Guideline for the management of chronic obstructive pulmonary disease--2011 update.

OBJECTIVE: To revise the South African Guideline for the Management of Chronic Obstructive Pulmonary Disease (COPD) based on emerging research that has informed updated recommendations. KEY POINTS: (1) Smoking is the major cause of COPD, but exposure to biomass fuels and tuberculosis are important additional factors. (2) Spirometry is essential for the diagnosis and staging of COPD. (3) COPD is either undiagnosed or diagnosed too late, so limiting the benefit of therapeutic interventions; performing spirometry in at-risk individuals will help to establish an early diagnosis. (4) Oral corticosteroids are no longer recommended for maintenance treatment of COPD. (5) A therapeutic trial of oral corticosteroids to distinguish corticosteroid responders from non-responders is no longer recommended. (6) Primary and secondary prevention are the most cost-effective strategies in COPD. Smoking cessation as well as avoidance of other forms of pollution can prevent disease in susceptible individuals and ameliorate progression. Bronchodilators are the mainstay of pharmacotherapy, relieving dyspnoea and improving quality of life. (7) Inhaled corticosteroids are recommended in patients with frequent exacerbations and have a synergistic effect with bronchodilators in improving lung function, quality of life and exacerbation frequency. (8) Acute exacerbations of COPD significantly affect morbidity, health care units and mortality. (9) Antibiotics are only indicated for purulent exacerbations of chronic bronchitis. (10) COPD patients should be encouraged to engage in an active lifestyle and participate in rehabilitation programmes. OPTIONS: Treatment recommendations are based on the following: annual updates of the Global Obstructive Lung Disease (GOLD), initiative, that provide an evidence-based comprehensive review of management; independent evaluation of the level of evidence in support of some of the new treatment trends; and consideration of factors that influence COPD management in South Africa, including lung co-morbidity and drug availability and cost. OUTCOME: Holistic management utilising pharmacological and nonpharmacological options are put in perspective. EVIDENCE: Working groups of clinicians and clinical researchers following detailed literature review, particularly of studies performed in South Africa, and the GOLD guidelines. BENEFITS, HARMS AND COSTS. The guideline pays particular attention to cost-effectiveness in South Africa, and promotes the initial use of less costly options. It promotes smoking cessation and selection of treatment based on objective evidence of benefit. It also rejects a nihilistic or punitive approach, even in those who are unable to break the smoking addiction. RECOMMENDATIONS: These include primary and secondary prevention; early diagnosis, staging of severity, use of bronchodilators and other forms of treatment, rehabilitation, and treatment of complications. Advice is provided on the management of acute exacerbations and the approach to air travel, prescribing long-term oxygen and lung surgery including lung volume reduction surgery. VALIDATION: The COPD Working Group comprised experienced pulmonologists representing all university departments in South Africa and some from private practice, and general practitioners. Most contributed to the development of the previous version of the South African guideline. GUIDELINE SPONSOR: The meeting of the Working Group of the South African Thoracic Society was sponsored by an unrestricted educational grant from Boehringer Ingelheim and Glaxo-Smith-Kline.

Genetic covariation between event-related potential (ERP) and behavioral non-ERP measures of working-memory, processing speed, and IQ.

The aim of this study was to identify genetic covariants for fundamental measures of brain function (event-related potentials (ERPs): P300 latency and slow wave amplitude recorded in a working-memory task) and more complex cognitive measures (behavioral non-ERP measures: working-memory performance, information processing speed, IQ). Data were collected from 252 monozygotic and 297 dizygotic twin pairs aged 16. Multivariate modeling identified two independent genetic factors associated with processing speed that also influenced working-memory performance (one reflected the duration of neural activity required to evaluate target information, the other reflected more general cognitive and speed-related abilities). However, the allocation of neural resources, as assessed by ERP slow wave amplitude measures, was not associated with the other cognitive measures investigated. Thus, of the ERP measures examined, P300 latency, but not slow wave amplitude, may be an informative measure to include (i.e., with working-memory performance) in future multivariate linkage and association analyses of cognitive function.

Guideline for the management of upper respiratory tract infections.

