Elevated stearoyl-CoA desaturase 1 activity is associated with alcohol-associated liver disease.

Chronic binge drinking induces hepatic lipid accumulation, but only certain individuals develop alcohol-associated liver disease (ALD). Specific patterns of lipid accumulation are thought to be associated with ALD, but this has not been comprehensively investigated to date. We analyzed plasma fatty acid levels, quantified by gas chromatography-mass spectrometry, in a sample of patients with alcohol use disorder (AUD). Given that elevation in serum alanine transaminase (ALT) levels are strongly associated with ALD, patients were stratified into two groups based on ALT levels: an ALD group (ALT >40 IU/L) and a non-ALD group (ALT ≤40 IU/L). There was a shift toward greater concentrations of monounsaturated fatty acids in the ALD group compared to the non-ALD group. Stearoyl-CoA desaturase (SCD1) activity in the ALD group was then estimated as the ratio of palmitoleic acid (16:1) to palmitic acid (16:0). SCD1 activity was greater in the ALD than the non-ALD group. A series of linear regression models demonstrated that SCD1 activity mediated the association between binge drinking and ALD. These findings provide initial evidence that SCD1 activity may be associated with ALD. If validated prospectively, elevated SCD1 activity could potentially be used as a biomarker to identify individuals at high risk for developing ALD.

Implementation of a pharmacist-led transitional care clinic.

PURPOSE: To describe a pharmacist-led transitional care clinic (TCC) for high-risk patients who were recently hospitalized or seen in the emergency department (ED). SUMMARY: The Memphis Veterans Affairs Medical Center (VAMC) established a pharmacist-led face-to-face and telephone follow-up TCC to improve posthospitalization follow-up care through medication optimization and disease state management, particularly for veterans with high-risk disease states such as chronic obstructive pulmonary disease (COPD) and heart failure (HF). The clinic's clinical pharmacy specialists (CPSs) ordered diagnostic and laboratory tests, performed physical assessments, and consulted other providers and specialty services in addition to performing medication reconciliation, compliance assessment, and evaluation of adverse drug events. TCC patients were typically seen within 2 weeks of discharge and subsequently referred back to their primary care provider or a specialty care provider for continued management. A retrospective review of 2016 TCC data found that 7.8% of patients seen in the TCC were readmitted within 30 days of discharge; readmission rates for COPD and HF were reduced to 13% and 10%, respectively, compared to hospital-wide readmission rates of 17% and 24%. A separate observational analysis found that 30-day readmissions for COPD and HF were reduced in TCC patients, with pharmacists documenting an average of 6.2 interventions and 3.3 medication-related problems per patient. To reduce clinic appointment no-shows, the CPSs worked with inpatient providers and schedulers to emphasize to patients the importance of clinic attendance; also, TCC services were expanded to include telehealth appointments to increase access for rural and/or homebound patients. CONCLUSION: A pharmacist-led TCC effectively reduced readmissions and prevented medication-related problems for high-risk patients who were hospitalized or seen in the ED.

The Fall Risk with Alpha blockers Given InitiaL dose or Elderly status (FRAGILE) Study.

Background: α-1 adrenergic antagonists are commonly prescribed, but there is question regarding their safety in patients at increased fall risk. Objective: The purpose of the FRAGILE study was to determine the risk for developing adverse drug events (ADEs) in veterans prescribed α-1 blockers. Methods: A single-center, retrospective, observational cohort analysis was conducted of veterans newly initiated on α-1 antagonists. Veterans were categorized into at-risk (patients who met at least 1 of 2 criteria: age 65 or older or high initial dose of α blockade) or control (veterans without either risk factor) groups. The primary outcome was the composite all-cause ADEs, including hospitalizations or emergency department (ED) visits. Secondary outcomes included number of fall-related ADEs and medication discontinuation rates with follow-up for 12 months. Results: A total of 300 veterans were evaluated. There was no significant difference in the composite outcome of all-cause ED visits between at-risk (n = 169) versus control (n = 131) groups (0.81 vs 1.17, P = 0.09) or all-cause hospitalizations (0.28 vs 0.39, P = 0.25). Seventy-three veterans in the at-risk group experienced an all-cause ADE versus 64 in the control group (P = 0.36). No significant differences in secondary outcomes were found. Fall-related side effects occurred in 8% of the total cohort. Conclusion and Relevance: Rates of all-cause or fall-related ADEs were not significantly different. An 8% discontinuation rate resulting from fall-related ADEs and high rates of coadministered medications that could increase fall risk. Pharmacists can play a key role in optimizing α-1 blocker administration.

