Implementation of the International Classification of Diseases 11th revision behavioural indicators for disorders of intellectual development with co-occurring autism spectrum disorder.

BACKGROUND: The classification of mental, behavioural and neurodevelopmental disorders in the World Health Organization's International Classification of Diseases 11th revision (ICD-11) includes a comprehensive set of behavioural indicators (BIs) within the neurodevelopmental disorders grouping. BIs can be used to assess the severity of disorders of intellectual development in situations in which standardised measures of intellectual functioning and adaptive behaviours are not available or feasible. This international study examines the implementation characteristics of the BIs and compares them to standardised measures for assessing the severity of intellectual impairment and adaptive behaviours in disorders of intellectual development and autism spectrum disorder (ASD). The clinical utility of the ICD-11 and the fidelity of its application in international clinical settings were also assessed. METHODS: A total of 116 children and adolescents (5-18 years old) with a suspected or established diagnosis of disorders of intellectual development were included across four sites [Italy (n = 18), Sri Lanka (n = 19) and two sites in India (n = 79)]. A principal component analysis was conducted to evaluate the application of the ICD-11 guidance for combining severity levels. RESULTS: Assessment using the BIs showed a higher proportion of individuals classified with mild severity, whereas the standardised measures indicated a higher proportion of severe ratings. Additionally, individuals with co-occurring ASD tended to have more severe impairments compared with those without ASD, as indicated by both BIs and standardised measures. Overall, the BIs were considered clinically useful, although more time and consideration were required when applying the guidelines for individuals with a co-occurring disorder of intellectual development and ASD. The principal component analysis revealed one principal component representing overall disorders of intellectual development severity levels. CONCLUSIONS: The ICD-11 BIs can be implemented as intended in international clinical settings for a broad range of presentations of individuals with neurodevelopmental disorders. Use of the BIs results in similar severity diagnoses to those made using standardised measures. The BIs are expected to improve the reliability of severity assessments in settings where appropriate standardised measures for intellectual and adaptive behaviours are not available or feasible.

An international field study of the ICD-11 behavioural indicators for disorders of intellectual development.

BACKGROUND: The World Health Organization (WHO) has approved the 11th Revision of the International Classification of Diseases (ICD-11). A version of the ICD-11 for Mental, Behavioural and Neurodevelopmental Disorders for use in clinical settings, called the Clinical Descriptions and Diagnostic Requirements (CDDR), has also been developed. The CDDR includes behavioural indicators (BIs) for assessing the severity of disorders of intellectual development (DID) as part of the section on neurodevelopmental disorders. Reliable and valid diagnostic assessment measures are needed to improve identification and treatment of individuals with DID. Although appropriately normed, standardised intellectual and adaptive behaviour assessments are considered the optimal assessment approach in this area, they are unavailable in many parts of the world. This field study tested the BIs internationally to assess the inter-rater reliability, concurrent validity, and clinical utility of the BIs for the assessment of DID. METHODS: This international study recruited a total of 206 children and adolescents (5-18 years old) with a suspected or established diagnosis of DID from four sites across three countries [Sri-Lanka (n = 57), Italy (n = 60) and two sites in India (n = 89)]. Two clinicians assessed each participant using the BIs with one conducting the clinical interview and the other observing. Diagnostic formulations using the BIs and clinical utility ratings were collected and entered independently after each assessment. At a follow-up appointment, standardised measures (Leiter-3, Vineland Adaptive Behaviour Scales-II) were used to assess intellectual and adaptive abilities. RESULTS: The BIs had excellent inter-rater reliability (intra-class correlations ranging from 0.91 to 0.97) and good to excellent concurrent validity (intra-class correlations ranging from 0.66 to 0.82) across sites. Compared to standardised measures, the BIs had more diagnostic overlap between intellectual and adaptive functioning. The BIs were rated as quick and easy to use and applicable across severities; clear and understandable with adequate to too much level of detail and specificity to describe DID; and useful for treatment selection, prognosis assessments, communication with other health care professionals, and education efforts. CONCLUSION: The inclusion of newly developed BIs within the CDDR for ICD-11 Neurodevelopmental Disorders must be supported by information on their reliability, validity, and clinical utility prior to their widespread adoption for international use. BIs were found to have excellent inter-rater reliability, good to excellent concurrent validity, and good clinical utility. This supports use of the BIs within the ICD-11 CDDR to assist with the accurate identification of individuals with DID, particularly in settings where specialised services are unavailable.

