Where are persons with intellectual disabilities in medical research? A survey of published clinical trials.

BACKGROUND: Persons with intellectual disabilities (ID) are exposed to the same medical interventions as everyone else. Given the unique health profiles of many persons with ID, it cannot be assumed that they will react to medical treatments the same as persons without ID. It is not clear if medical clinical trials routinely include persons with ID. The purpose of this research survey was to examine the inclusion of persons with ID in medical research trials, and to determine whether accommodations and/or study modifications could have been made to promote greater inclusion in medical research. METHOD: Three hundred randomised control and clinical trials published between 2007 and 2011 in the six highest impact medical journals were randomly selected. Each study was reviewed for inclusion of persons with ID, and possible accommodations that could have been put in place without compromising research integrity. Corresponding authors received a follow-up survey to determine whether persons with ID were included, but were not mentioned in the article. RESULTS: Only 6 (2%) of 300 randomly chosen studies clearly included persons with ID. Over 90% of studies were designed in ways that would automatically exclude persons with ID from participating. The author survey revealed three additional studies including persons with ID. Most persons with ID could have participated in at least 70% of the studies with simple accommodations and/or minor procedural modifications. DISCUSSION: The findings highlight the exclusion of persons with ID in medical research. Efforts are needed to increase inclusion through research policy initiatives and education.

Health self-advocacy training for persons with intellectual disabilities.

BACKGROUND: People with intellectual disabilities (ID) have unequal access to health care. While systemic efforts are addressing health inequalities, there remains a need to demonstrate that persons with ID can increase their health self-advocacy skills. METHOD: A randomised control design with up to 6-month follow-up was used to evaluate the 3Rs (Rights, Respect and Responsibility) health self-advocacy training program for persons with ID (n = 31). Training involved teaching participants to recognise and redress health rights violations in the context of respect and responsibility. Training materials included PowerPoint slides and interactive video scenarios illustrating health rights, respect and responsibility problem and non-problems. Two-hour training sessions were conducted twice a week in a group format where participants played a game and answered questions. RESULTS: The health rights training group made significantly more correct responses on post training and follow-up tests than the control group. Training effects generalised to untrained scenarios and in situ health interviews. CONCLUSIONS: The results of this study suggest that persons with ID can learn complex skills related to health self-advocacy. More research is needed to improve in situ generalisation.

Formal versus informal interventions for challenging behaviour in persons with intellectual disabilities.

BACKGROUND: Although effective, humane treatments exist for persons with intellectual disabilities (ID) who have challenging behaviour, little research has examined the extent to which clients receive formal, documented vs. undocumented interventions. METHODS: Caregivers (of 625 persons with ID living in community and institutional residences in Ontario, Canada) were interviewed to examine the prevalence of different types of interventions. RESULTS: Overall, 55% of the 2506 different interventions (for 1464 target behaviours) were informal (i.e. lacking documented input from a professional, written intervention plans, and systematic evaluation). No significant differences emerged on formality of intervention across participant gender, age, level of ID, and type of residence. There were significantly more informal than formal behavioural interventions and counselling/psychotherapy, and no significant difference in the overall prevalence of formal and informal intrusive procedures. Behaviour control medications were paired more often with formal (67%) than informal interventions for dangerous behaviours. Formal interventions were associated with higher caregiver-reported estimates of behavioural improvement, higher inter-rater agreement on the descriptions of an individual client's target behaviours and interventions, and more caregiver training and supervision. CONCLUSIONS: The low levels of intervention accountability, training and supervision may place many clients with challenging behaviour at increased risk for ineffective and unnecessary restrictive interventions, and physical abuse. The results of this survey stimulated the government to write province-wide standards (that have yet to be implemented).

Adverse intraoperative medical events and their association with anesthesia management strategies in cataract surgery.

