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The paper summarises the development of recent developments in relation to Quality of Life models in the field of intellectual disability. The information is applied to the development of professional practice and research. As examples, a series of research studies on Down syndrome are briefly described.
OBJECTIVE: To review the published literature in relation to prevalence of HIV infection and risk behaviours for HIV among the mentally ill to assist in the development of appropriate strategies for public health policy, surveillance and clinical management of HIV and HIV risk in these groups. METHOD: A search of published literature was carried out using 'Medline', in association with following up appropriate papers cited in the references of journals identified. RESULTS: The North American literature shows an increased risk of HIV infection in psychiatric patients receiving treatment in both inpatient or community settings. HIV infection is associated with a number of risk behaviours, particularly male homosexual sex and injecting drug use, and being the sexual partner of a person with a history of these. Impulsivity, high levels of sexual activity during acute exacerbations of psychiatric illness, poor skills at negotiating safe sex, homelessness and drug abuse are all risk behaviours common among those affected by some mental illnesses. The mentally ill also have a comparatively poorer knowledge of HIV/AIDS. There is a dearth of published Australian data addressing the question of HIV seroprevalence or risk in the mentally ill. Although there has been development and implementation of HIV risk-reduction programs overseas, the development and evaluation of any programs in Australia has not been published. CONCLUSIONS: Arguably, Australia has developed a comprehensive program of national surveillance for HIV infection and has been relatively successful in its response to the HIV epidemic, with the high rates of infection in the early to mid-1980s substantially reduced to around 600 new diagnoses per year. However, while risk behaviours which exposed those infected with the virus are recorded, underlying conditions which predispose them to these behaviours are not. Nevertheless, there is HIV infection amongst mentally ill and intellectually disabled people in Australia. Examination of the North American experience reveals opportunities to prevent a high rate of HIV infection in those with mental illness in Australia. Such a program would require adequate risk behaviour assessment, appropriate diagnostic testing and management, and development of specific educational interventions which are properly evaluated to ensure their effectiveness.
The occurrence of cognitive deficits in patients with multiple sclerosis (MS) has been recognized since 1877 when Charcot first observed "enfeeblement of memory" in his patients. Cognitive deficits have been reported in almost 50% of patients with a relapsing-remitting course and in a significantly higher percentage of patients with a chronic progressive course leading to intellectual disability which is often severe enough to preclude employment. MS is considered a form of subcortical dementia and the occurrence of classical cortical disorders such as aphasia, agnosia and apraxia is reported to be rare in the disease. However, in my experience alexia, a reading impairment unrelated to visual acuity or visual field defects, is common in patients with MS. Recently, I reported that treatment with picotesla range electromagnetic fields (EMFs) is an efficacious modality in the management of both the motor and cognitive symptoms of MS. Three patients with MS who developed alexia as a manifestation of the disease are presented. In all patients the alexia was reversed several months after they began treatment with EMFs. Since alexia usually reflects a disconnection syndrome whereby lesions involving the left visual cortex and the splenium of the corpus callosum disconnect language association areas from visual association areas, it is suggested that reversal of the alexia in these patients by EMFs was related to improved interhemispheric transcallosal transmission of visual information. In addition, it is conceivable that changes in the metabolism of monoamines, which are involved in visual information processing and reading comprehension, may have been important in causing reversal of the alexia. This report further supports the unique efficacy of this treatment modality in reversing specific cognitive deficits in MS.
