Operationalization of bi-directional screening for tuberculosis and diabetes in private sector healthcare clinics in Karachi, Pakistan.

BACKGROUND: Many countries are facing overlapping epidemics of tuberculosis (TB) and diabetes mellitus (DM). Diabetes increases the overall risk of developing Tuberculosis (TB) and contributes to adverse treatment outcomes. Active screening for both diseases can reduce TB transmission and prevent the development of complications of DM. We investigated bi-directional TB-DM screening in Karachi, Pakistan, a country that ranks fifth among high TB burden countries, and has the seventh highest country burden for DM. METHODS: Between February to November 2014, community-based screeners identified presumptive TB and DM through verbal screening at private health clinics. Individuals with presumptive TB were referred for a chest X-ray and Xpert MTB/RIF. Presumptive DM cases had random blood glucose (RBS) tested. All individuals with bacteriologically positive TB were referred for diabetes testing (RBS). All pre-diabetics and diabetics were referred for a chest X-ray and Xpert MTB/RIF test. The primary outcomes of this study were uptake of TB and DM testing. RESULTS: A total of 450,385 individuals were screened, of whom 18,109 had presumptive DM and 90,137 had presumptive TB. 14,550 of these individuals were presumptive for both DM and TB. The uptake of DM testing among those with presumptive diabetes was 26.1% while the uptake of TB testing among presumptive TB cases was 5.9%. Despite efforts to promote bi-directional screening of TB and DM, the uptake of TB testing among pre-diabetes and diabetes cases was only 4.7%, while the uptake of DM testing among MTB positive cases was 21.8%. CONCLUSION: While a high yield for TB was identified among pre-diabetics and diabetics along with a high yield of DM among individuals diagnosed with TB, there was a low uptake of TB testing amongst presumptive TB patients who were recorded as pre-diabetic or diabetic. Bi-directional screening for TB and DM which includes the integration of TB diagnostics, DM screening and TB-DM treatment within existing health care programs will need to address the operational challenges identified before implementing this as a strategy in public health programs.

The NHS Bowel cancer screening programme achieves the anticipated survival improvement, but participation must be improved.

Purpose The NHS Bowel cancer screening programme (NHSBCSP) aims to reduce colorectal cancer (CRC) cumulative mortality by up to 23 per cent; long-term outcomes at national level are not yet known. The purpose of this paper is to examine a local population of CRC patients of screening age for their characteristics and long-term survival in relation to their presentation, including through the NHSBCSP. Design/methodology/approach Retrospective analysis of a prospectively maintained CRC database for the years 2009-2014 in a single district hospital providing bowel cancer screening and tertiary rectal cancer services. Findings Of 528 CRC patients diagnosed in the screening age range, 144(27.3 per cent) presented through NHSBCSP, 308(58.3 per cent) electively with symptoms and 76(14.4 per cent) as emergency. NHSBCSP-diagnosed patients were younger (median 66 vs 68 and 69 years, respectively, p=0.001), had more often left-sided cancers (59(41.0 per cent) vs 82(26.6 per cent) and 24(31.6 per cent), respectively, p=0.001), more UICC-stage I (42(29.2 per cent) vs 49(15.9 per cent) and 2(2.6 per cent)), stage III (59(41.0 per cent) vs 106(34.4 per cent) and 20(26.3 per cent)) and less stage IV disease (8(5.6 per cent) vs 61(19.8 per cent) and 34 (44.7 per cent), respectively, p<0.001). Three-year overall survival was best for NHSBCSP and worst for emergency patients (87.5 per cent vs 69.0 per cent and 35.3 per cent, respectively, LogRank p<0.001). Originality/value Patients diagnosed within the NHSBCSP have improved outcome compared to both symptomatic elective and emergency presentations. A reduction in overall cumulative mortality in order of 25 per cent may well be achieved, but continuing high levels of emergency presentations and undetected right-sided disease emphasise need for further improvement in public participation in the NHSBCSP and research into more sensitive and acceptable alternative screening methods.

