Accountability for the human right to health through treaty monitoring: Human rights treaty bodies and the influence of concluding observations

Employing novel coding methods to evaluate human rights monitoring, this article examines the influence of United Nations (UN) treaty bodies on national implementation of the human right to health. The advancement of the right to health in the UN human rights system has shifted over the past 20 years from the development of norms under international law to the implementation of those norms through national policy. Facilitating accountability for this rights-based policy implementation under the right to health, the UN Committee on Economic, Social and Cultural Rights (CESCR) monitors state implementation by reviewing periodic reports from state parties, engaging in formal sessions of ‘constructive dialogue’ with state representatives, and issuing concluding observations for state response. These concluding observations recognise the positive steps taken by states and highlight the principal areas of CESCR concern, providing recommendations for implementing human rights and detailing issues to be addressed in the next state report. Through analytic coding of the normative indicators of the right to health in both state reports and concluding observations, this article provides an empirical basis to understand the policy effects of the CESCR monitoring process on state implementation of the right to health.     

Detrusor glycogen reflects the functional history of bladders with partial outlet obstruction

OBJECTIVE: To assess the relationship between glycogen content in bladder detrusor tissue and historical bladder function in a guinea-pig model of partial bladder outlet obstruction (PBOO). MATERIALS AND METHODS: In male immature guinea pigs PBOO was created with a silver ring around the proximal urethra; a control group had a sham operation for comparison. Longitudinal individual urodynamic data were obtained weekly, so that guinea pigs were killed at different levels of bladder dysfunction. Bladder sections were stained with periodic acid-Schiff (PAS) to assess overall morphology and glycogen granule density, scored from 0 (no glycogen) to 3. Glycogen scores were related to both the end-stage and historical extremes of bladder function values. RESULTS: Glycogen granules were seen only in the detrusor; as their number increased their location expanded from only close to the serosa (glycogen score 1), through the detrusor (score 2) up to the urothelium (score 3). A glycogen score of 0 correlated with normal values for all urodynamic variables. Compared with a glycogen score of 0 a score of 1 correlated with significant (P < 0.05) changes in end-stage compliance (decrease) and contractility (increase) and significantly higher historical values for contractility, pressure and number of unstable contractions (NUC). In the group with a glycogen score of 2 there were significant changes in both the end-stage values and historical extremes for compliance, pressure, contractility and NUC (all P < 0.05). In the group with a glycogen score of 3 all these changes were even more dramatic, except for the end-stage contractility, for which the increase was not significant. From glycogen score 0 to score 3 all changes increased in magnitude. CONCLUSION: A high glycogen content reflects a history of abnormal urodynamic function. This finding exemplifies the added value of structural analysis to urodynamic studies. Further studies are needed to relate bladder structure to the potential for functional recovery.     

“Keyhole” method for accelerating imaging of contrast agent uptake

Magnetic resonance (MR) imaging methods with good spatial and contrast resolution are often too slow to follow the uptake of contrast agents with the desired temporal resolution. Imaging can be accelerated by skipping the acquisition of data normally taken with strong phase-encoding gradients, restricting acquisition to weak-gradient data only. If the usual procedure of substituting zeros for the missing data is followed, blurring results. Substituting instead reference data taken before or well after contrast agent injection reduces this problem. Volunteer and patient images obtained by using such reference data show that imaging can be usefully accelerated severalfold. Cortical and medullary regions of interest and whole kidney regions were studied, and both gradientand spin-echo images are shown. The method is believed to be compatible with other acceleration methods such as half-Fourier reconstruction and reading of more than one line of k space per excitation.     

Neurodevelopmental, educational and behavioral outcome at 8 years after neonatal ECMO: a nationwide multicenter study

Purpose

Reporting neurodevelopmental outcome of 8-year-old children treated with neonatal extracorporeal membrane oxygenation (ECMO).

Methods

In a follow-up study in 135 8-year-old children who received neonatal ECMO between 1996 and 2001 we assessed intelligence (Revised Amsterdam Intelligence Test), concentration (Bourdon-Vos test), eye-hand coordination (Developmental Test of Visual-Motor Integration) and behavior (Child Behavior Checklist and Teacher Report Form).

