Washington state satellite HIV clinic program: a model for delivering highly effective decentralized care in under-resourced communities.

To improve access to high-quality HIV care in underserved regions of Western Washington (WA) State, we collaborated with the WA State Department of Health (DOH) and community partners to launch four satellite HIV clinics. Here, we describe this innovative clinical care model, present an estimate of costs, and evaluate patient care outcomes, including virologic suppression rates. To accomplish this, we assessed virologic suppression rates 12 months before and 12 months after the satellite clinics opened, comparing people living with HIV (PLWH) who enrolled in the satellite clinics versus all PLWH in the same regions who did not. We also determined virologic suppression rates in 2015 comparing satellite clinic versus non-satellite clinic patients and compared care quality indicators between the satellite clinics and the parent academic clinic. Results demonstrate that the change in virologic suppression rate 12 months before to 12 months after the satellite clinics opened was higher for patients who enrolled in the satellite clinics compared to all those in the same region who did not (18% versus 6%, p < 0.001). Virologic suppression in 2015 was significantly higher for satellite clinic than non-satellite clinic patients at three of four sites. Care quality indicators were met at a high level at the satellite clinics, comparable to the parent academic clinic. Overall, through community partnerships and WA DOH support, the satellite clinic program increased access to best practice HIV care and improved virologic suppression rates in difficult-to-reach areas. This model could be expanded to other regions with inadequate access to HIV practitioners, though financial support is necessary.

A pilot study of the characterization of hepatic tissue strain in children with cystic-fibrosis-associated liver disease (CFLD) by acoustic radiation force impulse imaging.

BACKGROUND: Progressive fibrotic alterations of liver tissue represent a major complication in children with cystic fibrosis. Correct assessment of cystic-fibrosis-associated liver disease (CFLD) in clinical routine is a challenging issue. Sonographic elastography based on acoustic radiation force impulse imaging (ARFI) is a new noninvasive approach for quantitatively assessing in vivo elasticity of biological tissues in many organs. OBJECTIVE: To characterize ARFI elastography as a diagnostic tool to assess alteration of liver tissue elasticity related to cystic fibrosis in children. MATERIALS AND METHODS: ARFI elastography and B-mode US imaging were performed in 36 children with cystic fibrosis. The children's clinical history and laboratory parameters were documented. According to the findings on conventional US, children were assigned to distinct groups indicating severity of hepatic tissue alterations. The relationship between US findings and respective elastography values was assessed. Additionally, differences between ARFI elastography values of each US group were statistically tested. RESULTS: Children with sonomorphologic characteristics of fibrotic tissue remodeling presented significantly increased values for tissue elasticity. Children with normal B-mode US or discrete signs of hepatic tissue alterations showed a tendency toward increased tissue stiffness indicating early tissue remodeling. CONCLUSION: Assessment of children with CFLD by means of ARFI elastography yields adequate results when compared to conventional US. For detection of early stages of liver disease with mild fibrotic reactions of hepatic tissue, ARFI elastography might offer diagnostic advantages over conventional US. Thus, liver stiffness measured by means of elastography might represent a valuable biological parameter for evaluation and follow-up of CFLD.

Major depression as a potential trigger for Tako Tsubo cardiomyopathy.

Tako-Tsubo cardiomyopathy (TTC) is characterized by the sudden onset of severe left ventricular contractile dysfunction following profound emotional or physical stress. The underlying pathomechanism still remains to be elucidated. In this case we present a, to date, unique case of a female patient suffering from an episode of major depression who shows characteristic features of TTC.

Activated cell survival cascade protects cardiomyocytes from cell death in Tako-Tsubo cardiomyopathy.

AIMS: Tako-Tsubo cardiomyopathy (TTC) is characterized by rapid regeneration of contractile dysfunction. From recent studies it is known that excessive catecholamine levels due to emotional or physical stress might play a central role. After sympathetic activation, the PIK3/AKT pathway is a key regulator of many cellular responses, including cytoprotective effects. Thus, the purpose of this study was to investigate whether the PIK3/AKT pathway plays a pivotal role in TTC. METHODS AND RESULTS: A total of 16 consecutive patients diagnosed with TTC were studied. Left ventricular biopsies were taken during the acute phase and after functional recovery. Specimens were examined by quantitative RT-PCR and western blotting. Representative genes of the PI3K/AKT pathway (PIK3-R1, PTEN, GSK3beta, mTOR, PP2A, eIF4E) were compared with left ventricular controls from non-transplanted healthy hearts. PI3K expression was increased during the acute phase and after functional recovery. AKT protein levels were unaltered, but phosphorylation significantly increased during the acute phase. Both PTEN (PI3K antagonist) and PP2 (unspecific phosphatase) were down-regulated. Phosphorylation of the PI3K/AKT downstream target mTOR was increased, while expression of both GSK3 isoforms was decreased. The Bax/Bcl2 ratio was increased in the acute and recovery phases. CONCLUSION: PI3K/AKT signalling is activated in TTC. This activated cell survival cascade might protect cardiomyocytes from cell death and also contribute to rapid regeneration in TTC.

Abnormalities in intracellular Ca2+ regulation contribute to the pathomechanism of Tako-Tsubo cardiomyopathy.