OBJECTIVE: To compare adverse medical events by different anesthesia strategies for cataract surgery. DESIGN: Prospective cohort study. PARTICIPANTS: Patients 50 years of age and older undergoing 19,250 cataract surgeries at nine centers in the United States and Canada between June 1995 and June 1997. INTERVENTION: Local anesthesia applied topically or by injection, with or without oral and intravenous sedatives, opioid analgesia, hypnotics, and diphenhydramine (Benadryl). MAIN OUTCOME MEASURES: Intraoperative and postoperative adverse medical events. RESULTS: Twenty-six percent of surgeries were performed with topical anesthesia and the remainder with injection anesthesia. There was no increase in deaths and hospitalizations associated with any specific anesthesia strategy. No statistically significant difference was observed in the prevalence of intraoperative events between topical and injection anesthesia without intravenous sedatives (0.13% and 0.78%, respectively). The use of intravenous sedatives was associated with a significant increase in adverse events for topical (1.20%) and injection anesthesia (1.18%), relative to topical anesthesia without intravenous sedation. The use of short-acting hypnotic agents with injection anesthesia was also associated with a significant increase in adverse events when used alone (1.40%) or in combination with opiates (1.75%), sedatives (2.65%), and with the combination of opiates and sedatives (4.04%). These differences remained after adjusting for age, gender, duration of surgery, and American Society of Anesthesiologists risk class. CONCLUSIONS: Adjuvant intravenous anesthetic agents used to decrease pain and alleviate anxiety are associated with increases in medical events. However, cataract surgery is a safe procedure with a low absolute risk of medical complications with either topical or injection anesthesia. Clinicians should weigh the risks and benefits of their use for individual patients.

Injectable versus topical anesthesia for cataract surgery: patient perceptions of pain and side effects. The Study of Medical Testing for Cataract Surgery study team.

OBJECTIVE: To compare patient reports of intraoperative pain and postoperative side effects by different anesthesia strategies for cataract surgery. DESIGN: Prospective cohort study. PARTICIPANTS: Men and women 50 years of age and older undergoing 19,250 cataract surgeries at nine centers in the United States and Canada from June 1995 through June 1997. INTERVENTION: Topical anesthesia or anesthesia with injection, with or without sedatives, opioid analgesia, hypnotics, and diphenhydramine (Benadryl). MAIN OUTCOME MEASURES: Patient ratings of intraoperative pain, satisfaction with pain management, and early postoperative side effects (drowsiness, nausea, vomiting, or a combination thereof). RESULTS: Twenty-six percent of surgeries were performed using topical anesthesia alone, and the remainder were performed with peribulbar, retrobulbar, or facial nerve block, or a combination thereof. Local anesthesia by injection with sedatives and diphenhydramine resulted in the lowest reporting of any intraoperative pain (1.3%), with postoperative drowsiness (9.6%) and nausea, vomiting, or both (1.5%) comparable with those administered topical anesthesia alone. Among those receiving topical anesthesia, use of sedatives and opioids reduced reports of any pain during surgery by 56% (95% confidence interval [CI], 34%, 70%), but increased nausea and vomiting (odds ratio, 2.27; 95% CI, 1.26, 4.09) compared with those administered topical anesthesia alone, after adjusting for age, gender, race, American Society of Anesthesiologists risk class, self-reported health status, and duration of surgery. Among those receiving local injections, use of opioids reduced reports of any pain among those receiving sedatives by 37% (95% CI, 15%, 54%), but did not increase postoperative side effects. The use of diphenhydramine among those receiving sedatives decreased reports of any pain by 59% (95% CI, 33%, 75%) and also reduced drowsiness and nausea and vomiting by 57% (95% CI, 48%, 65%) and by 60% (95% CI, 36%, 75%), respectively. Use of hypnotics with sedatives was associated with increased reports of any pain during surgery and increased nausea and vomiting after surgery. CONCLUSIONS: Patient reports of any pain during cataract surgery (5%) and postoperative side effects (16% drowsiness and 4% nausea and vomiting) were low, but varied by anesthesia strategy. Patient perceptions of pain and side effects can be helpful in guiding the appropriate choice of anesthesia strategy.

The value of routine preoperative medical testing before cataract surgery. Study of Medical Testing for Cataract Surgery.