Not all hip arthroplasties are created equal: increased complications and re-admissions after total hip arthroplasty for femoral neck fractures compared with osteoarthritis.

AIMS: Total hip arthroplasty (THA) is gaining popularity as a treatment for displaced femoral neck fractures (FNFs), especially in physiologically younger patients. While THA for osteoarthritis (OA) has demonstrated low complication rates and increased quality of life, results of THA for acute FNF are not as clear. Currently, a THA performed for FNF is included in an institutional arthroplasty bundle without adequate risk adjustment, potentially placing centres participating in fracture care at financial disadvantage. The purpose of this study is to report on perioperative complication rates after THA for FNF compared with elective THA performed for OA of the hip. PATIENTS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database between 2008 and 2016 was queried. Patients were identified using the THA Current Procedural Terminology (CPT) code and divided into groups by diagnosis: OA in one and FNF in another. Univariate statistics were performed. Continuous variables were compared between groups using Student's t-test, and the chi-squared test was used to compare categorical variables. Multivariate and propensity-matched logistic regression analyses were performed to control for risk factors of interest. RESULTS: Analyses included 139 635 patients undergoing THA. OA was the indication in 135 013 cases and FNF in 4622 cases. After propensity matching, mortality within 30 days (1.8% vs 0.3%; p < 0.001) and major morbidity (24.2% vs 19%; p < 0.001) were significantly higher among FNF patients. Re-operation (3.7% vs 2.7%; p = 0.014) and re-admission (7.3% vs 5.5%; p = 0.002) were significantly higher among FNF patients. Hip fracture patients had significantly longer operative time and length of stay (LOS), and were significantly less likely to be discharged to their home. Multivariate analyses gave similar results. CONCLUSION: This large database study showed a higher risk of postoperative complications including mortality, major morbidity, re-operation, re-admission, prolonged operative time, increased LOS, and decreased likelihood of discharge home in patients undergoing THA for FNF compared with OA. While THA is a good option for FNF patients, there are increased costs and financial risks to centres with a joint arthroplasty bundle programme participating in fracture care. Cite this article: Bone Joint J 2019;101-B(6 Supple B):84-90.

The OPRM1 A118G polymorphism: converging evidence against associations with alcohol sensitivity and consumption.

The endogenous opioid system may be involved in the development and maintenance of alcohol use disorder (AUD) and is a target for existing AUD pharmacotherapies. A functional polymorphism of the mu-opioid receptor gene (OPRM1 A118G, rs1799971) may alter the risk of developing AUD. Human laboratory studies have demonstrated that minor allele carriers self-administer more alcohol, show greater sensitivity to alcohol's effects, and exhibit increased alcohol-induced dopamine release. On the other hand, large genome-wide association studies and meta-analyses of candidate gene studies have not found an association between this genotype and alcohol dependence diagnosis. Given this discrepancy, the present study sought to verify whether OPRM1 A118G was associated with alcohol self-administration, subjective response to alcohol, and craving in a sample of 106 social drinkers of European ancestry who completed an intravenous alcohol self-administration session. We found no relationship between OPRM1 rs1799971 genotype and subjective response to alcohol or craving. OPRM1 genotype was not associated with total alcohol exposure or likelihood of attaining a binge-level exposure (80 mg%) during the intravenous alcohol self-administration session. Analysis of 90-day Timeline Followback interview data in a larger sample of 965 participants of European ancestry found no relationship between OPRM1 genotype and alcohol consumption in either alcohol dependent or non-dependent participants. These findings suggest that there may not be an association between OPRM1 rs1799971 genotype and alcohol consumption or sensitivity in individuals of European ancestry.

