Opportunities and challenges to non-communicable disease (NCD) research and training in Pakistan: a qualitative study from Pakistan.

INTRODUCTION: Most of the global non-communicable disease (NCD)-related death burden is borne by low and middle-income countries (LMICs). In LMICs like Pakistan, however, a major gap in responding to NCDs is a lack of high-quality research leading to policy development and implementation of NCDs. To assess institutional opportunities and constraints to NCD research and training we conducted a situational analysis for NCD research and training at Aga Khan University Pakistan. METHODS: We conducted a descriptive exploratory study using grounded theory as a qualitative approach: semistructured interviews of 16 NCD stakeholders (three excluded) and two focus group discussions with postgraduate and undergraduate trainees were conducted. A simple thematic analysis was done where themes were identified, and then recurring ideas were critically placed in their specific themes and refined based on the consensus of the investigators. RESULTS: The major themes derived were priority research areas in NCDs; methods to improve NCD research integration; barriers to NCD research in LMICs like Pakistan; design of NCD research programme and career paths; and NCD prevention at mass level, policy and link to the government. In general, participants opined that while there was an appetite for NCD research and training, but few high-quality research training programmes in NCDs existed, such programmes needed to be established. The ideal NCD research and training programmes would have in-built protected time, career guidance and dedicated mentorship. Most participants identified cardiovascular diseases as a priority thematic area and health information technology and data science as key methodological approaches to be introduced into research training. CONCLUSION: We conclude from this qualitative study on NCD research and training that high-quality research training programmes for NCDs are rare. Such programmes need to be established with in-built protected time, career guidance and mentorship for the trainees to improve their research capacity in Pakistan.

Pattern of neurological diseases in adult outpatient neurology clinics in tertiary care hospital.

OBJECTIVES: The burden of neurological diseases in developing countries is rising although little is known about the epidemiology and clinical pattern of neurological disorders. The objective of this study was to understand the burden of disease faced by neurologists a in tertiary care setting. RESULTS: A prospective observational study was conducted of all presentations to neurology clinics at Aga Khan University Hospital Karachi over a period of 2 years. A total of 16,371 out-patients with neurological diseases were seen during the study period. The mean age of the study participants were 46.2 ± 18.3 years and 8508 (52%) were male. Headache disorders were present in 3058 (18.6%) of patients followed by vascular diseases 2842 (17.4%), nerve and root lesions 2311 (14.1%) and epilepsies 2055 (12.5%). Parkinson's disease was more prevalent in male participants 564 (70.8%) as compared to female 257 (62.1%) (p = 0.002). Migraines and vertigo disease were more diagnosed in females as compared to males. Epilepsies were seen more in younger age groups. Parkinson's disease was seen in 50.9% of participants between the ages of 45 and 65 years, and the frequency increased with age.

A unique MRI presentation of fungal infection in the brain.

Fungal infections of CNS are common in certain geographic locations. MRI with or without contrast is a useful prediagnostic tool. However, the findings may sometimes be misleading. In this case report, the authors present unusual imaging findings in the MRI of fungal infection in an immunocompetent host, whereby hyper-intense signals were seen on T2-weighted images and patchy post-contrast enhancement was observed with surrounding edema. These findings were suggestive of a neoplastic lesion but it was identified as aspergillosis on subsequent histopathology. This unusual MRI finding of CNS highlights the need to consider fungal infection as a differential diagnosis of all mass lesions on MRI, irrespective of their signal characteristics.

Mortality and neurodevelopmental outcomes of acute bacterial meningitis in children aged <5 years in Pakistan.

OBJECTIVE: Significant neurodevelopmental sequelae are known to occur after acute bacterial meningitis (ABM). This study determined the burden of such sequelae in Pakistani children aged <5 years to guide policies for Haemophilus influenzae type b (Hib) and pneumococcal vaccination. STUDY DESIGN: Cases of ABM were recruited from hospital-based surveillance and assigned to 1 of 3 etiologic groups (Hib, Streptococcus pneumoniae, or unknown etiology). Two age-matched controls were recruited for each case. Six months after enrollment, each case underwent neurologic history and examination, neurodevelopmental evaluation, and neurophysiological hearing test. Controls were assessed in parallel. RESULTS: Of 188 cases, 64 (34%) died. Mortality among subgroups were 7 (27%), 14 (28%), and 43 (39%) for Hib, Streptococcus pneumoniae, and unknown etiology, respectively. Eighty cases and 160 controls completed the assessments. Sequelae among cases included developmental delay (37%), motor deficit (31%), hearing impairment (18.5%), epilepsy (14%), and vision impairment (14%). Sequelae were higher after pneumococcal meningitis (19, 73%) compared with Hib meningitis (8, 53%). Compared with controls, cases were at significantly higher risk for all sequelae (P < .0001). CONCLUSIONS: ABM causes a substantial long-term burden of poor neurodevelopmental outcomes. Hib and pneumococcal vaccines are very effective interventions to prevent meningitis and its disabling sequelae.