Volume-outcome relationship for colorectal cancer in primary care: a prospective cohort study.

Purpose Higher caseloads are associated with better outcomes for many conditions treated in secondary and tertiary care settings, including colorectal cancer (CRC). There is little known whether such volume-outcome relationship exist in primary care settings. The purpose of this paper is to examine general practitioner (GP) CRC-specific caseload for possible associations with referral pathways, disease stage and CRC patients' overall survival. Design/methodology/approach The paper retrospectively analyses a prospectively maintained CRC database for 2009-2014 in a single district hospital providing bowel cancer screening and tertiary rectal cancer services. Findings Of 1,145 CRC patients, 937 (81.8 per cent) were diagnosed as symptomatic cancers. In total, 210 GPs from 44 practices were stratified according to their CRC caseload over the study period into low volume (LV, 1-4); medium volume (MV, 5-7); and high volume (HV, 8-21 cases). Emergency presentation (LV: 49/287 (17.1 per cent); MV: 75/264 (28.4 per cent); HV: 105/386 (27.2 per cent); p=0.007) and advanced disease at presentation (LV: 84/287 (29.3 per cent); MV: 94/264 (35.6 per cent); HV: 144/386 (37.3 per cent); p=0.034) was more common amongst HV GPs. Three-year mortality risk was significantly higher for HV GPs (MV: (hazard ratio) HR 1.185 (confidence interval=0.897-1.566), p=0.231, and HV: HR 1.366 (CI=1.061-1.759), p=0.016), but adjustment for emergency presentation and advanced disease largely accounted for this difference. There was some evidence that HV GPs used elective cancer pathways less frequently (LV: 166/287 (57.8 per cent); MV: 130/264 (49.2 per cent); HV: 182/386 (47.2 per cent); p=0.007) and more selectively (CRC/referrals: LV: 166/2,743 (6.1 per cent); MV: 130/2,321 (5.6 per cent); HV: 182/2,508 (7.3 per cent); p=0.048). Originality/value Higher GP CRC caseload in primary care may be associated with advanced disease and poorer survival; more work is required to determine the reasons and to develop targeted intervention at local level to improve elective referral rates.

Association of Depression With Myocardial Infarction With Non-obstructive Coronary Arteries: A Systematic Review.

This systematic review examined the association between depression and myocardial infarction with non-obstructive coronary arteries (MINOCA). A comprehensive literature search was conducted using electronic databases, resulting in the inclusion of six small case-control and cohort studies reported from Spain, Australia, China, and Pakistan. The studies included various study designs, such as cohort studies, case-control studies, and prospective cohort studies. The results of the systematic review indicate a significant association between depression and MINOCA. Several studies reported a higher prevalence of depression among MINOCA patients compared to those with obstructive coronary artery disease. Additionally, depression was found to be associated with worse outcomes in MINOCA patients, including increased cardiovascular events, all-cause mortality, and reduced quality of life. Some studies suggest that psychological factors, such as chronic stress, inflammation, and altered sympathetic nervous system activity, may play a role in the development and progression of MINOCA in individuals with depression. The findings highlight the importance of considering depression as a potential risk factor and prognostic marker in MINOCA patients. Early identification and management of depression in these individuals may improve outcomes and quality of life. A multi-center randomized controlled trial is needed to better understand the underlying mechanisms and to develop targeted interventions for individuals with depression and MINOCA.

Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise.

