Stem Cells for Spinal Cord Injury - Are we Closer to Clinical Application in Humans?

Recovery after spinal cord injury (SCI) is highly variable, often leaving the victim disabled for life and having to deal with the complications of paraplegia. Stem cell therapy is a potential hope for these patients. Most of the research on use of stem cells for SCI has been on animal models in laboratories. Some recent clinical trials involving human subjects have shown positive outcomes with regards to tissue growth after transplantation, but meaningful functional recovery is yet to be seen. The emergence of lumbar cord simulation is a new approach and the recent identification of recovery organizing interneurons points to a pathway that could integrate neuromodulation with cellular therapy.

Third ventricular diverticulum of the suprapineal recess can be a rare and confounding complication of chronic hydrocephalus: A case report with 2-year follow-up.

PURPOSE: Chronic hydrocephalus is rarely seen in developed countries due to the widespread availability of CT scans for diagnosis and early treatment. In developing countries, it is more frequently encountered along with its rare complication of diverticulum formation. METHODS: We report a case of a previously healthy 6 year old girl who presented with a 10 day history of headache, 3 day history of drowsiness and a single episode of generalized tonic clonic seizures. We review the literature on such cases and include imagining studies at follow up. RESULTS: A CT scan done outside our hospital had been reported to be demonstrating a posterior fossa arachnoid cyst with resultant obstructive hydrocephalus. We first placed an external ventricular drain and performed an MRI of the brain to further characterize the lesion. It was again reported as an arachnoid cyst but on further scrutiny it was appreciated that it was in fact a third ventricular diverticulum of the suprapineal recess. She underwent ventriculoperitoneal shunt placement which led to resolution of the hydrocephalus as well as the diverticulum. CONCLUSION: These diverticulae develop secondary to ventricular rupture in the setting of chronic untreated hydrocephalus. This pathology was first described in 1940 and over the years its identification has decreased due to a much lower incidence of chronic untreated hydrocephalus.

Prioritizing Pituitary Adenoma Care in Pakistan: Analysis from an Epidemiological Study.

OBJECTIVE: To identify symptoms and risk factors and promptly diagnose, treat, and manage pituitary adenomas. Prioritizing care for pituitary adenomas will reduce the prolonged disability. Method: Patients with a histopathological diagnosis of a pituitary adenoma that presented at 32 tertiary care neurosurgical centres were included. The information recorded included demographics, treatment methods, adjuvant chemoradiotherapy and loss to follow-up. Data on tumour size, functionality, and laterality were collected. RESULTS: Of the 32 hospitals surveyed, 24 operated on pituitary adenomas, and treated 277 patients. The mean age at diagnosis was 39.8 ± 13 years, with a majority of males (63.5%) being diagnosed than females. Paediatric cases constituted only 4.7% of the total pituitary adenomas operated upon. Gross total resection was reported for 155 (56%) of all pituitary adenoma patients. Majority of the patients affected by pituitary adenomas (80.1%) were from the working class. CONCLUSIONS: Highlighting care for non-malignant brain tumours is important for Pakistan's health system. Evidence pertaining to gender and age disparities indicates that males in the younger age groups are predominantly affected, which takes a large socio-economic toll on patients and their households. This study also highlights the need to incorporate digital health technologies for postoperative follow-up and adjuvant treatment.

Private vs public care for intracranial tumours: Findings from Pakistan.

OBJECTIVE: To observe the patient characteristics and centres providing neuro-oncological care in public and private health hospitals in Pakistan. Method: The Pakistan Association of Neuro-oncology carried out a retrospective, cross-sectional study in 2019 on patients admitted to 32 hospitals in Pakistan, with dedicated neurosurgical facilities. Patients with a histopathological diagnosis of an intracranial tumour were included. RESULTS: Public health care facilities catered for 84% patients with ages between 20 and 60 years and children having intracranial tumours. Private centres were utilised by 66.7% patients from the upper socioeconomic sector. More patients were lost to follow-up in the public sector (n = 784) versus in the private sector (n = 356). Mortality was also higher in the public sector hospitals, (13.9%) as compared to 9.6% in the private sector. CONCLUSIONS: Public and private sector health services for neuro-oncological care in Pakistan still have a long way to go to cover the gaps for unmet needs. Strengthening health systems for brain tumour care is imperative to increase both the access to care and the quality of care to fulfil this need.

