Measuring adherence to antiretroviral therapy in children and adolescents in western Kenya

Introduction

High levels of adherence to antiretroviral therapy (ART) are central to HIV management. The objective of this study was to compare multiple measures of adherence and investigate factors associated with adherence among HIV-infected children in western Kenya.

Methods

We evaluated ART adherence prospectively for six months among HIV-infected children aged ≤14 years attending a large outpatient HIV clinic in Kenya. Adherence was reported using caregiver report, plasma drug concentrations and Medication Event Monitoring Systems (MEMS^®). Kappa statistics were used to compare adherence estimates with MEMS^®. Logistic regression analyses were performed to assess the association between child, caregiver and household characteristics with dichotomized adherence (MEMS^® adherence ≥90% vs. <90%) and MEMS^® treatment interruptions of ≥48 hours. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results

Among 191 children, mean age at baseline was 8.2 years and 55% were female. Median adherence by MEMS^® was 96.3% and improved over the course of follow-up (p<0.01), although 49.5% of children had at least one MEMS^® treatment interruption of ≥48 hours. Adherence estimates were highest by caregiver report, and there was poor agreement between MEMS^® and other adherence measures (Kappa statistics 0.04–0.37). In multivariable logistic regression, only caregiver-reported missed doses in the past 30 days (OR 1.25, 95% CI 1.14–1.39), late doses in the past seven days (OR 1.14, 95% CI 1.05–1.22) and caregiver-reported problems with getting the child to take ART (OR 1.10, 95% CI 1.01–1.20) were significantly associated with dichotomized MEMS^® adherence. The caregivers reporting that ART made the child sick (OR 1.12, 95% CI 1.01–1.25) and reporting difficulties in the community that made giving ART more difficult (e.g. stigma) (OR 1.14, 95% CI 1.02–1.27) were significantly associated with MEMS^® treatment interruptions in multivariable logistic regression.

Conclusions

Non-adherence in the form of missed and late doses, treatment interruptions of more than 48 hours and sub-therapeutic drug levels were common in this cohort. Adherence varied significantly by adherence measure, suggesting that additional validation of adherence measures is needed. Few factors were consistently associated with non-adherence or treatment interruptions.     

19F NMR as a Probe of Ligand Interactions with the iNOS Binding site of SPRY Domain‐Containing SOCS Box Protein 2

SPRY domain‐containing SOCS box protein 2 (SPSB2) regulates inducible nitric oxide synthase (iNOS) by targeting it for proteasomal degradation. Inhibiting this interaction prolongs the intracellular lifetime of iNOS, leading in turn to enhanced killing of infectious pathogens such as bacteria and parasites. SPSB2 recognizes a linear motif (DINNN) in the disordered N‐terminus of iNOS, and ligands that target the DINNN binding site on SPSB2 are potentially novel anti‐infective agents. We have explored ¹⁹F NMR as a means of probing ligand binding to SPSB2. All six Trp residues in SPSB2 were replaced with 5‐fluorotryptophan (5‐F‐Trp) by utilizing a Trp auxotroph strain of Escherichia coli. The labeled protein was well folded and bound a DINNN‐containing peptide with similar affinity to native SPSB2. Six well‐resolved 5‐F‐Trp resonances were observed in the ¹⁹F NMR spectrum and were assigned using site‐directed mutagenesis. The ¹⁹F resonance of W207 was significantly perturbed upon binding to DINNN‐containing peptides. Other resonances were perturbed to a lesser extent although in a way that was sensitive to the composition of the peptide. Analogues of compounds identified in a fragment screen also perturbed the W207 resonance, confirming their binding to the iNOS peptide‐binding site on SPSB2. ¹⁹F NMR promises to be a valuable approach in developing inhibitors that bind to the DINNN binding site.     

Repeated Radiofrequency Ablation of Atrial Tachycardia in Restrictive Cardiomyopathy Secondary to Myofibrillar Myopathy

Myofibrillar myopathy is characterized by nonhyaline and hyaline lesions due to mutations in nuclear genes encoding for extra‐myofibrillar or myofibrillar proteins. Cardiac involvement in myofibrillar myopathy may be phenotypically expressed as dilated, hypertrophic, or restrictive cardiomyopathy. Radiofrequency ablation of atrial fibrillation and flutter has so far not been reported in myofibrillar myopathy. We report the case of a young female with myofibrillar myopathy and deteriorating heart failure due to restrictive cardiomyopathy and recurrent atrial fibrillation and atrial tachycardias intolerant to pharmacotherapy. Cardiac arrhythmias were successfully treated with repeat radiofrequency ablations and resulted in regression of heart failure, thus postponing the necessity for cardiac transplantation.     

Bilateral Differences in Muscle Architecture and Increased Rate of Injury in National Basketball Association Players

Context

Professional basketball players have demanding schedules that, in combination with certain underlying physical characteristics and side-to-side strength and power imbalances, may make them vulnerable to lower extremity injuries.

Objective

To examine the relationship among skeletal muscle architecture, lower body power, and games missed because of lower extremity injury (%MISS) in professional basketball players.

Design

Cross-sectional study.

Setting

Human Performance Laboratory.

Patients or Other Participants

Nine players under contract for Orlando Magic were assessed. We compared athletes who were injured (n = 4, height = 203.2 ± 5.5 cm, mass = 105 ± 7.5 kg, age = 25.0 ± 2.8 years) and those who remained healthy (n = 5, height = 200.2 ± 12.2 cm, mass = 100.1 ± 16.6 kg, age = 22.4 ± 1.9 years) during the season.

