Barriers to colorectal cancer screening in Ghana: a qualitative study of patients and physicians.

PURPOSE: The incidence of colorectal cancer (CRC) in Ghana has increased eightfold since the 1960s. In 2011, national guidelines were set forth recommending all patients aged 50-70 years old undergo annual CRC screening with fecal occult blood testing (FOBT), but adherence to these guidelines is poor and screening rates remain low for unclear reasons. METHODS: We performed semi-structured interviews with 28 Ghanaians including physicians (n = 14) and patients (n = 14) from the Komfo Anokye Teaching Hospital in Kumasi, Ghana, to better understand the factors driving screening adherence and perceived barriers identified in an earlier quantitative study. RESULTS: Participants reported sociocultural factors such as reliance on alternative medicine or religion, lack of education, and financial burden as community-level barriers to CRC screening. At the system level, screening was limited by insufficient access to FOBT as well as a perceived lack of national prioritization. This was described as inadequate efforts from the Ministry of Health regarding national education as well as lack of incorporation of CRC screening into the National Health Insurance Scheme. CONCLUSION: Several community- and system-level barriers exist to widespread screening of CRC in Ghana. A multi-level approach will be required to improve rates of CRC screening and ultimately reduce the burden of CRC in Ghana.

How calls from carers, friends and family members of someone affected by cancer differ from those made by people diagnosed with cancer; analysis of 4 years of South Australian Cancer Council Helpline data.

PURPOSE: The purpose of this study is to determine how people diagnosed with cancer who call the Cancer Council Helpline in South Australia differ from carers/family/friends (caregivers) who call. METHOD: Descriptive, retrospective audit of calls from people who contacted Cancer Council Helpline in South Australia between 16 April 2009 and 16 April 2013 who were diagnosed with cancer (n = 5766) or were the caregivers (n = 5174) of a person with cancer. RESULTS: Caregivers were more likely to be female (p < 0.001); younger in age (p < 0.001); call regarding cancer that was metastasised/widespread/advanced, terminal or at an unknown stage (p < 0.001) and phone requesting general cancer information or emotional support (p < 0.001). This group was more distressed (p < 0.001) but less likely (p = 0.02) to be offered and/or accept referrals to counselling than people diagnosed with cancer who called. Follow-up care was required by 63.5 % of caregivers and 73.1 % of people with cancer according to distress management guidelines; 8.5 and 15.3 %, respectively, accepted referrals to internal services. The most frequently discussed topic for both groups was emotional/psychological concerns. There were no differences in remoteness of residence or call length between groups. CONCLUSIONS: Caregivers represented different demographic groups than people diagnosed with cancer who called this helpline. The two groups phoned for different issues, at different stages of disease progression, displayed different levels of distress and, therefore, may benefit from services being tailored to meet their unique needs. These results also demonstrate the capacity of helplines to complement other health services and confirm that callers to cancer helplines exhibit high levels of distress.

Supraspinal inputs reduce corticomotor excitability during passive movement: evidence from a pure sensory stroke.

Corticomotor excitability is reduced during rhythmic passive movement compared to rest, but it is not known whether the mechanism is purely segmental or includes a supraspinal pathway. To determine how interruption of sensory projections at a supraspinal level affects corticomotor excitability during passive movement, we measured the amplitude of motor evoked potential (MEP) during 1 Hz cyclic index finger movements in a patient with a brainstem and thalamus lesion that resulted in a pure sensory stroke. Measurements of MEP amplitude and proprioception were made 14 and 64 days post-stroke. In the first study, when subjective position sense was reduced for the index finger, MEP amplitude was significantly increased during passive movement compared to rest (4.6+/-0.2 SEM mV vs. 4.0+/-0.2 mV; p=0.0281). However in the second study, when position sense had returned to normal, MEP amplitude was significantly reduced during movement compared to rest (6.2+/-0.3 mV vs. 6.6+/-0.1 mV; p=0.0224). These observations provide evidence that supraspinal sensory pathways are involved in reducing corticomotor excitability during rhythmic passive movement.