The current active-latent paradigm of tuberculosis largely neglects the documented spectrum of disease. Inconsistency with regard to definitions, terminology, and diagnostic criteria for different tuberculosis states has limited the progress in research and product development that are needed to achieve tuberculosis elimination. We aimed to develop a new framework of classification for tuberculosis that accommodates key disease states but is sufficiently simple to support pragmatic research and implementation. Through an international Delphi exercise that involved 71 participants representing a wide range of disciplines, sectors, income settings, and geographies, consensus was reached on a set of conceptual states, related terminology, and research gaps. The International Consensus for Early TB (ICE-TB) framework distinguishes disease from infection by the presence of macroscopic pathology and defines two subclinical and two clinical tuberculosis states on the basis of reported symptoms or signs of tuberculosis, further differentiated by likely infectiousness. The presence of viable Mycobacterium tuberculosis and an associated host response are prerequisites for all states of infection and disease. Our framework provides a clear direction for tuberculosis research, which will, in time, improve tuberculosis clinical care and elimination policies.

Role of cytoreduction and hyperthermic intraperitoneal chemotherapy for metastatic gastroesophageal junction adenocarcinoma?

Gastric cancer is the fifth most prevalent cancer worldwide and the third leading cause of cancer- related mortality. Peritoneal carcinomatosis can develop in patients with a primary gastric tumor in a substantial proportion of patients, with estimates ranging from 14% to 43%. For patients with peritoneal carcinomatosis from gastric cancer, therapeutic options are limited. Intraperitoneal chemotherapy, combined with hyperthermia (HIPEC), provides regional dose intensification within the peritoneal cavity, effectively targeting peritoneal carcinomatosis with minimal systemic exposure. We report a case of gastroesophageal junction adenocarcinoma with peritoneal metastasis successfully treated with of cytoreductive surgery and HIPEC, and followed by surgery and systemic chemotherapy, highlighting HIPEC as one of the viable options and the importance of a multimodal approach for the treatment of this case.

An Unusual Presentation of Infective Endocarditis.

Introduction: Leukocytoclastic vasculitis is the inflammation of small blood vessels due to leukocyte migration that comprises a wide range of differentials. It can be caused by autoimmune disorders, infections, neoplasms, or certain medications and warrants prompt recognition and therapy for optimal patient outcomes. Case Presentation: Here we present a case of a 37-year-old male who presented with a painful, petechial rash on his torso and extremities. Skin biopsy revealed leukocytoclastic vasculitis, thereby prompting a comprehensive investigation into the underlying etiology leading to the diagnosis of Pseudomonas aeruginosa infective endocarditis. Conclusion: Pseudomonas aeruginosa is a rare cause of infective endocarditis with a high mortality and morbidity rate. This case highlights the importance of taking a thorough history and physical along with a complete workup of vasculitis as the underlying cause can be life-threatening.

Outcomes of a Modified Technique for Deflation of Distal Radial Artery Occlusion Device on Radial Artery Patency After Percutaneous Coronary Intervention.

Objective: This study aimed to compare two protocols of deflation with increased intervals versus late deflation with smaller intervals for distal radial artery occlusion device (DROAD) removal to assess for radial artery occlusion (RAO). Methods: All patients who underwent PCI with distal radial access were enrolled in the study. The DROAD was applied using an occlusive hemostasis method. Patients were assigned to either protocol 1 or protocol 2 at the primary physician's discretion. Protocol 1 involved the removal of 2 ml of air starting 1 h after the sheath removal and then the removal of 2 ml every 30 min until the band came off. Protocol 2 involved the removal of 4 ml of air 2 h after the sheath removal and then a further 4 ml of air every 15 min until the band came off. Results: A total of 446 patients were enrolled in this study (mean age; 61 ± 6 (Group 1) and 60 ± 5 (Group 2); females 45.83% (Group 1) and 46.34% (Group 2)). The baseline characteristics were the same, including mean hemostasis time (256 ± 25 min (Group 1) and 254 ± 28 min (Group 2), P-value = 0.611). Primary and secondary endpoints did not reach significance in either group (RAO; 21 (8.71) Group 1 and 18 (8.78) Group 2 (P-value = 0.932)). Age (OR (95%CI): 1.07 (0.57-1.45); P-value = 0.031), female gender (OR (95%CI): 1.42 (0.93-1.74); P-value = 0.012), distal artery diameter (OR (95%CI): 0.57 (0.21-0.93); P-value = 0.005), procedure time (OR (95%CI): 2.64 (0.95-4.32); P-value = 0.001), and sheath size (OR (95%CI): 2.47 (1.43-3.76); P-value = 0.044) were predictors of RAO in our cohort. Conclusion: This investigation shows no difference in the incidence of RAO with the standard versus accelerated deflation protocol after PCI. However, local vascular complications, including hematoma were increased with the accelerated protocol.