BACKGROUND: Routine preoperative medical testing is commonly performed in patients scheduled to undergo cataract surgery, although the value of such testing is uncertain. We performed a study to determine whether routine testing helps reduce the incidence of intraoperative and postoperative medical complications. METHODS: We randomly assigned 19,557 elective cataract operations in 18,189 patients at nine centers to be preceded or not preceded by a standard battery of medical tests (electrocardiography, complete blood count, and measurement of serum levels of electrolytes, urea nitrogen, creatinine, and glucose), in addition to a history taking and physical examination. Adverse medical events and interventions on the day of surgery and during the seven days after surgery were recorded. RESULTS: Medical outcomes were assessed in 9408 patients who underwent 9626 cataract operations that were not preceded by routine testing and in 9411 patients who underwent 9624 operations that were preceded by routine testing. The most frequent medical events in both groups were treatment for hypertension and arrhythmia (principally bradycardia). The overall rate of complications (intraoperative and postoperative events combined) was the same in the two groups (31.3 events per 1000 operations). There were also no significant differences between the no-testing group and the testing group in the rates of intraoperative events (19.2 and 19.7, respectively, per 1000 operations) and postoperative events (12.6 and 12.1 per 1000 operations). Analyses stratified according to age, sex, race, physical status (according to the American Society of Anesthesiologists classification), and medical history revealed no benefit of routine testing. CONCLUSIONS: Routine medical testing before cataract surgery does not measurably increase the safety of the surgery.

Using self-instructional pictorial manuals to teach child-care skills to mothers with intellectual disabilities.

Children of parents with intellectual disabilities (i.e., IQs less than 80, labeled as having mental retardation) are at risk for neglect due to inadequate parenting abilities. Previous studies have shown that these parents are responsive to parent-training packages consisting of instructions, pictorial cues, modeling, feedback, and reinforcement. This study evaluated the effectiveness of self-learning pictorial-parenting manuals in teaching basic child-care skills (diapering, treating diaper rash, bathing, safety) to parents with intellectual disabilities who are monitored by child protection agencies. The manuals alone increased child-care skills (to levels seen in parents without disabilities) in 9 out of the 10 mothers in the study and in 12 of 13 child-care skills. The remaining skill was acquired with the full training package. Follow-up indicated that the acquired skills were maintained for up to 3 years. Mean correct performance with the manual was positively correlated with the trainer's rating of the mother's reading level and acceptance of the manual when the mother was first given the manual. Consumer satisfaction ratings of the manuals were high. These results indicate that many parents with intellectual disabilities may improve their child-care skills without intensive training and that self-instruction may be an easily disseminable and cost-effective way of reducing the risk of child neglect due to parenting skill deficiencies.

Distinctive pattern of behavioral functioning in Angelman syndrome.

Angelman syndrome is a neurogenetic disorder that is characterized by impairments in neurological, motor, and intellectual functioning. This study compared 27 participants with Angelman syndrome to clinical and community participants with developmental disabilities of mixed etiology to determine whether Angelman syndrome is associated with a distinctive pattern of behavioral functioning. The groups with and without Angelman syndrome were matched on chronological age, gender, and level of intellectual functioning. The dependent measure was parent ratings of maladaptive behavior using the Aberrant Behavior Checklist. The Angelman syndrome group had significantly lower scores on measures of irritability and lethargy. Results contribute to the delineation of a behavior phenotype for the syndrome.

Channel microband electrode arrays for mechanistic electrochemistry. Two-dimensional voltammetry: transport-limited currents.

A channel electrode array, with electrodes ranging in size from the millimeter to the submicrometer scale, is used for the amperometric interrogation of mechanistically complex electrode processes. In this way, the transport-limited current, measured as a function of both electrode size and electrolyte flow rate (convection), is shown to provide a highly sensitive probe of mechanism and kinetics. The application of "two-dimensional voltammetry" to diverse electrode processes, including E, ECE, ECEE, EC', and DISP2 reactions, is reported.

Effects of maternal mental retardation and poverty on intellectual, academic, and behavioral status of school-age children.