Feasibility and effectiveness of nurses and clinical officers in implementing the WHO mhGAP intervention guide: Pilot study in Makueni County, Kenya.

OBJECTIVES: (1) To determine the feasibility and effectiveness of nurses and clinical officers in using the mental health Global Action Programme Intervention Guide (mhGAP-IG) as an intervention tool in reducing disability, improving quality of life in the clinical outcomes in patients with the mhGAP-IG priority mental disorders in a Kenyan rural setting. (2) To identify any gaps that can be contributed towards future research. METHODS: This study was conducted in 20 healthcare facilities across Makueni County in the South East of Kenya. This county had a population of approximately one million people, with no psychiatrist or clinical psychologist. We recruited 2306 participants from the healthcare facilities in the catchment areas that had previously been exposed to the community mental health awareness campaigns, while being subjected to screening for the mhGAP-IG disorders. We used the Mini-International Neuropsychiatric Interview for adults (MINI-Plus) for DSM-IV confirmatory diagnosis on those who screened positive on the mhGAP-IG. We measured disability using WHO-Disability Assessment Schedule II (DAS II), Quality of Life (QoL) using the WHO QoL-BREF, depression using Patient Health Questionnaire (PHQ-9), suicidality using The Beck Suicide Scale (BSS), psychosis using the Washington Early Recognition Center Affectivity and Psychosis (WERCAP), epilepsy using a seizure questionnaire and alcohol and substance abuse using The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). These measurements were at the baseline, followed by the training for the health professionals on using the WHO mhGAP-IG as an interventional tool. The measurements were repeated at 3 and 6 months post-intervention. RESULTS: Of the 2306 participants enrolled in the study, we followed 1718 at 3 months and 1371 at 6 months a follow-up rate of 74.5% and 59.4% respectively. All participants received psycho-education and most depending on condition also received medication. Overall, there was significant decline in disabilities, improvement in seizure control and improvement in clinical outcomes on the identified mental disorders. CONCLUSIONS: Trained, supervised and supported nurses and clinical officers can produce good outcomes using the mhGAP-IG for mental health.

Changing patterns of mental health knowledge in rural Kenya after intervention using the WHO mhGAP-Intervention Guide.

BACKGROUND: Despite the high prevalence of mental disorders, mental health literacy has been comparatively neglected. People's symptom-management strategies will be influenced by their mental health literacy. This study sought to determine the feasibility of using the World Health Organization mhGAP-Intervention Guide (IG) as an educational tool for one-on-one contact in a clinical setting to increase literacy on the specified mental disorders. METHODS: This study was conducted in 20 health facilities in Makueni County, southeast Kenya which has one of the poorest economies in Kenya. It has no psychiatrist or clinical psychologist. We recruited 3267 participants from a community that had already been exposed to community mental health services. We used Mental Health Knowledge Schedule to measure the changing patterns of mental health knowledge after a period of 3 months, following a training intervention using the WHO mhGAP-IG. RESULTS: Overall, there was a significant increase in mental health related knowledge [mean range 22.4-23.5 for both post-test and pre-test scores (p < 0.001)]. This increase varied with various socio-demographic characteristics such as sex, marital status, level of education, employment status and wealth index. CONCLUSIONS: mhGAP-IG is a feasible tool to increase mental health literacy in low-resource settings where there are no mental health specialists. Our study lends evidence that the WHO Mental Health Action Plan 2013-2020 and reduction of the treatment gap may be accelerated by the use of mhGAP-IG through improving knowledge about mental illness and potentially subsequent help seeking for early diagnosis and treatment.