Beyond latent and active tuberculosis: a scoping review of conceptual frameworks.

There is growing recognition that tuberculosis (TB) infection and disease exists as a spectrum of states beyond the current binary classification of latent and active TB. Our aim was to systematically map and synthesize published conceptual frameworks for TB states. We searched MEDLINE, Embase and EMcare for review articles from 1946 to September 2023. We included 40 articles that explicitly described greater than two states for TB. We identified that terminology, definitions and diagnostic criteria for additional TB states within these articles were inconsistent. Eight broad conceptual themes were identified that were used to categorize TB states: State 0: Mycobacterium tuberculosis (Mtb) elimination with innate immune response (n = 25/40, 63%); State I: Mtb elimination by acquired immune response (n = 31/40, 78%); State II: Mtb infection not eliminated but controlled (n = 37/40, 93%); State III: Mtb infection not controlled (n = 24/40, 60%); State IV: bacteriologically positive without symptoms (n = 26/40, 65%); State V: signs or symptoms associated with TB (n = 39/40, 98%); State VI: severe or disseminated TB disease (n = 11/40, 28%); and State VII: previous history of TB (n = 5/40, 13%). Consensus on a non-binary framework that includes additional TB states is required to standardize scientific communication and to inform advancements in research, clinical and public health practice.

Effect of COVID-19 on cardiac electrophysiology practice: a systematic review of literature.

The authors conducted a systematic review on the effect of coronavirus disease 2019 on electrophysiology (EP) practice and procedure volume in various settings. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed/MEDLINE, Scopus, Web of Science, CINAHL, and Embase were examined with combinations of medical subject headings terms for identification of the relevant studies. After excluding duplicates, irrelevant, and ineligible studies, 23 studies were included for full qualitative analysis. The overall study-level volume reduction of EP procedures ranged from 8 to 96.7%. All studies reported an overall reduction in EP physiology procedures being carried out except one in Poland, which reported an overall increase in the total EP procedures carried out in 2020. This study still reported a decrease in EP procedure volume during the first lockdown phase. Procedural volume reduction was seen most commonly for cardiovascular implantable electronic device placement (20/23 studies, 86.9%), electrophysiology studies (11/23 studies, 47.8%), and ablations (9/23, 39.1% studies). The most common reason stated for the observed decline in EP procedures was the cancellation and postponement of nonurgent elective cases in the hospitals (15/23 studies, 65.2%). There has been an overall reduction in EP procedure volume across different centers. The impact of the decline in EP procedures will be seen only after the services resume to prepandemic levels, but an increase in-patient volume and procedure waiting time is expected. This review will provide insights into improving healthcare service delivery in times of unprecedented public health emergencies.

Preparedness of Public Hospitals for the Coronavirus (COVID-19) Pandemic in Lahore District, Pakistan.

