Predictions of Colloidal Molecular Aggregation Using AI/ML Models.

To facilitate the triage of hits from small molecule screens, we have used various AI/ML techniques and experimentally observed data sets to build models aimed at predicting colloidal aggregation of small organic molecules in aqueous solution. We have found that Naïve Bayesian and deep neural networks outperform logistic regression, recursive partitioning tree, support vector machine, and random forest techniques by having the lowest balanced error rate (BER) for the test set. Derived predictive classification models consistently and successfully discriminated aggregator molecules from nonaggregator hits. An analysis of molecular descriptors in favor of colloidal aggregation confirms previous observations (hydrophobicity, molecular weight, and solubility) in addition to undescribed molecular descriptors such as the fraction of sp3 carbon atoms (Fsp3), and electrotopological state of hydroxyl groups (ES_Sum_sOH). Naïve Bayesian modeling and scaffold tree analysis have revealed chemical features/scaffolds contributing the most to colloidal aggregation and nonaggregation, respectively. These results highlight the importance of scaffolds with high Fsp3 values in promoting nonaggregation. Matched molecular pair analysis (MMPA) has also deciphered context-dependent substitutions, which can be used to design nonaggregator molecules. We found that most matched molecular pairs have a neutral effect on aggregation propensity. We have prospectively applied our predictive models to assist in chemical library triage for optimal plate selection diversity and purchase for high throughput screening (HTS) in drug discovery projects.

Treatment exit options for non-infectious uveitis registry: participant characteristics at 3 years.

PURPOSE: The Treatment exit Options For non-infectious Uveitis (TOFU) registry documents disease courses for non-anterior non-infectious uveitis entities with and without treatment to generate more evidence for clinical management recommendations including treatment exit strategies. In this article, we present the participants' baseline characteristics after the first 3 years. METHODS: TOFU is an observational, prospective registry and recruits patients ≥18 years of age with non-anterior non-infectious uveitis with or without a history of previous disease-modifying antirheumatic drugs (DMARDs) treatment. The data are collected in the electronic data capture software REDCap and include ophthalmological and general medical history as well as clinical findings. RESULTS: Between 24.10.2019 and 27.12.2022, 628 patients were enrolled at 25 clinical sites in Germany and Austria. Patients with intermediate uveitis were most frequently included (n=252; 40.1%) followed by posterior uveitis (181; 28.8%), panuveitis (n=154; 24.5%) and retinal vasculitis (n=41, 6.5%). At baseline, 39.6% were treated with systemic corticosteroids, 22.3% with conventional synthetic (cs) DMARDs, 20.5% with biological (b) DMARDs and 3.6% with other systemic treatments. Average best corrected visual acuity (BCVA) was 0.69 decimal. Patients with panuveitis had the worst BCVA with 0.63 decimal. Overall, only 8 patients (1.3%) suffered from severe visual impairment. CONCLUSIONS: Less than half of participants required DMARD treatment at baseline, with csDMARDs used more frequently than bDMARDs. The presence of severe visual impairment was low, mostly affecting patients with panuveitis. These findings are in line with comparable monocentric cross-sectional studies of tertiary uveitis centres in Germany and will allow us to generate generalisable evidence in TOFU.

HealthCall: Smartphone Enhancement of Brief Interventions to Improve HIV Medication Adherence Among Patients in HIV Care.

Heavy drinking among people living with HIV (PLWH) reduces ART adherence and worsens health outcomes. Lengthy interventions are not feasible in most HIV care settings, and patients infrequently follow referrals to outside treatment. Utilizing visual and video features of smartphone technology, we developed HealthCall as an electronic means of increasing patient involvement in a brief intervention to reduce drinking and improve ART adherence. The objective of the current study is to evaluate the efficacy of HealthCall to improve ART adherence among PLWH who drink heavily when paired with two brief interventions: the National Institute on Alcoholism and Alcohol Abuse (NIAAA) Clinician's Guide (CG) or Motivational Interviewing (MI). Therefore, we conducted a 1:1:1 randomized trial among 114 participants with alcohol dependence at a large urban HIV clinic. Participants were randomized to one of three groups: (1) CG only (n = 37), (2) CG and HealthCall (n = 38), or (3) MI and HealthCall (n = 39). Baseline interventions targeting drinking reduction and ART adherence were ~ 25 min, with brief (10-15 min) booster sessions at 30 and 60 days. The outcome was ART adherence assessed using unannounced phone pill-count method (possible adherence scores: 0-100%) at 30-day, 60-day, 3, 6, and 12 months. Analyses were conducted using generalized linear mixed models with pre-planned contrasts. Of the 114 enrolled patients, 58% were male, 75% identified as Black/African American, 28% were Hispanic, and 62% had less than a high school education. The mean age was 47.5 years (standard deviation [SD] 10 years) and the mean number of years since they were diagnosed with HIV was 18.6 (SD 7.6). Participants assigned to HealthCall to extend the CG had increased levels of ART adherence at 60-day and 6-month follow-up (compared to CG only), although there was no statistically significant difference by 12-month follow-up. Participants who were assigned to HealthCall to extend the MI never had statistically significant higher levels of ART adherence. These results suggest that the use of a smartphone app can be used to initially extend the reach of a brief drinking intervention to improve ART adherence over a short period of time; however, sustained long-term improvements in ART adherence after intervention activity ends remains a challenge.

