“The role of case management in HIV treatment adherence: HPTN 078”

AIDS and Behavior - Adherence to care and antiretroviral therapy is challenging, especially for people living with HIV (PLWH) with additional co-occurring risk factors. Case management...     

Life span differences in digoxin uptake and excretion

Little is known about the underlying mechanisms for the altered susceptibility to digitalis with age. To this end, we investigated the digoxin uptake and excretion in mice and rats of different ages through the life span, including the periods of growth, maturity, and aging. Digoxin uptake by cardiac slices was linear from 0 to 15 min, with steady state occuring at 45 min. The rate in the mature 12-month mouse was significantly less than that of the senescent 30-month mouse. The kinetic parameters revealed a significant decrease in Km with a concomitant increase in Vmax during senescense. On the other hand uptake by renal cortical slices was highest during growth, decreased to a maturation plateau and then declined further during senescence. Renal clearance and the secretory capacity for digoxin increased 30 and 62%, respectively, during growth and progressively decreased from maturity through senescence and were 59 and 77%, respectively, during aging. In summary, there was an increase in digoxin clearance and tubular activity during growth, and in increase in myocardial uptake of digoxin and a decrease in renal excretion during aging. Thus, these results may explain the clinical observations of altered susceptibility to digitalis with age.     

Monitoring recovery from diaphragm paralysis with ultrasound

BACKGROUND: Diaphragmatic paralysis is an uncommon, yet underdiagnosed cause of dyspnea. Data regarding the time course and potential for recovery has come from a few small case series. The methods that have been traditionally employed to diagnose diaphragmatic weakness or paralysis are either invasive or limited in sensitivity and specificity. A new technique utilizing two-dimensional, B-mode ultrasound (US) measurements of diaphragm muscle thickening during inspiration (Deltatdi%) has been validated in the diagnosis of diaphragm paralysis (DP). The purpose of this study was to assess whether serial US evaluation might be utilized to monitor the potential recovery of diaphragm function. METHODS: Twenty-one consecutive patients with clinically suspected DP were referred to the pulmonary physiology laboratory. Sixteen patients were found to have DP by US (unilateral, 10 patients; bilateral, 6 patients). Subjects were followed up for up to 60 months. On initial and subsequent visits, Deltatdi% was measured by US. Additional measurements included upright and supine vital capacity (VC), maximal inspiratory pressure (Pimax), and maximal expiratory pressure. RESULTS: Eleven of 16 patients functionally recovered from DP. The mean (+/- SD) recovery time was 14.9 +/- 6.1 months. No diaphragm thickening was noted in those patients who did not recover. Positive correlations were found between improvement in Deltatdi% and interval changes in VC, Pimax, and end-expiratory measurements of diaphragm thickness. CONCLUSIONS: US may be used to assess for potential functional recovery from diaphragm weakness or DP. As in previous series, recovery occurs in a substantial number of individuals, but recovery time may be prolonged.     

Polypharmacy and risk of falls and fractures for patients with HIV infection and substance dependence

Although people with HIV infection (PLWH) are at higher risk of polypharmacy and substance use, there is limited knowledge about potential harms associated with polypharmacy such as falls and fractures in this population. The study objective was to determine whether polypharmacy, as measured by the number and type of medication, is associated with falls and fractures among PLWH and DSM-IV substance dependence in the past year or ever injection drug use (IDU). We identified the number of medications by electronic medical record review in the following categories: (i) systemically active, (ii) non-antiretroviral (non-ARV), (iii) sedating, (iv) non-sedating as well as any opioid medication and any non-opioid sedating medication. Outcomes were self-reported (1) fall/accident requiring medical attention and (2) fracture in the previous year. Separate logistic regression models were fitted for medications in each category and each outcome. Among 250 participants, the odds of a fall requiring medical attention were higher with each additional medication overall (odds ratio [OR] 1.12, 95% Confidence Interval [CI]?=?1.05, 1.18), each additional non-ARV medication (OR 1.13, 95%CI?=?1.06, 1.20), each additional sedating medication (OR 1.36, 95%CI?=?1.14, 1.62), and a non-opioid sedating medication (OR 2.89, 95%CI?=?1.06, 7.85) but not with an additional non-sedating medication or opioid medication. In receiver operating characteristic (ROC) curve analyses, optimal cutoffs for predicting falls were: ≥8 overall and ≥2 sedating medications. Odds ratios for fracture in the previous year were OR 1.05, 95%CI?=?0.97, 1.13 for each additional medication overall and OR 1.11, 95%CI?=?0.89, 1.38 for each additional sedating medication. In PLWH and substance dependence or ever IDU, a higher number of medications was associated with greater odds of having a fall requiring medical attention. The association appeared to be driven largely by sedating medications. Future studies should determine if reducing such polypharmacy, particularly sedating medications, lowers the risk of falls.     