Spatial acquisition in the Morris water maze and hippocampal long-term potentiation in the adult guinea pig following brain growth spurt--prenatal ethanol exposure.

Previous work has demonstrated that in the guinea pig, chronic prenatal ethanol exposure throughout gestation can result in deficits in spatial learning in the Morris water maze and impaired hippocampal long-term potentiation (LTP). The behavioural effects are known to be dose dependent because water maze deficits occur at a dose of 4 g ethanol/kg maternal body weight/day, but not at a dose of 3 g/kg/day, administered throughout gestation. It is possible that the gradual, progressive development of tolerance to ethanol throughout gestation limits ethanol toxicity, especially for lower doses of ethanol. The present study examined whether neurobehavioural deficits are produced by prenatal ethanol exposure at a dose of 3 g/kg/day, administered only during the brain growth spurt (BGS), a regimen designed to limit the development of ethanol tolerance. Pregnant guinea pigs [term, about gestational day (GD) 68] received oral administration of ethanol (1.5 g/kg maternal body weight/day on GD 43 and 44 and then 3 g/kg maternal body weight/day from GD 45 to 62), isocaloric-sucrose/pair-feeding, or water. Offsprings were studied between postnatal days (PD) 40 and 80. The maternal blood ethanol concentration (BEC) on GD 57 or 58, at 1 h after the daily dose, was 245+/-19 mg/dl (n=7). This BGS--prenatal ethanol exposure regimen did not affect spatial learning performance in the Morris water maze over a 7-day test period or in the LTP recorded in the CA1 region of the hippocampus. Thus, even when limiting the development of ethanol tolerance seen with chronic ethanol treatment throughout gestation, ethanol exposure during the BGS does not result in deficits in the behavioural and electrophysiological measures of hippocampal integrity assessed in the present study. These data indicate that in the guinea pig, the BGS may not constitute a critical period of vulnerability for ethanol-induced deficits in spatial learning or hippocampal synaptic plasticity in young adult offspring.

Prevalence of cerebral vascular amyloid-beta deposition and stroke in an aging Australian population: a postmortem study.

Cerebral amyloid angiopathy (CAA) is a putative risk factor for lobar cerebral haemorrhage and infarction in the elderly. However, the prevalence of stroke in a population with CAA is not known. Amyloid-beta immunohistochemistry was used to assess CAA prevalence as a function of age, and the relationship between CAA and stroke in 100 individuals aged 50-91 years who died unexpectedly and had a Coroner's postmortem. Blocks were taken from several cortical areas and from areas of infarction or haemorrhage. Parenchymal Abeta was first found in the 6th decade, whereas vascular Abeta did not appear until the 7th decade. The prevalence of both vascular and parenchymal Abeta increased with age to a maximum in the 9th decade. The age at onset of vascular Abeta deposition was similar to that in an English study of CAA but a decade later than in Japanese studies. There was no association between the presence of vascular Abeta and cerebral haemorrhage or infarction. The findings indicate differences in the time-course of vascular and parenchymal Abeta deposition with age, as well as racial differences. The lack of association between vascular Abeta and cerebral haemorrhage or infarction indicates that, in the present population, CAA was usually asymptomatic.

Impaired acquisition in the water maze and hippocampal long-term potentiation after chronic prenatal ethanol exposure in the guinea-pig.

