Randomized Controlled Trials in Lung, Gastrointestinal, and Breast Cancers: An Overview of Global Research Activity

Background: In this study, we compared and contrasted design characteristics, results, and publications of randomized controlled trials (RCTs) in gastrointestinal (GI), lung, and breast cancer. Methods: A PUBMED search identified phase III RCTs of anticancer therapy in GI, lung, and breast cancer published globally during the period 2014–2017. Descriptive statistics, chi-square tests, and the Kruskal–Wallis test were used to compare RCT design, results, and output across the cancer sites. Results: A total of 352 RCTs were conducted on GI (36%), lung (29%), and breast (35%) cancer. Surrogate endpoints were used in 55% of trials; this was most common in breast trials (72%) compared to GI (47%) and lung trials (43%, p < 0.001). Breast trials more often met their primary endpoint (54%) than GI (41%) and lung trials (41%) (p = 0.024). When graded with the ESMO-MCBS, lung cancer trials (50%, 15/30) were more likely to meet the threshold for substantial benefit. GI trials were published in journals with a substantially lower impact factor (IF; median IF 13) than lung (median IF 21) and breast cancer trials (median IF 21) (p = 0.038). Conclusions: Important differences in RCT design and output exist between the three major cancer sites. Use of surrogate endpoints and the magnitude of benefit associated with new treatments vary substantially across cancer sites.

‘Coming home does not mean that the injury has gone’—exploring the lived experience of socioeconomic and quality of life outcomes in post-discharge trauma patients in urban India

Trauma results in long-term socioeconomic outcomes that affect quality of life (QOL) after discharge. However, there is limited research on the lived experience of these outcomes and QOL from low – and middle-income countries. The aim of this study was to explore the different socioeconomic and QOL outcomes that trauma patients have experienced during their recovery. We conducted semi-structured qualitative interviews of 21 adult trauma patients between three to eight months after discharge from two tertiary-care public hospitals in Mumbai, India. We performed thematic analysis to identify emerging themes within the range of different experiences of the participants across gender, age, and mechanism of injury. Three themes emerged in the analysis. Recovery is incomplete—even up to eight months post discharge, participants had needs unmet by the healthcare system. Recovery is expensive—participants struggled with a range of direct and indirect costs and had to adopt coping strategies. Recovery is intersocial—post-discharge socioeconomic and QOL outcomes of the participants were shaped by the nature of social support available and their sociodemographic characteristics. Provisioning affordable and accessible rehabilitation services, and linkages with support groups may improve these outcomes. Future research should look at the effect of age and gender on these outcomes.

Associations of On-arrival Vital Signs with 24-hour In-hospital Mortality in Adult Trauma Patients Admitted to Four Public University Hospitals in Urban India: A Prospective Multi-Centre Cohort Study

Introduction: In India, more than a million people die annually due to injuries. Identifying the patients at risk of early mortality (within 24 hour of hospital arrival) is essential for triage. A bilateral Government Australia-India Trauma System Collaboration generated a trauma registry in the context of India, which yielded a cohort of trauma patients for systematic observation and interventions. The aim of this study was to determine the independent association of on-arrival vital signs and Glasgow Coma Score (GCS) with 24-hour mortality among adult trauma patients admitted at four university public hospitals in urban India.

Methods: We performed an analysis of a prospective multicentre observational study of trauma patients across four urban public university hospitals in India, between April 2016 and February 2018. The primary outcome was 24-hour in-hospital mortality. We used logistic regression to determine mutually independent associations of the vital signs and GCS with 24-hour mortality.

Results: A total of 7497 adult patients (18 years and above) were included. The 24-hour mortality was 1.9%. In univariable logistic regression, Glasgow Coma Score (GCS) and the vital signs systolic blood pressure (SBP), heart rate (HR), respiratory rate (RR) and peripheral capillary oxygen saturation (SpO2) had statistically significant associations with 24-hour mortality. These relationships held in multivariable analysis with hypotension (SBP100bpm) and bradycardia (HR<60bpm), hypoxia (SpO220brpm) and severe (3-8) and moderate (9-12) GCS having strong association with 24-hour mortality. Notably, the patients with missing values for SBP, HR and RR also demonstrated higher odds of 24-hour mortality. The Injury Severity Scores (ISS) did not corelate with 24-hour mortality.