AIMS: The Tako-Tsubo cardiomyopathy (TTC) is characterized by a transient contractile dysfunction that has been assigned to excessive catecholamine levels after episodes of severe emotional or physical stress. Several studies have indicated that beta-adrenoceptor stimulation is associated with alteration in gene expression of Ca(2+)-regulatory proteins. Thus, the present study investigated the gene expression of crucial proteins [sarcoplasmic Ca(2+) ATPase (SERCA2a), sarcolipin (SLN), phospholamban (PLN), ryanodine receptor (RyR2), and sodium-calcium exchanger (NCX)] involved in the Ca(2+)-regulating system in TTC. METHODS AND RESULTS: In 10 consecutive patients, TTC was diagnosed by coronary angiography, ventriculography, and echocardiography. Endomyocardial biopsies were taken during the phase of severely impaired left ventricular (LV) function and after functional recovery. Non-diseased LV tissue from three donor hearts not used for transplantation served as healthy controls. Expression levels of Ca(2+)-regulatory proteins were analysed by means of real-time PCR, western blot, and immunohistochemistry. SLN, predominantly expressed in the atrial component, showed a remarkable ventricular expression in TTC patients. Gene expression of SERCA2a was significantly down-regulated. Conversely, PLN/SERCA2a ratio was increased. For PLN, dephosphorylation was documented using western blot and immunostaining of PLN-Ser(16) and PLN-Thr(17). No changes could be documented for NCX and RyR2. CONCLUSION: In TTC, ventricular expression of SLN and dephosphorylation of PLN potentially result in a reduced SERCA2a activity and its Ca(2+) affinity. Thus, the TTC is associated with specific alteration of Ca(2+)-handling proteins, which might be crucial for contractile dysfunction.

Challenges in the prevention, diagnosis, and treatment of malaria in human immunodeficiency virus infected adults in sub-Saharan Africa.

BACKGROUND: Many countries in sub-Saharan Africa currently report high prevalences of both human immunodeficiency virus (HIV) and Plasmodium falciparum malaria. The likelihood of HIV-malaria coinfection may affect clinical management of patients. The extent to which standard clinical guidelines address HIV-malaria coinfection is unclear. METHODS: We reviewed standard World Health Organization and other guidelines for diagnosis and treatment of malaria and/or HIV-related illness. We also searched PubMed (1990 to present) for literature on HIV-malaria interactions and treatment of coinfection. We restricted our review to the situation of the nonpregnant HIV-infected adult. RESULTS: We found only 6 articles describing the clinical presentation of HIV-malaria coinfection in adults. We also identified 10 clinical or laboratory syndromes that are shared by malaria and AIDS-related conditions and that might provoke diagnostic confusion. We identified 12 antimalarial medications whose coadministration with antiretrovirals is known or suspected to result in drug-drug interactions or overlapping toxicities. CONCLUSIONS: Substantial overlap in the clinical and laboratory characteristics of malaria and HIV-related syndromes generates potential difficulties in AIDS staging and in diagnosis and management of patients at risk for coinfection. Significant drug-drug interactions and overlapping drug toxicity profiles further complicate concurrent management of malaria and HIV. Standard clinical guidelines do not reflect the full complexity of the interactions and overlaps between the 2 infections. Clinicians who manage HIV-infected patients in malaria-affected regions should systematically consider malaria when evaluating patients with a broad spectrum of symptoms. Further research is urgently needed to define best practices for prevention, diagnosis, and management of HIV-malaria coinfection in this region.

Challenges in the concurrent management of malaria and HIV in pregnancy in sub-Saharan Africa.

Approximately one million pregnancies are complicated by both malaria and HIV infection in sub-Saharan Africa annually. Both infections have been associated with maternal and infant morbidity and mortality. Intermittent preventive treatment, usually with sulfadoxine-pyrimethamine, has been shown to prevent pregnancy-related malaria and its complications. Several different regimens of antiretroviral therapy are now available to prevent mother-to-child transmission of HIV and/or progression of maternal HIV infection during pregnancy. However, no published studies have yet shown whether standard intermittent preventive treatment and antiretroviral regimens are medically and operationally compatible in pregnancy. We reviewed existing policies regarding prevention and treatment of HIV and malaria in pregnancy, as well as published literature on adverse effects of antiretrovirals and antimalarials commonly used in pregnancy in developing countries, and found that concurrent prescription of sulfadoxine-pyrimethamine, co-trimoxazole (trimethoprim-sulfamethoxazole), and antiretroviral agents including nevirapine and zidovudine per existing protocols for prevention of malaria and vertical HIV transmission may result in adverse drug interactions or overlapping, diagnostically challenging drug toxicities. Insecticide-treated bednets should be provided for HIV-infected pregnant women at risk for malaria. Sulfadoxine-pyrimethamine should be prescribed cautiously in women concurrently receiving daily nevirapine and/or zidovudine, and should be avoided in women on daily co-trimoxazole. Further research is urgently needed to define safe and effective protocols for concurrent management of HIV and malaria in pregnancy, and to define appropriate interventions for different populations subject to differing levels of malaria transmission and antimalarial drug resistance.