OBJECTIVES: To examine the clinical effectiveness, tolerability and cost-effectiveness of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), tiagabine (TGB), topiramate (TPM) and vigabatrin (VGB) for epilepsy in adults. DATA SOURCES: Electronic databases. Internet resources. Pharmaceutical company submissions. REVIEW METHODS: Selected studies were screened and quality assessed. Separate analyses assessed clinical effectiveness, serious, rare and long-term adverse events and cost-effectiveness. An integrated economic analysis incorporating information on costs and effects of newer and older antiepileptic drugs (AEDs) was performed to give direct comparisons of long-term costs and benefits. RESULTS: A total of 212 studies were included in the review. All included systematic reviews were Cochrane reviews and of good quality. The quality of randomised controlled trials (RCTs) was variable. Assessment was hampered by poor reporting of methods of randomisation, allocation concealment and blinding. Few of the non-randomised studies were of good quality. The main weakness of the economic evaluations was inappropriate use of the cost-minimisation design. The included systematic reviews reported that newer AEDs were effective as adjunctive therapy compared to placebo. For newer versus older drugs, data were available for all three monotherapy AEDs, although data for OXC and TPM were limited. There was limited, poor-quality evidence of a significant improvement in cognitive function with LTG and OXC compared with older AEDs. However, there were no consistent statistically significant differences in other clinical outcomes, including proportion of seizure-free patients. No studies assessed effectiveness of AEDs in people with intellectual disabilities or in pregnant women. There was very little evidence to assess the effectiveness of AEDs in the elderly; no significant differences were found between LTG and carbamazepine monotherapy. Sixty-seven RCTs compared adjunctive therapy with placebo, older AEDs or other newer AEDs. For newer AEDs versus placebo, a trend was observed in favour of newer drugs, and there was evidence of statistically significant differences in proportion of responders favouring newer drugs. However, it was not possible to assess long-term effectiveness. Most trials were conducted in patients with partial seizures. For newer AEDs versus older drugs, there was no evidence to assess the effectiveness of LEV, LTG or OXC, and evidence for other newer drugs was limited to single studies. Trials only included patients with partial seizures and follow-up was relatively short. There was no evidence to assess effectiveness of adjunctive LEV, OXC or TPM versus other newer drugs, and there were no time to event or cognitive data. No studies assessed the effectiveness of adjunctive AEDs in the elderly or pregnant women. There was some evidence from one study (GBP versus LTG) that both drugs have some beneficial effect on behaviour in people with learning disabilities. Eighty RCTs reported the incidence of adverse events. There was no consistent or convincing evidence to draw any conclusions concerning relative safety and tolerability of newer AEDs compared with each other, older AEDs or placebo. The integrated economic analysis for monotherapy for newly diagnosed patients with partial seizures showed that older AEDs were more likely to be cost-effective, although there was considerable uncertainty in these results. The integrated analysis suggested that newer AEDs used as adjunctive therapy for refractory patients with partial seizures were more effective and more costly than continuing with existing treatment alone. Combination therapy, involving new AEDs, may be cost-effective at a threshold willingness to pay per quality-adjusted life year (QALY) greater than 20,000 pounds, depending on patients' previous treatment history. There was, again, considerable uncertainty in these results. There were few data available to determine effectiveness of treatments for patients with generalised seizures. LTG and VPA showed similar health benefits when used as monotherapy. VPA was less costly and was likely to be cost-effective. The analysis indicated that TPM might be cost-effective when used as an adjunctive therapy, with an estimated incremental cost-effectiveness ratio of 34,500 pounds compared with continuing current treatment alone. CONCLUSIONS: There was little good-quality evidence from clinical trials to support the use of newer monotherapy or adjunctive therapy AEDs over older drugs, or to support the use of one newer AED in preference to another. In general, data relating to clinical effectiveness, safety and tolerability failed to demonstrate consistent and statistically significant differences between the drugs. The exception was comparisons between newer adjunctive AEDs and placebo, where significant differences favoured newer AEDs. However, trials often had relatively short-term treatment durations and often failed to limit recruitment to either partial or generalised onset seizures, thus limiting the applicability of the data. Newer AEDs, used as monotherapy, may be cost-effective for the treatment of patients who have experienced adverse events with older AEDs, who have failed to respond to the older drugs, or where such drugs are contraindicated. The integrated economic analysis also suggested that newer AEDs used as adjunctive therapy may be cost-effective compared with the continuing current treatment alone given a QALY of about 20,000 pounds. There is a need for more direct comparisons of the different AEDs within clinical trials, considering different treatment sequences within both monotherapy and adjunctive therapy. Length of follow-up also needs to be considered. Trials are needed that recruit patients with either partial or generalised seizures; that investigate effectiveness and cost-effectiveness in patients with generalised onset seizures and that investigate effectiveness in specific populations of epilepsy patients, as well as studies evaluating cognitive outcomes to use more stringent testing protocols and to adopt a more consistent approach in assessing outcomes. Further research is also required to assess the quality of life within trials of epilepsy therapy using preference-based measures of outcomes that generate cost-effectiveness data. Future RCTs should use CONSORT guidelines; and observational data to provide information on the use of AEDs in actual practice, including details of treatment sequences and doses.
