Risk Factor Characterization of Ischemic Stroke Subtypes Among West Africans.

BACKGROUND AND PURPOSE: To identify the qualitative and quantitative contributions of conventional risk factors for occurrence of ischemic stroke and its key pathophysiologic subtypes among West Africans. METHODS: The SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with ischemic stroke who were etiologically subtyped using the A-S-C-O-D classification into atherosclerosis, small-vessel occlusion, cardiac pathology, other causes, and dissection. Controls were age- and gender-matched stroke-free adults. Detailed evaluations for vascular, lifestyle, and psychosocial factors were performed. We used conditional logistic regression to estimate adjusted odds ratios with 95% CI. RESULTS: There were 2431 ischemic stroke case and stroke-free control pairs with respective mean ages of 62.2±14.0 versus 60.9±13.7 years. There were 1024 (42.1%) small vessel occlusions, 427 (17.6%) large-artery atherosclerosis, 258 (10.6%) cardio-embolic, 3 (0.1%) carotid dissections, and 719 (29.6%) undetermined/other causes. The adjusted odds ratio (95% CI) for the 8 dominant risk factors for ischemic stroke were hypertension, 10.34 (6.91-15.45); dyslipidemia, 5.16 (3.78-7.03); diabetes, 3.44 (2.60-4.56); low green vegetable consumption, 1.89 (1.45-2.46); red meat consumption, 1.89 (1.45-2.46); cardiac disease, 1.88 (1.22-2.90); monthly income $100 or more, 1.72 (1.24-2.39); and psychosocial stress, 1.62 (1.18-2.21). Hypertension, dyslipidemia, diabetes were confluent factors shared by small-vessel, large-vessel and cardio-embolic subtypes. Stroke cases and stroke-free controls had a mean of 5.3±1.5 versus 3.2±1.0 adverse cardio-metabolic risk factors respectively (P<0.0001). CONCLUSIONS: Traditional vascular risk factors demonstrate important differential effect sizes with pathophysiologic, clinical and preventative implications on the occurrence of ischemic stroke among indigenous West Africans.

Epilepsy care during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has affected the care of all patients around the world. The International League Against Epilepsy (ILAE) COVID-19 and Telemedicine Task Forces examined, through surveys to people with epilepsy (PWE), caregivers, and health care professionals, how the pandemic has affected the well-being, care, and services for PWE. The ILAE included a link on their website whereby PWE and/or their caregivers could fill out a survey (in 11 languages) about the impact of the COVID-19 pandemic, including access to health services and impact on mental health, including the 6-item Kessler Psychological Distress Scale. An anonymous link was also provided whereby health care providers could report cases of new-onset seizures or an exacerbation of seizures in the context of COVID-19. Finally, a separate questionnaire aimed at exploring the utilization of telehealth by health care professionals since the pandemic began was available on the ILAE website and also disseminated to its members. Seventeen case reports were received; data were limited and therefore no firm conclusions could be drawn. Of 590 respondents to the well-being survey (422 PWE, 166 caregivers), 22.8% PWE and 27.5% caregivers reported an increase in seizure frequency, with difficulty in accessing medication and health care professionals reported as barriers to care. Of all respondents, 57.1% PWE and 21.5% caregivers had severe psychological distress (k score >13), which was significantly higher among PWE than caregivers (p<0.01). An increase in telemedicine use during the COVID-19 pandemic was reported by health care professionals, with 40% of consultations conducted by this method. Although 74.9% of health care providers thought that this impacted positively, barriers to care were also identified. As we move forward, there is a need to ensure ongoing support and care for PWE to prevent a parallel pandemic of unmet health care needs.

The initial impact of the SARS-CoV-2 pandemic on epilepsy research.

The COVID-19 pandemic has changed the face of many practices throughout the world. Through necessity to minimize spread and provide clinical care to those with severe disease, focus has been on limiting face-to-face contact. Research in many areas has been put on hold. We sought to determine the impact of the COVID-19 pandemic on epilepsy research from international basic science and clinical researchers. Responses to five questions were solicited through a convenience sample by direct email and through postings on the ILAE social media accounts and an ILAE online platform (utilizing Slack). Information was collected from 15 respondents in 11 countries by email or via Zoom interviews between May 19, 2020, and June 4, 2020. Several themes emerged including a move to virtual working, project delays with laboratory work halted and clinical work reduced, funding concerns, a worry about false data with regard to COVID research and concern about research time lost. However, a number of positive outcomes were highlighted, not least the efficiency of online working and other adaptations that could be sustained in the future.

