Combination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not ...been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000-2007 in the U.S. and Canada.
Participants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), aged ≥20 years and on ART. Mortality rates were calculated using participants' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables.
The crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 standard error (SE) 0.5 to 51.4 SE 0.5 years from 2000-2002 to 2006-2007. Men and women had comparable life expectancies in all periods except the last (2006-2007). Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts <350 cells/mm(3).
A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population. Differences by sex, race, HIV transmission risk group, and CD4 count remain.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
The optimal clinical management of oral precancer remains uncertain. We investigated the natural history of oral leukoplakia, the most common oral precancerous lesion, to estimate ...the relative and absolute risks of progression to cancer, the predictive accuracy of a clinician’s decision to biopsy a leukoplakia vis-à-vis progression, and histopathologic predictors of progression.
Methods
We conducted a retrospective cohort study (1996–2012) of patients with oral leukoplakia (n = 4886), identified using electronic medical records within Kaiser Permanente Northern California. Among patients with leukoplakia who received a biopsy (n = 1888), we conducted a case-cohort study to investigate histopathologic predictors of progression. Analyses included indirect standardization and unweighted or weighted Cox regression.
Results
Compared with the overall Kaiser Permanente Northern California population, oral cancer incidence was substantially elevated in oral leukoplakia patients (standardized incidence ratio = 40.8, 95% confidence interval CI = 34.8 to 47.6; n = 161 cancers over 22 582 person-years). Biopsied leukoplakias had a higher oral cancer risk compared with those that were not biopsied (adjusted hazard ratio = 2.38, 95% CI = 1.73 to 3.28). However, to identify a prevalent or incident oral cancer, the biopsy decision had low sensitivity (59.6%), low specificity (62.1%), and moderate positive–predictive value (5.1%). Risk of progression to oral cancer statistically significantly increased with the grade of dysplasia; 5-year competing risk-adjusted absolute risks were: leukoplakia overall = 3.3%, 95% CI = 2.7% to 3.9%; no dysplasia = 2.2%, 95% CI = 1.5% to 3.1%; mild-dysplasia = 11.9%, 95% CI = 7.1% to 18.1%; moderate-dysplasia = 8.7%, 95% CI = 3.2% to 17.9%; and severe dysplasia = 32.2%, 95% CI = 8.1%–60.0%. Yet 39.6% of cancers arose from biopsied leukoplakias without dysplasia.
Conclusions
The modest accuracy of the decision to biopsy a leukoplakia vis-à-vis presence or eventual development of oral cancer highlights the need for routine biopsy of all leukoplakias regardless of visual or clinical impression. Leukoplakia patients, particularly those with dysplasia, need to be closely monitored for signs of early cancer.
Background. Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex ...with men (MSM), other men, and women. There are also conflicting data regarding calendar trends. Methods. In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men). Results. Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval CI, 42.7—151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5—61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8—6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5—2.2). In comparison with the period 2000—2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3—.9) in 1996—1999 and 0.9 (95% CI, .6—1.2) in 2004—2007. Conclusions. Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.
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BFBNIB, NUK, PNG, UL, UM, UPUK
In two 16-week, placebo-controlled trials enrolling adults with moderate-to-severe atopic dermatitis, dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, was effective in ...controlling the signs and symptoms of atopic dermatitis.
Atopic dermatitis is a chronic, relapsing inflammatory skin disease that is characterized by the up-regulation of type 2 immune responses (including those involving type 2 helper T cells),
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an impaired skin barrier, and increased
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In patients with moderate-to-severe atopic dermatitis, skin lesions can encompass a large body-surface area and are frequently accompanied by intense, persistent pruritus, which leads to sleep deprivation, symptoms of anxiety or depression, and a poor quality of life.
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For patients with moderate-to-severe atopic dermatitis, topical therapies have limited efficacy, and systemic treatments are associated with substantial toxic effects. Thus, there . . .