Social and economic determinants of drug overdose deaths: a systematic review of spatial relationships.

PURPOSE: To synthesize the available evidence on the extent to which area-level socioeconomic conditions are associated with drug overdose deaths in the United States. METHODS: We performed a systematic review (in MEDLINE, EMBASE, PsychINFO, Web of Science, EconLit) for papers published prior to July 2022. Eligible studies quantitatively estimated the association between an area-level measure of socioeconomic conditions and drug overdose deaths in the US, and were published in English. We assessed study quality using the Effective Public Health Practice Project Quality Assessment Tool. The protocol was preregistered at Prospero (CRD42019121317). RESULTS: We identified 28 studies that estimated area-level effects of socioeconomic conditions on drug overdose deaths in the US. Studies were scored as having moderate to serious risk of bias attributed to both confounding and in analysis. Socioeconomic conditions and drug overdose death rates were moderately associated, and this was a consistent finding across a large number of measures and differences in study designs (e.g., cross-sectional versus longitudinal), years of data analyzed, and primary unit of analysis (e.g., ZIP code, county, state). CONCLUSIONS: This review highlights the evidence for area-level socioeconomic conditions are an important factor underlying the geospatial distribution of drug overdose deaths in the US and the need to understand the mechanisms underlying these associations to inform future policy recommendations. The current evidence base suggests that, at least in the United States, employment, income, and poverty interventions may be effective targets for preventing drug overdose mortality rates.

Knowledge about age-related eye diseases in the general population in Germany.

BACKGROUND: With a rising prevalence of age-related eye diseases, prevention and early diagnosis of these conditions are key goals of public eye health. Disease-related knowledge in the general public supports these goals but there is little data available. Thus, we have assessed knowledge of cataract, glaucoma, age-related macular degeneration (AMD) and diabetic eye disease in the German adult general population in a cross-sectional study and identified target groups for health education interventions. METHODS: Knowledge assessment content was identified based on a literature review, expert input, and a list of items was generated after a qualitative selection process. The resulting 16-item instrument (4 items per condition) was administered to 1,008 participants from a survey panel, demographically representative of the adult German population. Test properties were evaluated based on a Rasch model and multiple correspondence analysis (MCA). Binary-logistic regression analysis was performed to investigate associations with age, sex, education level, employment status, marital status, income, reported health status, visual difficulties, and recent general practitioner (GP) and ophthalmologist consultations. RESULTS: Replies were correct for a median of 9 out of 16 (range 2 - 16) items, which differed between conditions (p < 0.0001). Most responses were correct for cataract items (median: 3 / 4) and least were correct for AMD items (median: 2 / 4). 27%, 9%, 1% and 19% of respondents replied correctly to all cataract, glaucoma, AMD and diabetic eye disease-related items, respectively. Rasch analysis suggested an adequate targeting of items and in MCA, no evidence of multidimensionality was present. Older age, being retired, decreased general health and recent GP or ophthalmology consultations were significantly associated with more knowledge about common eye conditions (p ≤ 0.005). GP or ophthalmology consultations remained significant in a multivariable model (p ≤ 0.011). CONCLUSIONS: Knowledge gaps regarding eye health are considerable in the German general population and should therefore be addressed in educational interventions targeting the public. Special attention when designing such campaigns needs to be paid to infrequent users of the healthcare system. Knowledge of AMD seems to be poorer compared to other eye conditions.

Lymph node metastases and recurrence in pT1 colorectal cancer: Prediction with the International Budding Consortium Score-A retrospective, multi-centric study.