Clinical predictors of EMG-confirmed cervical and lumbosacral radiculopathy.

BACKGROUND: Electromyography (EMG) for suspected cervical or lumbosacral root compression is often negative, producing expense and physical discomfort that could have been avoided. To improve patient selection for testing, we sought to identify clinical features that would accurately predict presence of radiculopathy on EMG. METHODS: Adult patients consecutively evaluated for suspected cervical or lumbosacral root compression at an academic clinical neurophysiology laboratory were prospectively enrolled. Presence of clinical features suggesting root disease (neck or back pain, dermatomal pain or numbness, myotomal weakness, segmental reflex loss, and straight leg-raising) was recorded prior to testing. EMG examination to confirm root compression was conducted per standard protocols. Analysis was based on computation of sensitivity, specificity, predictive values, and accuracy. RESULTS: A total of 200 patients (55% male; mean age 46.4 years; 38% suspected of cervical and 62% of lumbosacral disease) were included. EMG evidence of root disease was detected in 31% of cervical and 62% of lumbosacral referrals. Dermatomal pain was the most sensitive, and segmental reflex loss and myotomal weakness the most specific individual predictors of root disease. Combined presence of dermatomal pain or numbness with segmental reflex loss and myotomal weakness approached specificities of 78% (lumbosacral disease) and 99% (cervical disease). In all cases, myotomal weakness was the most accurate predictor of root disease. CONCLUSION: The diverse symptoms and signs of cervical and lumbosacral root compression predict a positive electrodiagnosis of radiculopathy with varying degrees of accuracy, and may be used to guide patient selection for EMG testing.

Risk of multiple sclerosis after idiopathic optic neuritis in a Pakistani population.

BACKGROUND AND OBJECTIVE: Optic neuritis (ON) is associated with a 38% ten-year risk of developing multiple sclerosis (MS) in Western populations, but the corresponding risk in non-Western populations is unclear. We conducted this study to estimate the risk of progression to MS after an episode of ON in a South Asian population. METHODS: Two hundred and fifty-three patients with idiopathic ON were identified by reviewing records of visual evoked potentials and chart notes from a single academic center spanning the years 1990-2007. A structured telephone interview was then conducted to identify patients who had subsequently received a diagnosis of MS. The diagnosis was corroborated from chart notes, where possible. Cumulative probability of conversion to MS was calculated using Kaplan-Meier survival analysis. RESULTS: The five-year risk of developing MS was 14.6% and the ten-year risk was 24%. Patients (N = 218) who had one or more typical demyelinating lesions on baseline brain magnetic resonance imaging (MRI) had a 68% 10-year risk; those with no lesions or non-typical lesions had a 14% risk (p < 0.001). Female gender, recurrent ON, and occurrence of ON in winter months were also associated with increased risk (p < or = 0.001). Severity of ON and likelihood of detecting cerebrospinal fluid (CSF) oligoclonal bands were higher in patients who developed MS. CONCLUSION: Idiopathic ON in Pakistan carries a lower risk of progression to MS compared with Western data. As in Western populations, however, presence of abnormal baseline brain MRI and CSF oligoclonal bands correlate with increased MS risk.

Hypotension at presentation is an indicator of poor prognosis in acute intracerebral haemorrhage.

OBJECTIVE: To identify frequency of hypotension in a large cohort of patients with intracerebral haemorrhage and its prognostic significance. METHODS: We retrospectively reviewed medical records of 920 patients with spontaneous intracerebral haemorrhage (ICH). Patients were divided in three groups based on Diastolic blood pressure (DBP); hypotensive group (DBP < 70 mmHg), normotensive group (DBP; 71-90 mmHg) and hypertensive group (DBP > 90 mmHg). RESULTS: Of the total patients with ICH, 7% (64) presented with hypotension, 13% (120) were normotensive and 80% (736) were hypertensive. In the hypotensive group, 37% (24) patients died as compared to 25%(30) in normotensive group and 25% (182) in hypertensive group (p = 0.03). Hypotension at presentation, thalamic and lobar haemorrhages were predictors of poor outcome. Patients with diastolic BP of less than 70 were significantly more likely to die than with DBP 71-90 (OR = 1.9, 95% CI; 1.1-2.9, p = 0.03). This relationship was still significant after adjusting for age, sex, history of presentation, coma at presentation and location of haemorrhage (OR = 1.45, 95% CI; 1.0-2.2, p = 0.045). CONCLUSION: Our findings suggest that hypotension at presentation is a predictor of poor outcome in patients with ICH. Patients with diastolic blood pressure less than 70 are more likely to have a fatal outcome as compared to those with normal blood pressure.

