Health Research Alliance

Sickle cell disease (SCD) is a devastating genetic hematologic disorder affecting approximately 80,000 African Americans. Beyond the well-characterized vaso-occlusive pain crises, patients experience significant psychological morbidity, including kinesiophobia (fear of movement) and depression, which profoundly impact quality of life and functional outcomes. This comprehensive review synthesizes current evidence on the relationship between kinesiophobia and depression in SCD patients, with particular attention to gender differences, underlying pathophysiological mechanisms, and clinical implications for multidisciplinary care. We conducted a systematic examination of the literature on kinesiophobia, depression, and psychosocial factors in SCD, incorporating data from multiple cohort studies totaling 247 adult African American patients. Assessment instruments included the Tampa Scale for Kinesiophobia (TSK), Beck Depression Inventory (BDI), and Center for Epidemiologic Studies Depression Scale-Revised (CESD-r). Kinesiophobia prevalence in SCD patients (mean TSK score = 30.48) was comparable to patients with chronic back pain and fibromyalgia. Significant gender differences emerged, with women demonstrating strong positive correlations between kinesiophobia and depression (BDI r = 0.31, p = 0.045; CESD-r = 0.54, p = 0.009), while no significant relationships were observed in men (BDI r = 0.24, p > 0.05; CESD-r = 0.13, p > 0.05). The relationship appears mediated by psychomotor retardation, somatization, and pain catastrophizing behaviors. Fear of movement represents a clinically significant but underrecognized contributor to depressive symptomatology in women with SCD. These findings highlight the need for gender-specific psychological interventions and integrated care approaches that address both physical and mental health components of this complex genetic disorder.

Surfactants are widely employed across numerous applications due to their amphiphilic nature, which drives aggregate formation and enables the solubilization of hydrophobic compounds in aqueous solutions once the critical micelle concentration (CMC) is exceeded. In this work, we present a holistic modeling approach that considers both aggregation equilibria as well as phase equilibria in ternary systems of water, hydrophobic solutes (“oil”), and surfactants. For that purpose, PC-SAFT is incorporated into a novel mixed-aggregate formation model. Micellar solubilization effects are described by accounting for the formation of mixed oil-surfactant aggregates. Consequently, our model is based on a continuous distribution along all possible compositions and sizes of the mixed aggregates while calculating their equilibrium geometries. Our approach, for the first time, enables quasi-quantitative predictions of liquid–liquid equilibria in water–oil–surfactant systems. It accurately captures the sharp increase in oil solubility at surfactant concentrations just above the CMC and captures the influence of surfactant polarity on the maximum solubilization capacity for various hydrophobic solutes in very good agreement with experiments. Our methodology is validated for polyethoxylated alkyl ethers (CiEj) as surfactants and for alkanes and alkenes as example oil components, with the predicted binodal curves closely matching experimental LLE data.

ImportanceConsumer wearable technologies have wide applications, including some that have US Food and Drug Administration clearance for health-related notifications. While wearable technologies may have premarket testing, validation, and safety evaluation as part of a regulatory authorization process, information on their postmarket use remains limited. The Stanford Center for Digital Health organized 2 pan-stakeholder think tank meetings to develop an organizing concept for empirical research on the postmarket evaluation of consumer-facing wearables.ObservationsThe postmarket evaluation of consumer wearables involves broad consideration of an individual consumer’s journey from acquisition, intended and unintended use of the wearable, and access to health care resources on receipt of a notification. For individuals who do access the health care system, a wearable’s downstream effects can be studied through appropriate clinical evaluation, delivery of guideline-directed treatments, shared decision-making in areas of clinical equipoise, and analysis of clinical end points and patient harms. Effective postmarket research draws from denominators appropriate to the clinical question, with clearly defined parameters for success and failure. Generalizability related to data completeness and reliability should also be considered. As patients increasingly integrate wearables into their health monitoring, cross-platform data sharing with a focus on privacy and data quality can drive patient-centered innovation and identify opportunities to bridge gaps in medical care.RelevanceThe think tank identified priorities in postmarket research, comprising the journey from consumer to patient and accounting for patient, clinician, health care delivery system, and societal impacts of consumer wearables. Overall, this approach serves not only to organize the study of consumer wearables but also to act as a guidepost for using real-world data in postmarket research.