Background Pakistan reported more than a million cases during the coronavirus disease 2019 (COVID-19) pandemic, shuffling the already resource-constrained health system that is known for its high vulnerability and lack of adaption. Objective To find out the level of preparedness of public hospitals for the novel COVID-19 pandemic in Lahore district. Methods A descriptive cross-sectional study was conducted from April to July 2021 among all 18 public hospitals under Specialized Health Care and Medical Education (SHC&ME) in Lahore by administering World Health Organization (WHO) and SHC&ME modified and pre-tested interviewer based and observation checklist. The level of preparedness was assessed for 11 domains, and each domain was scored as a dichotomous variable (Yes and No). Hospital preparedness was labeled as 'acceptable,' 'insufficient,' and 'unacceptable.' Descriptive statistics were run by using SPSS version 26 (IBM Corp., Armonk, NY), and data are presented in the form of tables and bar graphs. Results Out of 18 hospitals, only three (17%) had an acceptable level of preparedness for COVID-19 (>70%). An unacceptable level of preparedness (<35%) was seen in one hospital (5%). Fourteen hospitals (78%) were insufficiently prepared (35-70%). Conclusion The study highlights the suboptimal preparedness in 83% of the public hospitals with a consistent pattern of deficiencies in surge capacity, logistics and resource management, essential services, including diagnostics, infection prevention, and control.

Investigating The Role of Inflammatory Markers at Admission in Defining the Severity of Moderate-to-Critical COVID-19: A Cross-Sectional Analysis.

Background and aims: The spectrum of Coronavirus disease-2019 (COVID-19) has been clinically defined from asymptomatic carriers to critical illness. Different inflammatory markers have been used to account for the severity and outcomes of this disease in different settings. Our study aims to investigate the role of these inflammatory markers in defining COVID-19 severity. Methods: This cross-sectional study included 200 confirmed cases of COVID-19. Inflammatory markers including lymphocyte count, D-Dimers, Ferritin, CRP, LDH were noted at admission. The moderate-to-critical disease was defined according to the WHO criteria. Descriptive statistics were applied. Mann-Whitney U-test was applied to compare the difference of markers between moderate-severe and critical patients. ROC was plotted to determine the cut-off values of these markers. Binary logistics regression analysis was used to assess which markers significantly predict the severity of COVID-19. Results: A D-dimer value of >775 ng/ml and LDH >495 U/L had a sensitivity of 72.9% and 79.2% and specificity of 57.9% and 53.6% respectively for critical COVID-19 illness. CRP levels of >100.5 mg/dl has a sensitivity of 66.7%. All inflammatory markers were significantly higher in a critical group of patients (p < 0.05) except for lymphopenia. Binary logistics regression analysis shows that LDH levels and D-dimers were only significant predictors of severity in COVID-19 patients. Conclusion: Inflammatory markers at admission are very useful in defining the severity of COVID-19 in addition to the clinical criteria. This is also useful in predicting adverse outcomes.

Level of Trust in Health Care Systems During COVID-19 Pandemic Among Health Care Workers of Pakistan.

This survey aimed to evaluate the levels of trust and satisfaction among healthcare workers towards the national healthcare delivery system and whether it has been affected by the global disruption created by COVID-19. This was an analytical cross-sectional study that took place from January to October 2021 at a tertiary level health care facility in Rawalpindi, Pakistan, using an online data collection tool. Our sample included 10, 133 healthcare workers of all cadres. Our study found a significant level of distrust of healthcare workers towards multiple aspects of the healthcare delivery system, particularly towards government agencies and other members of healthcare delivery. We noted a significant gender disparity between male and female respondents with males showing more trust than female healthcare workers. We conclude that significant efforts need to be made by policymakers in the government to alleviate this trust deficit before it worsens.

Pelvic Ring Injury Mortality: Are We Getting Better?