The timing of the initiation of antiretroviral therapy in asymptomatic patients with HIV infection is unclear. In this retrospective study involving patients in North America from 1996 through 2005, ...the deferral of therapy until the patient's CD4+ count had fallen below one of the two thresholds of interest (a range of 351 to 500 cells or >500 cells per cubic millimeter) was associated with a relative hazard of death of 1.69 and 1.94, respectively.
In this retrospective study involving patients in North America, deferral of therapy until the patient's CD4+ count had fallen below one of the two thresholds of interest (a range of 351 to 500 cells or >500 cells per cubic millimeter) was associated with an increase in the risk of death of 69% and 94%, respectively.
The use of antiretroviral therapy has dramatically reduced disease progression and death among patients with human immunodeficiency virus (HIV) infection,
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but the optimal time to begin therapy is uncertain.
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Current guidelines recommend treatment for asymptomatic patients who have a CD4+ count of less than 350 cells per cubic millimeter on the basis of accumulating observational data.
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However, these guidelines note the lack of data from randomized clinical trials regarding the timing of the initiation of antiretroviral therapy.
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Data from randomized trials are limited to an analysis of a subgroup of 477 patients
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BACKGROUND:It is unknown if a survival gap remains between HIV-infected and HIV-uninfected individuals with access to care.
METHODS:We conducted a cohort study within Kaiser Permanente California ...during 1996–2011, using abridged life tables to estimate the expected years of life remaining (“life expectancy”) at age 20.
RESULTS:Among 24,768 HIV-infected and 257,600 HIV-uninfected individuals, there were 2229 and 4970 deaths, with mortality rates of 1827 and 326 per 100,000 person-years, respectively. In 1996–1997, life expectancies at age 20 for HIV-infected and HIV-uninfected individuals were 19.1 and 63.4 years, respectively, corresponding with a gap of 44.3 years (95% confidence interval38.4 to 50.2). Life expectancy at age 20 for HIV-infected individuals increased to 47.1 years in 2008 and 53.1 years by 2011, narrowing the gap to 11.8 years (8.9–14.8 years) in 2011. In 2008–2011, life expectancies at age 20 for HIV-infected individuals ranged from a low of 45.8 years for blacks and 46.0 years for those with a history of injection drug use to a high of 52.2 years for Hispanics. HIV-infected individuals who initiated antiretroviral therapy with CD4 ≥500 cells per microliter had a life expectancy at age 20 of 54.5 years in 2008–2011, narrowing the gap relative to HIV-uninfected individuals to 7.9 years (5.1–10.6 years). For these HIV-infected individuals, the gap narrowed further in subgroups with no history of hepatitis B or C infection, smoking, drug/alcohol abuse, or any of these risk factors.
CONCLUSIONS:Even with early treatment and access to care, an 8-year gap in life expectancy remains for HIV-infected compared with HIV-uninfected individuals.
Venous thromboembolism (VTE), ischemic stroke, and myocardial infarction in transgender persons may be related to hormone use.
To examine the incidence of these events in a cohort of transgender ...persons.
Electronic medical record-based cohort study of transgender members of integrated health care systems who had an index date (first evidence of transgender status) from 2006 through 2014. Ten male and 10 female cisgender enrollees were matched to each transgender participant by year of birth, race/ethnicity, study site, and index date enrollment.
Kaiser Permanente in Georgia and northern and southern California.
2842 transfeminine and 2118 transmasculine members with a mean follow-up of 4.0 and 3.6 years, respectively, matched to 48 686 cisgender men and 48 775 cisgender women.
VTE, ischemic stroke, and myocardial infarction events ascertained from diagnostic codes through the end of 2016 in transgender and reference cohorts.
Transfeminine participants had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6 to 6.7) and 16.7 (CI, 6.4 to 27.5) per 1000 persons relative to cisgender men and 3.4 (CI, 1.1 to 5.6) and 13.7 (CI, 4.1 to 22.7) relative to cisgender women. The overall analyses for ischemic stroke and myocardial infarction demonstrated similar incidence across groups. More pronounced differences for VTE and ischemic stroke were observed among transfeminine participants who initiated hormone therapy during follow-up. The evidence was insufficient to allow conclusions regarding risk among transmasculine participants.