Primary trauma care course: Alternative basic trauma course in developing countries. "The Need Of The Hour".

OBJECTIVE: Low- and middle-income countries account for over 90% of all road traffic injury deaths. Despite this, formal training in trauma management is not widely adopted in these countries. No specific training was available in prehospital or emergency department for life support before primary trauma care (PTC) course. This study was conducted to assess the effectiveness of the PTC course in the improvement of knowledge and skills of trauma management among participant in Pakistan. METHOD: Two days of PTC courses were organised and conducted in various regions of Pakistan, participants per course comprising medical students, doctors, house officers, residents, and paramedics. The course comprises lectures of 5 hours and 30 minutes, skills workshops for 3 hours and discussion and multisystem trauma scenarios for 3 hours. Trauma management knowledge and clinical confidence of candidates were assessed using a predetermined multiple-choice questionnaire of 30 MCQs both at pre- and post-course, and using clinical scenarios, confidence matrix was assessed. RESULTS: A total 7852 of participants were trained, an average of 2 courses per month and 302 total courses. Mean score of pre-course MCQs was 60% and mean score of post-course MCQs was 82%. Among the participant postgraduate trainees, average in trauma knowledge and trauma clinical confidence were significantly higher in both pre- and post-course. The mean score of pre-course confidence matrix was 70% and the mean score of post-course confidence matrix was 93%; at the end of course, all participants showed a high level of confidence in managing trauma mock scenarios. A total of 5889 (75%) participants had a ≥78.5% post-workshop knowledge score. However, only 1963 (25%) participants had a trauma skill score with ≤75 marks. CONCLUSION: PTC workshop could be an alternative and cost-effective flexible course for gaining knowledge and clinical skills of initial trauma management and strengthening the capacity of trauma management training in developing countries with minimal resources for saving the life of trauma victims.

Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial.

BACKGROUND: The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death. METHODS: The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis. RESULTS: There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58-0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69-1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83-1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70-0.87) and death within 28 days (RR 0.88, 95% CI 0.82-0.94). CONCLUSIONS: Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury. TRIAL REGISTRATION: ISRCTN15088122 , registered on 19 July 2011; NCT01402882 , registered on 26 July 2011.

Early tranexamic acid in traumatic brain injury: Evidence for an effective therapy.

The guidelines for management of traumatic brain injury (TBI) are based largely on measures to maintain an optimum internal milieu for prevention of secondary brain injury and enhancing recovery. One of the most common reasons for worsening outcomes following TBI is expanding intracranial haematoma which is compounded by the fibrinolytic physiology that follows TBI. Tranexamic acid (TXA) has a time tested role in preventing poor outcomes linked to excessive haemorrhage in trauma patients. Historically, patients with isolated head trauma were excluded from TXA use due to a theoretical increased risk of thrombosis. Recent evidence that redefines the beneficial role of early TXA administration in preventing mortality amongst patients with TBI is now at hand and offers a real prospect of a pharmacological intervention that would be adopted as a recommendation based on Class l evidence.

Primary Trauma Care: A Training Course for Healthcare Providers in Developing Countries.

Outcomes of injury in low and middle income countries may be compromised by skill deficiencies of healthcare providers. Short subspecialty training courses can be a useful solution to skill-deficits. We report on the Primary Trauma Care programme, a 2-day course designed to train frontline health workers in resuscitation and early management of the injured with limited resources and equipment. Developed for use in weak health systems and now conducted in over 70 countries, the programme is cost-efficient with built-in design sustainability by way of early transfer of ownership to local partners to effect a cascade of trauma courses in their communities. Published studies report a significant improvement in both knowledge and skills of the participants with greater confidence in managing trauma victims. A trained health workforce could address the unmet needs identified by Global Surgery and thus contribute to achieving the Sustainable Development Goals.