OBJECTIVES: To determine if changes in pelvic trauma care and treatment protocols have affected overall mortality rates after pelvic ring injury. DESIGN: Retrospective cohort study. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: A total of 3314 patients with pelvic ring injuries who presented to a single referral center from 1999 to 2018 were included in the study. INTERVENTION: Pelvic ring management, years 1999-2006 versus years 2007-2018. MAIN OUTCOME MEASUREMENTS: In hospital mortality. Other examined variables included change in patient demographics, fracture characteristics, date of injury, associated injuries, length of hospital stay, Abbreviated Injury Severity Score. RESULTS: The composite mortality rate was 6.5% (214/3314). The earliest cohort presented a mortality rate of 9.1% [111/1224; 95% confidence interval (CI), 7.6%-10.8%] compared with the more recent cohort mortality rate of 4.9% (103/2090; 95% CI, 4.1%-5.9%). Overall mortality was significantly lower in the more recent period, a risk difference of 4.1% (95% CI, 2.3%-6.1%; P < 0.01). After adjusting for age and Abbreviated Injury Severity Score of the brain, chest, and abdomen, the mortality reduction was more pronounced with an adjusted risk difference of 6.4% (95% CI, 4.7%-8.1%; P < 0.01). CONCLUSION: Significant improvement in the mortality rate of pelvic ring injuries has been demonstrated in recent years (4.9% vs. 9.1%) and the difference is even large when accounting for known confounders. Improvement appears to coincide chronologically with changes in trauma resuscitation and implementation of adjuvant treatments for managing patients with severe hemorrhagic shock. Although the exact benefit of each treatment awaits further research, these data might indicate improved care over time for these difficult patients. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Perceptions of anti-smoking messages amongst high school students in Pakistan.

BACKGROUND: Surveys have provided evidence that tobacco use is widely prevalent amongst the youth in Pakistan. Several reviews have evaluated the effectiveness of various tobacco control programs, however, few have taken into account the perceptions of students themselves regarding these measures. The aim of this study was to determine the most effective anti-smoking messages that can be delivered to high-school students in Pakistan, based on their self-rated perceptions. It also aimed to assess the impact of pictorial/multi-media messages compared with written health warnings and to discover differences in perceptions of smokers to those of non-smokers to health warning messages. METHODS: This study was carried out in five major cities of Pakistan in private English-medium schools. A presentation was delivered at each school that highlighted the well-established health consequences of smoking using both written health warnings and pictorial/multi-media health messages. Following the presentation, the participants filled out a graded questionnaire form, using which they rated the risk-factors and messages that they thought were most effective in stopping or preventing them from smoking. The Friedman test was used to rank responses to each of the questions in the form. The Wilcoxon Signed Rank test used to analyze the impact of pictorial/multi-media messages over written statements. The Mann Whitney U test was used to compare responses of smokers with those of non-smokers. RESULTS: Picture of an oral cavity cancer, videos of a cancer patient using an electronic voice box and a patient on a ventilator, were perceived to be the most effective anti-smoking messages by students. Addiction, harming others through passive smoking and impact of smoking on disposable incomes were perceived to be less effective messages. Pictorial/multi-media messages were perceived to be more effective than written health warnings. Health warnings were perceived as less effective amongst smokers compared to non-smokers. CONCLUSION: Graphic pictorial/multi-media health warnings that depict cosmetic and functional distortions were perceived as effective anti-smoking messages by English-medium high school students in Pakistan. Smokers demonstrated greater resistance to health promotion messages compared with non-smokers. Targeted interventions for high school students may be beneficial.

Stability-indicating ultra-performance liquid chromatography method for the estimation of thymoquinone and its application in biopharmaceutical studies.

