The recent decline in US life expectancy is attributed, in part, to premature deaths from opioid overdose.¹ Prescription opioids were involved in approximately 36% of all deaths in the United States associated with opioid overdose in 2017.² The risk of opioid use disorder (commonly called addiction), overdose, and death increases as prescription opioids are taken in higher dosages,^3-5 for longer periods of time,^6-8 or as extended-release and long-acting formulations.^9-12 Duration of use is the strongest predictor of opioid use disorder and overdose. Each additional week of use has been associated with a 20% increased risk for the development of an opioid use disorder or occurrence of an overdose.^6,8 Dosage is also important. Overdose risk is dosage dependent, doubling from 50 to 99 morphine milligram equivalents (MME) per day and increasing up to 9-fold at dosages of 100 MME or greater per day compared with overdose risk at dosages less than or equal to 20 MME/d.^3-5 Use of extended-release and long-acting agents also increases risk; unintentional overdoses are twice as likely to occur in those initiating therapy with extended-release and long-acting formulations compared with those starting with immediate-release opioids, especially in the first 2 weeks of use.^10,12 Prescribing opioids in excess of the patient’s needs may harm the patient as well as others if unused pills are diverted to street sales or misused.¹³ Misuse refers to drugs taken for a purpose other than that directed by the prescribing physician, in greater amounts, more often, or for a longer duration than prescribed. Although the epidemic is shifting from prescription opioids toward street drugs (heroin, fentanyl, and fentanyl analogues), 66% to 83% of new users of heroin report that their addiction began with the misuse of a prescription opioid.^14,15

Efforts to improve opioid prescribing need to consider the unique needs of women and older adults while using multimodal approaches to pain management.

Hepatitis E viral (HEV) infection imposes a heavy health burden worldwide and is common in the United States. Previous investigations of risks addressed environmental and host behavioral/lifestyle factors, but host genetic factors have not been examined. We assessed strength of associations between antibody to HEV (anti‐HEV) immunoglobulin G seropositivity indicating past or recent HEV infection and human genetic variants among three major racial/ethnic populations in the United States, involving 2434 non‐Hispanic whites, 1919 non‐Hispanic blacks, and 1919 Mexican Americans from the Third National Health and Nutrition Examination Survey, 1991‐1994. We studied 497 single‐nucleotide polymorphisms across 190 genes (particularly those associated with lipid metabolism). The genomic control method was used to adjust for potential population stratification. Non‐Hispanic blacks had the lowest seroprevalence of anti‐HEV immunoglobulin G (15.3%, 95% confidence interval [CI] 12.3%‐19.0%) compared with non‐Hispanic whites (22.3%, 95% CI 19.1%‐25.7%) and Mexican Americans (21.8%, 95% CI 19.0%‐25.3%; P < 0.01). Non‐Hispanic blacks were the only population that showed association between anti‐HEV seropositivity and functional ε3 and ε4 alleles of the apolipoprotein E (APOE) gene, encoding the apolipoprotein E protein that mediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying APOE ε4 (odds ratio = 0.5, 95% CI 0.4‐0.7; P = 0.00004) and ε3 (odds ratio = 0.6, 95% CI 0.4‐0.8; P = 0.001) compared to those carrying APOE ε2. No significant associations were observed between other single‐nucleotide polymorphisms and anti‐HEV seropositivity in non‐Hispanic blacks or between any single‐nucleotide polymorphisms and anti‐HEV seropositivity in non‐Hispanic whites or Mexican Americans. Conclusion: Both APOE ε3 and ε4 are significantly associated with protection against HEV infection in non‐Hispanic blacks; additional studies are needed to understand the basis of protection so that preventive services can be targeted to at‐risk persons. (Hepatology 2015;62:1346–1352)

Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on the biological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and its receptors and SMA was examined. Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12A and IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in Asembo Bay region of western Kenya. An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with a decreased risk of SMA (P = 0.006; risk ratio, 0.52 for carrying one copy of allele C and 0.28 for two copies). Individuals possessing two copies of a rare variant (C) in IL12RB1 (rs429774) also appeared to be strongly protective against SMA (P = 0.00005; risk ratio, 0.18). In addition, children homozygous for another rare allele (T) in IL12A (rs22431348) were associated with reduced risk of severe anaemia (SA) (P = 0.004; risk ratio, 0.69) and of severe anaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant in IL12RB1 (rs383483) was associated with susceptibility to high-density parasitaemia (HDP) (P = 0.003; risk ratio, 1.21). This study has shown strong associations between polymorphisms in the genes of IL12A and IL12RB1 and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes may significantly contribute to the development of anaemia in malaria patients.

Importance: During the COVID-19 pandemic, US emergency department (ED) visits for psychiatric disorders (PDs) and drug overdoses increased. Psychiatric disorders and substance use disorders (SUDs) independently increased the risk of COVID-19 hospitalization, yet their effect together is unknown.Objective: To assess how comorbid PD and SUD are associated with the probability of hospitalization among ED patients with COVID-19.Design, Setting, and Participants: This retrospective cross-sectional study analyzed discharge data for adults (age ≥18 years) with a COVID-19 diagnosis treated in 970 EDs and inpatient hospitals in the United States from April 2020 to August 2021.Exposures: Any past diagnosis of (1) SUD from opioids, stimulants, alcohol, cannabis, cocaine, sedatives, or other substances and/or (2) PD, including attention-deficit/hyperactivity disorder (ADHD), anxiety, bipolar disorder, major depression, other mood disorder, posttraumatic stress disorder (PTSD), or schizophrenia.Main Outcomes and Measures: The main outcome was any hospitalization. Differences in probability of hospitalization were calculated to assess its association with both PD and SUD compared with PD alone, SUD alone, or neither condition.Results: Of 1 274 219 ED patients with COVID-19 (mean [SD] age, 54.6 [19.1] years; 667 638 women [52.4%]), 18.6% had a PD (mean age, 59.0 years; 37.7% men), 4.6% had a SUD (mean age, 50.1 years; 61.7% men), and 2.3% had both (mean age, 50.4 years; 53.1% men). The most common PDs were anxiety (12.9%), major depression (9.8%), poly (≥2) PDs (6.4%), and schizophrenia (1.4%). The most common SUDs involved alcohol (2.1%), cannabis (1.3%), opioids (1.0%), and poly (≥2) SUDs (0.9%). Prevalence of SUD among patients with PTSD, schizophrenia, other mood disorder, or ADHD each exceeded 21%. Based on significant specific PD-SUD pairs (Q < .05), probability of hospitalization of those with both PD and SUD was higher than those with (1) neither condition by a weighted mean of 20 percentage points (range, 6 to 36; IQR, 16 to 25); (2) PD alone by 12 percentage points (range, −4 to 31; IQR, 8 to 16); and (3) SUD alone by 4 percentage points (range, −7 to 15; IQR, −2 to 7). Associations varied by types of PD and SUD. Substance use disorder was a stronger predictor of hospitalization than PD.Conclusions and Relevance: This study found that patients with both PD and SUD had a greater probability of hospitalization, compared with those with either disorder alone or neither disorder. Substance use disorders appear to have a greater association than PDs with the probability of hospitalization. Overlooking possible coexisting PD and SUD in ED patients with COVID-19 can underestimate the likelihood of hospitalization. Screening and assessment of both conditions are needed.