In the hippocampus, the CA1 region is selectively vulnerable to the effects of chronic prenatal ethanol exposure. In the guinea-pig, the number of CA1 pyramidal cells is decreased after chronic prenatal ethanol exposure. We tested the hypotheses that chronic prenatal ethanol exposure (through maternal ethanol ingestion) results in impairments in spatial learning and short- and long-term plasticity in the CA1 region of the postnatal guinea-pig hippocampus. Timed, pregnant guinea-pigs were treated with ethanol (4 g/kg maternal body weight/day), isocaloric sucrose/pair-feeding, or water throughout gestation. Offspring were studied between postnatal days 40 and 80. In the Morris water maze, animals exposed to ethanol prenatally showed slower acquisition of an escape response to a hidden platform over 5 days of training. The amplitude of the field excitatory postsynaptic potential in the CA1 region in response to contralateral CA3 stimulation was decreased in offspring exposed to ethanol prenatally. Two forms of short-term plasticity (paired-pulse and frequency facilitation) were unaffected by chronic prenatal ethanol exposure. Long-term potentiation (LTP) in response to high-frequency CA3 stimulation was induced reliably and maintained over 60 min in isocaloric-sucrose and water control animals. However, LTP failed to be induced in the CA1 area of the hippocampus in prenatal ethanol-exposed offspring. These data show that chronic prenatal ethanol exposure, through maternal ethanol administration, impairs spatial performance and LTP in CA1 neurons. Hippocampal dysfunction could contribute importantly to the cognitive and behavioural deficits resulting from chronic prenatal ethanol exposure.

Effect of prenatal ethanol exposure during the brain growth spurt of the guinea pig.

This study tested the hypothesis that prenatal ethanol exposure during the last third of gestation, including the brain growth spurt (BGS), in the guinea pig produces neurobehavioural teratogenicity, manifesting as brain growth restriction and hyperactivity. Pregnant guinea pigs (term, about gestational day (GD) 68) received oral administration of ethanol (2 g/kg maternal body weight per day on GD 43 and/or GD 44 and then 4 g/kg maternal body weight per day from GD 45 to GD 62), isocaloric-sucrose/pair-feeding, or water. Maternal blood ethanol concentration (BEC) on GD 57 or 58, at 1 h after the daily dose, was 340+/-76 mg/dl (n=8). Ethanol treatment decreased brain, cerebral cortical, hippocampal, and cerebellar weights at GD 63 (P<0.05), and decreased brain and cerebral cortical weights at postnatal day 10 (P<0.05), with no effect on body weight and no apparent effect on spontaneous locomotor activity. The data demonstrate that, in the guinea pig, prenatal ethanol exposure during the last third of gestation, including the BGS, decreases brain weight that persists into postnatal life, which is associated with growth restriction of the cerebral cortex. However, this prenatal ethanol exposure regimen, including the BGS, does not increase spontaneous locomotor activity in contrast to the persistent hyperactivity that occurs after chronic ethanol exposure throughout gestation.

N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age.

BACKGROUND: The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy (as in N6 protocol [Kushner et al.: J Clin Oncol 12:2607-2613, 1994] but with lower dosing of vincristine) for induction, surgical resection and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2). PROCEDURE: The chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7. 131I-3F8 is dosed at 20 mCi/kg, which is myeloablative and therefore necessitates stem-cell support. RESULTS: Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis, 22 were stage 4 and two were unresectable stage 3 with MYCN amplification. Chemotherapy achieved CR/VGPR in 21 of 24 patients. Twenty patients to date have completed treatment with 131I-3F8, and 15 patients have completed all treatment. With a median follow-up of 19 months, 18 of 24 patients remain progression-free. CONCLUSIONS: Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy, and self-limited pain and urticaria during antibody treatment. Late effects include hearing deficits and hypothyroidism.

Differences in sensory and motor cortical organization following brain injury early in life.