Thymoquinone (THQ) is known for its neuroprotective and anti-convulsant properties in preclinical studies. We herewith describe a simple, rapid, selective, sensitive and stability-indicating UPLC method for the estimation of THQ and its application to biopharmaceutical studies such as in vitro release from nanoparticulate system and in vivo pharmacokinetic study. The method employed gradient elution using a Waters Acquity HSS-T3 C(18) (100 × 2.1 mm, 1.8 µm) UPLC column. The mobile phase consisted of water and acetonitrile, pumped at a flow rate of 0.5 mL/min. The injection volume was 5 µL and THQ was monitored at 294 nm wavelength with a total run time of 6 min. In solution as well as in plasma, the method was found to be linear (r ≥ 0.998), precise (CV ≤ 2.45%) and accurate (recovery ≥ 84.8%) in the selected concentration range of 0.1-0.8 µg/mL. Forced degradation studies revealed that THQ undergoes degradation under acidic, basic, oxidation and UV light stress conditions. However, the developed UPLC method could effectively resolve degradation product peaks from THQ. Further, no interference was found at the retention time of THQ from any plasma components, indicating selectivity of the developed method. For solutions, the limits of detection and quantitation of the method were found to be 0.001 and 0.0033 µg/mL, respectively; while in plasma they were 0.006 and 0.02 µg/mL, respectively. The validated method was successfully applied to quantify THQ in dissolution medium as well as oral in vivo pharmacokinetic study of THQ suspension and THQ- solid lipid nanoparticle (THQ-SLN) formulation. A 2-fold increase in the relative bioavailability was observed with the THQ-SLN compared with THQ. The results indicate that the SLN significantly increased plasma concentrations and retention within the systemic circulation.

Risk factors for treatment failure of fracture-related infections.

OBJECTIVE: Infection after fracture fixation is a potentially devastating outcome, and surgical management is frequently unsuccessful at clearing these infections. The purpose of this study is to determine if factors can be identified that are associated with treatment failure after operative management of a deep surgical site infection. METHODS: We retrospectively reviewed the billing system at a Level I trauma center between March 2006 and December 2015. We identified 451 patients treated for deep surgical site infection after fracture fixation at our center. A multivariate regression analysis was then performed to evaluate for factors associated with treatment failure. RESULTS: Mean follow-up was 2.3 years. One hundred fifty-six patients (35%) failed initial surgical management. Risk factors associated with treatment failure included initial culture results positive for polymicrobial organisms (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.4), removal of implants (OR, 1.9; 95% CI, 1.2-2.9), or Gustilo-Anderson IIIB/IIIC injury (OR, 2.0; 95% CI, 1.1-3.7). Increased body mass index and fulfilling the criteria to have a methicillin-resistant Staphylococcus aureus (MRSA) nasal swab screening showed a trend toward increased risk of failure. CONCLUSION: Treatment failure after deep surgical site infection was relatively common. Three distinct factors (polymicrobial infection, removal of implants, and IIIB/C fracture) were associated with failure to eradicate the infection in the first series of surgeries and antibiotics. These data might help guide clinicians as they counsel patients on the risk of treatment failure and might focus efforts to improve treatment toward patients at higher risk of treatment failure.

Association Between Femoral "Spike" Size After Intramedullary Nailing and Subsequent Knee Motion Surgery.

OBJECTIVES: To determine the association between displaced femoral shaft bone fragments ("spikes") seen on radiographs after intramedullary nail insertion and the need for future motion surgery. DESIGN: Retrospective case-control study. SETTING: Academic trauma center. PATIENTS: We included patients with femoral shaft fractures treated with intramedullary nail insertion. Case patients (n = 22) had developed knee stiffness treated with motion surgery. The control group was a randomly selected sample (1:3 ratio). MAIN OUTCOME MEASURES: Motion surgery to address knee stiffness. We defined a "spike distance ratio" and "spike area ratio" from initial postoperative anteroposterior and lateral radiographs. Multivariable logistic regression determined the effect of spike distance and area ratios on the likelihood of need for motion surgery, controlling for polytraumatic injuries and bilateral fractures. RESULTS: The case group had a median femoral spike distance ratio of 1.9 [interquartile range (IQR), 1.6-2.5] compared with 1.5 (IQR, 1.2-1.8) in the control group. An increased femoral spike distance ratio was associated with increased odds of motion surgery (P < 0.01). A femoral spike distance >2 times the femoral radius had 32 times the odds (95% confidence interval, 2-752) of motion surgery compared with patients with distance ratios <1.25. Median femoral spike area ratios were similar between the case (0.2; IQR, 0.1-0.5) and control (0.2; IQR, 0.0-0.5) groups and were not associated with increased odds of motion surgery (P = 0.34). CONCLUSIONS: A larger spike distance ratio is associated with increased odds of subsequent motion surgery. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Quantitative analysis of safranal in saffron extract and nanoparticle formulation by a validated high-performance thin-layer chromatographic method.