Background2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most extensively used herbicides in the United States. In 2012, 2,4-D was the most widely used herbicide in non-agricultural settings and the fifth most heavily applied pesticide in the US agricultural sector. The objective of this study was to examine trends in 2,4-D urinary biomarker concentrations to determine whether increases in 2,4-D application in agriculture are associated with increases in biomonitoring levels of urine 2,4-D.MethodsData from the National Health and Nutrition Examination Survey (NHANES) with available urine 2,4-D biomarker measurements from survey cycles between 2001 and 2014 were utilized. Urine 2,4-D values were dichotomized using the highest limit of detection (LOD) across all cycles (0.40 μg/L or 0.4 ppb). Agricultural use of 2,4-D was estimated by compiling publicly available federal and private pesticide application data. Logistic regression models adjusted for confounders were fitted to evaluate the association between agricultural use of 2,4-D and urine 2,4-D level above the dichotomization threshold.ResultsOf the 14,395 participants included in the study, 4681 (32.5%) had urine 2,4-D levels above the dichotomization threshold. The frequency of participants with high 2,4-D levels increased significantly (p < .0001), from a low of 17.1% in 2001–2002 to a high of 39.6% in 2011–2012. The adjusted odds of high urinary 2,4-D concentrations associated with 2,4-D agricultural use (per ten million pounds applied) was 2.268 (95% CI: 1.709, 3.009). Children ages 6–11 years (n = 2288) had 2.1 times higher odds of having high 2,4-D urinary concentrations compared to participants aged 20–59 years. Women of childbearing age (age 20–44 years) (n = 2172) had 1.85 times higher odds than men of the same age.ConclusionsAgricultural use of 2,4-D has increased substantially from a low point in 2002 and it is predicted to increase further in the coming decade. Because increasing use is likely to increase population level exposures, the associations seen here between 2,4-D crop application and biomonitoring levels require focused biomonitoring and epidemiological evaluation to determine the extent to which rising use and exposures cause adverse health outcomes among vulnerable populations (particularly children and women of childbearing age) and highly exposed individuals (farmers, other herbicide applicators, and their families).

Extensive 12‐lead electrocardiogram monitoring and drug concentrations were obtained during development of BUP‐XR, a monthly subcutaneous injection for the treatment of opioid use disorder (OUD). Matched QT and plasma drug concentrations (11,925) from 1,114 subjects were pooled from 5 studies in OUD. A concentration‐QT model was developed, which accounted for confounding factors (e.g., comedications) affecting heart rate and heart rate‐corrected QT interval (QTc). Bias‐corrected nonparametric two‐sided 90% confidence intervals (CIs) were derived for the mean predicted effect of BUP‐XR on QTc (ΔQTc) at therapeutic and supratherapeutic doses. Changes in QTc were associated with age, central vs. noncentral reading, sex, methadone, and barbiturates. The upper 90% CI of ΔQTc was 0.29, 0.67, and 1.34 ms at the steady‐state peak concentration (Cmax) for 100, 300, and 2 × 300 mg doses, respectively. An effect of BUP‐XR on QT can be ruled out at therapeutic and supratherapeutic doses of BUP‐XR, after accounting for covariates that may influence heart rate and QT interval in OUD.

