct was achieved using a 21-gauge needle and an 0.018-inch wire. Following advancement of a microcatheter, retrograde lymphangiography was performed to identify the location of thoracic duct injury. A combination of 2:1 ethiodized oil to cyanoacrylate mixtures, platinum microcoils, or stent-grafts were used to treat the chylous leaks. Technical successes, procedure durations, fluoroscopy times, blood losses, immediate adverse events, clinical successes, and follow-up durations were recorded. Technical success was defined as cannulation of the distal thoracic duct using a transcervical approach followed by treatment of the thoracic duct injury. Adverse events were classified according to the Society of Interventional Radiology guidelines. Clinical success was defined as resolution of the presenting chylothorax. Percutaneous transcervical retrograde thoracic duct access and treatment was technically successful in all patients (n=5). Median procedure duration was 173 minutes (range: 136-347 minutes) with a median fluoroscopy time of 94.7 minutes (range: 47-125 minutes). Median blood loss was 10 mL (range: 5-20 mL). No minor or major adverse occurred. Clinical success was achieved in all patients (n=5). Median follow-up was 372 days (range: 67-661 days). Percutaneous fluoroscopically- guided transcervical retrograde thoracic duct access is an effective and safe method to perform thoracic duct embolization following unsuccessful transabdominal cisterna chyli cannulation for the treatment of chylothorax.

A phase I and pharmacokinetic study of OSI-7904L, a liposomal thymidylate synthase inhibitor in combination with oxaliplatin in patients with advanced colorectal cancer.

PURPOSE: OSI-7904L is a liposomal formulation of a potent thymidylate synthase (TS) inhibitor. This phase I study evaluated the safety, tolerability and pharmacokinetics (PK) of OSI-7904L administered in combination with oxaliplatin every 21 days in patients with advanced colorectal carcinoma. METHOD: A 3+3 study design was utilized at predefined dose levels. Polymorphisms in the TS enhancer region and XPD enzyme were investigated as potential predictors of efficacy and toxicity. RESULTS: Fourteen patients received 76 cycles of treatment. At the highest dose level (OSI-7904L 9 mg/m(2), oxaliplatin 130 mg/m(2)) investigated, one of nine patients experienced dose-limiting toxicity of grade 3 oral mucositis with cycle 1 and five further patients required dose reductions. The toxicity profile of stomatitis, diarrhea, nausea, fatigue, sensory neuropathy and skin rash was consistent with that expected for a TS inhibitor/oxaliplatin combination regimen. PK analysis showed high interpatient variability with no detectable interaction between OSI-7904L and oxaliplatin. Partial radiological responses were documented in two patients. CONCLUSIONS: The recommended regimen for further investigation is OSI-7904L 9 mg/m(2) and oxaliplatin 130 mg/m(2).

Evaluating current and recent fellows' perceptions on the interventional radiology residency: Results of a United States survey.

PURPOSE: To evaluate current and recent interventional radiology (IR) fellows' perceptions on the new integrated IR residency. MATERIALS AND METHODS: An anonymous, web-based survey was distributed to 82 current and recent IR fellows across the Unites States. The survey contained 15 questions, most of which were based on a five-point Likert scale. The survey was open for a three-week period in September 2015. The results were analyzed by two trainees and three IR attending physicians. RESULTS: Sixty-four current or recent former IR fellows completed the survey (response rate 78%). Of these 18% decided to pursue a career in IR by the end of their third year of medical school. A majority believed that the integrated IR residency will be an improved IR training pathway (62%). Based on current medical school curricula, 74% either disagreed or strongly disagreed that IR residency applicants will be ready to select such a pathway by the end of their third year of medical school. CONCLUSIONS: Most current and recent IR fellows surveyed chose IR during their final year of medical school or during residency. Most respondents believe that the integrated IR residency will be an improved IR training pathway.

Two-year outcomes of balloon-occluded retrograde transvenous obliteration of gastric varices in liver transplant recipients: A multi-institutional study.

PURPOSE: To assess the 2-year effectiveness and safety of balloon-occluded retrograde transvenous obliteration (BRTO) for gastric varices (GVs) in liver transplant recipients. MATERIALS AND METHODS: Eleven liver transplant recipients underwent consecutive BRTO for GVs at four institutions. Patients included eight (73%) men and three (27%) women with mean age of 56 years±12 (SD) (range: 26-67 years). Underlying cause of liver transplantation was hepatitis C virus (HCV)-related cirrhosis in five (45%), alcohol- and HCV-related cirrhosis in three (27%), primary biliary cirrhosis in two (18%), and alcoholic cirrhosis in one (9%). Five (45%) patients underwent BRTO for actively bleeding GVs, three (17%) for high-risk GVs, and three (17%) for augmentation of portal venous flow through obliteration of gastrorenal shunts. Mean time between liver transplantation and BRTO was 78 months (range: 0.1-276 months). Technical success, GVs obliterative rates, and immediate complications were recorded. Post-BRTO hemorrhagic, transplant, and overall survival rates were evaluated at 6, 12, and 24 months. RESULTS: All (100%) procedures were technically successful. Complete GVs obliteration was achieved in ten patients (91%). Two major complications (18%) occurred in the immediate post-procedure period. One patient developed complete portal vein thrombosis, and another patient developed consumptive coagulopathy, ultimately leading to death. No post-BRTO hemorrhagic recurrences were seen at 6, 12, or 24 months. One patient (9%) had delayed upper gastrointestinal bleeding at 34 months after the procedure which was managed conservatively. Transplant and overall survival rates were 91% at 6, 12, and 24 months. CONCLUSION: BRTO has high technical success and complete GVs obliterative rates in liver transplant recipients with few complications and high graft survival rates.

