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1.  Enhanced Personal Contact With HIV Patients Improves Retention in Primary Care: A Randomized Trial in 6 US HIV Clinics 
Gardner, Lytt I. | Giordano, Thomas P. | Marks, Gary | Wilson, Tracey E. | Craw, Jason A. | Drainoni, Mari-Lynn | Keruly, Jeanne C. | Rodriguez, Allan E. | Malitz, Faye | Moore, Richard D. | Bradley-Springer, Lucy A. | Holman, Susan | Rose, Charles E. | Girde, Sonali | Sullivan, Meg | Metsch, Lisa R. | Saag, Michael | Mugavero, Michael J. | Drainoni, Mari-Lynn | Ferreira, Cintia | Koppelman, Lisa | McDoom, Maya | Naisteter, Michal | Osella, Karina | Ruiz, Glory | Skolnik, Paul | Sullivan, Meg | Gibbs-Cohen, Sophia | Desrivieres, Elana | Frederick, Mayange | Gravesande, Kevin | Holman, Susan | Johnson, Harry | Taylor, Tonya | Wilson, Tracey | Cheever, Laura | Malitz, Faye | Mills, Robert | Craw, Jason | Gardner, Lytt | Girde, Sonali | Marks, Gary | Batey, Scott | Gaskin, Stephanie | Mugavero, Michael | Murphree, Jill | Raper, Jim | Saag, Michael | Thogaripally, Suneetha | Willig, James | Zinski, Anne | Arya, Monisha | Bartholomew, David | Biggs, Tawanna | Budhwani, Hina | Davila, Jessica | Giordano, Tom | Miertschin, Nancy | Payne, Shapelle | Slaughter, William | Jenckes, Mollie | Keruly, Jeanne | McCray, Angie | McGann, Mary | Moore, Richard | Otterbein, Melissa | Zhou, Liming | Garzon, Carolyn | Jean-Simon, Jesline | Mercogliano, Kathy | Metsch, Lisa | Rodriguez, Allan | Saint-Jean, Gilbert | Shika, Marvin | Bradley-Springer, Lucy | Corwin, Marla
The intervention tested in the Retention in Care Study demonstrated improvement in retention in human immunodeficiency virus care. Enhanced personal contact with or without additional behavioral skills training significantly improved visit constancy and visit adherence over 12 months.
Background. The aim of the study was to determine whether enhanced personal contact with human immunodeficiency virus (HIV)–infected patients across time improves retention in care compared with existing standard of care (SOC) practices, and whether brief skills training improves retention beyond enhanced contact.
Methods. The study, conducted at 6 HIV clinics in the United States, included 1838 patients with a recent history of inconsistent clinic attendance, and new patients. Each clinic randomized participants to 1 of 3 arms and continued to provide SOC practices to all enrollees: enhanced contact with interventionist (EC) (brief face-to-face meeting upon returning for care visit, interim visit call, appointment reminder calls, missed visit call); EC + skills (organization, problem solving, and communication skills); or SOC only. The intervention was delivered by project staff for 12 months following randomization. The outcomes during that 12-month period were (1) percentage of participants attending at least 1 primary care visit in 3 consecutive 4-month intervals (visit constancy), and (2) proportion of kept/scheduled primary care visits (visit adherence).
Results. Log-binomial risk ratios comparing intervention arms against the SOC arm demonstrated better outcomes in both the EC and EC + skills arms (visit constancy: risk ratio [RR], 1.22 [95% confidence interval {CI}, 1.09–1.36] and 1.22 [95% CI, 1.09–1.36], respectively; visit adherence: RR, 1.08 [95% CI, 1.05–1.11] and 1.06 [95% CI, 1.02–1.09], respectively; all Ps < .01). Intervention effects were observed in numerous patient subgroups, although they were lower in patients reporting unmet needs or illicit drug use.
Conclusions. Enhanced contact with patients improved retention in HIV primary care compared with existing SOC practices. A brief patient skill-building component did not improve retention further. Additional intervention elements may be needed for patients reporting illicit drug use or who have unmet needs.
Clinical Trials Registration. CDCHRSA9272007.