Feasibility of WHO mhGAP-intervention guide in reducing experienced discrimination in people with mental disorders: a pilot study in a rural Kenyan setting.

AimsStigma can have a negative impact on help-seeking behaviour, treatment adherence and recovery of people with mental disorders. This study aimed to determine the feasibility of the WHO Mental Health Treatment Gap Interventions Guidelines (mhGAP-IG) to reduce stigma in face-to-face contacts during interventions for specific DSM-IV/ICD 10 diagnoses over a 6-month period. METHODS: This study was conducted in 20 health facilities across Makueni County in southeast Kenya which has one of the poorest economies in the country and has no psychiatrist or clinical psychologist. We recruited 2305 participants from the health facilities catchment areas that had already been exposed to community mental health services. We measured stigma using DISC-12 at baseline, followed by training to the health professionals on intervention using the WHO mhGAP-IG and then conducted a follow-up DISC-12 assessment after 6 months. Proper management of the patients by the trained professionals would contribute to the reduction of stigma in the patients. RESULTS: There was 59.5% follow-up at 6 months. Overall, there was a significant decline in 'reported/experienced discrimination' following the interventions. A multivariate linear mixed model regression indicated that better outcomes of 'unfair treatment' scores were associated with: being married, low education, being young, being self-employed, higher wealth index and being diagnosed with depression. For 'stopping self' domain, better outcomes were associated with being female, married, employed, young, lower wealth index and a depression diagnosis. In regards to 'overcoming stigma' domain; being male, being educated, employed, higher wealth index and being diagnosed with depression was associated with better outcomes. CONCLUSIONS: The statistically significant (p < 0.05) reduction of discrimination following the interventions by trained health professionals suggest that the mhGAP-IG may be a useful tool for reduction of discrimination in rural settings in low-income countries.

Propionyl-L-carnitine dilates human subcutaneous arteries through an endothelium-dependent mechanism.

PURPOSE: The vasoactive effects of propionyl-L-carnitine (PLC) on human arteries, including endothelial and smooth muscle cell influences, were studied. METHODS: Small (less than 200 microm) subcutaneous fat arteries (n = 19), obtained from human patients undergoing vascular surgery, were dissected and mounted in an arteriograph system that allowed measurement of lumen diameter and control of transmural pressure. To investigate the role of the endothelium, arteries were compared intact, intact and in the presence of either 0.3 mmol/L nitro-L-arginine (an inhibitor of nitric oxide synthesis) or 10 micromol/L indomethacin (an inhibitor of prostaglandin synthesis), or denuded of endothelium. After a 1-hour equilibration at a pressure of 50 mm Hg, arteries were precontracted 50% with an intermediate concentration of norepinephrine, and clinically relevant concentrations of PLC (0.1 to 100 micromol/L) were cumulatively added to the bath while the lumen diameter was continually measured. RESULTS: Intact arteries dose-dependently dilated to PLC, with the half maximal dilation occurring at 2.9 +/- 1.2 micromol/L, increasing diameter 91% +/- 5% at 100 micromol/L. In contrast, PLC had significantly less effect on deendothelialized arteries, increasing diameter only 24% +/- 11% at 100 micromol/L (P <.01 vs. intact). This indicates the endothelial dependency of this compound. Blockade of nitric oxide did not inhibit this vasodilation, with the half-maximal response occurring at 8.6 +/- 7 micromol/L, increasing diameter 85% +/- 8% at 100 micromol/L ( P >.05 vs. intact). However, this vasodilation was significantly diminished in the presence of indomethacin, which dilated arteries only 53% +/- 18% at 100 micromol/L (P <.01 vs. intact; P >.05 vs. denuded). CONCLUSION: PLC is an endothelium-dependent vasodilator, the mechanism of which is partially mediated by prostaglandin synthesis, not nitric oxide. The beneficial effects of this compound may, in part, be related to vasodilation and enhanced blood flow.

Abnormalities in hair trace elements as indicators of aberrant behavior.