Safety issues concerning the use of disulfiram in treating alcohol dependence.

Disulfiram is known to cause hepatitis, which is sometimes fatal. The best estimate of the frequency of disulfiram-induced fatal hepatitis is 1 case in 30,000 patients treated/year. Its appears to be more common in patients given disulfiram for the treatment of nickel sensitivity. Frequent blood testing for liver function is probably not necessary, but patients taking disulfiram should be in regular contact with a physician. There are rare reports of psychosis and confusional states in conjunction with disulfiram treatment and peripheral neuropathy and optic neuritis have been reported; these effects are dose-related. Psychiatric complications appear to be more common with the use of disulfiram in India than in Western countries. Of the less serious adverse effects, tiredness, headache and sleepiness are the most common. Deaths from the disulfiram-alcohol (ethanol) interaction have not been reported in recent years, possibly because the dosages used are lower than those used 40 years ago, and patients with cardiac disease are now excluded from treatment. There is no evidence to suggest that disulfiram causes cancer. Of note, there are drug interactions with compounds that utilise the cytochrome P450 enzyme system. Disulfiram can be viewed as a drug with a moderate record of adverse effects. Alcohol dependence, for which it can be a helpful treatment, is associated with a high morbidity and mortality.

Benno Pollak Lecture 1992. Alcohol dependence--an illness with a treatment?

Unlike some countries, Britain may have experienced a rise rather than a fall in alcohol-related illness during a decade when consumption has not risen. Objections to the "illness concept" may impede our vision and the range of services we develop. It is possible to agree with objectors to the illness concept that a unidimensional view is unhelpful; that explanations are often only attributions; that the construct "illness" is not needed for help to be offered, its use could undermine self-mastery, and its misuse can breach civil rights. Learning can explain much over-drinking. However, the concept need not imply bimodality of drinkers; the syndrome of alcohol dependence has uses and does not imply a cause; physical and mental explanations are not incompatible; genetic and biochemical research has promise. Developments in treatment are still limited, but the mysteries of the free-will dilemma should not prevent us seeing physiological, psychological and social contributants as partners rather than rivals.

Trends in alcoholism among male doctors in Scotland.

Alcohol abuse within the medical profession has long been an issue of concern. Recently, the General Medical Council reported that half of the doctors reported for health difficulties liable to affect professional competence were found to have an alcohol problem. This paper examines how rates of alcoholism among male doctors in Scotland have changed over the last three decades. Admission and discharge rates for doctors to psychiatric inpatient beds with diagnoses of alcoholism are compared with non-medical professions, for the years 1963-87. The results, assessed in the light of changing Standardized Mortality Rates for liver cirrhosis for the medical profession, suggest that doctors as a group remain at a higher risk of alcoholism compared to other professionals, but that this increased risk appears to be largely accounted for by a cohort of heavy-drinking doctors over the age of 45 years.

Comparison of two benzodiazepines in the treatment of alcohol withdrawal: effects on symptoms and cognitive recovery.

Forty newly admitted alcohol-dependent patients were randomly allocated to equivalent 6-day regimes of either lorazepam or diazepam, to compare involvement in physical, emotional and cognitive state during the first 8 days in hospital. Diazepam provided a more comfortable withdrawal period and was associated with slightly better cognitive functioning on the eighth day.

Carbohydrate deficient transferrin in detecting relapse in alcohol dependence.

Patients reports together with findings at clinical examination and information from an informant such as a relative were used to categorise patients as relapsed or not relapsed during a 6 month period of out-patient treatment at an alcohol problems clinic. At each fortnightly visit, blood was taken for measurement of serum gamma-glutamyl transferase and carbohydrate deficient transferrin (Pharmacia method). A total of 53 patients attended for at least one follow-up visit. Mean CDT differentiated relapsers from non-relapsers at seven of the 11 visits (P < 0.05), but at no visit did mean GGT differentiate. CDT tended to become elevated after a relapse more quickly than GGT. However, whether using upper limit of normal (ULN), or defining a 'positive test' as > last test and either > 20% above lowest previous test or > ULN, specificity (averaged over the 11 visits) was greater for GGT than CDT. Some of the false positive results for CDT were in patients who, shortly after having a positive test, relapsed, suggesting that a rising CDT can herald a relapse admitted by the patient. This could not be shown for false positive GGT results. Inspection of individual trajectories of alcohol consumption and blood test results shows that for some patients GGT is the more effective marker of relapse, whilst for others CDT operates better.