VA Great Lakes Health Care System

The aim was to describe the discovery of niacin, biotin, and pantothenic acid. By the 1920s, it became apparent that 'water-soluble B' (vitamin B) is not a single substance. In particular, fresh yeast could prevent both beriberi and pellagra, but the 'antipolyneuritis factor' in yeast is thermolabile, while the antipellagra factor is heat stable, suggesting that there are at least two water-soluble vitamins. Various terms were proposed for these water-soluble factors, but vitamins B(1) and B(2) were most widely used to refer to the thermolabile and heat-stable factors, respectively. Although vitamin B(1) proved to be a single chemical substance (thiamin), vitamin B(2) was ultimately found to be a complex of several chemically unrelated heat-stable factors, including niacin, biotin, and pantothenic acid. Recognition that niacin is a vitamin in the early 20th century resulted from efforts to understand and treat a widespread human disease - pellagra. American epidemiologist and US Public Health Service officer Joseph Goldberger (1874-1929) had been instrumental to elucidating the nutritional basis for pellagra. Goldberger conducted a classic series of observational and experimental studies in humans, combined with an extensive series of experiments with an animal model of the condition (black tongue in dogs). In contrast, recognition that biotin and pantothenic acid are vitamins occurred somewhat later as a result of efforts to understand microbial growth factors. The metabolic roles in humans of these latter substances were ultimately elucidated by human experiments using particular toxins and by studies of rare inborn errors of metabolism. Symptomatic nutritional deficiencies of biotin and pantothenic acid were, and continue to be, rare.

BACKGROUND: Quality-of-life considerations are important in metastatic prostate cancer. In this study, we interviewed physicians and patients about their assessments and expectations on quality of life as metastatic prostate cancer progresses. METHODS: Physicians and patients made utility assessments of three hypothetical health states for metastatic disease using the time trade-off technique. Scores were bounded on a scale from 0.0 (death) to 1.0 (perfect health). RESULTS: Patients rated each of the health states as less desirable than the physicians. CONCLUSIONS: Physicians and patients differ in their perspectives on expected quality of life with metastatic prostate cancer. Our results emphasize the need to assess patients' utilities directly.

Considerable morbidity, mortality, and economic costs result during remission induction therapy for elderly patients with acute myeloid leukemia (AML). In this study, the economic costs of adjunct granulocyte colony stimulating factor (G-CSF) are estimated for AML patients > 55 years of age who received induction chemotherapy on a recently completed Southwest Oncology Group study (SWOG). Clinical data were based on Phase III trial information from 207 AML patients who were randomized to receive either placebo or G-CSF post-induction therapy. Analyses were conducted using a decision analytic model with the primary source of clinical event probabilities based on in-hospital care with or without an active infection requiring intravenous antibiotics. Estimates of average daily costs of care with and without an infection were imputed from a previously reported economic model of a similar population. When compared to AML patients who received placebo, patients who received G-CSF had significantly fewer days on intravenous antibiotics (median 22 vs. 26, p = 0.05), whereas overall duration of hospitalization did not differ (median 29 days). The median cost per day with an active infection that required intravenous antibiotics was estimated to be $1742, whereas the median cost per day without an active infection was estimated to be $1467. Overall, costs were $49,693 for the placebo group and $50,593 for the G-CSF patients. G-CSF during induction chemotherapy for elderly patients with AML had some clinical benefits, but it did not reduce the duration of hospitalization, prolong survival, or reduce the overall cost of supportive care. Whether the benefits of G-CSF therapy justify its use in individual patients with acute leukemia for the present remains a matter of clinical judgment.