The impact of low maternal IQ and poverty was examined through comparison of 27 school-age children of mothers with mild mental retardation to 25 similarly impoverished children of mothers without mental retardation. The children whose mothers had mental retardation had lower IQs and academic achievement and more behavior problems. Not one child with a mother who had mental retardation was problem-free. Boys were affected more severely than were girls. Quality of the home environment and maternal social supports were lower in the group with maternal mental retardation; both measures were negatively correlated with child behavior disorders. Results suggest that being raised by a mother with mental retardation can have detrimental effects on child development that cannot be attributed to poverty alone.

Elemental mercury-induced skin granuloma: a case report and review of the literature.

BACKGROUND: Injection of elemental mercury is rare and only some 72 cases have been reported in the literature over the period 1923-1995. Direct subcutaneous injection or extravasation of mercury injected into blood vessels can produce local granulomata and abscesses. Unless intravascular mercury injection has occurred, clinical signs of mercury toxicity are usually absent though four cases of systemic toxicity have been reported following isolated subcutaneous injection without evidence of elemental mercury dissemination. CASE REPORT: We report a further case of subcutaneous injection by gunshot of elemental mercury, with subsequent granuloma formation, in a 19-year old man who was admitted with an eight month history of a tender enlarging mass in his left antecubital fossa, while on active military service. Surgical removal of mercury from a presumed mercury-tipped bullet was undertaken but was incomplete and the patient declined further operative intervention as he remained asymptomatic. Chelation therapy was not instituted. Serum and urine mercury concentrations were measured for six years after presentation. CONCLUSIONS: We recommend that cases of subcutaneous metallic mercury injection should be managed by complete surgical excision of the granuloma under X ray control and serial monitoring of blood and urine mercury concentrations.

Inactivated influenza virus, when presented on dendritic cells, elicits human CD8+ cytolytic T cell responses.

Inactivated or subunit virus preparations have been excellent vaccines for inducing antibody responses. Generation of cytolytic T cell responses, however, is thought to require replicating virus, primarily to provide sufficiently large amounts of cytoplasmic proteins for processing and presentation on major histocompatibility complex class I molecules by antigen-presenting cells. Potent human CD8+ cytolytic T cell responses to live replicating influenza A virus are generated when dendritic cells are used as the antigen-presenting cells. Here, we demonstrate that dendritic cells pulsed with poorly replicating, heat- or ultraviolet-inactivated influenza virus, induce equally strong CD8+ cytolytic T lymphocyte responses. The cytotoxic T lymphocytes are generated in the apparent absence of CD4+ helper cells or exogenous cytokines. Active viral protein synthesis is not required to charge class I molecules on dendritic cells. When pulsed with inactivated virus, < 1% of dendritic cells express nonstructural protein 1, which is only synthesized in the infectious cycle. To be optimally effective, however, the inactivated virus must retain its fusogenic activity, and presumably access the cytoplasm of dendritic cells. The data indicate, therefore, that dendritic cells require only small amounts of viral protein to charge class I molecules, most likely via traditional class I processing pathways. These results reopen the potential use of inactivated virus preparations as immunogens for cytotoxic T lymphocyte responses.

Do ophthalmologists, anesthesiologists, and internists agree about preoperative testing in healthy patients undergoing cataract surgery?

To assess variation in reported use of preoperative medical tests in patients undergoing cataract surgery and to identify factors that influence test use by different physician groups we performed a national survey of ophthalmologists, anesthesiologists, and internists. Participants included randomly selected members of American professional societies who provided care to one or more patients undergoing cataract surgery in 1991. Responses were obtained from 538 (82%) of 655 eligible ophthalmologists, 109 (76%) of 143 anesthesiologists, and 54 (44%) of 122 internists. Fifty percent of ophthalmologists, 40% of internists, and 33% of anesthesiologists frequently or always obtained a chest x-ray film, while 20% of ophthalmologists, 27% of internists, and 37% of anesthesiologists never obtained a chest x-ray film for patients being considered for cataract surgery who had no history of major medical problems (P < .01 for differences between ophthalmologists and the other groups). Similarly, 70% to 90% of ophthalmologists, 73% to 79% of internists, and 41% to 79% of anesthesiologists frequently or always obtained a complete blood cell count, electrolyte panel, and electrocardiogram, while 4% to 11% of ophthalmologists, 13% to 17% of internists, and 9% to 28% of anesthesiologists never obtained these tests for such patients. Many respondents (32% to 80%) believed tests were unnecessary but cited multiple reasons for obtaining tests (eg, medicolegal concerns and institutional requirements). Many physicians in each group viewed preoperative evaluations as screening opportunities or believed that one of the other two types of physicians "required" tests. We conclude that marked variation exists within and across physician specialties in the use and rationale for use of medical tests in patients undergoing cataract surgery.