There are long-standing viewpoints that impulsive and violent behavior may stem from brain dysfunction or damage secondary to head injury, disease, or toxic chemical substances. This research has aimed to examine the relationship between potentially toxic metals and aberrant behavior, especially violent activity, through the nonintrusive technique of hair analysis for trace elements. In an initial study, phase I, it was not possible to replicate findings of others who reported high levels of lead, cadmium, and copper in violent offenders. However, high levels of manganese were found in prison versus control groups. In phase II, the possibility of artifactual results arising from prison cooking utensils was controlled for by sampling early after incarceration. Phase III was included to substantiate the initial post hoc findings in an additional jail population. In both latter phases, significantly elevated manganese levels were found in the hair of violent versus nonviolent subjects (P less than .0001). A review of the effects of manganese at deficient and toxic levels does not provide a simple answer as to why manganese levels are elevated in the hair of individuals who have been incarcerated for violent behavior. Our study does not implicate the prison environment or soaps and shampoos used in California prisons. Other factors, such as alcohol, dietary, or psychosocial factors, might influence manganese levels in hair, or any of these factors might function in combination with mild manganese toxicity to contribute to aberrant behavior.

Trace enrichment of biological folates on solid-phase adsorption cartridges and analysis by high-pressure liquid chromatography.

A procedure involving solid-phase adsorption on bonded silica has been developed for trace enrichment and selective recovery of folate monoglutamates from liver tissue. A variety of reverse-phase (ethyl, octyl, octadecyl, phenyl) and anion-exchange (aminopropyl, quaternary amine, primary/secondary amine) cartridges were tested for their potential to adsorb and elute folate monoglutamates from standard solutions (50 nmol each of H4-pteroylglutamic acid (H4PteGlu), 5-CHO-H4PteGlu, 10-CHO-H4PteGlu, PteGlu, and 5-CH3-H4PteGlu). Quantitative recoveries were obtained from aminopropyl (-NH2) and all reverse-phase cartridges. For the analyses of rat liver folates, 20 ml of clear supernatant obtained from 5 g of tissue was treated with conjugase, which released folate monoglutamates from endogenous stores. Folate monoglutamates were then separated from nonfolate material by selective adsorption and recovery from -NH2 extraction cartridges. The procedure also provided a 10-fold concentrate, which allowed direct analysis by HPLC, using C-18 reverse-phase ion-pair columns coupled with uv detection (290 nm). Experiments with standard folates (n = 3) mixed with liver tissue and carried through the extraction, incubation, and trace-enrichment steps showed the following recoveries: 10-CHO-H4PteGlu, 55 +/- 5.0%; H4PteGlu, 80 +/- 5.0%; 5-CHO-H4PteGlu, 123 +/- 12.0%; and 5-CH3-H4PteGlu, 89 +/- 3.0%. Endogenous compositions of liver folates (n = 5) were as follows: 10-CHO-H4PteGlu, 1.03 +/- 0.3 nmol/g (6.7%); H4PteGlu, 5.70 +/- 1.0 (36.4%); 5-CHO-H4Pte Glu, 1.34 +/- 0.4 (8.7%); and 5-CH3-H4PteGlu, 7.34 +/- 1.2 (48.0%). Chromatographic peaks were identified by their retention times and by comparing their spectral profiles (obtained by a diode array detector) with respective pure folates. We found trace enrichment of biological folates on solid-phase extraction cartridges to be rapid and quantitative. The method allowed, for the first time, direct analysis of tissue folates by HPLC/uv methods.

Protein loss across burn wounds.