Results

Intelligence fell within normal range (mean IQ 99.9, SD 17.7, n = 125) with 91 % of the children following regular education. Significantly more children attended special education (9 %) or received extra support in regular education (39 %) compared with normative data. Slower working speed (χ² = 132.36, p < 0.001) and less accuracy (χ² = 12.90, p < 0.001) were found on the Bourdon-Vos test (n = 123) compared with normative data. Eye-hand coordination fell within the normal range (mean 97.6, SD 14.3, n = 126); children with congenital diaphragmatic hernia scored lowest but still normally (mean 91.0, SD 16.4, n = 28). Mothers (n = 117) indicated more somatic and attention behavior problems; teachers (n = 115) indicated more somatic, social, thought, aggression and total problems compared with normative data. Mothers indicated more somatic problems than teachers (p = 0.003); teachers reported more attention problems than mothers (p = 0.036; n = 111).

Conclusions

Eight-year-old children treated with neonatal ECMO fall in the normal range of intelligence with problems with concentration and behavior. Long-term follow-up for children treated with neonatal ECMO should focus on early detection of (subtle) learning deficits.     

Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First-Phase Glucose-Stimulated Insulin Secretion During Hyperglycemic Clamps

OBJECTIVE

At least 20 type 2 diabetes loci have now been identified, and several of these are associated with altered β-cell function. In this study, we have investigated the combined effects of eight known β-cell loci on insulin secretion stimulated by three different secretagogues during hyperglycemic clamps.

RESEARCH DESIGN AND METHODS

A total of 447 subjects originating from four independent studies in the Netherlands and Germany (256 with normal glucose tolerance [NGT]/191 with impaired glucose tolerance [IGT]) underwent a hyperglycemic clamp. A subset had an extended clamp with additional glucagon-like peptide (GLP)-1 and arginine (n = 224). We next genotyped single nucleotide polymorphisms in TCF7L2, KCNJ11, CDKAL1, IGF2BP2, HHEX/IDE, CDKN2A/B, SLC30A8, and MTNR1B and calculated a risk allele score by risk allele counting.

RESULTS

The risk allele score was associated with lower first-phase glucose-stimulated insulin secretion (GSIS) (P = 7.1 × 10⁻⁶). The effect size was equal in subjects with NGT and IGT. We also noted an inverse correlation with the disposition index (P = 1.6 × 10⁻³). When we stratified the study population according to the number of risk alleles into three groups, those with a medium- or high-risk allele score had 9 and 23% lower first-phase GSIS. Second-phase GSIS, insulin sensitivity index and GLP-1, or arginine-stimulated insulin release were not significantly different.