BACKGROUND: The International Collaboration on Cancer Reporting proposes histological tumour type, lymphovascular invasion, tumour grade, perineural invasion, extent, and dimensions of invasion as risk factors for lymph node metastases and tumour progression in completely endoscopically resected pT1 colorectal cancer (CRC). OBJECTIVE: The aim of the study was to propose a predictive and reliable score to optimise the clinical management of endoscopically resected pT1 CRC patients. METHODS: This multi-centric, retrospective International Budding Consortium (IBC) study included an international pT1 CRC cohort of 565 patients. All cases were reviewed by eight expert gastrointestinal pathologists. All risk factors were reported according to international guidelines. Tumour budding and immune response (CD8+ T-cells) were assessed with automated models using artificial intelligence. We used the information on risk factors and least absolute shrinkage and selection operator logistic regression to develop a prediction model and generate a score to predict the occurrence of lymph node metastasis or cancer recurrence. RESULTS: The IBC prediction score included the following parameters: lymphovascular invasion, tumour buds, infiltration depth and tumour grade. The score has an acceptable discrimination power (area under the curve of 0.68 [95% confidence intervals (CI) 0.61-0.75]; 0.64 [95% CI 0.57-0.71] after internal validation). At a cut-off of 6.8 points to discriminate high-and low-risk patients, the score had a sensitivity and specificity of 0.9 [95% CI 0.8-0.95] and 0.26 [95% 0.22, 0.3], respectively. CONCLUSION: The IBC score is based on well-established risk factors and is a promising tool with clinical utility to support the management of pT1 CRC patients.

Trends in Prevalence of Cannabis Use Disorder Among U.S. Veterans With and Without Psychiatric Disorders Between 2005 and 2019.

OBJECTIVE: Cannabis use disorder diagnoses are increasing among U.S. adults and are more prevalent among people with comorbid psychiatric disorders. Recent changes in cannabis laws, increasing cannabis availability, and higher-potency cannabis may have placed people with cannabis use and psychiatric disorders at disproportionately increasing risk for cannabis use disorder. The authors used Veterans Health Administration (VHA) data to examine whether trends in cannabis use disorder prevalence among VHA patients differ by whether they have psychiatric disorders. METHODS: VHA electronic health records from 2005 to 2019 (N range, 4,332,165-5,657,277) were used to identify overall and age-group-specific (<35, 35-64, and ≥65 years) trends in prevalence of cannabis use disorder diagnoses among patients with depressive, anxiety, posttraumatic stress, bipolar, or psychotic spectrum disorders and to compare these to corresponding trends among patients without any of these disorders. Given transitions in ICD coding, differences in trends were tested within two periods: 2005-2014 (ICD-9-CM) and 2016-2019 (ICD-10-CM). RESULTS: Greater increases in prevalence of cannabis use disorder diagnoses were observed among patients with psychiatric disorders compared to those without (difference in prevalence change, 2005-2014: 1.91%, 95% CI=1.87-1.96; 2016-2019: 0.34%, 95% CI=0.29-0.38). Disproportionate increases in cannabis use disorder prevalence among patients with psychiatric disorders were greatest among those under age 35 between 2005 and 2014, and among those age 65 or older between 2016 and 2019. Among patients with psychiatric disorders, the greatest increases in cannabis use disorder prevalences were observed among those with bipolar and psychotic spectrum disorders. CONCLUSIONS: The findings highlight disproportionately increasing disparities in risk of cannabis use disorder among VHA patients with common psychiatric disorders. Greater public health and clinical efforts are needed to monitor, prevent, and treat cannabis use disorder in this population.

Association of Cannabis Legalization with Cannabis Positive Drug Screening in US Veterans.

Background: Although cannabis legalization is associated with increases in self-report cannabis use, biological measures of cannabis use are needed to address potential bias introduced by improved self-reporting of cannabis use in states enacting medical cannabis laws (MCL) and recreational cannabis laws (RCL). Objective: Quantify the role of MCL and RCL enactment in cannabis positive urine drug screen (UDS) prevalence among Veterans Health Administration (VHA) emergency department (ED) patients from 2008 to 2019. Design: Staggered-adoption difference-in-difference analysis were used to estimate the role of MCL and RCL in cannabis positive UDS data, fitting adjusted linear binomial regression models to estimate the association between MCL and RCL enactment and prevalence of cannabis positive UDS. Participants: VHA enrolled veterans aged 18-75 years with ≥1 ED visit in a given year from 2008 to 2019. Main Measures: Receipt of ≥1 cannabis positive UDS during an ED visit were analyzed. Key Results: From 2008 to 2019, adjusted cannabis positive UDS prevalences increased from 16.4% to 25.6% in states with no cannabis law, 16.6% to 27.6% in MCL-only enacting states, and 18.2% to 33.8% in RCL-enacting states. MCL-only and MCL/RCL enactment was associated with a 0.8% (95% CI, 0.4-1.0) and 2.9% (95% CI, 2.5-3.3) absolute increase in cannabis positive UDS, respectively. Significant effect sizes were found for MCL and RCL, such that 7.0% and 18.5% of the total increase in cannabis positive UDS prevalence in MCL-only and RCL states could be attributed to MCLs and RCLs. Conclusions: In this study of VHA ED patients, MCL and RCL enactment played a significant role in the overall increases in cannabis positive UDS. The increase in a biological measure of cannabis use reduces concerns that previously documented increases in self-reported cannabis use from surveys are due to changes in patient willingness to report use as it becomes more legal.