Alzheimer disease therapeutics: perspectives from the developing world.

Although a majority of dementia patients live in middle-income and low-income countries, dementia represents an under-recognized public health burden in the developing world. Culturally and socially, it tends to be trivialized as an inevitable consequence of aging. Economic constraints are paramount, precluding the availability of institutionalized elder care and a state-sponsored health care system. Evidence-based practice for the management of dementia is also hampered by lack of a clear-cut expert consensus on the efficacy of anti-dementia drugs. Public health education, substantial health infrastructure development, and therapeutic advances are necessary for the developing world's looming dementia crisis to be adequately tackled.

Factors associated with helmet use among motorcycle users in Karachi, Pakistan.

OBJECTIVES: Wearing a helmet is the single most effective measure for preventing head injuries in motorcycle users. The authors undertook this study to estimate compliance and determine reasons for noncompliance with helmet use among motorcyclists in their community. METHODS: This was a cross-sectional survey of motorcyclists in three large randomly selected public-access parking spaces across Karachi, Pakistan's largest city. Questions covered personal demographics, frequency of helmet use, reasons for use or nonuse, and knowledge of local helmet laws. Analysis was based on frequencies and group comparisons using chi-square test or independent sample t-test. RESULTS: Of the 300 (100% male) subjects, 169 (56%) reported using helmets regularly. Users listed injury prevention (78%) as the major reason for compliance, while nonusers listed physical discomfort (44%) and limited vision (25%) as the leading reasons for noncompliance. In univariate analysis, helmet users were significantly better educated than nonusers and were more likely to believe that helmets are protective (p = 0.002) and that passengers should also wear helmets (p < 0.001). The significance of these variables persisted in multivariate analysis. Several other variables (such as mean age, marital status, and knowledge of helmet laws) did not differ between users and nonusers. CONCLUSIONS: Helmets are underused by motorcyclists in the authors' community. This study underscores the need for improved helmet design, public understanding, intense public education, and rigorous law enforcement in raising compliance with helmet use and minimizing the risk of preventable trauma.

Drug compliance after stroke and myocardial infarction: a comparative study.

BACKGROUND: Stroke and myocardial infarction (MI) are both life-threatening diseases of vascular origin with a tendency to recur. In both conditions, risk of recurrence is reduced through similar drug regimens. AIM: To determine if compliance with prescribed medication after stroke or MI was similar in the two populations. SETTING AND DESIGN: Retrospective data collection and cross-sectional telephonic survey of patients discharged from a single academic medical center. MATERIALS AND METHODS: Adult patients consecutively discharged over a two-year period with a diagnosis of first-ever stroke (ischemic or hemorrhagic) or first-ever MI (ST-elevation) were identified through ICD-9 codes. Clinical details were abstracted from hospital records. Medication compliance was assessed through a structured telephone interview. STATISTICAL ANALYSIS: Bivariate analysis using Chi-square and Fisher exact tests, to determine the prevalence of noncompliance in stroke versus MI patients and differences in baseline characteristics and multivariate analysis with logistic regression to determine independent predictors of noncompliance. RESULTS: Follow-up data was collected for 298 stroke and 275 MI patients. Compliance was lower in stroke patients (68% stroke patients compliant with at least half their discharge prescriptions versus 90% MI patients; P < 0.001). Literacy and post-discharge follow-up were associated with greater compliance (P < 0.05 for both). Compliance was highest with anti-hypertensive drugs (98% after MI, 78% after stroke), followed by anti-platelet agents (94% after MI, 75% after stroke) and anti-lipid agents (70% after MI, 59% after stroke). Patients reported simply not feeling the need, acquiring fresh medical advice or a perceived lack of benefit, as reasons for not complying with their discharge prescriptions. CONCLUSIONS: Although similar drugs are involved, compliance with prescribed regimens is appreciably lower after stroke than after MI. Our findings underscore the need for better patient education regarding secondary prevention after stroke.