PMCID: PMC4366591  PMID: 24837481
behavioral intervention trial; HIV infection; HIV specialty clinics; randomized controlled trial; retention in care
2.  A Low-Effort, Clinic-Wide Intervention Improves Attendance for HIV Primary Care 
Data from 6 human immunodeficiency virus clinics showed improvements in clinic attendance after versus before a clinic-wide intervention (7% on short-term measure; 3% on longer-term measure). Several subgroups showed larger improvements: younger patients, new or reengaging patients, and patients with elevated viral loads.
Background. Retention in care for human immunodeficiency virus (HIV)–infected patients is a National HIV/AIDS Strategy priority. We hypothesized that retention could be improved with coordinated messages to encourage patients' clinic attendance. We report here the results of the first phase of the Centers for Disease Control and Prevention/Health Resources and Services Administration Retention in Care project.
Methods. Six HIV-specialty clinics participated in a cross-sectionally sampled pretest-posttest evaluation of brochures, posters, and messages that conveyed the importance of regular clinic attendance. 10 018 patients in 2008–2009 (preintervention period) and 11 039 patients in 2009–2010 (intervention period) were followed up for clinic attendance. Outcome variables were the percentage of patients who kept 2 consecutive primary care visits and the mean proportion of all primary care visits kept. Stratification variables were: new, reengaging, and active patients, HIV RNA viral load, CD4 cell count, age, sex, race or ethnicity, risk group, number of scheduled visits, and clinic site. Data were analyzed by multivariable log-binomial and linear models using generalized estimation equation methods.
Results. Clinic attendance for primary care was significantly higher in the intervention versus preintervention year. Overall relative improvement was 7.0% for keeping 2 consecutive visits and 3.0% for the mean proportion of all visits kept (P < .0001). Larger relative improvement for both outcomes was observed for new or reengaging patients, young patients and patients with elevated viral loads. Improved attendance among the new or reengaging patients was consistent across the 6 clinics, and less consistent across clinics for active patients.
Conclusion. Targeted messages on staying in care, which were delivered at minimal effort and cost, improved clinic attendance, especially for new or reengaging patients, young patients, and those with elevated viral loads.
PMCID: PMC3657526  PMID: 22828593
3.  Three Generations and Six Family Members with a t(13q15q) Chromosome 
Journal of Medical Genetics  1973;10(1):94-96.
A patient with the clinical features of trisomy 13 without prosencephalic defects and with a 46,XX,15-,t(13q15q)+ karyotype is reported. The translocation chromosome was present in five other phenotypically normal family members and could be traced back to the maternal grandfather.
PMCID: PMC1012983  PMID: 4697861
4.  Otic Lesions and Congenital Hypothyroidism in the Developing Chick* 
Journal of Clinical Investigation  1967;46(11):1828-1839.
In an effort to elucidate the relation, if any, between thyroid abnormality and congenital deafness in Pendred's syndrome, an experiment was designed to study the effects of hypothyroidism on middle and inner ear hearing structures, including the auditory nerve and its central projection, in developing chick embryos. Propylthiouracil (PTU), 2 mg, was injected into the albumin of fertile chick eggs on the 10th incubation day. Single doses of L-thyroxine (range 1-100μg) were inoculated in a similar manner, either alone or with PTU. Control inocula included sterile saline or water. After hatching, each chick was examined for obvious malformations. The thyroid glands, middle and inner ear mechanisms, auditory nerve, and brainstem were studied grossly and with different histologic staining techniques. When compared to controls, chicks exposed to PTU on their 10th incubation day exhibited: increased mortality, delayed hatching, reduced size, incomplete yolk sac absorption, and death within 5 days unless exogenous thyroid hormone was provided in the first 24-48 hr after hatching. Specific, consistent, morphologic alterations were observed in their thyroid glands as well as in the sensory hair cells of the acoustic papilla and cells of the spiral ganglion of the cochlea. Our data also indicate that if 50-75 μg of L-thyroxine is given simultaneously with (or as long as 120 hr after) the PTU injection on the 10th incubation day, one cannot detect the gross defects, marked thyroid lesions, or abnormal histology in cells of the cochlea and its ganglion. A relationship between embryonic thyroid gland function and the hearing mechanism of the chick embryo is suggested.
PMCID: PMC292933  PMID: 6070327
7.  Measuring Retention in HIV Care: The Elusive Gold Standard 
Measuring retention in HIV primary care is complex as care includes multiple visits scheduled at varying intervals over time. We evaluated six commonly used retention measures in predicting viral load (VL) suppression and the correlation among measures.