PURPOSE: The methods and processes utilized to deploy the Pharmacists Achieve Results with Medications Documentation (PhARMD) Project intervention template across the largest integrated healthcare system in the United States are described. SUMMARY: The PhARMD Project team at the Department of Veterans Affairs (VA) designed, developed, and deployed a standardized template within VA's electronic health record (EHR) that allows the clinical pharmacy specialist (CPS) to efficiently document select interventions made during patient care encounters that specifically contribute to the overall care provided and patient outcomes. The template is completed by the CPSs as part of progress note documentation within the EHR. Using point-and-click functionality, a CPS selects the check boxes corresponding to specific interventions made during that patient care encounter. This improves workflow and negates the need to document interventions in a separate software system, streamlining documentation. The implementation and use of the PhARMD template at each VA facility are voluntary. From October 1, 2016, to September 30, 2017, 4,728 CPSs documented 3,805,323 interventions during 2,384,771 patient care encounters. These interventions were documented across 592,126 unique patients, with a mean of 6.4 interventions per patient during this period. Most interventions (95%) were performed by CPSs functioning as advanced practice providers and with autonomous prescriptive authority authorized under their scope of practice. CONCLUSION: The PhARMD template demonstrated that the capture of clinical pharmacy interventions and outcomes can be achieved across a large integrated healthcare system by thousands of CPSs in numerous practice settings.

Patient-specific (endogenous) and population-specific (exogenous) risk factor analysis is identifying novel physical and chemical exposures which might be time-linked to the development of amyotrophic lateral sclerosis (ALS) and other motor neuron diseases. Electric injury in a number of case-control studies as well as prolonged exposure at work and home to agricultural chemicals in pesticides and herbicides have been identified as significant risk factors. Heavy exercise, trauma with or without bone fractures and heavy metal exposure at work have not been confirmed as risk factors. Surprisingly, occupation as a pilot or navigator has recently been identified as a potential risk factor, which will need to be confirmed. The introduction of international patient registries in North America (ALS CARE) and in Europe (ALS HPS) will facilitate future studies on the prognosis of ALS, adherence to standards of practice, quality of life and patient outcome studies. An initial survey of the ALS Patient Care Database in January 1999, when nearly 1800 patients had been entered across North America, indicated the median time from ALS onset to diagnosis is 14 months when no second opinion is requested, 12 months if the patient requests a second opinion and 10 months when the neurologist requests an additional opinion. No significant difference was found in the median time to diagnose sporadic ALS patients compared with familial ALS patients.

INTRODUCTION: We evaluated the coronavirus disease 2019 (COVID-19) pandemic's impact on hepatocellular carcinoma (HCC) screening and diagnosis among patients with cirrhosis in the Veterans Health Administration. METHODS: Rates and predictors of screening and diagnosis were reviewed September 1, 2019-February 29, 2020 ("pre-COVID-19," N = 94,612) and April 1, 2020-September 30, 2020 ("post-COVID-19," N = 88,073). RESULTS: Screening and diagnosis rates declined by 44% and 13%, respectively, after the COVID-19 pandemic. Screening declined irrespective of liver disease severity, but diagnosis declined only in Model for End Stage Liver Disease-Sodium score <20 or Fibrosis-4 score <3.25. Fibrosis-4 score ≥3.25 and HCC risk ≥1.5%/year strongly predicted HCC diagnosis but only moderately predicted receipt of screening. DISCUSSION: Screening and diagnosis rates declined after the COVID-19 pandemic. Prioritizing screening for patients at greatest risk for HCC may reduce delays in diagnosis.

Motor fatigue, during 30 seconds of maximum voluntary isometric contraction (MVIC) was simultaneously evaluated by the decline in mechanical force output, and from the compression in the power spectrum obtained from surface electromyogram (sEMG). Measurements were performed in patients diagnosed with amyotrophic lateral sclerosis (ALS) and normal control (NC) in two muscle groups, elbow flexors (EF) and ankle dorsiflexors (DF). The decline in force output, as a manifestation of mechanical fatigue, was digitally calculated online by partitioning the force versus time curve to determine the percent of MVIC reduction over a 30 sec period and was expressed as force fatigue index (FFI). The compression in the sEMG power spectrum, as a manifestation of myoelectrical fatigue, was tracked by calculating the median frequency shift (MFS) from the first 5 sec to the last 5 sec of the 30 sec MVIC using digital Fast Fourier Transformation. In ALS patients, the significantly higher reduction in mechanical force output during the 30 sec MVIC (higher FFI) was accompanied with significantly less compression in the sEMG power spectrum (less MFS) as compared to NC (P < or =0.005) in the two muscle groups. This dissociation between the mechanical and myoelectrical manifestation of muscle fatigue in ALS indicates that a reduction in muscle fiber conduction velocity (MFCV) may be a contributing peripheral factor in the pathogenesis of muscle fatigue in ALS. Alterations in motor unit functionality, especially in type II fast motor unit muscle fibers, and structural damage in denervated muscle fibers may contribute to the lower MFCV during motor fatigue in ALS patients.