Conclusion: The routinely measured GCS and vital signs including SBP, HR, SpO2 and RR are independently associated with 24-hour in-hospital mortality in the context of university hospitals of urban India. These easily measured parameters in the emergency setting may help improve decision-making and guide further management in the trauma victims. A poor short-term prognosis was also observed in patients in whom these physiological variables were not recorded.

Clubfoot patients’ demographic profile and outcomes of using the ponseti method at three selected hospitals in Zimbabwe

Background: Clubfoot is the most common musculoskeletal congenital abnormality and the Ponseti method is regarded as the gold standard of treatment. It has proven to be affordable, simple, and effective in correcting this deformity, particularly in low resource settings similar to Zimbabwe. Aim: The aim of this study was to establish the demographic profile and outcomes of patients with clubfoot treated using the Ponseti method at 3 hospitals in Zimbabwe, as well as determine whether results obtained were similar to those from regional and international research. Methodology: A descriptive retrospective records review of patients with clubfoot treated between January 2013 and December 2015 at Parirenyatwa, Harare Central and Mutare Provincial Hospitals was conducted. The main outcome was the final Pirani score at the end of the corrective phase. Data was analysed using STATISTICA Version 13.5. Results: There were 310 participants, mostly male (64.2%), with the majority (79.7%) in the maintenance phase of treatment. A total of 88.3% of the were participants between zero and two years of age at initial presentation, and the median (IQR) age was 3months (0.15-11months). Clubfoot was mostly of idiopathic (90.5%) and bilateral (55.2%) presentation, with positive family history of the deformity reported in 14.5% of participants. Mean (SD)Pirani scores at initial assessment for the right and left feet were 3.92 (1.33) and 3.99 (1.25) respectively. The Mean (SD) number of casts applied before tenotomy was 7.14 (4.48) ranging from 0-26 casts, and 72.5% of the participants had a tenotomy done. The proportion of left and right feet that attained a Pirani score of one or less at the end of the corrective phase was 79.2% and 82.5% respectively. Relapse was reported for 42.6% of participants in braces. At time of data collection, as many as 73.6% of the participants had stopped attending the clinics. Conclusion: Clubfoot treated using the Ponseti method had a good outcome at the end of the corrective phase. The demographic profile of patients managed at the three clinics and their treatment outcomes were in line with literature findings. There is, however, evidence of poor compliance and a high loss to follow up during the bracing phase and these need to be addressed to improve long term results.

Emergency general surgery in a public hospital in Malaysia

Introduction: Patients undergoing emergency general surgery (EGS) are at risk for death and complications. Information on the burden of EGS is critical for developing strategies to improve the outcomes.

Methods: In this retrospective cohort study, medical records of all general surgical operations in a public hospital were reviewed for the period 1st January 2017 to 31st December 2017. Data on patient demographics, operative workload, case mix, time of surgery and outcomes were analysed.

Results: Of the 2960 general surgical operations that were performed in 2017, 1720 (58.1%) of the procedures were performed as emergencies. The mean age for the patients undergoing emergency general surgical procedures was 37.9 years (Standard Deviation, ±21.0), with male preponderance (57.5%). Appendicitis was the most frequent diagnosis for the emergency procedures (43%) followed by infections of the skin and soft tissues (31.6%). Disorders of the colon and rectum ranked as the third most common condition, accounting for 6.7% of the emergency procedures. Majority of emergency surgery (59.3%) took place after office hours and on weekends. Post-operative deaths and admissions to critical care facilities increased during EGS when compared to elective surgery, p<0.01.

Conclusions: EGS constitutes a major part of the workload of general surgeons and it is associated significant risk for death and post-operative complications. The burden of EGS must be recognised and patient care systems must evolve to make surgery safe and efficient.