Descriptive epidemiology of Karachi road traffic crash mortality in 2015.

The Karachi city's Road Traffic Injury Research and Prevention Center (RTIRPC), collects Road Traffic Crash (RTC) data on injuries and fatalities from three major public and private hospitals' emergency departments. In the year 2015, 1021 deaths were recorded; with 871 (85.3%) deaths in males. Cumulatively, 286 (28.0%) deaths were recorded in the 21-30year age group, and for 198 (19.4%) RTC fatal victims, the primary vehicle involved was motorbike. Highest number of fatalities were recorded in the month of January i.e. 153 (15.0%), while the lowest number was recorded for June, with 47 (4.6%) fatalities. RTIRPC is a unique surveillance system in Pakistan providing RTC morbidity and mortality burden and trends in the city that needs to be expanded in Karachi, and extended throughout the country to better choreograph preventive measures including health promotion campaigns.

Spatial distribution of road traffic crash fatalities in Karachi: Perspective from 2008-2012.

Road Traffic Crash (RTC) mortality and morbidity is one of the major public health problems in Karachi. In this study we used geographic information systems (GIS) to visualize and quantify the spatial distribution of RTC mortality and yearly trend from 2008 to 2012, for all 24 administrative subdivisions of Karachi, using Road Traffic Injury Research and Prevention Center's (RTIRPC) data. Cumulatively, 6040 deaths were recorded by RTIRPC, out of which we were able to map 4657 (77.1%) deaths based on location information available in the database. During the 5-year period, highest number of cumulative RTC fatalities were recorded for Kemari, Bin Qasim, and Gushan-e-Iqbal; while lowest were recorded in Malir, Orangi, Korangi Cantonment, and Karachi Cantonment. Use of GIS for studying spatial distribution of RTC would help craft better response to RTC in the city and design public policy.

Unintentional Head Injury in Children Less than 3 Years of Age: An Insight into Safety Practices in a Developing Country.

Being dependent on caretakers for their safety, children under the age of 3 years are particularly vulnerable to unintentional injury. To identify the circumstances and consequences of head injury in this age group and to assess preventability in a setting of low parental educational levels, we conducted a retrospective cohort study of children less than 3 years of age admitted to hospital with a head injury and in addition categorized the degree of preventability of injury. This study included 109 children, representing a third of head-injured children under the age of 16 years, and 23.4% of these were infants. A significant proportion of head injuries, i.e., 20.18%, were designated "serious" and there was an in-hospital mortality rate of 7.3%. Most of the injuries (80%) occurred in the home and 76% could have been prevented through improved parental supervision and safety measures. We conclude that, in a setting of low maternal education, head injuries in preschoolers largely result from a lack of diligence of the caretakers, presenting opportunities for prevention strategies via a multidimensional approach that integrates safety information into the preexisting national health programs.

Road traffic crash related injured and fatal victims in Karachi from 2007 to 2014: A time-series analysis.

Injuries and deaths due to road traffic crashes (RTC) are major public health concern. The Road Traffic Injury Research and Prevention Center, collects RTC data on injuries and fatalities from five emergency departments in Karachi. Data generating process (DGP) for RTC from 2007 to 2014, for monthly number of fatal and injured victims were analyzed using autoregressive integrated moving average and vector auto regression, time series models. Results provide strong evidence that the DGP for the current levels of the number of fatalities and injured owing to RTCs are significantly influenced by the own past history of the two series. The analysis with the impulse-response function also indicated that there is a slight seasonality pattern in the number of injured and fatalities. The similar behaviour and association of the two variables suggest that certain conditions e.g. road conditions, weather, volume of vehicles, and accidents might be persistent in time in Karachi.