After implementing a successful hepatitis C elimination program, the Veterans Health Administration’s (VHA) Hepatic Innovation Team (HIT) Collaborative pivoted to focus on improving cirrhosis care. This national program developed teams of providers across the country and engaged them in using systems redesign methods and population health approaches to improve care. The HIT Collaborative developed an Advanced Liver Disease (ALD) Dashboard to identify Veterans with cirrhosis who were due for surveillance for hepatocellular carcinoma (HCC) and other liver care, promoted the use of an HCC Clinical Reminder in the electronic health record, and provided training and networking opportunities. This evaluation aimed to describe the VHA’s approach to improving cirrhosis care and identify the facility factors and HIT activities associated with HCC surveillance rates, using a quasi-experimental design. Across all VHA facilities, as the HIT focused on cirrhosis between 2018–2019, HCC surveillance rates increased from 46% (IQR 37–53%) to 51% (IQR 42–60%, p &lt; 0.001). The median HCC surveillance rate was 57% in facilities with high ALD Dashboard utilization compared with 45% in facilities with lower utilization (p &lt; 0.001) and 58% in facilities using the HCC Clinical Reminder compared with 47% in facilities not using this tool (p &lt; 0.001) in FY19. Increased use of the ALD Dashboard and adoption of the HCC Clinical Reminder were independently, significantly associated with HCC surveillance rates in multivariate models, controlling for other facility characteristics. In conclusion, the VHA’s HIT Collaborative is a national healthcare initiative associated with significant improvement in HCC surveillance rates.

Successful management of patients with diabetes requires individualizing A1C and treatment goals in conjunction with identifying and managing hypoglycemia risk. This article describes the Veterans Health Administration's Choosing Wisely Hypoglycemia Safety Initiative (CW-HSI), a voluntary program that aims to reduce the occurrence of hypoglycemia through shared decision-making about deintensifying diabetes treatment in a dynamic cohort of patients identified as being at high risk for hypoglycemia and potentially overtreated. The CW-HSI incorporates education for patients and clinicians, as well as clinical decision support tools, and has shown decreases in the proportions of high-risk patients potentially overtreated and impacts on the frequency of reported hypoglycemia.