'Hot Joints' infection protocol reduces unnecessary post-operative re-admissions following total hip and knee arthroplasty.

AIMS: To evaluate the effectiveness of an institutionally developed algorithm for evaluation and diagnosis of prosthetic joint injection and to determine the impact of this protocol on overall hospital re-admissions.p PATIENTS AND METHODS: We retrospectively evaluated 2685 total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients prior to (1263) and following (1422) the introduction of an infection detection protocol. The protocol used conservative thresholds for C-reactive protein to direct the medical attendant to aspirate the joint. The protocol incorporated a clear set of laboratory and clinical criteria that allowed a patient to be discharged home if all were met. Patients were included if they presented to our emergency department within 120 days post-operatively with concerns for swelling, pain or infection and were excluded if they had an unambiguous infection or if their chief complaint was non-orthopaedic in nature. RESULTS: Concern for infection was the single most common (32%) reason for presentation. A total of 296 patients made an emergency visit and were included following THA or TKA. In the pre-protocol cohort, 11 of 27 patients were formally re-admitted to the hospital with concern for infection but only five (45%) patients had actual infections and received additional treatment. In comparison, in the post-protocol cohort, 11 patients were admitted for suspected infection, nine (82%) of whom were truly infected (p = 0.04). Sensitivity increased from 83% to 100% and specificity increased from 71% to 96%. Implementation of this protocol did not miss any infections. CONCLUSION: A standardised protocol for evaluation of THA and TKA infections significantly reduced unnecessary hospital re-admissions. The protocol was both sensitive and specific and did not compromise quality of care. Cite this article: Bone Joint J 2017;99-B:1603-10.

Outpatient influenza antiviral prescription trends with influenza-like illness in the USA, 2008-2010.

The 2009 novel H1N1 influenza A virus (H1N1) became a global pandemic. Data on antiviral prescriptions by location from 2008 to 2010 have not been reported. The purpose of this study was to assess antiviral geographic trends and correlation with influenza-like illness (ILI) over 3 years. Percent of outpatient ILI visits and antiviral prescriptions from 1 January 2008 to 31 December 2010 were included. Linear regression was used to assess correlation. In total, 14 million antivirals were dispensed during this period. A 115% increase was observed in 2009 compared with prescriptions dispensed in 2008, and an 84% decrease was observed in 2010 compared with 2009. The rate of antivirals was 1.32 prescriptions/100 persons in 2008, 2.85/100 persons in 2009 and 0.435/100 persons in 2010. 2009 regional growth was observed in most states and was highest in the West (293%) and the Northeast (272%). A positive correlation was observed between antivirals and ILI visits (R(2)=0.7853; P<0.0001). With the 2009 H1N1 pandemic, antivirals increased compared with 2008 or 2010. Without the concern of H1N1, antivirals decreased in 2010 to levels lower than 2008. Geographic trends were also observed, which may be a result of the different intensity of influenza transmission and difference practice patterns. ILI diagnoses correlate with influenza antiviral prescription use in the USA.

Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To assess the evidence for the use of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in the diagnosis of patients with acute ischemic stroke. METHODS: We systematically analyzed the literature from 1966 to January 2008 to address the diagnostic and prognostic value of DWI and PWI. RESULTS AND RECOMMENDATIONS: DWI is established as useful and should be considered more useful than noncontrast CT for the diagnosis of acute ischemic stroke within 12 hours of symptom onset. DWI should be performed for the most accurate diagnosis of acute ischemic stroke (Level A); however, the sensitivity of DWI for the diagnosis of ischemic stroke in a general sample of patients with possible acute stroke is not perfect. The diagnostic accuracy of DWI in evaluating cerebral hemorrhage is outside the scope of this guideline. On the basis of Class II and III evidence, baseline DWI volumes probably predict baseline stroke severity in anterior territory stroke (Level B) but possibly do not in vertebrobasilar artery territory stroke (Level C). Baseline DWI lesion volumes probably predict (final) infarct volumes (Level B) and possibly predict early and late clinical outcome measures (Level C). Baseline PWI volumes predict to a lesser degree the baseline stroke severity compared with DWI (Level C). There is insufficient evidence to support or refute the value of PWI in diagnosing acute ischemic stroke (Level U).

The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial.

BACKGROUND: Transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) can identify intracranial atherosclerosis but have not been rigorously validated against the gold standard, catheter angiography. The WASID trial (Warfarin Aspirin Symptomatic Intracranial Disease) required performance of angiography to verify the presence of intracranial stenosis, allowing for prospective evaluation of TCD and MRA. The aims of Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial were to define abnormalities on TCD/MRA to see how well they identify 50 to 99% intracranial stenosis of large proximal arteries on catheter angiography. STUDY DESIGN: SONIA standardized the performance and interpretation of TCD, MRA, and angiography. Study-wide cutpoints defining positive TCD/MRA were used. Hard copy TCD/MRA were centrally read, blind to the results of angiography. RESULTS: SONIA enrolled 407 patients at 46 sites in the United States. For prospectively tested noninvasive test cutpoints, positive predictive values (PPVs) and negative predictive values (NPVs) were TCD, PPV 36% (95% CI: 27 to 46); NPV, 86% (95% CI: 81 to 89); MRA, PPV 59% (95% CI: 54 to 65); NPV, 91% (95% CI: 89 to 93). For cutpoints modified to maximize PPV, they were TCD, PPV 50% (95% CI: 36 to 64), NPV 85% (95% CI: 81 to 88); MRA PPV 66% (95% CI: 58 to 73), NPV 87% (95% CI: 85 to 89). For each test, a characteristic performance curve showing how the predictive values vary with a changing test cutpoint was obtained. CONCLUSIONS: Both transcranial Doppler ultrasound and magnetic resonance angiography noninvasively identify 50 to 99% intracranial large vessel stenoses with substantial negative predictive value. The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis trial methods allow transcranial Doppler ultrasound and magnetic resonance angiography to reliably exclude the presence of intracranial stenosis. Abnormal findings on transcranial Doppler ultrasound or magnetic resonance angiography require a confirmatory test such as angiography to reliably identify stenosis.

Clinical experience with Alloderm: a one-staged composite dermal/epidermal replacement utilizing processed cadaver dermis and thin autografts.

UNLABELLED: Alloderm has been advocated for the management of acute burns. However, few studies have demonstrated the feasibility of this technique. METHODS: We reviewed the medical records of all patients treated in our burn center who received Alloderm since 1999. RESULTS: Alloderm was used in 21 burn patients and 6 patients with traumatic skin loss. The average size of Alloderm used in the burn patients was 517+/-144 cm(2) (range 24-3000 cm(2)). The average Alloderm thickness used was 0.008 in. and autografts were harvested at an average of 0.007 in. Overall, Alloderm was used in a variety of locations including the face in 3 patients (2 burns, 1 traumatic skin loss) and hands in 7 patients (6 burns, 1 traumatic skin loss). Successful take was observed in 26/27 patients. CONCLUSIONS: Alloderm can be used successfully in patients with acute burns requiring grafting.

Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. METHODS: The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. RESULTS: TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

Attrition and non-compliance in secondary stroke prevention trials.