Trends in Cannabis-positive Urine Toxicology Test Results: US Veterans Health Administration Emergency Department Patients, 2008 to 2019.

OBJECTIVES: This study aimed to examine trends in cannabis-positive urine drug screens (UDSs) among emergency department (ED) patients from 2008 to 2019 using data from the Veterans Health Administration (VHA) health care system, and whether these trends differed by age group (18-34, 35-64, and 65-75 years), sex, and race, and ethnicity. METHOD: VHA electronic health records from 2008 to 2019 were used to identify the percentage of unique VHA patients seen each year at an ED, received a UDS, and screened positive for cannabis. Trends in cannabis-positive UDS were examined by age, race and ethnicity, and sex within age groups. RESULTS: Of the VHA ED patients with a UDS, the annual prevalence positive for cannabis increased from 16.42% in 2008 to 27.2% in 2019. The largest increases in cannabis-positive UDS were observed in the younger age groups. Male and female ED patients tested positive for cannabis at similar levels. Although the prevalence of cannabis-positive UDS was consistently highest among non-Hispanic Black patients, cannabis-positive UDS increased in all race and ethnicity groups. DISCUSSION: The increasing prevalence of cannabis-positive UDS supports the validity of previously observed population-level increases in cannabis use and cannabis use disorder from survey and administrative records. Time trends via UDS results provide additional support that previously documented increases in self-reported cannabis use and disorder from surveys and claims data are not spuriously due to changes in patient willingness to report use as it becomes more legalized, or due to greater clinical attention over time.

Chronic pain, cannabis legalisation, and cannabis use disorder among patients in the US Veterans Health Administration system, 2005 to 2019: a repeated, cross-sectional study.

BACKGROUND: Cannabis use disorder is associated with considerable comorbidity and impairment in functioning, and prevalence is increasing among adults with chronic pain. We aimed to assess the effect of introduction of medical cannabis laws (MCL) and recreational cannabis laws (RCL) on the increase in cannabis use disorder among patients in the US Veterans Health Administration (VHA). METHODS: Data from patients with one or more primary care, emergency, or mental health visit to the VHA in 2005-19 were analysed using 15 repeated cross-sectional VHA electronic health record datasets (ie, one dataset per year). Patients in hospice or palliative care were excluded. Patients were stratified as having chronic pain or not using an American Pain Society taxonomy of painful medical conditions. We used staggered-adoption difference-in-difference analyses to estimate the role of MCL and RCL enactment in the increases in prevalence of diagnosed cannabis use disorder and associations with presence of chronic pain, accounting for the year that state laws were enacted. We did this by fitting a linear binomial regression model stratified by pain, with time-varying cannabis law status, fixed effects for state, categorical year, time-varying state-level sociodemographic covariates, and patient covariates (age group [18-34 years, 35-64 years, and 65-75 years], sex, and race and ethnicity). FINDINGS: Between 2005 and 2019, 3 234 382-4 579 994 patients were included per year. Among patients without pain in 2005, 5·1% were female, mean age was 58·3 (SD 12·6) years, and 75·7%, 15·6%, and 3·6% were White, Black, and Hispanic or Latino, respectively. In 2019, 9·3% were female, mean age was 56·7 (SD 15·2) years, and 68·1%, 18·2%, and 6·5% were White, Black, and Hispanic or Latino, respectively. Among patients with pain in 2005, 7·1% were female, mean age was 57·2 (SD 11·4) years, and 74·0%, 17·8%, and 3·9% were White, Black, and Hispanic or Latino, respectively. In 2019, 12·4% were female, mean age was 57·2 (SD 13·8) years, and 65·3%, 21·9%, and 7·0% were White, Black, and Hispanic or Latino, respectively. Among patients with chronic pain, enacting MCL led to a 0·135% (95% CI 0·118-0·153) absolute increase in cannabis use disorder prevalence, with 8·4% of the total increase in MCL-enacting states attributable to MCL. Enacting RCL led to a 0·188% (0·160-0·217) absolute increase in cannabis use disorder prevalence, with 11·5% of the total increase in RCL-enacting states attributable to RCL. In patients without chronic pain, enacting MCL and RCL led to smaller absolute increases in cannabis use disorder prevalence (MCL: 0·037% [0·027-0·048], 5·7% attributable to MCL; RCL: 0·042% [0·023-0·060], 6·0% attributable to RCL). Overall, associations of MCL and RCL with cannabis use disorder were greater in patients with chronic pain than in patients without chronic pain. INTERPRETATION: Increasing cannabis use disorder prevalence among patients with chronic pain following state legalisation is a public health concern, especially among older age groups. Given cannabis commercialisation and widespread public beliefs about its efficacy, clinical monitoring of cannabis use and discussion of the risk of cannabis use disorder among patients with chronic pain is warranted. FUNDING: NIDA grant R01DA048860, New York State Psychiatric Institute, and the VA Centers of Excellence in Substance Addiction Treatment and Education.

