Importance Alcohol consumption is associated with 88 000 US deaths annually. Although routine screening for heavy alcohol use can identify patients with alcohol use disorder (AUD) and has been recommended, only 1 in 6 US adults report ever having been asked by a health professional about their drinking behavior. Alcohol use disorder, a problematic pattern of alcohol use accompanied by clinically significant impairment or distress, is present in up to 14% of US adults during a 1-year period, although only about 8% of affected individuals are treated in an alcohol treatment facility. Observations Four medications are approved by the US Food and Drug Administration to treat AUD: disulfiram, naltrexone (oral and long-acting injectable formulations), and acamprosate. However, patients with AUD most commonly receive counseling. Medications are prescribed to less than 9% of patients who are likely to benefit from them, given evidence that they exert clinically meaningful effects and their inclusion in clinical practice guidelines as first-line treatments for moderate to severe AUD. Naltrexone, which can be given once daily, reduces the likelihood of a return to any drinking by 5% and binge-drinking risk by 10%. Randomized clinical trials also show that some medications approved for other indications, including seizure disorder (eg, topiramate), are efficacious in treating AUD. Currently, there is not sufficient evidence to support the use of pharmacogenetics to personalize AUD treatments. Conclusions and Relevance Alcohol consumption is associated with a high rate of morbidity and mortality, and heavy alcohol use is the major risk factor for AUD. Simple, valid screening methods can be used to identify patients with heavy alcohol use, who can then be evaluated for the presence of an AUD. Patients receiving a diagnosis of the disorder should be given brief counseling and prescribed a first-line medication (eg, naltrexone) or referred for a more intensive psychosocial intervention.

https://jamanetwork.com/journals/jama/articlepdf/2698498/jama_kranzler_2018_rv_180006.pdf

Diagnosis and Pharmacotherapy of Alcohol Use Disorder: A Review.

Background: The US National Institutes of Mental Health Research Domain Criteria (RDoC) seek to stimulate research into biologically validated neuropsychological dimensions across mental illness symptoms and diagnoses. The RDoC framework comprises 39 functional constructs designed to be revised and refined, with the overall goal of improving diagnostic validity and treatments. This study aimed to reach a consensus among experts in the addiction field on the ‘primary’ RDoC constructs most relevant to substance and behavioural addictions. Methods: Forty-four addiction experts were recruited from Australia, Asia, Europe and the Americas. The Delphi technique was used to determine a consensus as to the degree of importance of each construct in understanding the essential dimensions underpinning addictive behaviours. Expert opinions were canvassed online over three rounds (97% completion rate), with each consecutive round offering feedback for experts to review their opinions. Results: Seven constructs were endorsed by ≥ 80% of experts as ‘primary’ to the understanding of addictive behaviour: five from the Positive Valence System (reward valuation, expectancy, action selection, reward learning, habit); one from the Cognitive Control System (response selection/inhibition); and one expert-initiated construct (compulsivity). These constructs were rated to be related differentially to stages of the addiction cycle, with some linked more closely to addiction onset and others more to chronicity. Experts agreed that these neuropsychological dimensions apply across a range of addictions. Conclusions: The study offers a novel and neuropsychologically informed theoretical framework, as well as a cogent step forward to test transdiagnostic concepts in addiction research, with direct implications for assessment, diagnosis, staging of disorder, and treatment.

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A transdiagnostic dimensional approach towards a neuropsychological assessment for addiction: an international Delphi consensus study

Efficacy, tolerability, and safety of low-dose and high-dose baclofen in the treatment of alcohol dependence: A systematic review and meta-analysis.

Objectives The aim of this review was to explore the notion of alcohol-related presenteeism; that is, whether evidence in the research literature supports an association between employee alcohol consumption and impaired work performance. Design Systematic review of observational studies. Data sources MEDLINE, Web of Science, PsycINFO, CINAHL, AMED, Embase and Swemed+ were searched through October 2018. Reference lists in included studies were hand searched for potential relevant studies. Eligibility criteria We included observational studies, published 1990 or later as full-text empirical articles in peer-reviewed journals in English or a Scandinavian language, containing one or more statistical tests regarding a relationship between a measure of alcohol consumption and a measure of work performance. Data extraction and synthesis Two independent reviewers extracted data. Tested associations between alcohol consumption and work performance within the included studies were quality assessed and analysed with frequency tables, cross-tabulations and χ 2 tests of independence. Results Twenty-six studies were included, containing 132 tested associations. The vast majority of associations (77%) indicated that higher levels of alcohol consumption were associated with higher levels of impaired work performance, and these positive associations were considerably more likely than negative associations to be statistically significant (OR=14.00, phi=0.37, p<0.001). Alcohol exposure measured by hangover episodes and composite instruments were over-represented among significant positive associations of moderate and high quality (15 of 17 associations). Overall, 61% of the associations were characterised by low quality. Conclusions Evidence does provide some support for the notion of alcohol-related presenteeism. However, due to low research quality and lack of longitudinal designs, evidence should be characterised as somewhat inconclusive. More robust and less heterogeneous research is warranted. This review, however, does provide support for targeting alcohol consumption within the frame of workplace interventions aimed at improving employee health and productivity. PROSPERO registration number CRD42017059620.