BACKGROUND: Attrition and non-compliance of subjects in secondary stroke prevention trials due to study drug-induced adverse events and loss to follow-up could lead to bias and loss of information, thus affecting the analysis of study results. METHODS: We reviewed results from ten antiplatelet stroke prevention clinical trials: CAN TIA, DUTCH TIA, SWED ASA, SALT, UK TIA, CATS, TASS, ESPS, ESPS-2, and CAPRIE to tabulate the frequencies for total subject discontinuation, voluntary withdrawal, and loss to follow-up. RESULTS: Forty thousand seven hundred and thirty (40,730) subjects participated in the aforementioned secondary stroke prevention trials. The range of outcomes was 11.8-52.0% for subjects discontinued for any reason (n = 9 trials); 3.0-20.9% for study drug-induced adverse events (n = 9 trials), and 4.2-7.8% for voluntary withdrawal (n = 10 trials). CONCLUSION: There is a substantial discrepancy (up to 20%) between the frequencies of total subject discontinuation for any reason and the sum of study drug-induced adverse events, voluntary withdrawal and loss to follow-up. Underestimation of these important outcomes may limit the ability of clinicians to translate results from clinical trials into medical practice.

Nonsteroidal anti-inflammatory drug use and breast cancer risk.

Findings from previous epidemiological studies are inconclusive, though they suggest nonsteroidal anti-inflammatory drug (NSAID) use is associated with a reduction in breast cancer risk. In addition, animal studies report that NSAIDs inhibit mammary tumor development. The association between NSAID use and breast cancer risk was evaluated using a case-control study design. Cases were a random sample of women diagnosed with a first primary cancer of the breast, aged 25-74 years, identified through the Ontario Cancer Registry, and diagnosed between July 1996 and September 1998. Controls were an age-matched random sample of the female population of Ontario. Cases (n = 3133) and controls (n = 3062) completed a mailed questionnaire with information on their past use of NSAID and other medications, as well as many risk factors thought to be associated with breast cancer. Multivariate logistic regression analysis was used to obtain adjusted odds ratio (OR) estimates. Use of any NSAID medication (daily use for > or =2 months) was found to be associated with a significant 24% reduction in breast cancer risk (OR = 0.76; 95% confidence interval: 0.66, 0.88). The reduced risk was strongest for use lasting > 8 years, compared with nonusers (OR = 0.68; 95% confidence interval: 0.54, 0.86). No marked trends were observed for time since first use or last use or age at first use. Our results suggest a reduction in breast cancer risk associated with any regular NSAID use. NSAID use is a modifiable factor, and any protective effect attributed to its use could be of great public health importance.

Hormonal factors and pancreatic cancer in women.

PURPOSE: The aim of the study was to evaluate hormonal risk factors for carcinoma of the exocrine pancreas among postmenopausal women. METHODS: Mailed questionnaire data from 52 cases and 233 population-based controls in Ontario were used to assess parity, age at first birth, and other hormonal factors on pancreatic cancer risk. RESULTS: Reduced risk was seen with three or more pregnancies [adjusted odds ratio (OR) = 0.22, 95% confidence interval (CI) = 0.07-0.65] and use of oral contraceptives (adjusted OR = 0.36, 95% CI = 0.13-0.96), whereas no significant associations were found for age at menarche or menopause, or estrogen replacement therapy. Among parous women, later age at first full-term pregnancy significantly increased the risk of this cancer (adjusted OR = 4.05, 95% CI = 1.50-10.92 for ages 25-29 years, adjusted OR = 3.78, 95% CI = 1.02-14.06 for ages 30+ years). CONCLUSIONS: Our data support the hypothesis that pancreatic cancer is, at least in part, an estrogen-dependent disease; there is growing epidemiological evidence that aspects of reproductive history and hormonal exposure are associated with risk of this disease.

Should identification audiometry include a screening for depression among residents of upper socioeconomic retirement centers?