There have been a number of physiological studies of motor recovery in hemiplegic cerebral palsy which have identified the presence of novel ipsilateral projections from the undamaged hemisphere to the affected hand. However, little is known regarding the afferent projection to sensory cortex and its relationship to the reorganized cortical motor output. We used transcranial magnetic stimulation (TMS) to investigate the corticomotor projection to the affected and unaffected hands in a group of subjects with hemiplegic cerebral palsy, and also performed functional magnetic resonance imaging (fMRI) studies of the patterns of activation in cortical motor and sensory areas following active and passive movement of the hands. Both TMS and fMRI demonstrated a normal contralateral motor and sensory projection between the unaffected hand and the cerebral hemisphere. However, in the case of the affected hand, the TMS results indicated either a purely ipsilateral projection or a bilateral projection in which the ipsilateral pathway had the lower motor threshold, whereas passive movement resulted in fMRI activation in the contralateral hemisphere. These results demonstrate that there is a significant fast-conducting corticomotor projection to the affected hand from the ipsilateral hemisphere in this group of subjects, but that the predominant afferent projection from the hand is still directed to the affected contralateral hemisphere, resulting in an interhemispheric dissociation between afferent kinesthetic inputs and efferent corticomotor output. The findings indicate that there can be differences in the organization of sensory and motor pathways in cerebral palsy, and suggest that some of the residual motor dysfunction experienced by these subjects could be due to an impairment of sensorimotor integration at cortical level as a result of reorganization in the motor system.

Long-term changes in motor cortical organisation after recovery from subcortical stroke.

The present study has investigated the long-term changes in the organisation of the corticomotor projection to the hand in a group of subjects who had sustained a subcortical hemispheric stroke up to 15 years previously and had subsequently recovered normal or near-normal motor function. Transcranial magnetic cortical stimulation (TMCS) was employed to map the topography of the primary corticomotor projection to the hand and to obtain measures of cortical motor threshold, long-latency intracortical inhibition and corticospinal conduction. Changes in motor threshold and in motor-evoked potential (MEP) amplitude and latency in keeping with persisting impairment of conduction in the corticospinal pathway were still present in the majority of subjects, whereas the duration of the post-MEP silent period, reflecting the strength of long-latency intracortical inhibition, was usually normal. Topographic shifts in the corticomotor representation relative to the unaffected side were found in the majority of subjects. In some the shifts were in the mediolateral axis suggesting reorganisation within the primary motor cortex, while in the others anteroposterior shifts were present in keeping with recruitment of premotor or postcentral cortex. The present findings indicate that changes in the physiological properties of the corticomotor projection to the hand are frequently present in subjects who have recovered motor function after a subcortical stroke and may persist indefinitely. We postulate that these changes are the result of reorganisation at cortical level and that cortical reorganisation is one of the processes which contribute to motor recovery after a subcortical lesion and which may compensate for persisting impairment of conduction in the corticospinal pathway.

Changes in corticomotor excitability after fatiguing muscle contractions.

To investigate whether the type and duration of activity influences corticomotor excitability following fatiguing exercise, we compared motor evoked potential (MEP) responses of the biceps brachii to transcranial magnetic stimulation (TMS) during recovery from two different exercise regimens. Responses were recorded in both the resting state and during a weak contraction. Ten subjects performed a 60-s maximal voluntary contraction (MVC) and, on a subsequent occasion, a sustained 20% MVC to the point of exhaustion. Resting MEP amplitude declined following maximal and submaximal protocols, reaching 34% and 31% of pre-exercise means, respectively (P < 0.001 for both). In contrast, mean facilitated MEP amplitude showed a smaller and more transient decrement following the sustained submaximal effort (64%; P < 0.05), but not the 60-s MVC. Abolition of the postexercise depression in resting MEP amplitude by a weak tonic contraction indicates that decreases in excitability at the spinal level contribute to the reduced corticomotor excitability observed after fatiguing exercise.

Registered nurses' clinical reasoning abilities: a study of self perception.

Effective clinical reasoning by nurses is an essential component of nursing practice. The purpose of this study was to gain increased awareness and insight into registered nurses' perception of their clinical reasoning ability. A convenience sample of post-registration nursing students (n = 520) who enrolled in a Bachelor of Nursing program from 1993 to 1996 participated in the study. Perceptions of clinical reasoning abilities were assessed using the Jenkins' Clinical Decision Making in Nursing Scale (CDMNS). Analysis of CDMNS total scores indicated these students entered the program with positive perceptions of how they go about making clinical decisions. Measurement of aspects of these perceptions in relation to searching for alternatives (Subscale A), canvassing objectives (Subscale B) and evaluating consequences (Subscale C) indicated moderately positive perceptions of clinical reasoning abilities. However, highly positive perceptions were evident for assimilating new information (Subscale D). These results indicate some dissonance between the perceived abilities and the actual abilities reported in clinical reasoning literature and frequently observed in practice.