Inability to determine which transgender members received hormones elsewhere.
The patterns of increases in VTE and ischemic stroke rates among transfeminine persons are not consistent with those observed in cisgender women. These results may indicate the need for long-term vigilance in identifying vascular side effects of cross-sex estrogen.
Patient-Centered Outcomes Research Institute and Eunice Kennedy Shriver National Institute of Child Health and Human Development.
OBJECTIVESThis paper describes characteristics of opioid use episodes for noncancer pain and defines thresholds for de facto long-term opioid therapy.
METHODSCONSORT (CONsortium to Study Opioid Risks ...and Trends) includes adult members of 2 health plans serving over 1% of the US population. Opioid use episodes beginning in the years 1997 to 2005 were classified as acute, episodic, long-term/lower dose, or long-term/higher dose.
RESULTSOn the basis of evaluation of the likelihood of opioid use continuing, long-term opioid therapy was defined by episodes lasting longer than 90 days with 10+ opioid prescriptions or 120+ days supply of opioids dispensed. Long-term/higher dose episodes (<1.5% of all opioid use episodes) were characterized by daily or near daily use, a mean duration of about 1000 days, and an average daily dose of about 55 mg. They accounted for more than half the total morphine equivalents dispensed from the years 1997 to 2006. Short-acting, non-Schedule II opioids (eg, hydrocodone with acetaminophen) were, by far, the most commonly prescribed medications for acute, episodic, and long-term episodes. Long-acting (sustained-release) opioids were the predominately prescribed medication in a minority of long-term episodes (6% to 12%).
DISCUSSIONLong-term opioid therapy was characterized by the diversity in medications prescribed, dosage levels, and frequency of use. The proposed threshold for long-term opioid therapy provides a checkpoint for physicians to review whether an explicit decision to sustain opioid therapy has been reached, and to ensure that a documented treatment plan and provisions for monitoring medication use and patient outcomes are in place.
Few studies have compared cancer risk between HIV-infected individuals and a demographically similar HIV-uninfected internal comparison group, adjusting for cancer risk factors.
We followed 20,775 ...HIV-infected and 215,158 HIV-uninfected individuals enrolled in Kaiser Permanente (KP) California for incident cancer from 1996 to 2008. Rate ratios (RR) were obtained from Poisson models comparing HIV-infected (overall and stratified by recent CD4 count and HIV RNA) with HIV-uninfected individuals, adjusted for age, sex, race/ethnicity, calendar period, KP region, smoking, alcohol/drug abuse, and overweight/obesity.
We observed elevated RRs for Kaposi sarcoma (KS; RR = 199; P < 0.001), non-Hodgkin lymphoma (NHL; RR = 15; P < 0.001), anal cancer (RR = 55; P < 0.001), Hodgkin lymphoma (HL; RR = 19; P < 0.001), melanoma (RR = 1.8; P = 0.001), and liver cancer (RR = 1.8; P = 0.013), a reduced RR for prostate cancer (RR = 0.8; P = 0.012), and no increased risk for oral cavity/pharynx (RR = 1.4; P = 0.14), lung (RR = 1.2; P = 0.15), or colorectal (RR = 0.9; P = 0.34) cancers. Lung and oral cavity/pharynx cancers were elevated for HIV-infected subjects in models adjusted only for demographics. KS, NHL, anal cancer, HL, and colorectal cancer had significant (P < 0.05) trends for increasing RRs with decreasing recent CD4. The RRs for lung and oral cavity/pharynx cancer were significantly elevated with CD4 < 200 cells/μL and for melanoma and liver cancer with CD4 < 500 cells/μL. Only KS and NHL were associated with HIV RNA.
Immunodeficiency was positively associated with all cancers examined except prostate cancer among HIV-infected compared with HIV-uninfected individuals, after adjustment for several cancer risk factors.
Earlier antiretroviral therapy initiation to maintain high CD4 levels might reduce the burden of cancer in this population.
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