https://bmjopen.bmj.com/content/bmjopen/9/7/e029184.full.pdf

Association between alcohol consumption and impaired work performance (presenteeism): a systematic review

These practice guidelines for the biological treatment of alcohol use disorders are an update of the first edition, published in 2008, which was developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). For this 2016 revision, we performed a systematic review (MEDLINE/PUBMED database, Cochrane Library) of all available publications pertaining to the biological treatment of alcoholism and extracted data from national guidelines. The Task Force evaluated the identified literature with respect to the strength of evidence for the efficacy of each medication and subsequently categorised it into six levels of evidence (A-F) and five levels of recommendation (1-5). Thus, the current guidelines provide a clinically and scientifically relevant, evidence-based update of our earlier recommendations. These guidelines are intended for use by clinicians and practitioners who evaluate and treat people with alcohol use disorders and are primarily concerned with the biological treatment of adults with such disorders.

Guidelines for biological treatment of substance use and related disorders, part 1: Alcoholism, first revision

AIMS: Alcohol dependence is associated with high rates of co-occurring disorders which impact health-related quality of life (HRQoL) and add to the cost-of-illness. This study investigated the burden of alcohol dependence and associated co-occurring conditions on health and productivity. METHODS: A cross-sectional survey was conducted in eight European countries. Physicians (Psychiatrists and General Practitioners) completed patient record forms, which included assessment of co-occurring conditions, and patients completed matching self-completion forms. Drinking risk level (DRL) was calculated and the relationship between DRL, co-occurring conditions, work productivity, hospitalisations and rehabilitation stays was explored. RESULTS: Data were collected for 2979 alcohol-dependent patients (mean age 48.8 ± 13.6 years; 70% male). In total, 77% of patients suffered from moderate-to-severe co-occurring psychiatric and/or somatic conditions. High DRL was significantly associated with depression, greater work productivity losses, increased hospitalisations and rehabilitation stays. Co-occurring conditions were significantly associated with poorer HRQoL and decreased work productivity, with a statistical trend towards an increased frequency of rehabilitation stays. CONCLUSIONS: Alcohol-dependent patients manifest high rates of co-occurring psychiatric and somatic conditions, which are associated with impaired work productivity and HRQoL. The continued burden of illness observed in these already-diagnosed patients suggests an unmet need in both primary and secondary care. Language: en

/pdf/alcohol-dependence-co-occurring-conditions-and-attributable-2j60nrvss6.pdf

Alcohol Dependence, Co-occurring Conditions and Attributable Burden.

Myasthenia gravis (MG) is a rare, debilitating, chronic disorder caused by the production of pathogenic immunoglobulin G autoantibodies against the neuromuscular junction. A lack of real-world studies in rare diseases reflects a relatively limited understanding of the significant unmet needs and burden of disease for patients. We aimed to provide comprehensive real-world insights into the management and burden of MG from treating physicians in the United States (US).Data were collected using the Adelphi Real World MG Disease Specific Programme™, a point-in-time survey of physicians and their patients with MG, in the US between March and July 2020. Physician-reported clinical data, including demographics, comorbidities, symptoms, disease history, treatments, and healthcare resource utilization, were collected.In total, 456 patient record forms were completed by 78 physicians based in the US. At time of survey completion, patient mean age was 54.5 years. Mean time from symptom onset to diagnosis was 9.0 months (n = 357). Ocular symptoms were reported in 71.7% of patients. General fatigue affected 47.1% of patients and over half of those reported the severity as moderate or severe (59.5%, n = 128). Acetylcholinesterase inhibitors and/or steroids were the most frequently prescribed first-line treatment type among patients receiving treatment at time of survey completion and with moderate-to-severe symptoms (77.9%, n = 159/204). High-dose steroids (n = 14) and intravenous immunoglobulin (n = 13) were the most prescribed acute treatments among those receiving an acute treatment at time of survey completion (n = 36), with symptom exacerbations or myasthenic crises being the most common reasons for acute treatment. On average, 2.5 healthcare professionals were involved in patient management and 5.0 consultations were made per patient over the last 12 months.Our findings indicated that, despite treatment, there is a proportion of patients with MG in the US who had a significant need for improved disease management. 

/pdf/physician-reported-perspectives-on-myasthenia-gravis-in-the-20r4pspa.pdf

Physician-Reported Perspectives on Myasthenia Gravis in the United States: A Real-World Survey


 
 
 Immunoglobulin A nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis worldwide with an estimated annual incidence of 25 cases per million people. Many patients are not diagnosed until they develop kidney dysfunction, such as hematuria and proteinuria. Proteinuria >1g/day is associated with a high risk of progression. The aim of the present study is to describe symptom control and consider treatment satisfaction for patients undergoing treatment for IgAN.
 