INTRODUCTION: Inappropriate use of antibiotics for upper respiratory tract infections (URTIs), many of which are viral, adds to the burden of antibiotic resistance. Antibiotic resistance is increasing in Streptococcus pneumoniae, responsible for most cases of acute otitis media (AOM) and acute bacterial sinusitis (ABS). METHOD: The Infectious Diseases Society of Southern Africa held a multidisciplinary meeting to draw up a national guideline for the management of URTIs. Background information reviewed included randomised controlled trials, existing URTI guidelines and local antibiotic susceptibility patterns. The initial document was drafted at the meeting. Subsequent drafts were circulated to members of the working group for modification. The guideline is a consensus document based upon the opinions of the working group. OUTPUT: Penicillin remains the drug of choice for tonsillopharyngitis. Single-dose parenteral administration of benzathine penicillin is effective, but many favour oral administration twice daily for 10 days. Amoxycillin remains the drug of choice for both AOM and ABS. A dose of 90 mg/ kg/day is recommended in general, which should be effective for pneumococci with high-level penicillin resistance (this is particularly likely in children < or = 2 years of age, in day-care attendees, in cases with prior AOM within the past 6 months, and in children who have received antibiotics within the last 3 months). Alternative antibiotic choices are given in the guideline with recommendations for their specific indications. These antibiotics include amoxycillin-clavulanate, some cephalosporins, the macrolide/azalide and ketolide groups of agents and the respiratory fluoroquinolones. CONCLUSION: The guideline should assist rational antibiotic prescribing for URTIs. However, it should be updated when new information becomes available from randomised controlled trials and surveillance studies of local antibiotic susceptibility patterns.

Lowered plasma vitamin C, but not vitamin E, concentrations in dementia patients.

BACKGROUND: Alzheimer s disease (AD), according to the free radical hypothesis, affects brain regions where free radical damage occurs. Antioxidant nutrients may help to protect these brain regions. OBJECTIVE: To investigate whether plasma vitamin C and E status is lowered in subjects with AD and dementia. DESIGN: A case control study was conducted in 93 institutionalized subjects aged 65 + yrs. The dementia group (N = 43) included 15 subjects with Alzheimer s Disease (AD) and 28 subjects with senile dementia, while the control group included 50 subjects with no cognitive impairment. Subjects with uncontrolled hypertension and/or diabetes were excluded from the study. Plasma vitamin C and E was determined using the 2,6- dichlorophenolindophenol and the HPLC methods, respectively. Dietary intake, including dietary supplements, was assessed using a 2-day plate-waste method. Cognitive function was measured using the MMSE and nutritional status assessed using the Mini Nutritional Assessment (MNA) tool. RESULTS: The control group had significantly higher scores for the MNA, MMSE and Activities of Daily Living, compared with the dementia group. Controls had a significantly higher plasma vitamin C concentration than dementia patients (median = 0.84 (IQR = 0.54) mg/dl and 0.56 (0.80) mg/dl, respectively; P<0.05). The dementia group were more likely to have sub-optimal plasma vitamin C levels (< 0.6 mg/dl) than control subjects (OR = 2.99; 95 % CI = 0.95 9.79; P<0.05), despite having similar dietary vitamin C intakes. Plasma vitamin C was positively associated with MMSE score (r = 0.21; P<0.05). No difference was found between the groups for either plasma or dietary vitamin E. CONCLUSION: Plasma vitamin C levels were lower in subjects with dementia compared to controls, which was not explained by their dietary vitamin C intakes. This data supports the free radical theory of oxidative neuronal damage. Further investigations of whether supplementation with this vitamin may prevent or delay the progression of cognitive decline in patients with AD and senile dementia appear warranted.

Slow binocular rivalry in bipolar disorder.

BACKGROUND: The rate of binocular rivalry has been reported to be slower in subjects with bipolar disorder than in controls when tested with drifting, vertical and horizontal gratings of high spatial frequency. METHOD: Here we assess the rate of binocular rivalry with stationary, vertical and horizontal gratings of low spatial frequency in 30 subjects with bipolar disorder, 30 age- and sex-matched controls, 18 subjects with schizophrenia and 18 subjects with major depression. Along with rivalry rate, the predominance of each of the rivaling images was assessed, as was the distribution of normalized rivalry intervals. RESULTS: The bipolar group demonstrated significantly slower rivalry than the control, schizophrenia and major depression groups. The schizophrenia and major depression groups did not differ significantly from the control group. Predominance values did not differ according to diagnosis and the distribution of normalized rivalry intervals was well described by a gamma function in all groups. CONCLUSIONS: The results provide further evidence that binocular rivalry is slow in bipolar disorder and demonstrate that rivalry predominance and the distribution of normalized rivalry intervals are not abnormal in bipolar disorder. It is also shown by comparison with previous work, that high strength stimuli more effectively distinguish bipolar from control subjects than low strength stimuli. The data on schizophrenia and major depression suggest the need for large-scale specificity trials. Further study is also required to assess genetic and pathophysiological factors as well as the potential effects of state, medication, and clinical and biological subtypes.