Parenting education for parents with intellectual disabilities: a review of outcome studies.

Parents with intellectual disabilities (i.e., IQ < 80; mental retardation) are overrepresented in child maltreatment cases and have a variety of parenting skill deficits. Their children are at risk for neglect, developmental delay, and behavioral disorders. This review of parenting education interventions for such parents identified 20 published studies with adequate outcome data. A total of 190 such parents (188 mothers, 2 fathers), with IQs ranging from 50 to 79 were involved. Parenting skills trained included basic child-care, safety, nutrition, problem solving, positive parent-child interactions, and child behavior management. The most common instructional approach was behavioral (e.g., task analysis, modeling, feedback, reinforcement). Overall, initial training, follow-up, and social validity results are encouraging. Generalization and child outcome data are weak. Further research is needed to (a) identify variables associated with responsiveness to intervention, and (b) develop and compare innovative programs that teach parents with cognitive disabilities the necessary generalized skills to demonstrate long-term beneficial effects on their children.

Effectiveness of home-based early intervention on the language development of children of mothers with mental retardation.

The authors evaluated the effects of a home-based parent training program for mothers with mental retardation on the language development of their children who were at risk for language delay. The participants, 28 mothers labelled mentally retarded with children under 28 months of age, initially showed significantly fewer positive mother-child interactions and child vocalizations and verbalizations than did a comparison group of 38 families with children of similar age whose mothers were not mentally retarded. The 28 mothers with low IQ were then matched on child entry age and randomly assigned to either an interaction training or attention-control group (this group received training in safety and emergency skills unrelated to interactions). Interaction training consisted of verbal instruction, modelling, feedback, and tangible reinforcement. After training, the training group scores were no longer lower than those of the comparison group of mothers without mental retardation and were also significantly higher than the scores of the attention-control group on all maternal positive interactions, child vocalizations, verbalizations, and language and social domains of the Bayley Scales of Infant Development. Speech emerged significantly sooner in the training group as compared to the control group. The training group parents and children maintained improvements up to 82 weeks following training, and the attention-control group, when subsequently trained, replicated the original training group results. Thus, home-based parent training increased positive maternal interactions of mothers with mental retardation, which facilitated language development in their young children.

Measurement of benzodiazepine receptor number and affinity in humans using tracer kinetic modeling, positron emission tomography, and [11C]flumazenil.

Kinetic methods were used to obtain regional estimates of benzodiazepine receptor concentration (Bmax) and equilibrium dissociation constant (Kd) from high and low specific activity (SA) [11C]flumazenil ([11C] Ro 15-1788) positron emission tomography studies of five normal volunteers. The high and low SA data were simultaneously fit to linear and nonlinear three-compartment models, respectively. An additional inhibition study (pretreatment with 0.15 mg/kg of flumazenil) was performed on one of the volunteers, which resulted in an average gray matter K1/k2 estimate of 0.68 +/- 0.08 ml/ml (linear three-compartment model, nine brain regions). The free fraction of flumazenil in plasma (f1) was determined for each study (high SA f1: 0.50 +/- 0.03; low SA f1: 0.48 +/- 0.05). The free fraction in brain (f2) was calculated using the inhibition K1/k2 ratio and each volunteer's mean f1 value (f2 across volunteers = 0.72 +/- 0.03 ml/ml). Three methods (Methods I-III) were examined. Method I determined five kinetic parameters simultaneously [K1, k2, k3 (= konf2Bmax), k4, and konf2/SA] with no priori constraints. An average kon value of 0.030 +/- 0.003 nM-1 min-1 was estimated for receptor-rich regions using Method I. In Methods II and III, the konf2/SA parameter was specifically constrained using the Method I value of kon and the volunteer's values of f2 and low SA (Ci/mumol). Four parameters were determined simultaneously using Method II. In Method III, K1/k2 was fixed to the inhibition value and only three parameters were estimated. Method I provided the most variable results and convergence problems for regions with low receptor binding. Method II provided results that were less variable but very similar to the Method I results, without convergence problems. However, the K1/k2 ratios obtained by Method II ranged from 1.07 in the occipital cortex to 0.61 in the thalamus. Fixing the K1/k2 ratio in Method III provided a method that was physiologically consistent with the fixed value of f2 and resulted in parameters with considerably lower variability. The average Bmax values obtained using Method III were 100 +/- 25 nM in the occipital cortex, 64 +/- 18 nM in the cerebellum, and 38 +/- 5.5 nM in the thalamus; the average Kd was 8.9 +/- 1.0 nM (five brain regions).