INTRODUCTION: Safranal is an effective anticonvulsant shown to act as an agonist at GABA(A) receptors. Nose to brain delivery via nanoparticle formulation might improve its brain delivery. A selective and sensitive analytical method is required for evaluation of safranal-based novel drug delivery systems. OBJECTIVE: To develop and validate a high-performance thin-layer chromatographic (HPTLC) method for the quantitative analysis of safranal as bulk, in saffron extract and in developed safranal-loaded nanoparticle formulation. METHODOLOGY: Chromatographic separation was achieved on silica gel pre-coated TLC aluminium plates 60F-254, using n-hexane:ethyl acetate (9 : 1, v/v) as the mobile phase. Quantitative analysis was carried out by densitometry at a wavelength of 310 nm. The method was validated and applied to detect related impurities, to analyse safranal in saffron extract and to evaluate safranal-loaded nanoparticles. RESULTS: Compact spots of safranal were observed at R(f) value 0.51 +/- 0.02. The method was linear (r = 0.9991) between 0.5 and 5.0 ng/spot. The intra- and inter-day precisions were 1.08-2.17 and 1. 86-3.47%, respectively. The limit of detection was 50 ng/spot and the limit of quantification was 150 ng/spot. The method proved to be accurate (recovery 97.4-102.0%) and was selective for safranal. Evaluation of safranal-loaded nanoparticle formulation demonstrated drug loading of 23.0%, encapsulation efficiency of 42.0% and sustained drug release following biphasic pattern. CONCLUSION: The present method is useful for the quantitative and qualitative analysis of safranal and safranal-loaded nanoparticle formulation. It provides significant advantages in terms of greater specificity and rapid analysis.

Posterolateral plating is a safe alternative for the treatment of distal tibial fractures.

INTRODUCTION: We assessed the outcome and safety of posterior plating of distal tibial fractures. METHODS: We conducted a retrospective case series at a Level I trauma center. Seventy-four consecutive patients with distal tibial fractures treated with anatomically contoured 3.5-mm T-shaped locking compression plate using a posterolateral approach from January 2008 through April 2018 were included in the study. The mean patient age was 48 years (range, 18-87 years). Fifty-nine percent of the patients were male patients, 47% of the fractures were open fractures; and 27% of the patients had multiple traumatic injuries. Eleven fractures were AO/OTA type 42, 22 were type 43A, and 41 were type 43C. Sixty-two (84%) patients were treated with initial spanning external fixation (median time, 23 days) and staged open reduction and internal fixation. The main outcome measure was unplanned reoperation to address implant failure, nonunion, deep surgical site infection, or symptomatic implant. RESULTS: Overall risk of unplanned reoperation was 15% (11 of 74 patients, 95% confidence interval, 9%-25%). Four (5%) reoperations were for nonunion, three (4%) were for surgical site infection, two (3%) were for infected nonunion, and two (3%) were for implant prominence. Loss of alignment >10 degrees occurred in one patient who underwent unplanned reoperation for nonunion. No plate breakage occurred. Median time to reoperation was 221 days (range, 22-436 days). Only one other complication was noted: wound dehiscence associated with the posterolateral approach, which was treated with irrigation and débridement and a 6-week regimen of oral antibiotics. CONCLUSIONS: Use of a posterolateral approach with a pre-contoured locking compression T-plate for the treatment of distal tibial fractures led to reasonable outcomes with an acceptable risk of unplanned reoperation, even with a high proportion of open fractures commonly staged with external fixation.