Development and validation of a questionnaire to assess the doctors and nurses knowledge of acute oxygen therapy.

BACKGROUND: Prescription and administration of oxygen in emergencies by healthcare providers are reported to be inappropriate in most settings. There is a huge gap in the knowledge of health care providers on various aspects of oxygen therapy, and this may be a barrier to optimal oxygen administration. Hence, it is essential to ascertain providers' knowledge of acute oxygen therapy so that appropriate educational interventions are instituted for better delivery. There is no available validated instrument to assess knowledge of acute oxygen therapy. The study aimed to develop, validate and evaluate the test-retest reliability of a questionnaire to determine the doctors and nurses understanding of acute oxygen therapy. METHODS: This study involved the development of the questionnaire contents by a literature review, assessment of face validity (n = 5), content validity, using a panel of experts (n = 10), item analysis and test-retest reliability among a sample (n = 121) of doctors and nurses. RESULTS: Face validity indicated that the questionnaire was quick to complete (10-15 min), most items were easy to follow and comprehensible. The global content validity index (S-CVI) was 0.85. The test-retest reliability statistics showed a kappa coefficient of 0.546-0.897 (all P<0.001) and percentage agreement of 80-98.3% indicating high temporal stability in the target population. In total, 90% of the items fulfilled the reliability acceptance criteria. Item discrimination analysis showed that most questions were at an acceptable level. The final questionnaire included 37 item questions and eight sections. CONCLUSION: The designed questionnaire is a reliable and valid tool for assessing knowledge of acute oxygen therapy among doctors and nurses.

Determining the feasibility and preliminary efficacy of a stroke instructional and educational DVD in a multinational context: a randomized controlled pilot study.

OBJECTIVE: To assess the feasibility of conducting a randomized controlled trial of an instructional and educational stroke DVD and determine the feasibility and preliminary efficacy of this intervention in a multinational context. DESIGN: Non-funded, pilot randomized controlled trial of intervention versus usual care. SETTING: International, multicentre, community-based. PARTICIPANTS: Community-living adults up to three years post stroke with moderate to severe disability and their nominated informal caregivers. INTERVENTIONS: Intervention patients viewed and practised rehabilitation techniques demonstrated in the DVD over six weeks. MAIN MEASURES: Trial feasibility by number of active recruitment sites, recruitment efficiency, randomization and follow-up. Intervention feasibility by patient and caregiver impressions. Preliminary efficacy by the quality of life - 5-level EuroQol-5D (EQ-5D) health status measure, General Health Questionnaire and Centre for Epidemiological Studies-Depression at two months. RESULTS: In total, 14 recruitment sites were established across eight countries. Recruitment was achieved at nine (64%) sites. Over 16 months, 66 participants were recruited (mean (SD) age = 63.5 (12.47) years) and randomized to intervention ( n = 34) and control ( n = 32) groups. In total, 54 (82%) completed a follow-up assessment. Patient and/or caregiver comments about the benefits and barriers to accessing the intervention were mixed. There were no significant between-group differences in outcomes at two months ( P > 0.05). CONCLUSION: Conducting a multinational trial of a stroke DVD requires full funding. The intervention was acceptable to some patients and their caregivers, yet a generalized education approach did not fully meet their needs and/or expectations. A more individualized method may be required to meet peoples' changing needs during stroke recovery.

Impact of Operational Definitions on the Predictors and Prevalence of Asthma Estimates: Experience from a University Students' Survey and Implications for Interpretation of Disease Burden.