Chronic Pain, Cannabis Legalization and Cannabis Use Disorder in Veterans Health Administration Patients, 2005 to 2019.

Background: The risk for cannabis use disorder (CUD) is elevated among U.S. adults with chronic pain, and CUD rates are disproportionately increasing in this group. Little is known about the role of medical cannabis laws (MCL) and recreational cannabis laws (RCL) in these increases. Among U.S. Veterans Health Administration (VHA) patients, we examined whether MCL and RCL effects on CUD prevalence differed between patients with and without chronic pain. Methods: Patients with ≥1 primary care, emergency, or mental health visit to the VHA and no hospice/palliative care within a given calendar year, 2005-2019 (yearly n=3,234,382 to 4,579,994) were analyzed using VHA electronic health record (EHR) data. To estimate the role of MCL and RCL enactment in the increases in prevalence of diagnosed CUD and whether this differed between patients with and without chronic pain, staggered-adoption difference-in-difference analyses were used, fitting a linear binomial regression model with fixed effects for state, categorical year, time-varying cannabis law status, state-level sociodemographic covariates, a chronic pain indicator, and patient covariates (age group [18-34, 35-64; 65-75], sex, and race and ethnicity). Pain was categorized using an American Pain Society taxonomy of painful medical conditions. Outcomes: In patients with chronic pain, enacting MCL led to a 0·14% (95% CI=0·12%-0·15%) absolute increase in CUD prevalence, with 8·4% of the total increase in CUD prevalence in MCL-enacting states attributable to MCL. Enacting RCL led to a 0·19% (95%CI: 0·16%, 0·22%) absolute increase in CUD prevalence, with 11·5% of the total increase in CUD prevalence in RCL-enacting states attributable to RCL. In patients without chronic pain, enacting MCL and RCL led to smaller absolute increases in CUD prevalence (MCL: 0·037% [95%CI: 0·03, 0·05]; RCL: 0·042% [95%CI: 0·02, 0·06]), with 5·7% and 6·0% of the increases in CUD prevalence attributable to MCL and RCL. Overall, MCL and RCL effects were significantly greater in patients with than without chronic pain. By age, MCL and RCL effects were negligible in patients age 18-34 with and without pain. In patients age 35-64 with and without pain, MCL and RCL effects were significant (p<0.001) but small. In patients age 65-75 with pain, absolute increases were 0·10% in MCL-only states and 0·22% in MCL/RCL states, with 9·3% of the increase in CUD prevalence in MCL-only states attributable to MCL, and 19.4% of the increase in RCL states attributable to RCL. In patients age 35-64 and 65-75, MCL and RCL effects were significantly greater in patients with pain. Interpretation: In patients age 35-75, the role of MCL and RCL in the increasing prevalence of CUD was greater in patients with chronic pain than in those without chronic pain, with particularly pronounced effects in patients with chronic pain age 65-75. Although the VHA offers extensive behavioral and non-opioid pharmaceutical treatments for pain, cannabis may seem a more appealing option given media enthusiasm about cannabis, cannabis commercialization activities, and widespread public beliefs about cannabis efficacy. Cannabis does not have the risk/mortality profile of opioids, but CUD is a clinical condition with considerable impairment and comorbidity. Because cannabis legalization in the U.S. is likely to further increase, increasing CUD prevalence among patients with chronic pain following state legalization is a public health concern. The risk of chronic pain increases as individuals age, and the average age of VHA patients and the U.S. general population is increasing. Therefore, clinical monitoring of cannabis use and discussion of the risk of CUD among patients with chronic pain is warranted, especially among older patients. Research in Context: Evidence before this study: Only three studies have examined the role of state medical cannabis laws (MCL) and/or recreational cannabis laws (RCL) in the increasing prevalence of cannabis use disorder (CUD) in U.S. adults, finding significant MCL and RCL effects but with modest effect sizes. Effects of MCL and RCL may vary across important subgroups of the population, including individuals with chronic pain. PubMed was searched by DH for publications on U.S. time trends in cannabis legalization, cannabis use disorders (CUD) and pain from database inception until March 15, 2023, without language restrictions. The following search terms were used: (medical cannabis laws) AND (pain) AND (cannabis use disorder); (recreational cannabis laws) AND (pain) AND (cannabis use disorder); (cannabis laws) AND (pain) AND (cannabis use disorder). Only one study was found that had CUD as an outcome, and this study used cross-sectional data from a single year, which cannot be used to determine trends over time. Therefore, evidence has been lacking on whether the role of state medical and recreational cannabis legalization in the increasing US adult prevalence of CUD differed by chronic pain status.Added value of this study: To our knowledge, this is the first study to examine whether the effects of state MCL and RCL on the nationally increasing U.S. rates of adult cannabis use disorder differ by whether individuals experience chronic pain or not. Using electronic medical record data from patients in the Veterans Health Administration (VHA) that included extensive information on medical conditions associated with chronic pain, the study showed that the effects of MCL and RCL on the prevalence of CUD were stronger among individuals with chronic pain age 35-64 and 65-75, an effect that was particularly pronounced in older patients ages 65-75.Implications of all the available evidence: MCL and RCL are likely to influence the prevalence of CUD through commercialization that increases availability and portrays cannabis use as 'normal' and safe, thereby decreasing perception of cannabis risk. In patients with pain, the overall U.S. decline in prescribed opioids may also have contributed to MCL and RCL effects, leading to substitution of cannabis use that expanded the pool of individuals vulnerable to CUD. The VHA offers extensive non-opioid pain programs. However, positive media reports on cannabis, positive online "information" that can sometimes be misleading, and increasing popular beliefs that cannabis is a useful prevention and treatment agent may make cannabis seem preferable to the evidence-based treatments that the VHA offers, and also as an easily accessible option among those not connected to a healthcare system, who may face more barriers than VHA patients in accessing non-opioid pain management. When developing cannabis legislation, unintended consequences should be considered, including increased risk of CUD in large vulnerable subgroups of the population.