Main Outcome Measure(s)

Bilateral ultrasonographic measurements of muscle thickness, pennation angle, echo intensity, and cross-sectional area of the rectus femoris and vastus lateralis were collected before regular-season play. Subsequently, muscle thickness and pennation angle were used to compute fascicle length. Along with unilateral jumping power, inferences were made upon the magnitude of the relationship between the percentage bilateral difference in these measures and %MISS, as well as between injured and healthy athletes.

Results

The data indicated likely relationships between %MISS and age (r = 0.772), and between %MISS and bilateral differences in rectus femoris cross-sectional area (7.8% ± 6.4%; r = 0.657) and vastus lateralis cross-sectional area (6.2% ± 4.8%; r = 0.521), as well as a possible relationship with vastus lateralis muscle thickness (7.9% ± 8.9%; r = 0.444). Echo-intensity differences in the vastus lateralis were greater in injured (8.0% ± 2.4%) versus healthy athletes (3.2% ± 2.0%). Although a 2-fold difference in mean jumping power was observed between injured (26.3 ± 14.9 W) and healthy athletes (13.6 ± 8.7 W), these differences were not statistically significant (P = .20).

Conclusions

In the present sample, lower extremity side-to-side differences may be related to an increased risk for lower extremity injury. Future researchers using larger sample sizes need to identify normal versus at-risk ranges for bilateral differences in muscle structure and power of the lower extremities of professional basketball players and athletes in other sports.Key Words: sport science, bilateral deficits, jump power, muscle imbalances, elite athletes

Key Points

• Bilateral differences in the lower extremity may be related to an increased risk for injury.
• A 2-fold difference in power performance was noted between injured and healthy athletes, but this difference in a small sample of participants was not statistically significant.

Physiologically, a professional basketball game is quite demanding.¹ In one 48-minute game, a single player may travel a distance¹ greater than 6000 m via a variety of short, moderate- to high-intensity exertions² that include sprints and quick changes of direction as well as powerful jumps. Over the course of an entire National Basketball Association (NBA) season, a player may participate in 82 regular-season competitions (2–5 games per week), in addition to daily practice sessions and preseason and postseason practices and games. Although the total demand on a single player may vary as a result of a player''s specific roles (eg, position responsibilities), playing time, travel schedule, and days off,³ the ability to remain healthy during such a demanding schedule may depend on underlying physical factors that may make some athletes more susceptible to injury.In the NBA, 60% of all game-related injuries (and 64.6% of all injuries) affect the lower extremity.⁴ This equates to an injury rate of 11.6 lower extremity injuries per 1000 game appearances.⁴ It has been reported that previous injury to the lower extremity,^5–7 bilateral lower limb imbalances,^8–11 and age⁵ are all risk factors for lower extremity injury in anaerobic team sports. Authors of several studies of professional basketball players have examined injury-prediction models using bilateral measurements of skeletal structure,¹² connective tissue,¹³ and isokinetic strength,¹¹ as well as drop-jump and 10-second jump performance.¹¹ However, there has been little to no examination of the effect of bilateral muscle architecture and muscle performance on injury risk. Recent technologic advances have provided a valid, reliable, noninvasive method to assess skeletal muscle architecture using ultrasound.^14,15 To date, we are unaware of any researchers who have examined bilateral differences in muscular architecture and power performance in NBA athletes, and only a few have explored bilateral performance differences in basketball players in general.A certain degree of bilateral strength or power imbalance is apparent in elite basketball players,^11,16 which is likely related to the athlete''s dependence on the dominant leg during cutting, pivoting, and jumping. However, what is deemed to be an acceptable degree of imbalance versus what may potentially lead to injury is not well understood. An imbalance that continues over the course of a season may become magnified, leading to a greater accumulation of fatigue, microtrauma, and eventually injury.^10,11 Considering the demanding stress on the lower extremities of an NBA player during a competitive basketball season, injury to the lower extremity may be related in part to bilateral abnormalities that were present at the start of the season. Given that specific skeletal muscle architectural properties have been associated with force, speed, and power production,^17–20 an investigation of their relationship with lower extremity injury may also prove to be beneficial. Therefore, the purpose of our study was to examine the relationships between bilateral differences in skeletal muscle architecture, measurements of power, and games missed because of injury in the lower extremities of NBA players.     

Sideroblastic changes of the bone marrow can be predicted by the erythrogram of peripheral blood

The diagnosis of sideroblastic anemia is based on bone marrow aspiration, and the detection of ring sideroblasts (RS) in iron staining. The finding of laboratory parameters to approach this diagnosis still remains a great challenge. In this study, we analyzed the value of a specific erythrogram pattern from peripheral blood, produced by the ADVIA^®120 cell counter, to predict sideroblastic changes in the bone marrow. In a two step-design study, we first showed that 32/38 consecutive patients reporting ≥15% RS had such a pattern in the erythrogram. In the second step, we prospectively identified over a period of 32 months 21 patients with this typical erythrogram; 20/21 had ≥15% RS in the bone marrow. Hence, by this validation, we confirm that the erythrogram is highly predictive of RS in the bone marrow. The interpretation of the erythrogram should become daily practice in hematology to improve the efficacy to detect sideroblastic changes.     

JBR-10 Ⅲ期研究：长春瑞滨＋顺铂化疗术后Ⅰb和Ⅱ期非小细胞肺癌获益

对于完全切除的Ⅱ和Ⅲa期非小细胞肺癌（NSCLC），基于顺铂的辅助化疗方案（ACT）为公认的标准方案。长期跟踪随访对评价长期疗效及迟发毒性反应甚为重要。JCO中最近发表了JBR-10Ⅲ期研究总生存期（OS）和疾病特异性生存期（DSS）的最新数据。