Importance: Type 2 diabetes is a prevalent and morbid condition. Poor engagement with self-management can contribute to diabetes-associated distress and hinder diabetes control. Objective: To evaluate the implementation and effectiveness of Empowering Patients in Chronic Care (EPICC), an evidence-based intervention to improve diabetes-associated distress and hemoglobin A1c (HbA1c) levels after the intervention and after 6-month maintenance. Design, Setting, and Participants: This hybrid (implementation-effectiveness) randomized clinical trial was performed in Veterans Affairs clinics across Illinois, Indiana, and Texas from July 1, 2015, to June 30, 2017. Participants included adults with uncontrolled type 2 diabetes (HbA1c level >8.0%) who received primary care during the prior year in participating clinics. Data collection was completed on November 30, 2018, and data analysis was completed on June 30, 2020. All analyses were based on intention to treat. Interventions: Participants in EPICC attended 6 group sessions based on a collaborative goal-setting theory led by health care professionals. Clinicians conducted individual motivational interviewing sessions after each group. Usual care was enhanced (EUC) with diabetes education. Main Outcomes and Measures: The primary outcome consisted of changes in HbA1c levels after the intervention and during maintenance. Secondary outcomes included the Diabetes Distress Scale (DDS), Morisky Medication Adherence Scale, and Lorig Self-efficacy Scale. Secondary implementation outcomes included reach, adoption, and implementation (number of sessions attended per patient). Results: A total of 280 participants with type 2 diabetes (mean [SD] age, 67.2 [8.4] years; 264 men [94.3]; 134 non-Hispanic White individuals [47.9%]) were equally randomized to EPICC or EUC. Participants receiving EPICC had significant postintervention improvements in HbA1c levels (F1, 252 = 9.12, Cohen d = 0.36 [95% CI, 0.12-0.59]; P = .003) and DDS (F1, 245 = 9.06, Cohen d = 0.37 [95% CI, 0.13-0.60]; P = .003) compared with EUC. During maintenance, differences between the EUC and EPICC groups remained significant for DDS score (F1, 245 = 8.94, Cohen d = 0.36 [95% CI, 0.12-0.59]; P = .003) but not for HbA1c levels (F1, 252 = 0.29, Cohen d = 0.06 [95% CI, -0.17 to 0.30]; P = .60). Improvements in DDS scores were modest. There were no differences between EPICC and EUC in improvements after intervention or maintenance for either adherence or self-efficacy. Among all 4002 eligible patients, 280 (7.0%) enrolled in the study (reach). Each clinic conducted all planned EPICC sessions and cohorts (100% adoption). The EPICC group participants attended a mean (SD) of 4.34 (1.98) sessions, with 54 (38.6%) receiving all 6 sessions. Conclusions and Relevance: A patient-empowerment approach using longitudinal collaborative goal setting and motivational interviewing is feasible in primary care. Improvements in HbA1c levels after the intervention were not sustained after maintenance. Modest improvements in diabetes-associated distress after the intervention were sustained after maintenance. Innovations to expand reach (eg, telemedicine-enabled shared appointments) and sustainability are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT01876485.

Screening for prostate cancer is controversial. Treatment choices for verified cases of prostate cancer provide another level of controversy as to which treatment, if any, is best. This controversy and uncertainty create a dilemma for the newly diagnosed patient. A great deal of information must be assimilated if the patient is to make an informed decision to pursue any treatment A metropolitan Veterans Affairs hospital has created a model to assist the newly diagnosed prostate cancer patient in acquiring this information, while helping him through the decision tree. This model, which utilizes the skills of the advanced practice nurse, strives toward maintaining the patient's autonomy while clarifying these uncertainties, introduces the concept of shared decision making, and provides a potential support group.

IMPORTANCE: Understanding the frequency and correlates of redundant lipid testing could identify areas for quality improvement initiatives aimed at improving the efficiency of cholesterol care in patients with coronary heart disease (CHD). OBJECTIVE: To determine the frequency and correlates of repeat lipid testing in patients with CHD who attained low-density lipoprotein cholesterol (LDL-C) goals and received no treatment intensification. DESIGN, SETTING, AND PARTICIPANTS: We assessed the proportion of patients with LDL-C levels of less than 100 mg/dL and no intensification of lipid-lowering therapy who underwent repeat lipid testing during an 11-month follow-up period. We performed logistic regression analyses to evaluate facility, provider, and patient characteristics associated with repeat testing. In total, we analyzed 35,191 patients with CHD in a Veterans Affairs network of 7 medical centers with associated community-based outpatient clinics. MAIN OUTCOMES AND MEASURES: Frequency and correlates of repeat lipid testing in patients having CHD with LDL-C levels of less than 100 mg/dL and no further treatment intensification with lipid-lowering therapies. RESULTS: Of 27,947 patients with LDL-C levels of less than 100 mg/dL, 9200 (32.9%) had additional lipid assessments without treatment intensification during the following 11 months (12 ,686 total additional panels; mean, 1.38 additional panel per patient). Adjusting for facility-level clustering, patients with a history of diabetes mellitus (odds ratio [OR], 1.16; 95% CI, 1.10-1.22), a history of hypertension (OR, 1.21; 95% CI, 1.13-1.30), higher illness burden (OR, 1.39; 95% CI, 1.23-1.57), and more frequent primary care visits (OR, 1.32; 95% CI, 1.25-1.39) were more likely to undergo repeat testing, whereas patients receiving care at a teaching facility (OR, 0.74; 95% CI, 0.69-0.80) or from a physician provider (OR, 0.93; 95% CI, 0.88-0.98) and those with a medication possession ratio of 0.8 or higher (OR, 0.75; 95% CI, 0.71-0.80) were less likely to undergo repeat testing. Among 13,114 patients who met the optional LDL-C target level of less than 70 mg/dL, repeat lipid testing was performed in 8177 (62.4% of those with LDL-C levels of <70 mg/dL) during 11 follow-up months. CONCLUSIONS AND RELEVANCE: One-third of patients having CHD with LDL-C levels at goal underwent repeat lipid panels. Our results highlight areas for quality improvement initiatives to reduce redundant lipid testing. These efforts would be more important if the forthcoming cholesterol guidelines adopt a medication dose-based approach in place of the current treat-to-target approach.