Heparin in the treatment of cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is a potentially life-threatening condition requiring rapid diagnosis and urgent treatment. Heparin anticoagulation is the time-honoured treatment, and is advocated in all cases of CVT, irrespective of etiology or presence of haemorrhage. The supportive evidence is largely observational; data from randomized placebo-controlled trials shows a nonsignificant trend favouring heparin. Current practice is to begin heparin (unfractionated or low-molecular weight) immediately on confirmation of the diagnosis. Newer antithrombotic agents such as ximelagatran may offer advantages over heparin and need to be investigated in the treatment of CVT.

Association of phosphodiesterase 4D gene with ischemic stroke in a Pakistani population.

BACKGROUND AND OBJECTIVES: Identification of STRK1 locus by the deCODE group followed by the discovery of phosphodiesterase 4D (PDE4D) gene in strong association with ischemic stroke patients has provided useful insights toward understanding the genetic etiology of the disease. In this study, we aimed at investigating the association between 3 polymorphisms of the PDE4D gene and ischemic stroke in the Pakistani population. METHODS: Three polymorphisms in PDE4D gene were analyzed in 200 patients of ischemic stroke and 250 controls of Pakistani origin using polymerase chain reaction-restriction fragment length polymorphism method. Data were coded and entered in SPSS Windows (version 12.0). Odds ratios and 95% CIs were calculated using multivariate logistic regression analysis. RESULTS: Marker SNP83(rs966221) was found significantly associated with ischemic stroke on univariate and multivariate analysis (P<0.005; odds ratio, 1.64 [1.13 to 2.40]). Haplotype analysis for markers in linkage disequilibrium failed to show any association with the disease. CONCLUSIONS: The association of PDE4D variation with ischemic stroke extends to the Pakistani population and supports a role for phosphodiesterases in stroke pathogenesis.

Functional recovery following rehabilitation after hemorrhagic and ischemic stroke.

OBJECTIVES: To quantify recovery after rehabilitation therapy and to identify factors that predicted functional outcome in survivors of intracerebral hemorrhage (ICH) compared with cerebral infarction. DESIGN: Retrospective study of consecutive ICH and cerebral infarction admissions to a rehabilitation hospital over a 4-year period. SETTING: Free-standing urban rehabilitation hospital. PARTICIPANTS: A total of 1064 cases met the inclusion criteria (545 women, 519 men; 871 with cerebral infarction, 193 with ICH). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional status was measured using the FIM trade mark instrument, recorded at admission and discharge. Recovery was quantified by the change in FIM total score (DeltaFIM total score). Outcome measures were total discharge FIM score and DeltaFIM total score. Univariate and multivariate analyses were performed. RESULTS: Total admission FIM score was higher in patients with cerebral infarction than in patients with ICH (59 vs 51, P=.0001). No difference in total discharge FIM score was present. Patients with ICH made a significantly greater recovery than those with cerebral infarction (DeltaFIM total score, 28 vs 23.3; P=.002). On multivariate analysis, younger age, longer length of stay, and admission FIM cognitive subscore independently predicted total discharge FIM and DeltaFIM total score. The severity of disability at admission, indicated by total admission FIM score, independently predicted total discharge FIM score, but not DeltaFIM total score. The ICH patients with the most severely disabling strokes had significantly greater recovery than cerebral infarction patients with stroke of similar severity. CONCLUSIONS: The patients with ICH had greater functional impairment than the cerebral infarction patients at admission, but made greater gains. Patients with the most severely disabling ICH improved more than those with cerebral infarction of comparable severity. Initial severity of disability, age, and duration of therapy best predicted functional outcome after rehabilitation.

Patient knowledge and expectations for functional recovery after stroke.

OBJECTIVE: Understanding the causes and outcomes of stroke is important for stroke survivors and may affect their success in rehabilitation and their risk of recurrent stroke; therefore, this study was performed to assess the knowledge and expectation of functional recovery in stroke patients undergoing acute inpatient rehabilitation. DESIGN: Survey study of 50 consecutive stroke patients undergoing inpatient rehabilitation at a single urban rehabilitation hospital. RESULTS: Forty-six percent of participants were able to correctly identify whether they had sustained a cerebral infarct or hemorrhage. Rehabilitation length of stay was, on average, 1 wk longer than anticipated by patients. Patients overestimated their functional abilities on initial assessment and at discharge compared with staff assessments, with some improvement in accuracy for discharge predictions. Ninety-four percent of participants expected to be discharged home, and most achieved this goal. Although no participant anticipated discharge to a nursing home, 10% of patients were discharged to this location. CONCLUSIONS: Knowledge of stroke and its treatment was limited, and expectations for recovery tended to exceed actual accomplishments. There are significant areas of opportunity for enhanced educational efforts for stroke patients undergoing inpatient rehabilitation.