OBJECTIVE: To explore the pathogenicity and prenatal counseling strategies for five Chinese pedigrees harboring a hemizygous c.-32C>G (NM_001139500.2) variant of fibroblast growth factor 13 (FGF13) gene. METHODS: Five Chinese pedigrees found to carry a hemizygous c.-32C>G variant of the FGF13 gene at the Prenatal Diagnosis Center of Henan Provincial People's Hospital between January 2024 and January 2025 were selected as study subjects. The pedigrees had undergone prenatal diagnosis for a family history of genetic disorders, abnormal fetal ultrasound findings, or advanced maternal age. A retrospective analysis was carried out, wherein clinical data for all members of the pedigrees were obtained through the medical records system and outpatient visit system. Peripheral blood samples were collected from all pedigree members, and amniotic fluid samples were obtained from the probands. Following extraction of genomic DNA, prenatal diagnosis was performed using chromosomal microarray analysis (CMA) and trio whole-exome sequencing (trio-WES). Sanger sequencing was used to determine the carrier status for the candidate variant, and Mini-Mental State Examination (MMSE) was used to assess the cognitive function of hemizygous individuals carrying the FGF13 gene c.-32C>G variant. Pathogenicity of candidate variant was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-171). RESULTS: CMA and trio-WES revealed no pathogenic variants in all probands, whilst trio-WES and Sanger sequencing had identified 11 male individuals carrying a hemizygous c.-32C>G variant of the FGF13 gene from the five pedigrees, which included six adult males, a young boy, and four fetuses. One fetus had undergone termination of pregnancy due to hydrocephalus, one was born pre-term at 34+1 weeks of gestation owing to maternal hypertension, and other two were delivered at full term. Follow-up of the survived males revealed no phenotypic manifestations related to language or intellectual impairment. Among these, three adult males underwent the MMSE assessment, all of whom showed normal cognitive function. Search of the gnomAD database suggested the carrier frequency of FGF13 c.-32C>G variant in the East Asian population to be 0.125%, with 11 hemizygous males documented. Three male patients harboring the variant showed severe intellectual disability. Both in vitro and in vivo studies suggested that it could reduce the translation levels of FGF13 protein. Based on the ACMG guidelines, it was classified as variant of uncertain significance (BS4+PS3_Supporting). CONCLUSION: There is insufficient evidence to classify the FGF13 c.-32C>G as a pathogenic variant in clinical practice, and its presence should not be considered an indication for pregnancy termination due to major birth defects.
A 7-year-old Chinese boy presented with severe postnatal growth failure (height <3rd percentile at age 7 years), global developmental delay, moderate intellectual disability, and characteristic dysmorphic features including hypertelorism, short palpebral fissures, low-set ears, and a broad nasal bridge. A single electrocardiogram demonstrated a borderline corrected QT interval (QTc = 450 ms). No arrhythmias, QT-prolonging medications, electrolyte abnormalities, or relevant family cardiac history were identified. This finding warrants longitudinal cardiology follow-up and should not be interpreted as definitive Long QT syndrome. Whole-exome sequencing identified two novel missense variants in the PCNT gene (NM_006031.5): c.5675A>G (p.Glu1892Gly) in exon 28 and c.9734G>T (p.Arg3245Ile) in exon 45. Both variants were absent from gnomAD, ExAC, the 1000 Genomes Project database, and Chinese population databases, fulfilling ACMG criterion PM2. Although classified as variants of uncertain significance (VUS) because of limited functional evidence and conflicting in silico predictions, the variants occur in a gene associated with primordial dwarfism and are accompanied by partial phenotypic overlap with Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II). However, parental segregation analysis was unavailable; therefore, the variant phase could not be confirmed, and a recessive disease mechanism could not be established. These findings support the presence of candidate PCNT variants in an atypical primordial dwarfism phenotype and illustrate the utility of whole-exome sequencing for generating testable molecular hypotheses in genetically heterogeneous growth disorders. A definitive molecular diagnosis cannot be established at present, and the isolated borderline QTc finding requires further clinical evaluation.