OBJECTIVE: Describe the influence of S. Weir Mitchell's (1829-1914) work, and in particular his ideas on causalgia, on European physicians who treated peripheral nerve injuries during World War I (WWI). BACKGROUND: During the American Civil War (1861-1865), Mitchell studied peripheral nerve injuries with colleagues George Read Morehouse and William Williams Keen. Three monographs resulted from this work. All were important landmarks in the evolution of knowledge of peripheral nerve injuries. A subsequent occasion to improve knowledge came in WWI. METHODS: The most important European monographs or series on peripheral nerve injuries from WWI were studied with special interest in references to causalgia and Mitchell's works on peripheral nerve injuries. We included works by Tinel, Athanassio-Benisty, Purves-Stewart & Evans and Carter, Foerster and Oppenheim. RESULTS: Tinel and Athanassio-Benisty provided the most detailed information on peripheral nerve injuries and causalgia and often referred to Mitchell. Both mentioned a possible sympathetic origin. Athanassio-Benisty described tremor and other movement disorders in relation to causalgia. Purves-Stewart and Evans mentioned Mitchell and causalgia in the second edition of their book. They advocated the term "thermalgia." Carter, who had access to data of many cases, concentrated his work on causalgia, referring to Mitchell. Foerster provided data of a great number of peripheral nerve injuries, but did not refer to Mitchell. However, he described the symptoms of causalgia cursorily, applying the term Reflexschmerz (reflexpain). Oppenheim was particularly interested in muscle innervation and referred to Mitchell with respect to hypertrichosis and glossy skin. Oppenheim did not use the term causalgia, although he described the syndrome in some of his patients. It wasn't until around 1920 that German physicians devoted significant attention to causalgia and began using the term. CONCLUSION: Knowledge of peripheral nerve injuries was greatly advanced during and after WWI. Mitchell's influence was mainly found in the French medical literature, where his findings provided the basis for further research on the origin of causalgia. In England, Mitchell and causalgia were also well-known. We found evidence to suggest that some of the English knowledge came from French physicians. German physicians described the symptoms of causalgia, but did not use the term, nor did they refer to Mitchell. This variation in Mitchell's influence by country probably reflects the fact that Mitchell's Injuries of nerves and their consequences was translated into French but not German.

As part of the International Congress of the Movement Disorder Society in Barcelona, June 2000, the society sponsored an exhibit devoted to History of Movement Disorders. With the help of numerous members of the MDS and loans from libraries, private collections, and laboratories, the authors developed a series of explanatory panels, accompanied by photographs, diagrams and original artifacts that traced the early history of movement disorders from several perspectives. These materials have been adapted for publication in Movement Disorders and are presented in an ongoing series. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

This project sought to identify characteristics and lasting contributions of 19th-century members of the American Neurological Association (ANA). Members were categorized by elite status, citation frequency, founder or charter member, elected to honorary membership, published a monograph on a neurologic or psychiatric topic, born in the United States or Canada, and received any medical training outside the United States or Canada. Citations to 19th-century publications in Science Citation Index were analyzed for the period 1974-1995. ANA membership was restrictive, but membership nevertheless increased dramatically in the first 25 years from its founding in 1875. 19th-century ANA members frequently served in a leadership capacity within the organization, published neurologic or psychiatric monographs, and received medical training abroad. Highly cited members were more likely to be instrumental in founding and developing the organization, and were likely to be recognized by their contemporaries as eminent. 19th-century ANA members made significant and lasting contributions in many areas of neurology and psychiatry. Articles with lasting relevance were early descriptions, points of comparison, and controversial articles.

