Prevalence and Characteristics of Self-Reported Hypothyroidism and Its Association with Nonorgan-Specific Manifestations in US Sarcoidosis Patients: A Nationwide Registry Study

Little is known about the prevalence, clinical characteristics and impact of hypothyroidism in patients with sarcoidosis. We aimed to determine the prevalence and clinical features of hypothyroidism and its relation to organ involvement and other clinical manifestations in patients with sarcoidosis. We conducted a national registry-based study investigating 3835 respondents to the Sarcoidosis Advanced Registry for Cures Questionnaire between June 2014 and August 2019. This registry is based on a self-reported, web-based questionnaire that provides data related to demographics, diagnostics, sarcoidosis manifestations and treatment. We compared sarcoidosis patients with and without self-reported hypothyroidism. We used multivariable logistic regression and adjusted for potential confounders to determine the association of hypothyroidism with nonorgan-specific manifestations. 14% of the sarcoidosis patients self-reported hypothyroidism and were generally middle-aged white women. Hypothyroid patients had more comorbid conditions and were more likely to have multiorgan sarcoidosis involvement, especially with cutaneous, ocular, joints, liver and lacrimal gland involvement. Self-reported hypothyroidism was associated with depression (adjusted odds ratio (aOR) 1.3, 95% CI 1.01–1.6), antidepressant use (aOR 1.3, 95% CI 1.1–1.7), obesity (aOR 1.7, 95% CI 1.4–2.1), sleep apnoea (aOR 1.7, 95% CI 1.3–2.2), chronic fatigue syndrome (aOR 1.5, 95% CI 1.2–2) and was borderline associated with fibromyalgia (aOR 1.3, 95% CI 1–1.8). Physical impairment was more common in patients with hypothyroidism. Hypothyroidism is a frequent comorbidity in sarcoidosis patients that might be a potentially reversible contributor to fatigue, depression and physical impairment in this population. We recommend considering routine screening for hypothyroidism in sarcoidosis patients especially in those with multiorgan sarcoidosis, fatigue and depression

Cross‐cultural assessment of HIV‐associated cognitive impairment using the Kaufman assessment battery for children: a systematic review

Introduction: Despite improved efficacy of, and access to, combination antiretroviral therapy (cART), HIV‐associated cognitive impairments remain prevalent in both children and adults. Neuropsychological tests that detect such impairment can help clinicians formulate effective treatment plans. The Kaufman Assessment Battery for Children (KABC), although developed and standardized in the United States, is used frequently in many different countries and cultural contexts to assess paediatric performance across various cognitive domains. This systematic review investigated the cross‐cultural utility of the original KABC, and its 2nd edition (KABC‐II), in detecting HIV‐associated cognitive impairment in children and adolescents.Methods: We entered relevant keywords and MeSH terms into the PubMed, PsycInfo, EBSCOHost, ProQuest, and Scopus databases, with search limits set from 1983–2017. Two independent reviewers evaluated the retrieved abstracts and manuscripts. Studies eligible for inclusion in the review were those that (a) used the KABC/KABC‐II to assess cognitive function in children/adolescents aged 2–18 years, (b) featured a definition of cognitive impairment (e.g. >2 SD below the mean) or compared the performance of HIV‐infected and uninfected control groups, and (c) used a sample excluded from population on which the instruments were normed.Results and discussion: We identified nine studies (eight conducted in African countries, and one in the United Kingdom) to comprise the review’s sample. All studies detected cognitive impairment in HIV‐infected children, including those who were cART‐naïve or who were cART treated and clinically stable. KABC/KABC‐II subtests assessing simultaneous processing appeared most sensitive. Evaluation of the methodological quality of the selected studies by two independent reviews suggested that shortcomings included reporting and selection biases.Conclusions: This systematic review provides evidence for the cross‐cultural utility of the KABC/KABC‐II, particularly the simultaneous processing subtests, in detecting cognitive impairment in HIV‐infected children (including those who are clinically stable). Although the current results suggest there is justification for using the KABC/KABC‐II primarily in East Africa, further investigation is required to explore the instrument’s utility in other HIV‐prevalent regions of the globe.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138351/1/jia21412.pd

Income and Other Contributors to Poor Outcomes in US Patients with Sarcoidosis

Rationale: Socioeconomic factors are associated with worse disease severity at presentation in sarcoidosis, but the relative importance of socioeconomic variables on morbidity and disease burden has not been fully elucidated.Objectives: To determine the association between income and sarcoidosis outcomes after controlling for socioeconomic and disease-related factors.Methods: Using the Sarcoidosis Advanced Registry for Cures database, we analyzed data from 2,318 patients with sarcoidosis in the United States to determine the effect of income and other variables on outcomes. We divided comorbidities arising after diagnosis into those likely related to steroid use and those likely related to sarcoidosis. We assessed the development of health-related, functional, and socioeconomic outcomes following the diagnosis of sarcoidosis.Measurements and Main Results: In multivariate analysis, low-income patients had significantly higher rates of new sarcoidosis-related comorbidities (=$85,000 [reference (Ref)]) and new steroid-related comorbidities (=$85,000 [Ref]), had lower health-related quality of life as assessed by the Sarcoidosis Health Questionnaire (P =$85,000 [Ref]). The use of supplemental oxygen, need for assistive devices, and job loss were more common in lower income patients. Development of comorbidities after diagnosis of sarcoidosis occurred in 63% of patients and were strong independent predictors of poor outcomes. In random forest modeling, income was consistently a leading predictor of outcome.Conclusions: These results suggest the burden from sarcoidosis preferentially impacts the economically disadvantaged