Descriptive epidemiology of Karachi road traffic crash mortality from 2007 to 2014.

According to World Health Organization's estimate for Pakistan, there were 25,781 (95% CI: 20,979-30582) Road Traffic Collision (RTC) fatalities in year 2013. The Road Traffic Injury Research and Prevention Center, collects RTC data on injuries and fatalities from five major public and private hospitals' emergency departments in Karachi. For the eight-year period, from 2007-2014, 9129 fatalities were recorded. Males accounted for 8008 (87.7%) all RTC fatalities. Highest number of fatalities were recorded in the 21-25 age group with 1329 (15.3%) fatalities, while fatalities in 16-30 years old, recorded 3446 (39.7%) of all fatalities out of the total 8684 records for which age information was available. Motorbikes as primary vehicles were responsible for 3871 (44.7%) RTC fatalities out of the 8654, for which this information was available. Among women, housewives were the single largest group to have died as a result of RTCs.

Epidemiology of Karachi road traffic crash mortality in 2013.

Road Traffic Crash (RTC) is the eighth leading cause of death globally. In a recent World Health Organization report, there were 5,192 RTC deaths reported from Pakistan in 2010. The Road Traffic Injury Research and Prevention Center (RTIRPC) is a unique public-private public health enterprise in Karachi, and collects data from five major public and private hospitals' emergency departments in the city. Cumulatively, 1130 deaths were recorded in the year 2013. Males accounted for 981 (86.8%) deaths. The most vulnerable decades of life were twenties and thirties; accounting for 307 (27.2%) of all deaths. In terms of involvement of vehicle type in fatalities; over half 577 (51.1%) of all fatalities involved motorbikes, while the second most common type of vehicle involved were buses/coasters which accounted for 108 (9.6%) fatalities. In the burgeoning cities of developing countries, road injury and fatality surveillance can fulfill a vital role in highlighting the human cost of rapid motorization.

Differences in risk-adjusted outcome of road traffic injuries in urban tertiary care centers of Pakistan.

OBJECTIVE: To assess the differences in road injury survival in three tertiary care hospitals in an urban setting. METHODS: The study was conducted in and comprised all road traffic injury victims presenting to the three state-run tertiary care centres in Karachi from September 2006 to October 2009. Patients' age, gender, mode, and delay in arrival, severity of injury were noted. Data was stratified by hospital of presentation. A logistic regression model was developed and probability of survival was assessed after adjusting for various risk factors, including patient characteristics and injury severity. RESULTS: There were 93,657victims in the study, but complete information was missing in 6,458(6.89%) study subjects, including survival information. Overall, 83,837(89.5%) were males; 64,269(74%) were aged between 16 and 45 years; 84,016(95%) had injury severity score of ?15; and overall survival was 84,141(96.5%). CONCLUSIONS: Significant differences existed in risk-adjusted survival of road injury victims presenting to public hospitals of Karachi. These differences pointed to variations in the process of care, and highlighted opportunities for improvement.

Vulnerable road users are at greater risk during Ramadan -- results from road traffic surveillance data.

OBJECTIVE: To assess how the frequency, nature and outcome of road traffic crashes differ during the fasting month of Ramadan. METHODS: The retrospective study was conducted in Karachi and comprised data from the Road Traffic Injury Surveillance Project which entailed information on all road traffic injury victims presenting to Emergency Departments in the city between September 2006 and September 2011. Data was analysed to find the frequency of road traffic crashes according to time of incident, road user group and survival. Ramadan and Non-Ramadan groups were compared with respect to time and frequency of incidents, road user group and mortality. SPSS 16 was used for statistical analysis. RESULTS: There were 163,022 subjects from whom 13,640(8.36%) came during Ramadan and 149,382 (91.6%) during the non-Ramadan months. Frequency of road traffic crashes did not change significantly during Ramadan, but was clustered around the breaking of Fast and the Taravih prayers. The most commonly affected road user group was motorbike riders followed by pedestrians. Overall survival of the RTI victims was 96.1% with a mortality rate of 4.1% which was higher than the figure of 3.5% in the non-Ramadan period. CONCLUSIONS: Vulnerable road users were more frequently involved in road traffic injuries during Ramadan. Moreover, the frequency of crashes increased around evening which requires more careful planning of traffic controls, especially for the vulnerable road users.