BACKGROUND: Complex regional pain syndrome (CRPS) type 1 is a disorder of the extremities characterized by pain, edema, limited range of motion, integument changes, and vasomotor instability often after an inciting event. In the pediatric population, CRPS may be misdiagnosed, or missed entirely, as CRPS literature for this patient population is lacking. METHODS: Twenty-seven pediatric patient medical records with the diagnosis of CRPS type 1 from the institutional and private practices of the principal investigator (E.J.H.) were reviewed for demographics, inciting event, lower-extremity clinical examination, ancillary testing, previous treatments, time to diagnosis, treatment after diagnosis, and time to resolution of symptoms. RESULTS: Females composed 85.2% of the patient population (n = 23) (mean age of females, 11.11 years). An inciting event preceded pain in 74.1% of patients (n = 20). On physical examination, more than 50% of patients were identified as having changes in skin color and temperature, edema to the affected lower extremity, painful or decreased range of motion in affected joints, and intact lower-extremity motor function. The average time to resolution of symptoms was 6.8 weeks for the entire population. CONCLUSIONS: Diagnosis of CRPS type 1 should be considered in a preadolescent female complaining of pain out of proportion after an inciting event with a physical examination demonstrating change in skin color, decrease in skin temperature, edema, and painful or diminished range of motion in affected joints. Prompt diagnosis can decrease the time to resolution of symptoms.

The 2nd Consensus Conference (Versailles) recommended that an ALS knowledge-base for initial healthcare providers, diagnosing neurologists and confirming neurologists should be defined to include a simplified version of diagnostic criteria less formal than the World Federation of Neurology El Escorial Revisted Criteria ('ALS diagnosis - An algorithm'), a set of rules concerning red flags which should increase the suspicion of ALS as the diagnosis and minimize the time between suspicion and referral for confirmation of diagnosis ('ALS axioms of referral'), as well as a site of symptom onset-specific checklist of minimal clinical examination, neuroimaging, electrodiagnostic, pulmonary function and laboratory test information required to confirm the diagnosis of ALS ('Versailles minimal dataset'). Although introductory discussions addressed the advantages and disadvantages of earlier diagnosis, false-positive or false-negative diagnosis, the frequency of follow-up and what potential biological markers to be followed, these issues will have to be further evaluated at future consensus conferences.