A CASE OF HEPATOCELLULAR ADKNOMATOSIS WITH A FOLLOW-UP OF 11 YEARS

Hepatoccllular adenomatosis is characterized by the presence of numerous (arbitrarily > 10) adenomas within an otherwise normal liver without a history of glycogen storage disease or steroid hormone therapy. Although the disease is rare, its importance lies in its tendency to produce symptoms such as abdominal pain and its potential for abdominal hemorrhages. However, the prognosis of hepatocellular adenomatosis remains uncertain. Here we describe the ease of a -40-yr-old female with hepatoccllular adenomatosis without evidence of serious complications, who was observed over a period of 11 yr.     

In vivo targeting of human DC‐SIGN drastically enhances CD8+ T‐cell‐mediated protective immunity

Vaccination is one of the oldest yet still most effective methods to prevent infectious diseases. However, eradication of intracellular pathogens and treatment of certain diseases like cancer requiring efficient cytotoxic immune responses remain a medical challenge. In mice, a successful approach to induce strong cytotoxic CD8⁺ T‐cell (CTL) reactions is to target antigens to DCs using specific antibodies against surface receptors in combination with adjuvants. A major drawback for translating this strategy into one for the clinic is the lack of analogous targets in human DCs. DC‐SIGN (DC‐specific‐ICAM3‐grabbing‐nonintegrin/CD209) is a C‐type lectin receptor with potent endocytic capacity and a highly restricted expression on human immature DCs. Therefore, DC‐SIGN represents an ideal candidate for DC targeting. Using transgenic mice that express human DC‐SIGN under the control of the murine CD11c promoter (hSIGN mice), we explored the efficacy of anti‐DC‐SIGN antibodies to target antigens to DCs and induce protective immune responses in vivo. We show that anti‐DC‐SIGN antibodies conjugated to OVA induced strong and persistent antigen‐specific CD4⁺ and CD8⁺ T‐cell responses, which efficiently protected from infection with OVA‐expressing Listeria monocytogenes. Thus, we propose DC targeting via DC‐SIGN as a promising strategy for novel vaccination protocols against intracellular pathogens.     

Health Related Quality of Life and Emotional Health in Children with Chronic Granulomatous Disease: A Comparison of Those Managed Conservatively with Those That Have Undergone Haematopoietic Stem Cell Transplant

Purpose

Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency that predisposes to life-threatening infections and inflammation. Haematopoietic stem cell transplant (HSCT) can cure CGD. Chronic illness reduces quality of life. Children with haematological malignancies report improved quality of life post-HSCT. There are no data for children with CGD. This study evaluated quality of life and emotional well-being in CGD children treated conventionally or transplanted.

Methods

Parents and children completed the Pediatric Quality of Life Inventory v4.0 (PedsQL) and Strengths and Difficulties Questionnaires (SDQ). Mean scores were compared with published UK norms. Comparisons were made for those that had or had not undergone HSCT.

Results

Forty-seven parents completed PedsQL (children aged 3–15). Twenty-one were post-HSCT. Forty-two completed SDQ (children aged 3–15). Nineteen post-HSCT. Median age for non-HSCT group 9 years. Median age for post-HSCT group 10 years. The HSCT group were median 3 years post-HSCT (range 1–9 years). HSCT survival was 90 %—two died without completing questionnaires Parent and self-reported quality of life for non-transplanted children was significantly lower than healthy children. Parents reported increased emotional difficulties compared to published norms. PedsQL and SDQ scores for transplanted children were not significantly different from healthy norms.

Conclusions

This study demonstrates the quality of life is reduced in CGD. Transplanted patients have quality of life comparable to levels reported in healthy children. This data will help inform families and clinicians when deciding about treatment and may have relevance for other immunodeficiencies treated with transplant.     

Correction to: “Best Things”: Parents Describe Their Children with Autism Spectrum Disorder Over Time

Journal of Autism and Developmental Disorders -