The role of the supplementary motor area in externally timed movement: the influence of predictability of movement timing.

A significant role in the planning and preparation for voluntary movement has been ascribed to secondary motor areas located on the medial wall of the cerebral hemispheres, and in particular to the supplementary motor area (SMA). Within the SMA, rostral and caudal subdivisions have been described, and differential roles have been attributed to these regions in relation to movement planning, preparation and execution. We have used functional magnetic resonance imaging (fMRI) to investigate the role of the SMA in the timing of movement execution, by recording the fMRI signal from mesial pre-motor areas and primary sensorimotor cortex (SM1) during the execution of a simple motor task externally cued at predictable (regular) and unpredictable (irregular) time intervals. The mean rate of movement was matched in both experiments. There was a greater activation of caudal than rostral SMA with both predictably and unpredictably cued movements, and a doubling of the signal when the timing of the motor response was unpredictable. In contrast, there was no difference in the activation of primary sensorimotor cortex with the two tasks. The data demonstrate that the caudal SMA has an important role in the execution of externally cued movements. The results also suggest a greater role for this region in the performance of unpredictably timed compared with predictably timed movements, however a model is proposed (based on electrophysiological data) which shows how the difference in functional signal in these two situations can be explained on the basis of a difference in the time course of neuronal activation in the SMA, rather than in the overall degree of activation.

The measurement of symptoms in children with cancer.

The purpose of this study was to determine symptom prevalence, characteristics, and distress in children with cancer. The Memorial Symptom Assessment Scale (MSAS) 10-18, a 30-item patient-rated instrument adapted from a previously validated adult version, provided multidimensional information about the symptoms experienced by children with cancer. This instrument was administered to 160 children with cancer aged 10-18 (45 inpatients, 115 outpatients). To confirm the instrument's reliability and validity, additional data about symptoms were collected from both the parents and the medical charts, and retesting was performed on a subgroup of inpatients. Patients could easily complete the scale in a mean of 11 minutes. The analyses supported the reliability and validity of the MSAS 10-18 subscale scores as measures of physical, psychological, and global symptom distress, respectively. Symptom prevalence ranged from 49.7% for lack of energy to 6.3% for problems with urination. The mean (+/- SD) number of symptoms per inpatient was 12.7 +/- 4.9 (range, 4-26), significantly more than the mean 6.5 +/- 5.7 (range, 0-28) symptoms per outpatient. Patients who had recently received chemotherapy had significantly more symptoms than patients who had not received chemotherapy for more than 4 months (11.6 +/- 6.0 vs. 5. 2 +/- 5.1), and those patients with solid tumors had significantly more symptoms than patients with either leukemia, lymphoma, or central nervous system malignancies (9.9 +/- 7.0 vs. 6.8 +/- 5.5 vs. 6.8 +/- 5.0 vs. 8.0 +/- 6.1). The most common symptoms (prevalence > 35%) were lack of energy, pain, drowsiness, nausea, cough, lack of appetite, and psychological symptoms (feeling sad, feeling nervous, worrying, feeling irritable). Of the symptoms with prevalence rates > 35%, those that caused high distress in more than one-third of patients were feeling sad, pain, nausea, lack of appetite, and feeling irritable. Subscale scores demonstrated large variability in symptom distress and could identify subgroups with high distress. The prevalence, characteristics, and distress associated with physical and psychological symptoms could be quantified in older children with cancer. The data confirm a high prevalence of symptoms overall and the existence of subgroups with high distress associated with one or multiple symptoms. Symptom distress is relatively higher among inpatients, children with solid tumors, and children who are undergoing antineoplastic treatment. Systematic symptom assessment may be useful in future epidemiological studies of symptoms and in clinical chemotherapeutic trials. Symptom epidemiology may also provide a focus for future clinical trials related to symptom management in children with cancer.