Management of neuroblastoma in limited-resource settings

Neuroblastoma (NB) is a heterogeneous disease with variable outcomes among countries. Little is known about NB in low- and middle-income countries (LMICs).

The aim of this review was to evaluate regional management protocols and challenges in treating NB in paediatric oncology units in LMICs compared to high-income countries (HICs).

PubMed, Global Health, Embase, SciELO, African Index Medicus and Google Scholar were searched for publications with keywords pertaining to NB, LMICs and outcomes. Only English language manuscripts and abstracts were included. A descriptive review was done, and tables illustrating the findings were constructed.

Limited information beyond single-institution experiences regarding NB outcomes in LMICs was available. The disease characteristics varied among countries for the following variables: sex, age at presentation, MYCN amplification, stage and outcome. LMICs were found to be burdened with a higher percentage of stage 4 and high-risk NB compared to HICs. Implementation of evidence-based treatment protocols was still a barrier to care. Many socioeconomic variables also influenced the diagnosis, management and follow-up of patients with NB.

Patients presented at a later age with more advanced disease in LMICs. Management was limited by the lack of resources and genetic studies for improved NB classification. Further research is needed to develop modified diagnostic and treatment protocols for LMICs in the face of limited resources.

A review of the epidemiology, post-neurosurgical closure complications and outcomes of neonates with open spina bifida

Background. Spina bifida (SB) is a neural tube defect (NTD) that has an increased risk of fatal and disabling effects if not repaired early, i.e. within the first 24 to 48 hours of life. Its diagnosis holds an increased burden for the patient and the caregiver owing to secondary complications. The effects of the disease are detrimental even with early repair, because of the long-term disabling nature of the disease.

Objective. This retrospective study aimed to assess the effects of demographics, immediate post-surgical complications and impact of time to surgical intervention on the outcome of neonates with open SB (OSB) admitted to the neonatal intensive care unit (NICU) at Inkosi Albert Luthuli Central Hospital (IALCH) in KwaZulu-Natal, South Africa (SA), between January 2011 and December 2015.

Methods. A retrospective chart review was conducted at the NICU of IALCH. All neonates diagnosed with SB were identified. The study period was from 1 January 2011 to 31 December 2015. Data were collected from the IALCH electronic database. All neonates with SB admitted to the IALCH NICU were included; any patient who presented beyond the neonatal period (i.e. >28 days) was excluded from the study. Data collected included maternal demographics. Additionally, neonatal history was reviewed and post surgery complications evaluated. Outpatient management post discharge was reviewed.

Results. One hundred and fifty neonates were included (58% male). The mean (standard deviation) maternal age was 26.7 (6.6) years. Only 10% had an antenatal diagnosis of OSB. Seventy-eight percent were born at term and 22% prematurely. The lumbar/sacral region was the most commonly affected. More males (14%) had thoraco/lumbar lesions than females (7.8%). Forty-eight percent presented before 3 days of life (early presentation). In the late-presentation group, there was an association with wound sepsis (p=0.003). Twenty-five percent were repaired between days 0 and 3 of life and 75% after 3 days. Postoperative complications in patients whose open SBs were repaired beyond 3 days of life were not statistically significant compared with those with early repair; all were p>0.05. There was a borderline association of prolonged hospitalisation with wound sepsis (p=0.07). Long-term outcomes showed that 68% had lower limb dysfunction, 18% urological complications, 14% limb deformity, and 11% hydrocephalus. A minority had psychomotor (7%) and developmental (15%) disorders. Ten percent required readmission secondary to shunt complications, and 7% died.

Conclusion. SB remains a significant disease burden that affects outcome and survival of neonates in SA. Lack of good antenatal care, which includes early ultrasound and timely referral to centres, are barriers to good outcomes. Long-term follow-up is also necessary to prevent morbidity.