BACKGROUND: Inconsistent operational definitions during asthma surveillance can lead to inaccurate estimation of disease burden and formulation of health policy. This study aimed to evaluate the impact of different definitions on the prevalence estimates and predictors of asthma among university students in Ilorin, Nigeria. The secondary aim was to compare level of agreement of the different definitions. METHODS: This cross-sectional study was carried out from June to August 2015. The European Community Respiratory Health Survey (ECRHS) questionnaire was self-administered by 1485 students. Asthma diagnosis was based on five definitions used in previous studies in the country. These were ECRHS, International Study of Asthma, Allergies in Childhood (ISAAC), Probable, Modified ECRHS and Modified Probable asthma definitions. RESULTS: The prevalence rates varied from 10.4 to 24.1% depending on the definition. Prevalence obtained by using ECRHS definition significantly differed from estimates by other definitions (Z score ≥ 1.96 p<0.0001) except modified probable asthma. Identified predictors of asthma varied from five to six depending on the definition, and their strength also differed by definition. Regardless of the definition, reported nasal allergy, skin allergy, family history of nasal allergy, asthma and parental smoking were the predictors of asthma. The Kappa statistics demonstrated a fair to almost perfect association between the ECRHS and other asthma definitions (Kappa = 0.334-0.841, p < 0.001). CONCLUSION: The prevalence rates and predictors of asthma are affected by operational definitions. Researchers need to adopt a uniform definition for accurate estimation of disease burden, international comparison of result and formulation of prevention policy.

Carpal Tunnel Syndrome and Other Entrapment Neuropathies.

Entrapment neuropathy is the result of pressure on a peripheral nerve as it passes through a narrow canal that is bounded by stiff tissues. In spite of their ubiquitous nature, they are underdiagnosed, underreported, and sometimes not properly managed, especially in developing countries. Entrapment neuropathies are of various types, but the most common type is carpal tunnel syndrome. Mechanisms involved in the pathophysiology of entrapment neuropathies include mechanical compression and nerve ischemia. A clear understanding of the various types and the underlying mechanisms of entrapment neuropathies are invaluable in the decision-making process involved in the management of every patient with the condition.

Identifying patients at high risk for obstructive sleep apnoea syndrome in Nigeria: A multicentre observational study.

BACKGROUND: Obstructive sleep apnoea is associated with significant health consequences. A significant proportion of hospitalized patients at risk for obstructive sleep apnoea were never identified and referred for polysomnography for diagnosis. The objective of this study was to determine the factors associated with high risk for obstructive sleep apnoea and use it to identify patients at risk for the condition in tertiary hospitals in Nigeria. METHODS: This was a multicentre observational study of adult patients hospitalized in three selected hospitals from 15th January to 17th March 2015. Berlin questionnaire and Epworth sleepiness scale were used to assess for obstructive sleep apnoea risk and excessive daytime sleepiness respectively. Additional questions on traditional risk factors for obstructive sleep apnoea were also obtained. RESULTS: Nine hundred and twenty-six patients were recruited into the study. Respondents' mean age was 44.3 years ± 15.2years, 486 (52.5%) were females and 556 (60.0%) had one or more medical co-morbidity and none of the patients had a previous diagnosis of obstructive sleep apnoea. Factors that were independently associated with high risk for obstructive sleep apnoea include systemic hypertension(aOR-10.33;95%: CI 6.42-16.61), obesity(aOR-7.87;95% CI: 4.33-14.29); excessive daytime sleepiness (aOR-3.77;95% CI :2.28-6.22), tobacco smoking (aOR-2.99;95% CI: 1.76-5.07), snoring in a first-degree relative (aOR-1.83;95% CI: 1.19-2.81); and the use of sedative (aOR-1.82;95% CI: 1.06-3.15). CONCLUSIONS: This study shows that patients with systemic hypertension, obesity, excessive daytime sleepiness, history of smoking, snoring in a first-degree relative and use of sedatives are at high risk of obstructive sleep apnoea. None of the patients at high risk had a previous diagnosis of sleep apnoea by a physician, highlighting the diagnostic challenges of this condition. The results of this study will assist health care professionals in early identification of individuals at risk of obstructive sleep apnoea and subsequent referral for a sleep study.

Blood Pressure Control among Hypertensive Stroke Survivors in Nigeria.