Test-Retest Reliability of the Impact of Vision Impairment-Very Low Vision Questionnaire.

Purpose: Most patient-reported outcome measures used in ophthalmology show floor effects in a very low vision population, which limits their use in vision restoration trials. The Impact of Vision Impairment-Very Low Vision scale (IVI-VLV) was developed to specifically target a very low vision population, but its test-retest reliability has not been investigated yet. Methods: The German version of the IVI-VLV was administered twice to patients with stable disease of a low vision clinic. Test and retest person measures of the IVI-VLV subscales were obtained from Rasch analysis. Test-retest reliability was investigated by intraclass correlation coefficients and Bland-Altman plots. Results: We included 134 patients (72 women, 62 men) at a mean age of 62 ± 15 years. The intraclass correlation coefficients were 0.920 (95% confidence interval, 0.888-0.944) for the activities of daily living and mobility subscale of the IVI-VLV and 0.929 (95% confidence interval, 0.899-0.949) for the emotional well-being subscale. Bland-Altman plots did not indicate any systematic bias. In linear regression analysis, test-retest differences were not significantly associated with visual acuity or administration interval. Conclusions: Both subscales of the IVI-VLV showed excellent repeatability independent of visual acuity and length of repeat interval. Further validation steps including an assessment of the patient-reported outcome measure's responsiveness are required for use in vision restoration trials. Translational Relevance: The results support repeated use of the IVI-VLV as a patient-reported end point in future studies in very low and ultralow vision populations.

Increasing risk of cannabis use disorder among U.S. veterans with chronic pain: 2005-2019.