 
 
 Data were drawn from the Adelphi IgAN Disease Specific Programme (DSP)™, a point-in-time survey of IgAN-treating nephrologists and their consulting patients conducted in the United States (US), Europe (EU5: France, Germany, Italy, Spain, United Kingdom [UK]), Japan, and China, from June to October 2021. Nephrologists completed structured online patient record forms for successive patients presenting with IgAN including demographics, clinical characteristics and treatment patterns. Patients voluntarily completed questionnaires that corresponded with the nephrologist records, with questions about their IgAN on that day regarding symptoms experienced, disease severity, and treatment satisfaction. Patients who were receiving IgAN treatment at the time of survey are included in the presented analysis.
 
 
 
 The mean (standard deviation [SD]) age of patients (n = 869) was 42 (13.7) years and 57% were male. IgAN symptoms were deemed severe by 10% of patients at the time of survey and 14% before the initiation of their current treatment. Overall, 91% of patients reported having symptoms of IgAN at the time of survey, the most common were: foamy urine, feeling tired or lack of energy, and swelling, with many patients in China reporting hematuria. The top reported most bothersome symptoms were fatigue, swelling, and high blood pressure, with many patients in China also reporting proteinuria. Satisfaction with their current treatment was reported by patients; 61% reported that they were satisfied, 27% said they were neither satisfied or dissatisfied, and 12% said they were dissatisfied with their medication. This dissatisfaction was due to their current medication not working quickly enough (54%, n = 103) or that it had not helped with their IgAN symptoms (45%, n = 103). This was consistent with the physician-reported data; where proteinuria was reported across treatment lines (L), levels remained high amongst patients (mean (SD) proteinuria [g/day] at L1: 2.2 (2.3), n = 629; L2: 1.8 (2.0), n = 257; L3: 1.9 (1.4), n = 95) and estimated glomerular filtration rate (eGFR) continued to fall (mean (SD) eGFR [mL/min/1.73m2] at L1: 77.1 (29.6), n = 615; L2: 72.2 (30.3), n = 246; L3: 66.9 (31.1), n = 96).
 
 
 
 Despite treatment, most patients with IgAN continued to experience symptoms. Many of these symptoms were considered bothersome by patients, including fatigue, swelling and high blood pressure which may have an impact on their everyday lives. These data highlight an unmet need for effective IgAN management and future treatments should aim to target better symptom relief and disease progression.


https://academic.oup.com/ndt/article-pdf/38/Supplement_1/gfad063c_5424/50593337/gfad063c_5424.pdf

#5424 symptom control with currently available immunoglobulin a nephropathy treatment: results from a real-world survey in eight countries

RWD104 Delayed Diagnosis Amongst gMG Patients: Results From a European Real-World Study


 
 
 Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, with an estimated annual incidence of 25 per million. Patients with persistent proteinuria ≥ 1 g/day are at increased risk of disease progression, with 30% or more progressing to kidney failure within 10 years. Hematuria and proteinuria are among the most common clinical manifestations of IgAN. The aim of this analysis was to better understand the clinical characteristics of IgAN patients from Europe, Asia and the USA, at the time of diagnosis.
 
 
 
 A retrospective analysis was conducted using data from the Adelphi IgAN Disease Specific Programme (DSP), a cross-sectional survey of IgAN-treating nephrologists in EU4 (France, Germany, Italy, UK), USA, China and Japan between June and October 2021. Nephrologists completed structured forms administered via online links for successive patients presenting with IgAN in their practice. The forms included demographic and clinical information including signs, symptoms and lab values amongst others.
 
 
 
 A total of 269 nephrologists completed records for 1685 patients in this survey. Mean patient age was 43.3 years, and most were male (58%). The diagnosis was confirmed by biopsy in 86% of the patients. The mean eGFR at diagnosis ranged from 58.1 (median 55.5) in the USA to 78.3 (median 79.0) mL/min/1.73 m2, in China and Japan. Mean proteinuria ranged from 2.7 (median 2.0) in the USA to 3.4 (median 2.1) g/day in EU4 (Table 1). The main clinical signs at diagnosis were proteinuria (75%) and visible hematuria (63%). Edema and fatigue were reported in 38% and 27% of patients; 10% and 9% of patients reported appetite loss and sleep problems. A sizable proportion of patients (31%) also experienced pain in various parts of the body.
 
 
 
 This comprehensive study of IgAN patients across varied geographies presents evidence that patients experience substantial symptomatic and clinical burden at diagnosis, irrespective of the region. The relatively high levels of proteinuria and low eGFR levels, especially in the USA, suggest that the disease is often severe and advanced by the time of diagnosis. Facilitating early diagnosis of IgAN—perhaps through better recognition of clinical signs and symptoms—could be beneficial in optimizing early treatment and preventing disease progression.


J. DeCourcy

Papers

Alcohol Dependence, Co-occurring Conditions and Attributable Burden.

Physician-Reported Perspectives on Myasthenia Gravis in the United States: A Real-World Survey

#5424 symptom control with currently available immunoglobulin a nephropathy treatment: results from a real-world survey in eight countries

RWD104 Delayed Diagnosis Amongst gMG Patients: Results From a European Real-World Study

MO233: Real-World Signs and Symptoms at Diagnosis in Patients With IGA Nephropathy