<h3>Abstract</h3> The origin and evolution of genes that have common base pairs (overlapping genes) are of particular interest due to their influencing each other. Especially intriguing are gene pairs with long overlaps. In prokaryotes, co-directional overlaps longer than 60 bp were shown to be nonexistent except for some instances. A few antiparallel prokaryotic genes with long overlaps were described in the literature. We have analyzed putative long antiparallel overlapping genes to determine whether open reading frames (ORFs) located opposite to genes (antiparallel ORFs) can be protein-coding genes. We have confirmed that long antiparallel ORFs (AORFs) are observed reliably to be more frequent than expected. There are 10 472 000 AORFs in 929 analyzed genomes with overlap length more than 180 bp. Stop codons on the opposite to the coding strand are avoided in 2 898 cases with Benjamini-Hochberg threshold 0.01. Using Ka/Ks ratio calculations, we have revealed that long AORFs do not affect the type of selection acting on genes in a vast majority of cases. This observation indicates that long AORFs translations commonly are not under negative selection. The demonstrative example is 282 longer than 1 800 bp AORFs found opposite to extremely conserved <i>dnaK</i> genes. Translations of these AORFs were annotated “glutamate dehydrogenases” and were included into Pfam database as third protein family of glutamate dehydrogenases, PF10712. Ka/Ks analysis has demonstrated that if these translations correspond to proteins, they are not subjected by negative selection while <i>dnaK</i> genes are under strong stabilizing selection. Moreover, we have found other arguments against the hypothesis that these AORFs encode essential proteins, proteins indispensable for cellular machinery. However, some AORFs, in particular, <i>dnaK</i> related, have been found slightly resisting to synonymous changes in genes. It indicates the possibility of their translation. We speculate that translations of certain AORFs might have a functional role other than encoding essential proteins. Essential genes are unlikely to be encoded by AORFs in prokaryotic genomes. Nevertheless, some AORFs might have biological significance associated with their translations. <h3>Author summary</h3> Genes that have common base pairs are called overlapping genes. We have examined the most intriguing case: if gene pairs encoded on opposite DNA strands exist in prokaryotes. An intersection length threshold 180 bp has been used. A few such pairs of genes were experimentally confirmed. We have detected all long antiparallel ORFs in 929 prokaryotic genomes and have found that the number of open reading frames, located opposite to annotated genes, is much more than expected according to statistical model. We have developed a measure of stop codon avoidance on the opposite strand. The lengths of found antiparallel ORFs with stop codon avoidance are typical for prokaryotic genes. Comparative genomics analysis shows that long antiparallel ORFs (AORFs) are unlikely to be essential protein-coding genes. We have analyzed distributions of features typical for essential proteins among formal translations of all long AORFs: prevalence of negative selection, non-uniformity of a conserved positions distribution in a multiple alignment of homologous proteins, the character of homologs distribution in phylogenetic tree of prokaryotes. All of them have not been observed for the majority of long AORFs. Particularly, the same results have been obtained for some experimentally confirmed AOGs. Thus, pairs of antiparallel overlapping essential genes are unlikely to exist. On the other hand, some antiparallel ORFs affect the evolution of genes opposite that they are located. Consequently, translations of some antiparallel ORFs might have yet unknown biological significance.

INTRODUCTION: We aimed to assess rates and predictors of hepatocellular carcinoma (HCC) screening among patients with cirrhosis. METHODS: We reviewed electronic health records of 11,361 patients with cirrhosis from 11 U.S. Veterans Health Administration facilities for receipt of HCC screening in the 6 months preceding October 1, 2019. RESULTS: Nearly half of the cohort (46%) received HCC screening over a 6-month period. Screening rates and modalities (ultrasound, computed tomography, magnetic resonance imaging, serum alpha fetoprotein) varied by facility. Screening was associated with race/ethnicity, body mass index ≥ 25, cirrhosis etiology, thrombocytopenia, Fibrosis-4 ≥ 3.25, and lower Model for End-Stage Liver Disease-Sodium. DISCUSSION: HCC screening rates varied by facility. Higher risk patients were more likely to receive screening.

BACKGROUND: Injection drug use (IDU) can increase mortality and morbidity. Therefore, identifying IDU early and initiating harm reduction interventions can benefit individuals at risk. However, extracting IDU behaviors from patients' electronic health records (EHR) is difficult because there is no other structured data available, such as International Classification of Disease (ICD) codes, and IDU is most often documented in unstructured free-text clinical notes. Although natural language processing can efficiently extract this information from unstructured data, there are no validated tools. METHODS: To address this gap in clinical information, we design a question-answering (QA) framework to extract information on IDU from clinical notes for use in clinical operations. Our framework involves two main steps: (1) generating a gold-standard QA dataset and (2) developing and testing the QA model. We use 2323 clinical notes of 1145 patients curated from the US Department of Veterans Affairs (VA) Corporate Data Warehouse to construct the gold-standard dataset for developing and evaluating the QA model. We also demonstrate the QA model's ability to extract IDU-related information from temporally out-of-distribution data. RESULTS: Here, we show that for a strict match between gold-standard and predicted answers, the QA model achieves a 51.65% F1 score. For a relaxed match between the gold-standard and predicted answers, the QA model obtains a 78.03% F1 score, along with 85.38% Precision and 79.02% Recall scores. Moreover, the QA model demonstrates consistent performance when subjected to temporally out-of-distribution data. CONCLUSIONS: Our study introduces a QA framework designed to extract IDU information from clinical notes, aiming to enhance the accurate and efficient detection of people who inject drugs, extract relevant information, and ultimately facilitate informed patient care.