BACKGROUND: Hypertension is the dominant risk factor for first-ever and recurrent stroke. The objective of the present study was to assess control of blood pressure (BP) among hypertensive stroke survivors seen at 2 tertiary hospitals in Nigeria. METHODS: Using a cross-sectional design, stroke survivors with hypertension as a risk factor were consecutively recruited in the outpatient clinics of the participating hospitals. After the necessary demographic and clinical information had been obtained, participants had their BP assessed in a standardized manner. A BP of <140/< 90 mmHg was defined as good control. Univariate binary logistic regression analysis was performed to determine the predictors of good BP control. RESULTS: There were 284 subjects with a mean age of 59.0 ± 13.1 years. The overall mean systolic blood pressure was 142.7 ± 22.5 mmHg (male 144.9 ± 22.7, female 138.4 ± 21.6; P > .05) while the overall mean diastolic blood pressure was 85.6 ± 14.5 mmHg (male 85.8 ± 14.6, female 85.2 ± 14.4; P > .05). In spite of the fact that 270 (95.1%) of the subjects were on antihypertensives, only 39.8% (male 37.0%, female 44.1%; P > .05) had good BP control. In univariate analysis, having at least 12 years of formal education (OR 1.672, 95% CI 1.035-2.699; P < .05) and good compliance to antihypertensive medications (OR 9.732, 95% CI 3.391-27.930; P < .001) were the only variables associated with good BP control. CONCLUSIONS: Control of BP is poor among Nigerian hypertensive stroke survivors and is associated with the level of formal education and drug compliance. Urgent measures are needed to improve on this poor BP control as these may potentially reduce stroke recurrence rate.

Costs and Cost-Effectiveness of Hypertension Screening and Treatment in Adults with Hypertension in Rural Nigeria in the Context of a Health Insurance Program.

BACKGROUND: High blood pressure is a leading risk factor for death and disability in sub-Saharan Africa (SSA). We evaluated the costs and cost-effectiveness of hypertension care provided within the Kwara State Health Insurance (KSHI) program in rural Nigeria. METHODS: A Markov model was developed to assess the costs and cost-effectiveness of population-level hypertension screening and subsequent antihypertensive treatment for the population at-risk of cardiovascular disease (CVD) within the KSHI program. The primary outcome was the incremental cost per disability-adjusted life year (DALY) averted in the KSHI scenario compared to no access to hypertension care. We used setting-specific and empirically-collected data to inform the model. We defined two strategies to assess eligibility for antihypertensive treatment based on 1) presence of hypertension grade 1 and 10-year CVD risk of >20%, or grade 2 hypertension irrespective of 10-year CVD risk (hypertension and risk based strategy) and 2) presence of hypertension in combination with a CVD risk of >20% (risk based strategy). We generated 95% confidence intervals around the primary outcome through probabilistic sensitivity analysis. We conducted one-way sensitivity analyses across key model parameters and assessed the sensitivity of our results to the performance of the reference scenario. RESULTS: Screening and treatment for hypertension was potentially cost-effective but the results were sensitive to changes in underlying assumptions with a wide range of uncertainty. The incremental cost-effectiveness ratio for the first and second strategy respectively ranged from US$ 1,406 to US$ 7,815 and US$ 732 to US$ 2,959 per DALY averted, depending on the assumptions on risk reduction after treatment and compared to no access to antihypertensive treatment. CONCLUSIONS: Hypertension care within a subsidized private health insurance program may be cost-effective in rural Nigeria and public-private partnerships such as the KSHI program may provide opportunities to finance CVD prevention care in SSA.

A survey on doctors' knowledge and attitude of treating chronic pain in three tertiary hospitals in Nigeria.

BACKGROUND: Chronic non-cancer pain (CP) is one of the most common complaints that bring patients to the hospital. When pain persists, people move from doctor-to-doctor seeking for help, thus the burden of CP is huge. This study, therefore was aimed at assessing attitude and knowledge of doctors in three teaching hospitals in Nigeria to CP. MATERIALS AND METHODS: Structured questionnaire was administered to doctors practicing at the University of Ilorin Teaching Hospital, Usmanu Danfodio University Teaching Hospital and University of Maiduguri Teaching Hospital. Responses were graded on maximum scale of five. RESULTS: Of the 410 doctors who participated in study, 79.7% were men. Their years of practice varied from 1 year to 20 years (mean SD = 4.5 ± 1.7 years). Close to 58% of participants were resident doctors, 36.4% medical officers and 8.6% consultants. Only 23.3% of participants had basic medical or postgraduate training on pain management. The physicians' mean goal of treating CP in patients was 3.7 ± 1.1, compared to 4.0 ± 1.1 in close relative and 4.1 ± 0.9 for doctors'-self pain. Only 9.5% of doctors use opioids for CP compared to 73% who use Nonsteroidal anti-inflammatory drugs (NSAIDs). Few doctors (23%) use ≥2 drugs to treat CP. Doctors were indifferent on the appropriateness of patients with CP to request for additional analgesics (mean score = 3.1 + 1.4). Doctors' self-rated knowledge of CP was 1.8 ± 0.7 compared to 4.1 ± 0.9 for acute and 0.8 ± 0.3 for cancer pains (P = 0. 003). CONCLUSION: Incorporation of pain management into continuing medical education could help improve observed deficiency in doctors' knowledge of pain treatment which resulted from lack of basic medical education on pain.