The impact of polio eradication on routine immunization and primary health care: a mixed-methods study.

BACKGROUND: After 2 decades of focused efforts to eradicate polio, the impact of eradication activities on health systems continues to be controversial. This study evaluated the impact of polio eradication activities on routine immunization (RI) and primary healthcare (PHC). METHODS: Quantitative analysis assessed the effects of polio eradication campaigns on RI and maternal healthcare coverage. A systematic qualitative analysis in 7 countries in South Asia and sub-Saharan Africa assessed impacts of polio eradication activities on key health system functions, using data from interviews, participant observation, and document review. RESULTS: Our quantitative analysis did not find compelling evidence of widespread and significant effects of polio eradication campaigns, either positive or negative, on measures of RI and maternal healthcare. Our qualitative analysis revealed context-specific positive impacts of polio eradication activities in many of our case studies, particularly disease surveillance and cold chain strengthening. These impacts were dependent on the initiative of policy makers. Negative impacts, including service interruption and public dissatisfaction, were observed primarily in districts with many campaigns per year. CONCLUSIONS: Polio eradication activities can provide support for RI and PHC, but many opportunities to do so remain missed. Increased commitment to scaling up best practices could lead to significant positive impacts.

Polio travel restrictions: a sledgehammer to crack a nut?

Imposition by WHO of mandatory vaccination for international travelers from Pakistan has caused confusion and panic amongst travelers besides the adverse effect on the country's image from the widely reported statement. It is felt that the announced measure is not primarily supported by science but is rather a response to disillusionment in the donors about the repeatedly missed eradication targets set by WHO. In the past few years, exportation of poliovirus from Pakistan has caused outbreaks in China, Iraq and Syria besides the ongoing two way transmission with Afghanistan, but the carriers in these spreads are mainly land route travelers. Vaccinating all air travelers is unnecessarily punitive besides being probably ineffectual in halting exportation. The unrelenting focus on polio eradication may have negative impact on fragile health systems besides arousing suspicions of religious elements opposed to vaccination. Routine vaccination and polio campaigns as part of community development measures such as provision of clean drinking water and elimination of surface sewage drainage would be more accepted. The government would be well advised to assume control of the polio eradication program and make it a national development issue.

Political determinants of Health: Lessons for Pakistan.

There is much concern about the capacity of the health system of Pakistan to meet its goals and obligations. Historically, the political thrust has been absent from the health policy formulation and this is reflected in the low and stagnant public allocations to health. Successive political leaderships have averred from considering healthcare is a common good rather than a market commodity and health has not been recognized as a constitutional right. Over 120 of world's nation states have accepted health as a constitutional right but the 1973 Constitution of Pakistan does not mandate health or education as a fundamental right and the recently adopted 18th constitutional amendment missed the opportunity to extend access to primary health care as an obligation of the State. It is argued in this communication that missing from the calculations of policy formulation and agenda setting is the political benefits of providing health and other social services to underserved populations. Across the developing world, many examples are presented of governments undertaking progressive health reforms that bring services where none existed and subsequently reaping electoral benefit. The political determinant of healthcare will be realized when the political leaders of poorly performing countries can be convinced that embracing distributive policies and successfully bringing healthcare to the poor can be major factors in their re-elections.

Why we must provide better support for Pakistan's female frontline health workers.

Svea Closser and Rashid Jooma argue that achieving polio eradication and strengthening Pakistan's health system must focus not just on international engagement but also on local partnerships with Lady Health Workers and other ground-level staff. Please see later in the article for the Editors' Summary.