Functional reorganisation of the corticomotor projection to the hand in skilled racquet players.

While it is known that relatively rapid changes in functional representation may occur in the human sensorimotor cortex in short-term motor-learning studies, there have been few studies of changes in organisation of the corticomotor system associated with the long-term acquisition of motor skills. In the present study, we have used transcranial magnetic stimulation (TMS) to investigate the corticomotor projection to the hand in a group of elite racquet players, who have developed and maintained a high level of skill over a period of many years, and have compared the findings with those in a group of social players and a group of non-playing control subjects. Increased motor-evoked-potential (MEP) amplitudes and shifts in the cortical motor maps for the playing hand were found in all of the elite players and cortical motor thresholds were reduced in some players, whereas in the social players all parameters were within the normal range. The findings in the elite players are interpreted as being indications of a process of functional reorganisation with the motor cortex or corticomotor pathway that are associated with the acquisition and retention of complex motor skills.

Corticomotor excitability and perception of effort during sustained exercise in the chronic fatigue syndrome.

OBJECTIVE: We have investigated the possibility of a central basis for the complaints of fatigue and poor exercise tolerance in subjects with chronic fatigue syndrome (CFS). METHODS: Transcranial magnetic stimulation of the motor cortex was used to measure sequential changes in motor evoked potential (MEP) amplitude, post-excitatory silent period (SP) duration and twitch force of the biceps brachii muscle during a 20% maximum isometric elbow flexor contraction maintained to the point of exhaustion. Ten patients with post-infectious CFS and 10 age- and sex-matched control subjects were studied. Results were analysed using non-parametric repeated measures analysis of variance (Friedman's test) and Mann-Whitney U-tests for intra- and inter-group comparisons respectively. RESULTS: Mean endurance time for the CFS group was lower (13.1+/-3.2 min, mean +/- SEM) than controls (18.6+/-2.6 min, P < 0.05) and CFS subjects reported higher ratings of perceived exertion. During the exercise period MEP amplitude and SP duration increased in both groups but to a lesser extent in CFS subjects. Interpolated twitch force amplitude also increased during exercise, being more pronounced in CFS subjects. CONCLUSION: The findings are in keeping with an exercise-related diminution in central motor drive in association with an increased perception of effort in CFS.

A model of the effect of MEP amplitude variation on the accuracy of TMS mapping.

We have modelled the effect of motor evoked potential (MEP) amplitude variation on transcranial magnetic stimulation (TMS) maps. The range of variability in TMS map parameters was estimated by randomly altering the MEP amplitude associated with each stimulus site and re-calculating the map parameters. TMS map position and area were remarkably stable, with variations of the order of 1 mm for map position and less than 5% for map area. The results indicate that reliable and accurate mapping studies can be carried out in the presence of an intrinsic variability in MEP amplitude measurements.

Differences in functional magnetic resonance imaging of sensorimotor cortex during static and dynamic finger flexion.

Functional magnetic resonance imaging (fMRI) studies of the human motor system have commonly used movement paradigms which contain a dynamic component; however, the relationship between the fMRI signal for motor tasks with and without a dynamic component is not known. We have investigated the relationship between the fMRI signal during a static finger flexion task and during dynamic finger flexion at 1-3 Hz, each at two levels of force (5% and 10% of maximum voluntary contraction). A small fMRI response could be recorded from only a few subjects during the static tasks. In contrast, a substantial fMRI response occurred during dynamic tasks in all subjects at both levels of force. The fMRI response was not significantly correlated with force or movement rate during the dynamic tasks. It is concluded that the factors responsible for generating an fMRI response are fundamentally different during steady contractions compared to those involving a dynamic component, and that the fMRI signal may be more sensitive to changes in the pattern of neural activation rather than the ongoing firing rate or extent of activation.