Genetics of cognition: outline of a collaborative twin study.

A multidisciplinary collaborative study examining cognition in a large sample of twins is outlined. A common experimental protocol and design is used in The Netherlands, Australia and Japan to measure cognitive ability using traditional IQ measures (i.e., psychometric IQ), processing speed (e.g., reaction time [RT] and inspection time [IT]), and working memory (e.g., spatial span, delayed response [DR] performance). The main aim is to investigate the genetic covariation among these cognitive phenotypes in order to use the correlated biological markers in future linkage and association analyses to detect quantitative-trait loci (QTLs). We outline the study and methodology, and report results from our preliminary analyses that examines the heritability of processing speed and working memory indices, and their phenotypic correlation with IQ. Heritability of Full Scale IQ was 87% in the Netherlands, 83% in Australia, and 71% in Japan. Heritability estimates for processing speed and working memory indices ranged from 33-64%. Associations of IQ with RT and IT (-0.28 to -0.36) replicated previous findings with those of higher cognitive ability showing faster speed of processing. Similarly, significant correlations were indicated between IQ and the spatial span working memory task (storage [0.31], executive processing [0.37]) and the DR working memory task (0.25), with those of higher cognitive ability showing better memory performance. These analyses establish the heritability of the processing speed and working memory measures to be used in our collaborative twin study of cognition, and support the findings that individual differences in processing speed and working memory may underlie individual differences in psychometric IQ.

The n-back as a dual-task: P300 morphology under divided attention.

The n-back task was hypothesized to be a dual task, permitting the imposition of parametrically increasing attentional and working memory demands, while keeping constant the demands of an embedded matching subtask. Visual targets were presented for 200 ms every 2.2 s at pseudorandomly varying positions on a computer screen. Participants were required to remember the most recent 0, 1, 2, or 3 positions and responded with a choice button push to whether the current target position matched the position presented n items previously. P300 peak latency was constant across n-back tasks, reflecting constant perceptual and cognitive demands of the matching subtask. P300 peak amplitude decreased with increasing memory load, reflecting reallocation of attention and processing capacity away from the matching subtask to working memory activity. These data support a dual-task nature of the n-back, which should be considered when employing this paradigm.

Genetic influence on the variance in P3 amplitude and latency.

The P3(00) event-related potential (ERP) component is widely used as a measure of cognitive functioning and provides a sensitive electrophysiological index of the attentional and working memory demands of a task. This study investigated what proportion of the variance in the amplitude and latency of the P3, elicited in a delayed response working memory task, could be attributed to genetic factors. In 335 adolescent twin pairs and 48 siblings, the amplitude and latency of the P3 were examined at frontal, central, and parietal sites. Additive genetic factors accounted for 48% to 61% of the variance in P3 amplitude. Approximately one-third of the genetic variation at frontal sites was mediated by a common genetic factor that also influenced the genetic variation at parietal and central sites. Familial resemblance in P3 latency was due to genetic influence that accounted for 44% to 50% of the variance. Genetic covariance in P3 latency across sites was substantial, with a large part of the variance found at parietal, central, and frontal sites attributed to a common genetic factor. The findings provide further evidence that the P3 is a promising phenotype of neural activity of the brain and has the potential to be used in linkage and association analysis in the search for quantitative trait loci (QTLs) influencing cognition.

Genetic covariance among measures of information processing speed, working memory, and IQ.

The genetic relationship between lower (information processing speed), intermediate (working memory), and higher levels (complex cognitive processes as indexed by IQ) of mental ability was studied in a classical twin design comprising 166 monozygotic and 190 dizygotic twin pairs. Processing speed was measured by a choice reaction time (RT) task (2-, 4-, and 8-choice), working memory by a visual-spatial delayed response task, and IQ by the Multidimensional Aptitude Battery. Multivariate analysis, adjusted for test-retest reliability, showed the presence of a genetic factor influencing all variables and a genetic factor influencing 4- and 8-choice RTs, working memory, and IQ. There were also genetic factors specific to 8-choice RT, working memory, and IQ. The results confirmed a strong relationship between choice RT and IQ (phenotypic correlations: -0.31 to -0.53 in females, -0.32 to -0.56 in males; genotypic correlations: -0.45 to -0.70) and a weaker but significant association between working memory and IQ (phenotypic: 0.26 in females, 0.13 in males; genotypic: 0.34). A significant part of the genetic variance (43%) in IQ was not related to either choice RT or delayed response performance, and may represent higher order cognitive processes.