40 older residents living in three upper socioeconomic retirement centers were screened for hearing loss, hearing handicap, and depression. Those participants who showed loss on the hearing screening or the hearing handicap screening were no more likely to score as depressive on the Geriatric Depression Scale than were those who showed no loss on screening. Results suggest that hearing loss and depression should be routinely but independently monitored in settings with affluent older adult residents.

Misclassification of exposure: coffee as a surrogate for caffeine intake.

This study was conducted to assess the effect of exposure misclassification when coffee is used as a surrogate measure of caffeine exposure. Subjects were randomly selected from the telephone directories of four regional municipalities in southern Ontario, CANADA: Data on daily caffeine intake from foods, beverages, and medications were collected from June to November 1995 through self-administered, mailed questionnaires from 481 men and women aged 30-75 years. Although coffee was the main source of caffeine, cross-tabulations of exposure to coffee by total caffeine intake showed that assessment of coffee alone severely underestimated caffeine intake by at least one exposure level. A hypothetical 10-fold increase in risk was completely obscured when only coffee was used to estimate total caffeine intake. The results of this study suggest that measuring coffee instead of caffeine intake may contribute to a lack of positive findings in studies of coffee as a risk factor for disease occurrence, if in fact caffeine is the exposure of interest. On the other hand, measurement of coffee, tea, and cola soft drink intake in the present study appeared to approximate caffeine intake sufficiently and not affect risk estimates adversely.

Cancer prevention in the community: a survey of community residents.

Lifestyle exposures account for the greatest proportion of risk factors for cancer, yet these exposures have proven most difficult to alter. Despite intensive intervention efforts, many behaviour change programs are ill suited to the community. This research was undertaken to increase our understanding of prevention activities of interest to a sample of residents in two Ontario communities. 248 (62.3%) adult residents responded to a semi-structured self-administered questionnaire including open-ended questions on health issues, exposures and prevention activities of interest. While some of the beliefs expressed by respondents might have been anticipated (e.g., cigarette smoking and family history increase risk of cancer), others were not (e.g., only between 40 and 75% of respondents thought a high fat diet increased risk). Furthermore, many of those with personal health concerns expressed an interest in prevention. This process is proposed as a first step in launching more appropriate and sustainable community-based health promotion programs for cancer prevention.

Alcohol intake, type of beverage, and the risk of cerebral infarction in young women.

BACKGROUND AND PURPOSE: The relationship between alcohol consumption and cerebral infarction remains uncertain, and few studies have investigated whether the relationship varies by alcohol type or is present in young adults. We examined the relationship between alcohol consumption, beverage type, and ischemic stroke in the Stroke Prevention in Young Women Study. METHODS: All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. Case patients (n=224) were aged 15 to 44 years with a first cerebral infarction, and control subjects (n=392), identified by random-digit dialing, were frequency matched by age and region of residence. The interview assessed lifetime alcohol consumption and consumption and beverage type in the previous year, week, and day. ORs were obtained from logistic regression models controlling for age, race, education, and smoking status, with never drinkers as the referent. RESULTS: Alcohol consumption, up to 24 g/d, in the past year was associated with fewer ischemic strokes (<12 g/d: OR 0.57, 95% CI 0. 38 to 0.86; 12 to 24 g/d: OR 0.38, 95% CI 0.17 to 0.86; >24 g/d: OR 0.95, 95% CI 0.43 to 2.10) in comparison to never drinking. Analyses of beverage type (beer, wine, liquor) indicated a protective effect for wine consumption in the previous year (<12 g/wk: OR 0.58, 95% CI 0.35 to 0.97; 12 g/wk to <12 g/d: OR 0.55, 95% CI 0.28 to 1.10; >/=12 g/d: OR 0.92, 95% CI 0.23 to 3.64). CONCLUSIONS: Light to moderate alcohol consumption appears to be associated with a reduced risk of ischemic stroke in young women.