Profile and causes of mortality among elderly patients seen in a tertiary care hospital in Nigeria.

BACKGROUND: Old age is one of the factors associated with increased risk of dying when admitted to hospital. Therefore, aim of this study was to examine causes and pattern of death among elderly patients managed in a tertiary care hospital in Nigeria with scanty mortality records. MATERIALS AND METHODS: This prospective study was on deaths that occurred in patients 60 years and above admitted to University of Ilorin Teaching Hospital (UITH), Ilorin, between January 2005 and June 2007. Excluded were all brought-in-dead during the study period. Information obtained included demographic data, duration on admission, and diagnosis. Causes of death were determined from clinical progress notes and diagnosis. RESULTS: A total of 1298 deaths occurred during the study period, of which 297 occurred in persons 60 years and above with crude death rate of 22.8%. The mean age at death was 68 ± 9 years (ranged 60-100 years). This consisted of 59% males and 41% females. Mean age at death for females was 69.7 ± 8.7 years and for males 68.1 ± 9.8 years (P = 0.05). Mean values of serum chemistry were sodium 137 ± 8 mMol/l, potassium 3.6 ± 1 mMol/l, urea 11 ± 8 mMol/l, and creatinine 126 ± 91 µmol/l. The value of mean haemogram concentration was 10.5 ± 3 gm/dl and white cell count was 12 ± 2 × 10(9)/mm3. The three most common diagnoses at deaths were stroke (19.8%), sepsis (16.5%), and lower respiratory tract disease (8.1%). Infectious diseases accounted for 38.2% of all diagnoses. Collective mean length of hospital stay (LOS) at death was 6.8 ± 8.6 (ranged 15 minutes-60 days). Close to 27.4% of the deaths occurred within 24 hours and neurological disorder had shortest hospital stay (4.6 ± 6.3 days), followed by endocrine disorders (6.8 ± 8.4 days) and respiratory diseases (8.4 ± 5.6 days) [P = 0.001]. CONCLUSION: Hospital mortality is high amongst older people. Stroke and infectious diseases are leading causes of death. Efforts should be geared toward reducing risk for cardiovascular diseases and improvement on level of personal and community hygiene.

Interest in neurology during medical clerkship in three Nigerian medical schools.

BACKGROUND: This study sought to ascertain perception of Nigerian medical students of neurology in comparison with 7 other major medical specialties. To also determine whether neurology was the specialty students consider most difficult and the reasons for this and to appraise their opinion on how neurosciences and neurology were taught in their different universities. METHODS: Self-administered questionnaires were used to obtain information from randomly selected clinical students from 3 medical colleges in Nigeria (University of Ibadan, Ibadan; University of Ilorin, Ilorin; Ladoke Akintola University of Technology, Osogbo). RESULTS: Of 320 questionnaires sent out, 302 were returned given 94% response rate. Students felt they knew neurology least of all the 8 medical specialties, and were not confident of making neurological diagnoses. About 82% of the students indicated they learnt neurology best from bedside teaching, followed by use of medical textbooks. Close to 15% found online resources very useful for learning neurology and 6% indicated that group discussion was quite useful in the acquisition of knowledge on neurology. Histology and biochemistry were the preclinical subjects participants opined were least useful in learning neurology. The most frequent reasons students felt neurology was difficult were problems with understanding neuroanatomy (49%), insufficient exposure to neurological cases (41%), too many complex diagnoses (32%) and inadequate neurology teachers (32%). CONCLUSIONS: Nigerian medical students perceived neurology as the most difficult medical specialty and are not interested in specializing in it. Neurology education could be improved upon by provision of more bedside tutorials and increased availability of online resources to enhance learning. There is need to emphasize increased frequency of small group discussions amongst students so that they will be used to teamwork after graduation.