The role men who have sex with men and women (MSMW) play in heterosexual HIV transmission is not well understood. We analyzed baseline data from Project MIX, a behavioral intervention study of substance-using men who have sex with men (MSM), and identified correlates of unprotected vaginal intercourse, anal intercourse, or both with women (UVAI). Approximately 10% (n=194) of the men reported vaginal sex, anal sex, or both with a woman; of these substance-using MSMW, 66% (129) reported UVAI. Among substance-using MSMW, multivariate analyses found unemployment relative to full/part-time employment (OR=2.28; 95% CI 1.01, 5.17), having a primary female partner relative to no primary female partner (OR=3.44; CI 1.4, 8.46), and higher levels of treatment optimism (OR=1.73; 95% CI 1.18, 2.54) increased odds of UVAI. Strong feelings of connection to a same-race gay community (OR=0.71; 95% CI 0.56, 0.91) and Viagra use (OR=0.31; 95% CI 0.10, 0.95) decreased odds of UVAI. This work suggests that although the proportion of substance-using MSM who also have sex with women is low, these men engage in unprotected sex with women, particularly with primary female partners. This work highlights the need for further research with the substance using MSMW population to inform HIV prevention interventions specifically for MSMW.

BackgroundAccess to STD screening and HIV testing are important components of sexual and reproductive health care for adolescents. However, few youth have ever had an STD or HIV test, suggesting a need for new approaches to linking adolescents to care. Project Connect is an 8 year, quasi-experimental study of a multi-level intervention to prevent STD, HIV, and teen pregnancy. The Health Systems Intervention component was designed to provide an effective conduit to link youth to available health care services. Community health care providers who offered adolescents high quality care were identified and recruited for a referral system implemented through school nurses.MethodsSix intervention and six control high schools in a public school district in the Los Angeles, California area participated in the study. Analyses included survey data from 6623 sexually experienced (ever engaged in sexual intercourse) and 4703 sexually active (engaged in intercourse in the past 3 months) female high school students across 5 years (T1–T5). Both samples were 78% Latino and 13% African American; the mean age was 16.6. A mixed model logistic regression analysis was used to test for intervention effects. Random effects on the student level were included to control for repeated measures.ResultsStatistically significant intervention effects were observed overall among both samples (see O2-S2.01 table 1 for adjusted OR and 95% CIs for sexually experienced sample) for receiving STD testing or treatment in the past year and ever being tested for HIV. At T1, for example, 18% of sexually experienced intervention females reported being tested/treated for an STD in the past year; at T5, 29.2% reported having done so. In the control condition, 17% reported STD testing/treatment in the past year at T1, which remained relatively stable by T5, at 19.9%. Among sexually experienced females statistically significant increases were also found for ever being tested for an STD. O2-S2.01 Table 1Adjusted OR for the change between time points in sexually experienced femalesTime point paired differenceAOR (95% CI)STD test/Tx past yearEver STD testEver HIV testT2-T11.12 (0.66 to 1.98)1.06 (0.57 to 1.97)1.16 (0.59 to 2.26)T3-T11.73 (1.02 to 2.95)*1.44 (0.77 to 2.70)1.42 (0.73 to 2.28)T4-T11.67 (0.965 to 2.87)1.97(1.03 to 3.77)*2.20 (1.10 to 4.39)*T5-T11.93 (1.14 to 3.26)*1.28 (0.68 to 2.41)1.94 (0.99 to 3.81)T3-T21.55 (0.93 to 2.56)1.36 (0.75 to 2.45)1.23 (0.65 to 2.32)T4-T21.49 (0.88 to 2.51)1.86 (0.99 to 3.48)1.90 (0.97 to 3.71)T5-T21.72 (1.04 to 2.85)*1.21 (0.66 to 2.22)1.67 (0.86 to 3.24)T4-T30.96 (0.57 to 1.62)1.36 (0.74 to 2.50)1.55 (0.81 to 2.96)T5-T31.11 (0.67 to 1.84)0.89 (0.49 to 1.61)1.37 (0.72 to 2.59)T5-T41.16 (0.70 to 1.91)0.65 (0.36 to 1.18)0.88 (0.47 to 1.65)* p<0.05.ConclusionsProject Connect was successful in linking female adolescents to sexual and reproductive health care through high school nurses. Rather than attempting to change provider behaviour, this structural intervention capitalises on existing, adolescent-focused expertise among local medical providers. It is a low-cost, sustainable strategy for linking (or ensuring access for) adolescents to care and could be widely implemented.