Gastroesophageal reflux (GER) is a common episode in pediatric patients with severe motor and intellectual disabilities (SMID) and occasionally leads to a severe clinical state accompanied with nausea, hematemesis, melena, wheezing, pneumonia, anemia and/or failure to thrive. We report here a case of a 14-year-old male with Lennox syndrome who had been treated with a histamine H2 blocker intravenously or via a nasogastric tube for repeated gastric hemorrhage due to severe GER. Since his gastric hemorrhage became resistant to the H2 blocker, we decided to replace it with a proton pump inhibitor (PPI). Although lansoprazole can be decapsulated for administration via a nasogastric tube, it tends to block fine tubes. The acid-sensitive drug omeprazole, another oral PPI, is commercially available as enteric-coated tablets. Therefore, we pulverized the tablets and administered omeprazole, mixed with a small amount of antacid, via a nasogastric tube. The patient's gastric hemorrhage was dramatically improved. Thus, administration of pulverized omeprazole concomitantly with antacid via a fine nasogastric tube may provide a novel approach for the treatment of chronic GER in pediatric patients with SMID.
OBJECTIVES: To estimate the number of women of childbearing age in New South Wales whose children are at risk of the maternal phenylketonuria (PKU) syndrome (intellectual disability, microcephaly, congenital malformations). SETTING: New South Wales, 1996. DESIGN: Comparison of number of women with PKU aged 15-44 years on the NSW PKU database (observed number) with expected number derived from population data. MAIN OUTCOME MEASURES: Observed and expected numbers of women with PKU (defined as blood phenylalanine levels > or = 400 mumol/L, and phenylalanine-restricted diet recommended) by age; number with no clinical contact with the PKU service in previous year; outcomes of pregnancies in women with PKU (January 1994 to July 1996). RESULTS: 110 women aged 15-44 years with PKU were listed on the database. The expected number was 145 (95% confidence interval, 122-171). The difference was greatest in the 30-44 years age group (born before comprehensive newborn screening), with only 55% of the expected number listed. Sixteen women who had been diagnosed with PKU at birth were not having regular follow-up, while 18 women had been diagnosed only after investigation of abnormalities in their children. Of 28 pregnancies managed by the NSW PKU service, 19 were considered unaffected by the maternal PKU syndrome and five affected (another three did not reach term; one outcome was unknown). Of 46 unmanaged pregnancies, all were affected. CONCLUSION: There is an urgent need for better follow-up of women with PKU and for education of health professionals about the MPKU syndrome, its recognition, the risks of untreated pregnancy and the benefits of dietary treatment.
An adolescent with autism and intellectual disability presented with severe depression related to menstruation. Because of the complex medical, psychiatric and ethical issues involved, her care was coordinated by a hospital-based adolescent medicine unit. After trials of other therapies over an extended period and interdisciplinary and intersectoral case conferencing, it was decided that hysterectomy was the most appropriate management. This case highlights the complexity of adolescent health care in a tertiary hospital, the importance of intersectoral cooperation between hospital and community, and the integral role of interdisciplinary care of adolescent patients with chronic conditions.
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We studied the usefulness of melatonin for sleep disorders and emotional/behavior disturbances of patients with developmental disorders. The efficacy and side effects of melatonin at bedtime were evaluated in 50 children and young adults with sleep disorders (3-28 years old, 41 males and 9 females, autism [AU] in 27 patients, mentally retardation [MR] in 20 patients, and severe motor and intellectual disability [SMID] in 3 patients). The sleep disorders consisted of various types of insomnia in 44 patients and of circadian rhythm sleep disorders in 6 patients. Thirty nine of the insomnia patients and 3 of the circadian rhythm sleep disorder patients experienced improvement in response to melatonin. In some cases, the efficacies were diminished after the daily medication of melatonin. With the emotional/behavior disturbances, excitabilities were often improved in cases whose sleep disorders were also improved. There was almost no change in contrariness, stereotyped behavior and in school/workshop refusal. Melatonin at bedtime was efficacious in 42 of the 50 patients with sleep disorders. In 17 patients, there were side effects (residual drowsiness on the next morning, awakening in the middle of sleep, excitement after awakening and before going to sleep, etc.). But these side effects were not serious. The effects of melatonin were influenced by the type of sleep disturbances, the factors of the environment and the mental conditions. Taking side effects into account, we judged melatonin to be useful in 34 patients.