ABSTRACT: In the United States, cannabis is increasingly used to manage chronic pain. Veterans Health Administration (VHA) patients are disproportionately affected by pain and may use cannabis for symptom management. Because cannabis use increases the risk of cannabis use disorders (CUDs), we examined time trends in CUD among VHA patients with and without chronic pain, and whether these trends differed by age. From VHA electronic health records from 2005 to 2019 (∼4.3-5.6 million patients yearly), we extracted diagnoses of CUD and chronic pain conditions ( International Classification of Diseases [ ICD ]- 9-CM , 2005-2014; ICD-10-CM , 2016-2019). Differential trends in CUD prevalence overall and age-stratified (<35, 35-64, or ≥65) were assessed by any chronic pain and number of pain conditions (0, 1, or ≥2). From 2005 to 2014, the prevalence of CUD among patients with any chronic pain increased significantly more (1.11%-2.56%) than those without pain (0.70%-1.26%). Cannabis use disorder prevalence increased significantly more among patients with chronic pain across all age groups and was highest among those with ≥2 pain conditions. From 2016 to 2019, CUD prevalence among patients age ≥65 with chronic pain increased significantly more (0.63%-1.01%) than those without chronic pain (0.28%-0.47%) and was highest among those with ≥2 pain conditions. Over time, CUD prevalence has increased more among VHA patients with chronic pain than other VHA patients, with the highest increase among those age ≥65. Clinicians should monitor symptoms of CUD among VHA patients and others with chronic pain who use cannabis, and consider noncannabis therapies, particularly because the effectiveness of cannabis for chronic pain management remains inconclusive.

State Cannabis Legalization and Cannabis Use Disorder in the US Veterans Health Administration, 2005 to 2019.

Importance: Cannabis use disorder (CUD) is increasing among US adults. Few national studies have addressed the role of medical cannabis laws (MCLs) and recreational cannabis laws (RCLs) in these increases, particularly in patient populations with high rates of CUD risk factors. Objective: To quantify the role of MCL and RCL enactment in the increases in diagnosed CUD prevalence among Veterans Health Administration (VHA) patients from 2005 to 2019. Design, Setting, and Participants: Staggered-adoption difference-in-difference analyses were used to estimate the role of MCL and RCL in the increases in prevalence of CUD diagnoses, fitting a linear binomial regression model with fixed effects for state, categorical year, time-varying cannabis law status, state-level sociodemographic covariates, and patient age group, sex, and race and ethnicity. Patients aged 18 to 75 years with 1 or more VHA primary care, emergency department, or mental health visit and no hospice/palliative care within a given calendar year were included. Time-varying yearly state control covariates were state/year rates from American Community Survey data: percentage male, Black, Hispanic, White, 18 years or older, unemployed, income below poverty threshold, and yearly median household income. Analysis took place between February to December 2022. Main Outcomes and Measures: As preplanned, International Classification of Diseases, Clinical Modification, ninth and tenth revisions, CUD diagnoses from electronic health records were analyzed. Results: The number of individuals analyzed ranged from 3 234 382 in 2005 to 4 579 994 in 2019. Patients were largely male (94.1% in 2005 and 89.0% in 2019) and White (75.0% in 2005 and 66.6% in 2019), with a mean (SD) age of 57.0 [14.4] years. From 2005 to 2019, adjusted CUD prevalences increased from 1.38% to 2.25% in states with no cannabis laws (no CLs), 1.38% to 2.54% in MCL-only enacting states, and 1.39% to 2.56% in RCL-enacting states. Difference-in-difference results indicated that MCL-only enactment was associated with a 0.05% (0.05-0.06) absolute increase in CUD prevalence, ie, that 4.7% of the total increase in CUD prevalence in MCL-only enacting states could be attributed to MCLs, while RCL enactment was associated with a 1.12% (95% CI, 0.10-0.13) absolute increase in CUD prevalence, ie, that 9.8% of the total increase in CUD prevalence in RCL-enacting states could be attributed to RCLs. The role of RCL in the increases in CUD prevalence was greatest in patients aged 65 to 75 years, with an absolute increase of 0.15% (95% CI, 0.13-0.17) in CUD prevalence associated with RCLs, ie, 18.6% of the total increase in CUD prevalence in that age group. Conclusions and Relevance: In this study of VHA patients, MCL and RCL enactment played a significant role in the overall increases in CUD prevalence, particularly in older patients. However, consistent with general population studies, effect sizes were relatively small, suggesting that cumulatively, laws affected cannabis attitudes diffusely across the country or that other factors played a larger role in the overall increases in adult CUD. Results underscore the need to screen for cannabis use and CUD and to treat CUD when it is present.

Changes in Opioid and Benzodiazepine Poisoning Deaths After Cannabis Legalization in the US: A County-level Analysis, 2002-2020.