Abnormal heart rate and blood pressure responses to baroreflex stimulation in multiple sclerosis patients.

Cardiovascular autonomic neuropathy has been previously reported in patients with multiple sclerosis (MS) using standard reflex tests. However, no study has separately evaluated both parasympathetic and sympathetic cardiovascular autonomic regulation. We therefore assessed the baroreflex-mediated vagal and sympathetic control of the heart rate and sympathetic control of the blood vessels in MS patients using sinusoidal neck stimulation. We studied 13 multiple sclerosis patients aged 28-58 years and 18 healthy controls aged 26-58 years. The carotid baroreflex was stimulated by sinusoidal neck suction (0 to -30 mmHg) at 0.1 Hz to assess the autonomic control of the heart and blood vessels, and at 0.2 Hz to assess the vagal control of the heart. Continuous recordings were made of blood pressure, electrocardiographic RR-interval and respiration, with breathing paced at 0.25 Hz. Spectral analysis was used to evaluate the magnitude of the low frequency (LF, 0.03-0.14 Hz) and high frequency (HF, 0.15-0.50 Hz) oscillations in RR-interval and blood pressure in response to the sinusoidal baroreceptor stimulation. Responses to the applied stimulus were assessed as the change in the spectral power of the RR-interval and blood pressure fluctuations at the stimulating frequency from the baseline values. The increase in the power of 0.1 Hz RR-interval oscillations during the 0.1 Hz neck suction was significantly smaller (p<0.01) in the MS patients (4.47+/-0.27 to 5.62+/-0.25 ln ms(2)) than in the controls (4.12+/-0.37 to 6.82+/-0.33 ln ms(2)). The increase in the power of 0.1 Hz systolic BP oscillations during 0.1 Hz neck suction was also significantly smaller (p<0.01) in the MS patients (0.99+/-0.19 to 1.96+/-0.39 mmHg(2)) than in the healthy controls (1.27+/-0.34 to 9.01+/-4.10 mmHg(2)). Neck suction at 0.2 Hz induced RR-interval oscillations at 0.2 Hz that were significantly smaller (p<0.05) in the patients (3.22+/-0.45 ln ms(2)) than in the controls (5.27+/-0.29 ln ms(2)). These results indicate that in MS patients, baroreflex dysfunction is not only restricted to the cardiovagal limb of the baroreflex, but that the sympathetic modulation of the blood vessels is also affected.

Effect of cold face stimulation on cerebral blood flow in humans.

BACKGROUND AND PURPOSE: In humans, activation of the diving reflex by a cold stimulus to the face results in bradycardia, peripheral vasoconstriction and an increase in blood pressure. However, responses of the cerebral blood flow have not yet been evaluated. We undertook this study to assess the effect of cold face stimulation on the cerebral circulation in humans. METHODS: Seventeen healthy volunteers, aged 27+/-5 years were evaluated during application of a cold stimulus (0 degrees C) to the forehead for 60s. We continuously monitored mean arterial pressure (MAP), mean flow velocity (MFV) of the middle cerebral artery, cardiac output, skin blood flow, heart rate and end-tidal CO2. Total peripheral resistance (TPR) was calculated as MAP divided by cardiac output. Cerebrovascular resistance index (CVRi) was calculated as MAP divided by MFV. RESULTS: Cold face stimulation did not significantly affect cardiac output but resulted in significant decreases in heart rate and skin blood flow and an increase in MAP. MFV in the mid-cerebral artery showed a slight, but significant increase. The maximum increase in CVRi (14.2+/-11.4%) was significantly (P<0.01) less than the maximum increase in TPR (23.9+/-5.7%). End-tidal CO2 did not change significantly during the cold stimulation. CONCLUSIONS: In contrast to other sympathetic stimulations (e.g. lower body negative pressure), facial cooling results in an increase in cerebral blood flow. The amount of cerebral vasoconstriction was less than the amount of total peripheral vasoconstriction. These results suggest that although there is some constriction of the cerebral resistance vessels during cold face stimulation, cerebral perfusion was maintained, possibly by opposing parasympathetic activation.