Comparison of staff training strategies to promote generalized teaching skills.

Two studies compared the effectiveness of different strategies for promoting generalization of staff skills in teaching self-care routines to clients with developmental disabilities. In Study 1, 9 direct-care staff members of group homes were trained sequentially through four conditions; (a) the provision of written instructions, (b) performance-based training using a single client program exemplar and simulated clients (single case training), (c) performance-based training using actual developmentally delayed clients as trainees (common stimuli training), and (d) performance-based training using multiple client program exemplars with simulated clients (general case training). The results indicated that staff members did not reach all generalization criteria until general case training was provided. Because staff members had been trained sequentially through several conditions in Study 1, a second study controlled for potential sequence effects. In Study 2, 7 staff members were trained using only the general case strategy after baseline. All staff members reached generalizations criteria with only general case training, replicating the findings of Study 1. Together, the two studies demonstrated that the general case training strategy was more effective at promoting generalized training effects across clients, settings, and client programs than other commonly used staff training approaches.

Teaching child-care skills to mothers with developmental disabilities.

The present study identified and remediated child-care skill deficits in parents with developmental disabilities to reduce their risk of child neglect. Eleven mothers with developmental disabilities who were considered by social service and child welfare agencies to be providing neglectful child care were found in baseline to have several important child-care skill deficits (e.g., bathing, diaper rash treatment, cleaning baby bottles) compared to nonhandicapped mothers. Parent training (consisting of verbal instructions, pictorial manuals, modeling, feedback, and reinforcement) resulted in rapid acquisition and maintenance of child-care skills in all mothers. Mean percentage correct scores increased from 58% in baseline to 90% in training and 91% in follow-up (M = 31 weeks). The latter two scores compare favorably to the mean score (87%) of 20 nonhandicapped mothers on the same skills. Where observable, parent training was associated with corresponding benefits to the children (e.g., elimination of diaper rash and cradle cap, increased weight gain, successful toilet training). These results indicate that parent training may be a viable option to the removal of the child from the home when parenting skill deficits place the child's well-being in jeopardy.

Quantification of human opiate receptor concentration and affinity using high and low specific activity [11C]diprenorphine and positron emission tomography.

[11C]Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration (Bmax) and affinity (Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769-5,920 Ci/mmol) and low (27-80 Ci/mmol) specific activity (SA) [11C]diprenorphine. Two subjects were studied a third time using high SA [11C]diprenorphine after a pretreatment with 1-1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/k4 ratio varied from 1.0 +/- 0.2 (occipital cortex) to 8.6 +/- 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the konf2 product. The measured free fraction of [11C]diprenorphine in plasma (f1) was 0.30 +/- 0.03, the average K1/k2 ratio from the two naloxone studies was 1.1 +/- 0.2, and the calculated free fraction of [11C]diprenorphine in the brain (f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 +/- 0.5 (occipital cortex) to 20.6 +/- 7.3 (cingulate cortex) nM. The average Kd (eight brain regions) was 0.85 +/- 0.17 nM.