Intracellular Pharmacokinetics of Once versus Twice Daily Zidovudine and Lamivudine in Adolescents▿ ‡

Zidovudine (ZDV) and lamivudine (3TC) metabolism to triphosphates (TP) is necessary for antiviral activity. The aims of this study were to compare ZDV-TP and 3TC-TP concentrations in adolescents receiving twice daily (BID) and once daily (QD) regimens and to determine the metabolite concentrations of ZDV and 3TC during chronic therapy on a QD regimen. Human immunodeficiency virus-infected patients (12 to 24 years) taking ZDV (600 mg/day) and 3TC (300 mg/day) as part of a highly active antiretroviral therapy regimen received QD and BID regimens of ZDV and 3TC for 7 to 14 days in a crossover design. Serial blood samples were obtained over 24 h on the QD regimen. Intracellular mono-, di-, and triphosphates for ZDV and 3TC were measured. The median ratio of BID/QD for ZDV-TP predose concentrations was 1.28 (95% confidence interval [CI] = 1.00 to 2.45) and for 3TC-TP was 1.12 (95% CI = 0.81 to 1.96). The typical population estimated half-lives (± the standard error of the mean) were 9.1 ± 0.859 h for ZDV-TP and 17.7 ± 2.8 h for 3TC-TP. Most patients had detectable levels of the TP of ZDV (24 of 27) and 3TC (24 of 25) 24 h after dosing, and half-lives on a QD regimen were similar to previously reported values when the drugs were given BID. Lower, but not significantly different, concentrations of ZDV-TP were demonstrated in the QD regimen compared to the BID regimen (P = 0.056). Although findings were similar between the BID and QD groups, the lower concentrations of ZDV and the number of patients below the level of detection after 24 h suggests that ZDV should continue to be administered BID

Short-Cycle Therapy in Adolescents after Continuous Therapy with Established Viral Suppression: The Impact on Viral Load Suppression

This was a proof-of-principle study to evaluate the impact of short cycle therapy (SCT; 4 days on/3 days off) in adolescents and young adults with good viral suppression on a protease inhibitor-based antiretroviral regimen. Subjects were recruited by the Adolescent Trials Network for HIV/AIDS Interventions and the Pediatric AIDS Clinical Trials Group. Subjects were infected either through perinatal/early childhood transmission or later via risk behaviors. All subjects were required to have at least 6 months of documented viral suppression below 400 copies/ml plus a preentry value below 200 copies/ml and an entry CD4+ T cell count above 350 cells/mm3. Of the 32 subjects enrolled, 12 (37.5%) had confirmed viral load rebound >400 copies, with 18 subjects (56%) coming off for any reason. The majority of subjects resuppressed when placed back onto continuous therapy using the same agents. Although no difference was found in virologic rebound rates between the early and later transmission groups, those infected early in life had higher rates of coming off SCT for any reason. There was no impact of SCT on the CD4+ T cell counts in those who remained on study or those who came off SCT for any reason. Subjects demonstrated good adherence to the SCT regimen. This study suggests that further evaluation of SCT may be warranted in some groups of adolescents and young adults infected with HIV

Early initiation of lopinavir/ritonavir in infants less than 6 weeks of age: pharmacokinetics and 24-week safety and efficacy

BACKGROUND: With increasing recognition of the benefits of early antiretroviral therapy initiation in perinatally HIV-infected infants, data are needed regarding the pharmacokinetics (PK), safety, and efficacy of recommended first-line protease inhibitors such as lopinavir/ritonavir (LPV/r). METHODS: A prospective, phase I/II, open-label, dose-finding trial evaluated LPV/r at a dose of 300/75 mg/m twice daily plus 2 nucleoside analogs in HIV-1-infected infants \u3e or =14 days to /r therapy, and doses were modified to maintain LPV predose concentrations \u3e1 microg/mL and area under the curve (AUC) /mL. RESULTS: Ten infants enrolled [median age 5.7 (range, 3.6-5.9) weeks] with median HIV-1 RNA of 6.0 (range, 4.7-7.2) log10 copies/mL; all completed 24 weeks of follow-up. Nine completed the intensive PK evaluation at a median LPV dose of 267 (range, 246-305) mg/m q12 hours; median measures were AUC = 36.6 (range, 27.9-62.6) microg hr/mL; predose concentration = 2.2 (range, 0.99-4.9) microg/mL; maximum concentration = 4.76 (range, 2.84-7.28) microg/mL and apparent clearance (L/h/m) = 6.75 (range, 2.79-12.83). Adverse events were limited to transient grade 3 neutropenia in 3 subjects. By week 24, 2 of 10 subjects had experienced a protocol-defined virologic failure. CONCLUSIONS: Although the LPV AUC in this population was significantly lower than that observed in infants ages 6 weeks to 6 months, LPV/r-based antiretroviral therapy in doses of 300/75 mg/m BID was well tolerated and resulted in virologic control in 8 of 10 infants by 24 weeks. Additional investigation is needed to understand the long-term implications of the lower LPV exposure in this age group