Clinic-wide patient-level data from six academic HIV clinics were used for 12-months preceding implementation of the CDC/HRSA Retention in Care intervention. Six retention measures were calculated for each patient based upon scheduled primary HIV provider visits: count and dichotomous missed visits, visit adherence, 6-month gap, 4-month visit constancy, and the HRSA HAB retention measure. Spearman correlation coefficients and separate unadjusted logistic regression models compared retention measures to one another and with 12-month VL suppression, respectively. The discriminatory capacity of each measure was assessed with the c-statistic.
Among 10,053 patients, 8,235 (82%) had 12-month VL measures, with 6,304 (77%) achieving suppression (VL<400 c/mL). All six retention measures were significantly associated (P<0.0001) with VL suppression (OR;95%CI, c-statistic): missed visit count (0.73;0.71–0.75,0.67), missed visit dichotomous (3.2;2.8–3.6,0.62), visit adherence (3.9;3.5–4.3,0.69), gap (3.0;2.6–3.3,0.61), visit constancy (2.8;2.5–3.0,0.63), HRSA HAB (3.8;3.3–4.4,0.59). Measures incorporating “no show” visits were highly correlated (Spearman coefficient=0.83–0.85), as were measures based solely upon kept visits (Spearman coefficient=0.72–0.77). Correlation coefficients were lower across these two groups of measures (Range=0.16–0.57).
Six retention measures displayed a wide range of correlation with one another, yet each measure had significant association and modest discrimination for VL suppression. These data suggest there is no clear gold standard, and that selection of a retention measure may be tailored to context.
PMCID: PMC3508092  PMID: 23011397
Retention in care; Adherence; Engagement in care; Viral load
Human immunology  2011;72(4):312-318.
Populations of African ancestry continue to account for a disproportionate burden of human immunodeficiency virus type 1 (HIV-1) epidemic in the US. We investigated the effects of human leukocyte antigen (HLA) class I markers in association with virologic and immunologic control of HIV-1 infection among 338 HIV-1 subtype B-infected African Americans in two cohorts: REACH (Reaching for Excellence in Adolescent Care and Health) and HERS (HIV Epidemiology Research Study). One-year treatment-free interval measurements of HIV-1 RNA viral loads and CD4+ T-cells were examined both separately and combined to represent three categories of HIV-1 disease control (76 “controllers,” 169 “intermediates,” and 93 “non-controllers”). Certain previously or newly implicated HLA class I alleles (A*32, A*36, A*74, B*14, B*1510, B*3501, B*45, B*53, B*57, Cw*04, Cw*08, Cw*12, and Cw*18) were associated with one or more of the endpoints in univariate analyses. After multivariable adjustments for other genetic and non-genetic risk factors of HIV-1 progression, the subset of alleles more strongly or consistently associated with HIV-1 disease control included A*32, A*74, B*14, B*45, B*53, B*57, and Cw*08. Carriage of infrequent HLA-B but not HLA-A alleles was associated with more favorable disease outcomes. Certain HLA class I associations with control of HIV-1 infection span the boundaries of race and viral subtype; while others appear confined within one or the other of those boundaries.
PMCID: PMC3778654  PMID: 21262311
HLA class I; Allele frequency; HIV-1 control; African American
9.  Human Leukocyte Antigen Class I Supertypes and HIV-1 Control in African Americans▿  
Journal of Virology  2009;84(5):2610-2617.