Modern defense services depend on a policy of the vigorous promotion of research to ensure that they retain an advantage in any future operational context. Research involving personnel within the armed forces, however, has certain constraints with respect to contemporary, best-practice medical ethics. Service members are one example of a class of "captive subjects" who require special protection in the context of medical research. (Prisoners, students, children, and the intellectually disabled are other such examples.) The majority of national defense forces now have ethical watchdog groups--institutional ethics committees--that oversee research involving service members. Such groups monitor the special considerations and constraints under which subjects in uniform can volunteer for biological research. These committees audit particularly the ethical themes of confidentiality, equality, and justice. Themes inherent in medical research in the military include the standard Beauchamp-Childress paradigm of autonomy, beneficence, nonmaleficence, and justice, to which are added the traditional military values of loyalty, respect, courtesy, and chivalry. Contemporary thinking is that the general principle of affording service members the opportunity to volunteer for research should be maintained within the constraints of compromised training time, national security, and operational necessity. Most biological research (and its outcome) does not in practice compromise confidentiality or military security. This paper presents an audit of the functioning of one national military medical ethics committee, the Australian Defence Medical Ethics Committee, and presents a discussion of its philosophies and influence within the broader military context. The Australian Defence Medical Ethics Committee believes that most research should, as an a priori condition of approval, be intended for open publication in peer-reviewed journals.
UNLABELLED: The aim of study is to discuss from a clinicians viewpoint the use of tiagabine in the clinical setting, in particular how we can relate our current knowledge to individuals in our clinics. The choice for individual and the clinician is multi-layered dependent on many factors. Namely is based on patient characteristics, their beliefs and wishes, age, seizure type or syndrome and comorbidity. The next factor influencing choice is drug characteristics; pharmacology, mode of action, efficacy, tolerability, practical use and cost. Very important is fear of unknown. Particularly important are new drugs, which can be safety use in groups of special concern like children, women of reproductive age, the elderly, patients with psychiatric illness and mental handicaps. In these cases the risk of fetal malformations, interactions with other drugs, safety profile should be taken into consideration. Tiagabine represents an important new therapeutic option for patients with drug resistant partial seizures. The role of tiagabine in the management of patients with intellectual disability is especially emphasised since tiagabine has a low side-effects profile in the cognitive area. Comparison of data for new antiepileptic drugs provide information for selection among treatments when a second drugs is needed to improve control of seizures. However, there are numerous caveats in use of these summary data. First, the data from clinical trials cannot be compared directly because of variability in placebo response and potentially in other population characteristics. Second, the needs of individual patients differ. CONCLUSION: There is important to stress that no controlled clinical trials have provided algorithm for the best add-on drug or combination of drugs. So there is need to describe the homogenic groups of patients and final choice should be based on the need of the individual patient (sex, age, pregnancy, mental status) for superior seizure control versus minimal adverse effects.
Problem of psychosocial support and home physical therapy of children and adolescent with Cerebral palsy we treated with Project with same name. Project is implementing together with Association of persons with Cerebral Palsy of Canton Sarajevo. Project is part of City of Sarajevo Project--"Sarajevo healthy town". 36 children and adolescents with Cerebral palsy, from 7 to 20 years, are included in six months home physical therapy. We included intellectually disabled and not disabled children and adolescents from Canton Sarajevo. Target population, except children, are parents and families of this children. Social worker and clinical psychologist are trainers of the Parents workshops. More psychosocial support we will have on Round table "Social integration of persons with Cerebral Palsy" and first brochure of the Association.
One hundred and sixteen children with an acquired damage to the central nervous system (CNS) during the last decade were studied to determine the causes and sequelae and to find strategies for prevention. The etiology was CNS infections and related disorders in 46 cases (39.4%), non-infectious diseases (epileptic, hypoxic etc.) in 16 cases (13.8%), iatrogenic brain injury in 15 cases (12.9%), accident-related brain damage in 31 cases (26.7%), and vascular disorders in 8 cases (6.9%). Since infections and accidents accounted for as much as 66.4%, prevention of their sequelae is important. Of 37 patients (31.9%) with severe motor and intellectual disabilities syndrome (SMIDS), 18 were due to infectious diseases. SMIDS cases accounted for 39.1% of the infectious diseases group, 25% of the non-infectious diseases group, 40% of the iatrogenic group, 25.8% of the accident-related group and 12.5% of the vascular group. The prevalence rate of acquired CNS damage was estimated to be 0.5/10(3)/year and that of SMIDS due to acquired damage to be 0.16/10(3)/year. A monitoring system for patients with an acquired brain damage and for their treatment is important.
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