One factor contributing to negative nitrogen balance in burned patients is protein loss through the burn wound. There is, however, little information on the amount and type of protein lost by this route. This study was designed to quantitate protein loss through burn wounds. Multiple full- and partial-thickness burns on 29 patients were studied. Sampled burn sites were dried and occlusive sponge dressings (2'' X 2'') were applied and left in place for 1 hour. The central 1 square-inch portion of the dressing was then removed, rinsed in distilled water, and total protein, albumin, and globulin were measured in the water wash. Considerable protein losses were measured. These losses were greatest in the first 3 postburn days, being somewhat greater in full-thickness burns (0.98 +/- 0.82 mg/cm2/hr) compared to partial-thickness burns (0.59 +/- 0.41 mg/cm2/hr) during this period mean +/- SD). Subsequent to the first 3 postburn days, protein loss in all burn types decreased to a relatively steady rate of loss of approximately 0.25 mg/cm2/hr. Based upon these data, average daily protein losses during the first postburn week can be estimated by the following equation: 24-hour protein loss through burn surface (gm) = 1.2 X body surface area (m2) X % burn (%). On subsequent days, protein is lost at approximately half this rate. These data demonstrate significant protein losses through burn wounds greater than recent studies have considered. It is possible that inadequate nutritional replacement of these protein losses is partly responsible for the marked negative nitrogen balance of the early postburn period.

Recommendations of nutrition support team promote cost containment.

Traditionally, Nutrition Support Teams (NST) have been employed in an advisory capacity to recommend the most beneficial type of total nutritional support. Frequently, this form of therapy is also the most economical, particularly when enteral nutrition can replace parenteral nutrition. In a retrospective study, we reviewed the files of 31 patients who had received total nutritional support and compared the nutritional therapy initiated by their attending physicians to the therapy recommended by the NST. Based on guidelines established by the NST, we evaluated patient records for appropriateness of therapy and potential monetary savings had the NST's recommendations been followed. In the majority of cases in which compliance with the NST's recommendations was not accepted, the NST had encouraged the use of enteral nutritional support rather than parenteral nutrition. In the 14 noncompliant cases (representing 280 days of nutritional support) the potential savings to these patients was estimated at $70,200 (more than $5,000 per patient).

The effect of oral zinc administration on sebum free fatty acids in acne vulgaris.

Free fatty acids in sebum arise from lipolytic action of bacterial lipases. We have demonstrated an inhibitory effect of zinc on the lipase of the three Propionibacterium species found in human pilosebaceous follicles. We were also able to show a small corresponding fall in the free fatty acid content of skin surface lipid in vivo in acne patients treated with zinc, though this failed to reach statistical significance.

Gastrocnemius muscle lipids in relation to diet in two mouse mutants, 129Re-dy and A2G-adr, with abnormal muscle function.

The lipids of gastrocnemius muscle from normal and dystrophic (dy) mice of the Bar Harbor, 129Re strain were studied. Animals were fed diets containing either 3.1% or 1.1% of total calories as linoleic acid. Lipid analyses were also done on muscle from a new mouse mutant, A2G-adr, which has abnormal muscle function, characterised by an arrested development of the righting response. These animals were fed the "high" linoleic acid diet only. Total lipid, triacylglycerol, and cholesterol were elevated in the 129Re-dy irrespective of the diet, whereas A2G-adr possessed significantly higher levels of cholesterol. Total phosphorus (micrograms P/g muscle) and cholesterol/phospholipid ratios were elevated in the dy strains only. Cardiolipin was raised in the dy ("low" linoleic diet) and adr muscle, whereas phosphatidylcholine was lower in the adr strain only. Linoleic acid esterified to phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine was elevated whereas arachidonic acid in phosphatidylserine was decreased in both mutants. Docosahexanoic acid (22:6) in all three dy phospholipids was decreased, independent of dietary treatment. The adr strain possessed normal levels of this fatty acid. The results specifically point to an abnormality in long-chain polyunsaturated fatty acid metabolism in gastrocnemius muscle in the 129Re-dy mutant; in the adr mutant they could reflect an abnormal increase in the number of muscle mitochondria.

Dietary changes and their possible effect on blood pressure.