Comparison of intraarticular distal humerus fracture outcomes treated with or without olecranon osteotomy – A case series

A case series was extracted from the trauma registry at Aga Khan University Hospital from the period June 2015 to June 2019. Included were 16 adult patients who presented with intra-articular distal humerus fracture type C2. The functional, clinical and radiological outcomes of fractures treated with or without olecranon osteotomy up to 12 months follow-up were compared. Outcomes were assessed at 6 weeks, 3, 6 and 12 months re-visits. Among the 16 studied patients, 9 (56%) were males and 7 (44%) were females. In the group without osteotomy, there was a good functional and clinical outcome with a mean Quick Disability of the Arm, Shoulder and Hand score of 32±30 at 3 months post-procedure. Bone healing was noticed at 6 months after surgery. In the osteotomy group, 50%-70% bone union was seen at 3 months post-surgery while fair functional and clinical outcome was achieved at 6 months after surgery

Functional and clinical outcomes of open versus closed radius and ulna shaft fractures in adults: A prospective cohort study

Objective: To compare functional and clinical outcomes of open versus closed radius ulna shaft fractures in adults treated by internal fixation.

Methods: A prospective cohort study was conducted on patients presenting with traumatic radius and ulna shaft fractures to Aga Khan University and undergoing internal fixation between July 2015 to June 2019. Data was extracted from an ongoing orthopaedic trauma registry. Functional and clinical outcomes were assessed by Price et al. criteria at 6 weeks, 3, 6 and 12 months follow-up. Outcome scores of open versus closed fractures were compared.

Results: Twenty-nine adult patients with isolated radius and ulna shaft fracture were identified. Cause of injury was road traffic accident in 18 (62%) and fall in 11 (38%) patients. Seventeen (59%) were closed and 12 (41%) were open fractures. At 6week follow-up, better outcomes were observed in closed fracture group (p=0.01) with near-full range of motion and activity in 10(83%) patients as compared to 3(27%) in the open fracture group. No significant difference in outcomes was observed at 3 months and thereafter.

Conclusions: Earlier recovery of function at 6 weeks was observed in majority of patients in the closed fracture group. Our data shows that good-excellent functional and clinical results are achievable by internal fixation in both open as well as closed fractures of the shaft of radius and ulna in adults.

Stricture of Urethra: Patterns and Outcomes of Management From a Single Centre in Pakistan Over 7 Years

Objective: To determine the outcomes of urethroplasty and its complications from a large cohort of patients managed in a single centre.

Study design: Descriptive study.

Place and duration of study: Department of Urology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, from January 2010 to December 2016.

Methodology: A total of 546 patients with stricture urethra at different locations underwent urethroplasty from January 2010 to December 2016 were included. All patients had an ascending urethrogram followed by retrograde ± antegrade urethroscopy to assess the location and length of the stricture. Technique of urethroplasty was chosen according to the site, length and etiology. Following appropriate procedure, patients were followed up in the dedicated urethral stricture clinic. Procedure was considered successful if either no further therapeutic intervention was required and the maximum flow rate (Qmax) was >20 ml/sec with a voided volume of at least 200 mls. The procedure was regarded as unsuccessful, if further treatment was required or Qmax was <10ml/sec.

Results: A total of 546 patients with mean age of 32.3 +13.1 years (range: 12-74) involving anterior (n=323, 59.2%) or posterior (n=223, 40.8%) urethra were treated. Mean follow-up was 43.6 months (range: 3-84). The success rates of bulbar urethral strictures after excision and primary anastomosis (EPA) was 93. 3%, non-transecting urethroplasty 84.6% and oral mucosal graft (OMG), 81.8%. In penile urethral strictures, OMG, Orandi procedure and Johanson's techniques yielded success rates of 88.4%, 66.6% and 57.1%, respectively. In posterior urethral strictures, after excision and bulboprostatic anastomosis, good results were seen in 88.3%. In pan-urethral strictures, abdominal skin graft repair, combined tissue transfer and OMG urethroplasty yielded success rates of 74%, 78.5% and 75%, respectively. The complications/ adverse events were encountered in 251 / 546 (45.9%) patients in this series.

Conclusion: Anastomotic urethroplasty yielded best outcomes followed by OMG urethroplasty. In the long-term follow-up, erectile dysfunction (ED), infertility and recurrence of stricture are the main complications which need individualised management.