BACKGROUND: Cannabis legalization for medical and recreational purposes has been suggested as an effective strategy to reduce opioid and benzodiazepine use and deaths. We examined the county-level association between medical and recreational cannabis laws and poisoning deaths involving opioids and benzodiazepines in the US from 2002 to 2020. METHODS: Our ecologic county-level, spatiotemporal study comprised 49 states. Exposures were state-level implementation of medical and recreational cannabis laws and state-level initiation of cannabis dispensary sales. Our main outcomes were poisoning deaths involving any opioid, any benzodiazepine, and opioids with benzodiazepines. Secondary analyses included overdoses involving natural and semi-synthetic opioids, synthetic opioids, and heroin. RESULTS: Implementation of medical cannabis laws was associated with increased deaths involving opioids (rate ratio [RR] = 1.14; 95% credible interval [CrI] = 1.11, 1.18), benzodiazepines (RR = 1.19; 95% CrI = 1.12, 1.26), and opioids+benzodiazepines (RR = 1.22; 95% CrI = 1.15, 1.30). Medical cannabis legalizations allowing dispensaries was associated with fewer deaths involving opioids (RR = 0.88; 95% CrI = 0.85, 0.91) but not benzodiazepine deaths; results for recreational cannabis implementation and opioid deaths were similar (RR = 0.81; 95% CrI = 0.75, 0.88). Recreational cannabis laws allowing dispensary sales was associated with consistent reductions in opioid- (RR = 0.83; 95% CrI = 0.76, 0.91), benzodiazepine- (RR = 0.79; 95% CrI = 0.68, 0.92), and opioid+benzodiazepine-related poisonings (RR = 0.83; 95% CrI = 0.70, 0.98). CONCLUSIONS: Implementation of medical cannabis laws was associated with higher rates of opioid- and benzodiazepine-related deaths, whereas laws permitting broader cannabis access, including implementation of recreational cannabis laws and medical and recreational dispensaries, were associated with lower rates. The estimated effects of the expanded availability of cannabis seem dependent on the type of law implemented and its provisions.

Stressful life events and incident depression among U.S. military personnel.

PURPOSE: Although stressful life events (i.e., stressors) and depression are often assumed to be linked, the relation between stressors and incident depression is rarely studied, particularly in the military. The National Guard is a part-time subset of the U.S. military for whom civilian life stressors may be particularly salient, due to the soldiers' dual roles and frequent transitions between military and civilian life. METHODS: We used a dynamic cohort study of National Guard members from 2010 to 2016 to investigate the relationship between recent stressful experiences (e.g., divorce) and incident depression, with an exploratory analysis of effect modification by income. RESULTS: Respondents endorsing at least one of nine past-year stressful events (a time-varying exposure, lagged by 1 year) had almost twice the adjusted rate of incident depression compared to those with no stressful events (HR = 1.8; 95% CI 1.4, 2.4). This association may be modified by income: among individuals making under $80,000 per year, those with past-year stressors had twice the rate of depression compared to those with no stressors, but among those making over $80,000, past-year stressors were associated with only 1.2 times the rate of depression. CONCLUSION: Stressful life events outside of deployment are important determinants of incident depression among National Guard servicemembers, but the effect of these events may be buffered by higher income.

Adult use of highly-potent Δ9-THC cannabis concentrate products by U.S. state cannabis legalization status, 2021.

BACKGROUND: Compared to plant/flower cannabis products, cannabis concentrates have higher average potency of delta-9-tetrahydrocannabinol (Δ9-THC), which may be associated with greater likelihood of cannabis-related harms. Information on factors associated with use of cannabis concentrates is needed. METHODS: Respondents were 4,328 adult past-7-day cannabis users from all 50 U.S. states and Washington DC (DC) who participated in an online 2021 survey. Using logistic regression to generate adjusted odds ratios (aOR), we investigated whether participants in states that enacted recreational cannabis laws (RCL, 12 states plus DC [treated as a state], n = 1,236) or medical cannabis laws (MCL-only, 23 states, n = 2,030) by December 31, 2020 were more likely than those in states without cannabis laws (no-CL, 15 states, n = 1,062) to use cannabis concentrate products in the prior 7 days. RESULTS: Most participants (92.4%) used plant material in the prior 7 days; 57.0% used cannabis concentrates. In RCL, MCL and no-CL states, concentrate use was reported by 61.5%, 56.6%, and 52.5%, respectively. Compared to participants in no-CL states, odds of using cannabis concentrate products were greater among those in RCL states (aOR = 1.47; CI = 1.17-1.84) and MCL-only states (aOR = 1.29; CI = 1.08-1.55). Whether states had legally-authorized dispensaries had little effect on results. CONCLUSION: Results suggest that individuals in MCL-only and RCL states are more likely to use cannabis concentrate products. Determining mechanisms underlying these results, e.g., commercialization, could provide important information for prevention. Clinicians should be alert to patient use of concentrates, especially in MCL-only and RCL states. Continued monitoring is warranted as additional states legalize cannabis use.