CONCLUSIONS

A combined risk allele score for eight known β-cell genes is associated with the rapid first-phase GSIS and the disposition index. The slower second-phase GSIS, GLP-1, and arginine-stimulated insulin secretion are not associated, suggesting that especially processes involved in rapid granule recruitment and exocytosis are affected in the majority of risk loci.Type 2 diabetes is a polygenic disease in which the contribution of a number of detrimental gene variants in combination with environmental factors is thought to be necessary for the development of disease. In the past 2 years, results of several genome-wide association studies (GWASs) have been published (1–5), leading to a rapidly increasing number of detrimental type 2 diabetes susceptibility loci. More recently, it has indeed been shown that combining information from these diabetes loci into a risk allele score for all loci enhances diabetes risk (6–9). However, the predictive power of this combined risk allele score is yet insufficient to substitute or largely improve predictive power of known clinical risk factors (8,9). At present, little is known about how these gene variants in combination affect insulin secretion or insulin resistance. Based on recent data, mainly obtained from oral glucose tolerance tests (OGTTs), it was shown that a combined risk allele score from gene variants associated with type 2 diabetes is associated with insulin secretion and not with insulin sensitivity (10–13). However, the OGTT is unable to distinguish between first- and second-phase insulin secretion. Furthermore, other secretagogues, like glucagon-like peptide (GLP)-1 and arginine, were not included in these studies.It is thought that the rapid recruitment and release of insulin granules from the readily releasable pool (RRP) is responsible for the first phase of insulin secretion, whereas the slower prolonged second phase involves recruitment to the membrane of more distant granules and de novo insulin synthesis. Although the exact pathways regulating both phases of glucose-stimulated insulin secretion (GSIS) are not completely resolved, it seems logical that they are at least in part different. This is further corroborated by our recent observation that the heritability for both phases of GSIS in twins is derived from partly nonoverlapping sets of genes (13a).Also, other nonglucose, stimuli-like incretins and amino acids can evoke an insulin response. Detailed phenotypic investigations of the response to these different stimuli may help to elucidate which processes are primarily affected by these loci. Previously, we have already shown that type 2 diabetes genes/loci can have different effects on first- and second-phase GSIS, as measured using hyperglycemic clamps. Also, based on the method of stimulation (i.e., oral versus intravenous), the outcome may differ substantially (14–17), which provides further clues about the mechanism by which they affect insulin secretion.In this study, we genotyped gene variants in TCF7L2, KCNJ11, HHEX/IDE, CDKAL1, IGF2BP2, SLC30A8, CDKN2A/CDKN2B, and MTNR1B in 447 hyperglycemic clamped subjects (256 with normal glucose tolerance [NGT] and 191 with impaired glucose tolerance [IGT]) from four independent studies in the Netherlands and Germany. These eight loci were chosen based on the fact that they were reproducibly associated with β-cell function in various studies (rev. in 18,19). A combined risk allele score of all eight gene variants was calculated for each individual and tested against the various detailed measurements of β-cell function using the hyperglycemic clamp, generally considered to be the gold standard for quantification of first- and second-phase GSIS (20). Furthermore, we also assessed the combined effect of these eight genes on two other stimuli, GLP-1 and arginine-stimulated insulin secretion during hyperglycemia, in a subset of the study sample (n = 224). The latter test provides an estimation of the maximal insulin secretion capacity of a subject and may, according to animal studies, serve as a proxy for β-cell mass (21).     

Diagnostic Value of History Taking and Physical Examination to Assess Effusion of the Knee in Traumatic Knee Patients in General Practice

Kastelein M, Luijsterburg PA, Wagemakers HP, Bansraj SC, Berger MY, Koes BW, Bierma-Zeinstra SM. Diagnostic value of history taking and physical examination to assess effusion of the knee in traumatic knee patients in general practice.

Objective

To assess the diagnostic value of history taking and physical examination for knee joint effusion in patients with a knee injury who consult their general practitioner (GP). In addition, to determine the association between effusion seen on magnetic resonance imaging (MRI) and internal derangement of the knee.

Design

Prospective, observational cohort study.

Setting

Primary care.

Participants

Patients (N=134) aged 18 to 65 years with a traumatic knee injury who consulted their GP.

Interventions

Not applicable.

Main Outcome Measures

Patients filled out a questionnaire, underwent a standardized physical examination and underwent an MRI scan to assess the presence of effusion. Multivariate logistic regression analysis was used to determine the diagnostic value of history taking and physical examination (P<0.10) as assessed by sensitivity, specificity, predictive values, and likelihood ratios. The relationship between effusion and internal derangement of the knee was assessed with a chi-square test.

Results

Of the 134 participating patients, 42 had knee joint effusion seen on MRI. Multivariate analysis showed an association with knee joint effusion for the symptom “self-noticed swelling” (history taking) and for the “ballottement test” (physical examination). The likelihood ratio positive (LR+) was 1.5 for self-noticed swelling and 1.6 for the ballottement test. These 2 combined improved the diagnostic value to an LR+ of 3.6. Effusion showed a positive association with internal derangement of the knee (chi-square 9.5); 31 of the 42 patients with knee joint effusion had internal derangement of the knee.

Conclusions

In patients with traumatic knee injury, knee joint effusion is frequently seen on MRI. The combination of self-noticed swelling and the ballottement test was of diagnostic value. Knee joint effusion was associated with internal derangement of the knee.