The role of human leukocyte antigen (HLA) class I supertypes in controlling human immunodeficiency virus type 1 (HIV-1) infection in African Americans has not been established. We examined the effects of the HLA-A and HLA-B alleles and supertypes on the outcomes of HIV-1 clade B infection among 338 African American women and adolescents. HLA-B58 and -B62 supertypes (B58s and B62s) were associated with favorable HIV-1 disease control (proportional odds ratio [POR] of 0.33 and 95% confidence interval [95% CI] of 0.21 to 0.52 for the former and POR of 0.26 and 95% CI of 0.09 to 0.73 for the latter); B7s and B44s were associated with unfavorable disease control (POR of 2.39 and 95% CI of 1.54 to 3.73 for the former and POR of 1.63 and 95% CI of 1.08 to 2.47 for the latter). In general, individual alleles within specific B supertypes exerted relatively homogeneous effects. A notable exception was B27s, whose protective influence (POR, 0.58; 95% CI, 0.35 to 0.94) was masked by the opposing effect of its member allele B*1510. The associations of most B supertypes (e.g., B58s and B7s) were largely explained either by well-known effects of constituent B alleles or by effects of previously unimplicated B alleles aggregated into a particular supertype (e.g., B44s and B62s). A higher frequency of HLA-B genotypic supertypes correlated with a higher mean viral load (VL) and lower mean CD4 count (Pearson's r = 0.63 and 0.62, respectively; P = 0.03). Among the genotypic supertypes, B58s and its member allele B*57 contributed disproportionately to the explainable VL variation. The study demonstrated the dominant role of HLA-B supertypes in HIV-1 clade B-infected African Americans and further dissected the contributions of individual class I alleles and their population frequencies to the supertype effects.
PMCID: PMC2820922  PMID: 20032191
10.  Mortality rates and causes of death in a cohort of HIV-infected and uninfected women, 1993–1999 
HIV/AIDS-associated and non-HIV/AIDS-associated death rates and causes of death between 1993 and 1999 were examined in 885 HIV-infected women and 425 uninfected women of the HIV Epidemiology Research Study cohort. Causes of death were determined by review of death certificates and the National Death Index. Adjusted bazard ratios were calculated for mortality risk factors. In the 885 HIV-infected women and 425 uninfected women, 234 deaths and 8 deaths, respectively, occurred by December 31, 1999. All-cause death rates in the HIV-infected women were unchanged between the pre-HAART (1993–1996) and HAART eras (1997–1999) —5.1 versus 5.4 deaths per 100 person-years (py). AIDS as a cause of death decreased from 58% of all deaths in 1996 to 19% in 1999, while HAART use increased to 42% by the end of 1999. In spite of the modest proportion ever using HAART, HIV-related mortality rates did decline, particularly in women with CD4+cell counts less than 200/mm3. Drug-related factors were prominent: for the 129 non-AIDS-defining deaths, hepatitis C positivity (relative bazard [RH] 2.6, P<0.001) and injection drug use (RH 1.7, P=0.02) were strong predictors of mortality, but were not significant in the Cox model for 105 AIDS-defining deaths (RH 0.9, P>30 and RH 0.7, P>.30, respectively. The regression analysis findings, along with the high percentage of non-AIDS deaths attributable to illicit drug use, suggest that high levels of drug use in this population offset improvements in mortality from declining numbers of deaths due to AIDS.
PMCID: PMC3456216  PMID: 14709715
Women; Mortality; Cause of death; HIV; AIDS; Injection drug use
The Journal of General Physiology  1952;36(2):153-159.
Albino rats weighing 160 to 175 gm. were fed a complete synthetic diet containing 0.003 per cent potassium and 0.7 per cent sodium for 40 days. Controls were given the same diet plus adequate added potassium. 1. Data from analyses of serum and skeletal muscle showed (a) a fall in serum chloride concentration and an increase in serum carbon dioxide concentration and pH in the potassium-deficient rats; (b) increases of sodium, magnesium, and calcium and a decrease of potassium in the muscle of the potassium-deficient rats; (c) no change of muscle chloride or carbon dioxide concentrations in the potassium-deficient rats. (2) Application of the Wallace-Hastings calculations to these data revealed (a) intracellular pH of the skeletal muscle of the normal rat to be 6.98 ± 0.08; (b) an increase in serum partial pressure of carbon dioxide (pCO2) in potassium deficiency, together with increases in concentrations of [H2CO2] and [HCO3-] per kg. extracellular water and [H2CO3] per kg. cell water; (c) a decrease in values for [CO2] and [HCO3-] per kg. intracellular water; (d) a fall of intracellular pH in potassium deficiency to 6.42 ± 0.05. (3) Analyses of sacrospinalis muscle from five men undergoing operation for ruptured intervertebral disc showed a mean value of 9.46 ± 1.31 mM carbon dioxide per kg. blood-free tissue. Some problems of interpretation of data are briefly discussed.
PMCID: PMC2147370  PMID: 13011273

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