In this summary, the authors have attempted to examine reports of associations between various dietary habits and practices on one hand, and serum lipids or clinical disease on the other hand. There seems to be little doubt that both hypertension and ischemic heart disease have a nutritional background, but in all likelihood, there are other factors such as hereditary traits, occupational hazards, and perhaps personal habits including cigarette smoking, alcohol abuse and prolonged ingestion of medicinal drugs. One of the strongest correlates seems to be the role of complex carbohydrates in regulating blood lipid concentrations. Carbohydrates not only have an effect on the endocrine system that regulates blood volume, but they also influence absorption of fat soluble substances from the digestive tract and if natural fiber is included, it has an effect on fecal bulk, transit time of the fecal stream, and reabsorption of bile acids and neutral sterols. Epidemiologically, there is some evidence that the changes that occurred in the American diet in the years between 1914-1944 may well have played a permissive role in the genesis of a portion of the coronary heart disease, high blood pressure and stroke that occurred in the United States. It is not too farfetched to suggest that had the American servicemen been given more cereal food products including bread and other baked food items, instead of excessive amounts of meat and fats, the dietary pattern of America might well have been substantially different. Furthermore, this difference could easily have influenced the pattern of atherosclerosis and hypertension. A great deal more work is needed to confirm or refute these suggestions.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term effects of various sugars on antinatriuresis and blood pressure changes in normotensive young men.

This is a report of the effects of sugars on salt metabolism and on blood pressure. Twenty young men, none of whom had a personal or family history of hypertension, were orally hydrated after an overnight fast and required to lie recumbent for 6 h except for urinary voiding and blood pressure measurements which were performed at 1/2 h intervals. Venous blood samples were drawn at hourly intervals. The volunteers were kept constantly hydrated by giving them water to drink equivalent to the volumes of urine voided. Two hours from the start of the experiment each subject was given one of the following sugars: glucose, fructose, sucrose, galactose, lactose, or water alone. After oral hydration the subjects appeared to develop natriuresis and kaliuresis. This was quickly abolished by ingestion of either glucose, fructose, sucrose, or lactose, but not by galactose or water alone. Fructose was the most potent antinatriuretic agent. Both glucose and sucrose significantly elevated systolic blood pressure. This lasted for 2 h after glucose ingestion and 1 h after sucrose ingestion.

Carbohydrates and blood pressure.

High blood pressure is recognized as a major risk factor for both coronary heart disease and stroke. The role of diet in the genesis of hypertension has been hotly disputed. Recently, sucrose was reported to augment the hypertensive effects of salt in experimental animals. A review of many reports suggests that not only carbohydrates but also proteins and fats can alter blood pressure. Whether salt retention is a cause of elevated blood pressure remains to be ascertained. We have shown recently that sucrose and glucose elevate blood pressure transiently, and sucrose and fructose cause different degrees of salt retention in humans who have been fasting.

Picolinic acid in milk, pancreatic juice, and intestine: inadequate for role in zinc absorption.

Picolinic acid (PA) was measured by high pressure liquid chromatography in human milk and other fluids and tissues. Skimmed human milk, intestinal homogenates from human infants and rats, and human and rat pancreatic juice were ultrafiltered and analyzed by high pressure liquid chromatography using an anion-exchange column. Identity of sample components was verified by comparing retention times with those of pure nicotinic acid and PA. The detection limit for PA was 2.5 microM. Human milk contained less than 3.7 microM PA. PA was undetectable in human infant or rat intestine or in human or rat pancreatic juice. The extremely low concentration of PA in milk and its apparent absence in pancreatic juice and intestine provide additional evidence that PA is not the low molecular weight zinc binding ligand of human milk and that it does not have an important physiological role in intestinal zinc absorption.

An investigation in rats, into the metabolic consequences of early ingestion of dietary carbohydrates.

Weanling rats were given diets containing a high proportion of either glucose, sucrose or fructose until they reached 200 g weight, when they were either transferred to a control (chow) diet for 4 weeks or killed. The results were compared with rats receiving a control diet throughout. The triglyceride (TG) and cholesterol levels in liver and in serum had returned to values similar to the control animals 4 weeks after being given the control diet. The fatty acid profile of liver TG and adipose lipid tended to take longer to return to normal.