Genetic influence on ERP slow wave measures of working memory.

Individual differences in the variance of event-related potential (ERP) slow wave (SW) measures were examined. SW was recorded at prefrontal and parietal sites during memory and sensory trials of a delayed-response task in 391 adolescent twin pairs. Familial resemblance was identified and there was a strong suggestion of genetic influence. A common genetic factor influencing memory and sensory SW was identified at the prefrontal site (accounting for an estimated 35%-37% of the reliable variance) and at the parietal site (51%-52% of the reliable variance). Remaining reliable variance was influenced by unique environmental factors. Measurement error accounted for 24% to 30% of the total variance of each variable. The results show genetic independence for recording site, but not trial type, and suggest that the genetic factors identified relate more directly to brain structures, as defined by the cognitive functions they support, than to the cognitive networks that link them.

Concussion in contact sports: reliable change indices of impairment and recovery.

This paper reports a follow-up study to an article on the sensitivity of three tests of speed of information processing to impairment after concussion (Hinton-Bayre, Geffen, & McFarland, 1997). Group analyses showed that practice effects can obscure the effects of concussion on information processing, thereby making the assessment of functional impairment and recovery after injury unreliable. A Reliable Change Index (RCI) was used to assess individual variations following concussion. It was found that 16 of the 20 concussed professional rugby league players were impaired 1-3 days following injury. It was also demonstrated that 7 players still displayed cognitive deficits at 1-2 weeks, before returning to preseason levels at 3-5 weeks. The RCI permits comparisons between different tests, players, and repeated assessments, thereby providing a quantitative basis for decisions regarding return to play.

The development of passive health surveillance by a sentinel network of family practitioners in South Africa.

OBJECTIVE: For the South African Sentinel Practitioner Research Network (SASPREN), a volunteer network of family practitioners in South Africa, to develop a health surveillance system through the surveillance of important health events. MOTIVATION: The incidence of important preventable diseases and the burden of disease are not reliably known in South Africa, both in the public and private sector. Incidence rates determined at primary care level could help with planning and delivery of appropriate health services and monitoring of the impact of intervention programmes. METHODS: Altogether 183 sentinel practitioners were recruited in nine provinces, from 2,478 doctors invited to participate. Of these 120 were active in reporting all their new cases of 13 selected health events to the study centre on mailed postcards. After data-capturing, incidence rates were calculated for defined periods. Feedback was given to the sentinels through a newsletter and personalised reports. RESULTS: A network of sentinel family practitioners has been established in South Africa, and can provide incidence rates for both diseases and interventions through a simple and cheap surveillance system. The calculated rates demonstrated periodic trends for certain events, as well as inter-provincial, -gender and -population group differences. CONCLUSIONS: As the validity of the dataset and its generalisation to the whole population is uncertain, its usefulness as point estimates of incidence rates is unknown. This information serves as an important pointer for further research. The trends of these rates may provide a valuable tool for monitoring the impact of public health policies.

Comparative effects of ageing and dementia of the Alzheimer type on orientation of visual attention.

Age-related changes and the effects of dementia of the Alzheimer type (DAT) were investigated during a visual orienting attention task in which attention was pre-cued to one or other hemifields. Central cues were either valid, neutral, invalid or NoGo (inhibitory). The response time cost-benefit analysis showed a decreased benefit after valid cueing in the old compared with the young group with no change in the cost of invalid cueing. The older group were also slower over all cue types. These results suggest there is an age-related reduced ability to covertly orient attention in a visual hemifield before target onset. In contrast, the DAT group showed an increased response time benefit and showed a trend for a decreased cost in response time compared with controls. This was due to slowest response times after neutral cues. They also made significantly more response errors particularly following neutral cueing, and were less able to inhibit responses on NoGo trials than controls. The increased benefit and reduced cost found in the DAT group was interpreted as an impairment in dividing attention between left and right target locations.

Thoracic spinal fracture in a rugby league footballer.

PURPOSE: The report describes the mechanisms and sequelae of the first case of thoracic vertebral fracture to be reported in a rugby league footballer. CASE SUMMARY: The injury was sustained as the result of a legal shoulder tackle. The player exhibited no sign other than dorsal midthoracic tenderness and paraspinal muscle spasm. Investigations commenced the next day because of persistent pain. CT and MRI revealed complex T6/7 fractures not evident on plain x-ray. The player was managed conservatively with analgesia and rest and has made a full recovery. DISCUSSION: Football is the most common cause of cervical spinal fractures in sport, whereas thoracic spinal fractures are very rare. Although in this case significant damage occurred to the posterior elements of the column, there were no neurological complications. RELEVANCE: The anatomical and physiological bracing of the thoracic spine accounts for the rarity of fractures in contact sport and favors conservative management.

Effects of memory load and distraction on performance and event-related slow potentials in a visuospatial working memory task.

Brain electrical activity related to working memory was recorded at 15 scalp electrodes during a visuospatial delayed response task. Participants (N = 18) touched the remembered position of a target on a computer screen after either a 1 or 8 sec delay. These memory trials were compared to sensory trials in which the target remained present throughout the delay and response periods. Distractor stimuli identical to the target were briefly presented during the delay on 30% of trials. Responses were less accurate in memory than sensory trials, especially after the long delay. During the delay slow potentials developed that were significantly more negative in memory than sensory trials. The difference between memory and sensory trials was greater at anterior than posterior electrodes. On trials with distractors, the slow potentials generated by memory trials showed further enhancement of negativity, whereas there were minimal effects on accuracy of performance. The results provide evidence that engagement of visuospatial working memory generates slow wave negativity with a timing and distribution consistent with frontal activation. Enhanced brain activity associated with working memory is required to maintain performance in the presence of distraction.

ERP measures of stimulus processing during an auditory oddball task in Parkinson's disease: Evidence for an early information processing deficit.

Seventeen non-demented patients with idiopathic Parkinson's disease were compared with an age and sex matched control group on an auditory oddball task. Low probability target tones were either counted silently or responded to by a button press. N1 amplitude in the Parkinson group was attenuated to both target and non-target tones suggesting an impairment in early information processing. In contrast amplitudes of P2, N2 and P3 did not differentiate patients from controls. Several peak latencies (P2, N2 and P3) were increased in the Parkinson group when targets were counted, whereas only N2 was delayed when targets were identified by a button press. The longer N2 latency is suggestive of an increase in the time needed to categorize stimuli. The amplitude and latency changes of early ERP components provide evidence for impairment in early information processing in Parkinson's disease.

Event related potentials during covert orientation of visual attention: effects of cue validity and directionality.

Covert orientation of attention was studied in 30 adults who fixated warning cues and pressed a button at target onset. Directional cues (arrows) indicated the most probable (p = 0.8) side of target occurrence. Subjects responded fastest when validly cued, slowest to invalidly cued targets, and at an intermediate rate when the cue (a cross) was not directional. Directional cues took longer to evaluate (increased N1 and P2 latencies) and produced more focussed attention and greater response preparation (enhanced CNV and P3 amplitude) than non-directional cues. These findings indicate that the expectancy of a target can be manipulated by a spatial cue at three levels, sensory, attention, and response preparation, and lead to changes in the sensory perceptual processing of the target. Validly cued targets produced an increase in P1 amplitude reflecting attention enhanced sensory processing whereas invalidly cued targets increased N1 and P3 amplitudes reflecting the re-orientation of attention, and further processing and updating of information required of low probability stimuli respectively. P3 latency to invalidly cued targets was also delayed reflecting the additional processes required to shift attention to a new location. The P3 latency validity effect was smaller than that found for response time suggesting response execution may also be affected by spatial attention.

Interhemispheric control of manual motor activity.

The interhemispheric control of manual motor processes is reviewed, focusing on the clinical evidence from patients with commissurotomies and with agenesis of the corpus callosum. There is little evidence for a role of the corpus callosum in transferring explicit motor commands. Rather, the corpus callosum seems important for transferring lateralised information (such as verbal or visuospatial activity) of the pre-motor variety. Also, the corpus callosum may become very significant when movement begins: there appears to be a transcallosal passage of corollary motor signals and feedback sensory signals that are used to control asychronous bimanual movements and to inhibit the opposite hemisphere from interfering when a simple unimanual movement is required.