Sociodemographic determinants of gender disparity in primary percutaneous coronary intervention in Pakistan.

OBJECTIVES: This study aims to contribute to the body of literature on gender disparities after acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PPCI). METHODS: We identified all adult patients who had AMI between January 2017, and December 2022 and were in follow-up at our institute. We collected data on PPCI, revascularization strategy, sociodemographic characteristics, and in-hospital complications in the years following the procedure. RESULTS: A total of 5,872 patients who underwent PCI for AMI were included in the study, out of which 2,058 (35%) were women and 3,814 (65%) were men. Regarding the timing of PCI, female patients had a significantly longer median door-to-balloon time compared to male patients (136 minutes vs 108 minutes, P-value = 0.006). Female patients had a significantly higher rate of in-hospital mortality compared to male patients (5.5% vs 1.2%, P-value = 0.011). Multivariate logistic regression analysis showed that female gender, older age, and lower household income were independent predictors of longer door-to-balloon time. CONCLUSION: This study highlights gender disparities in PPCI in Pakistan, with female patients facing longer door-to-balloon times and higher in-hospital mortality rates. The findings suggest the need for targeted interventions to improve the access and quality of care for female patients with AMI.

Social Determinants of Clinical Visits After Left Main Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting.

This study aims to investigate the social determinants of clinical visits after LM-PCI versus CABG and their impact on post-treatment care and outcomes. We identified all adult patients who underwent LM-PCI or CABG between January 1, 2015, and December 31, 2022, and were in follow-up at our institute. We collected data on clinical visits, including outpatient visits, emergency department visits, and hospitalizations, in the years following the procedure. The study included 3816 patients, of which 1220 underwent LM-PCI and 2596 underwent CABG. The majority of patients were Punjabi (55.8%), males (71.8%), and had low socioeconomic status (69.2%). The strongest predictors of having a follow-up visit were age (OR (95%CI): 1.41 (0.87-2.35); P value = 0.03), female gender (OR (95%CI): 2.16 (1.58-4.21); P value = 0.07), LM-PCI (OR (95%CI): 2.32 (0.94-3.64); P-value = 0.01), government entitlement (OR (95%CI): 0.67 (0.15-0.84); P value = 0.16), high SYNTAX (OR (95%CI): 1.07 (0.83-2.58); P value = 0.02), 3-vessel disease (OR (95%CI): 1.76 (1.05-2.95); P value <0.01), and peripheral arterial disease (OR (95%CI): 1.52 (0.91-2.45); P value = 0.01). Hospitalizations, outpatient, and emergency visits were more in the LM-PCI cohort as compared to CABG. In conclusion, the social determinants of health, including ethnicity, employment, and socioeconomic status were associated with differences in clinical follow-up visits after LM-PCI and CABG.

Bullying in Cardiology: Pakistan's Perspective.

This survey aimed to investigate the extent of bullying among junior physicians in cardiology departments, by way of an anonymous web-based questionnaire in Pakistan. A survey of Pakistan cardiology trainees was piloted as a cross-sectional qualitative survey of junior cardiologists (including resident physicians and senior registrars) from teaching institutes all over Pakistan. Negative Acts Questionnaire-Revised was used as the tool for monitoring and reporting bullying nationwide. Of 1852 trainees, bullying was reported by 10.2% of males and 13.4% of females. Women had higher odds of reporting being bullied (odds ratio [OR] {95% confidence interval [CI]}: 1.42 [1.07-2.36]; P-value = 0.018), and the religious minority group (Hindu) reported more bullying (OR [95% CI]: 3.27 [2.16-4.73]; P-value < 0.001). Women were more likely than men to report sexist language (24.1% vs 7.5%; P-value < 0.001) while men reported more racist language (4.2% vs 16.5%; P-value < 0.001). Consultants in cardiology (75.4%) and other specialties (68.3%) commonly perpetrated bullying on cardiology trainees. Bullying in cardiology is a common finding and proportionally affects both males and females, religious minorities, and trainees working in tertiary care hospitals. In addition, females are reporting more sexist language being used by consultants as the majority.

Social determinants of pacemaker reuse among patients and family members in Pakistan.

OBJECTIVES: This survey aimed to quantify the opinions of CIED reuse among patients and family members in Pakistan and to identify the social determinants which may predict these views. METHODS: A questionnaire formulating attitudes toward PPM reuse was administered to patients and family members at cardiology institutes in Pakistan from 1 July 2022 to 30 September 2022. The eligibility criteria (age > 18 years; inline for PPM placement) were taken into account and incomplete responses were excluded from the final analysis. RESULTS: A total of 9,246 participants recorded their responses, of which 7,152 (78.16%) accepted pre-used PPMs. The lower social class had more PPM reuse acceptance rate than the middle and upper class (92.72% vs. 60.52% vs. 35.38%), respectively. Age ≥ 65 (OR(95%CI): 0.68 (0.41-0.99); P-value = 0.023), male gender (OR(95%CI): 0.55 (0.35-0.72), P-value = 0.016), unemployment (OR(95%CI): 0.47 (0.25-0.64); P-value = 0.007), poor health status (OR(95%CI): 0.72 (0.53-0.92); P-value = 0.041), and lower social class (OR(95%CI): 0.36 (0.28-0.53); P-value = 0.003) were social determinants of PPM reuse acceptance. CONCLUSION: Patients and their family members endorse the concept of PPM reuse in Pakistan who cannot afford new devices.

Development of dual anti-biofilm and anti-bacterial medical devices.

The rising occurrence of antimicrobial resistance demands new strategies for delivering antibiotics to ensure their effective use. In this study, a multi-functional strategy to address medical device associated infections is explored whereby an anti-attachment and an antibacterial mechanism have been combined. Silicone catheters impregnated with multiple antibiotics are coated with polyacrylate coatings previously shown to reduce bacterial attachment and biofilm formation. Antibiotics are delivered through the applied coating and the delivery rate depends on the coating thickness and the calculated log P. Coated devices achieve a zone of inhibition and TK100 to Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus similar to those of uncoated devices, whilst maintaining anti-attachment properties. No adverse immunological responses of the coatings were observed. The multi-functional nature of the device developed in the study represents an important approach to combatting medical device associated infections.

Propidium monoazide-polymerase chain reaction for detection of residual periprosthetic joint infection in two-stage revision.

False negative culture results in periprosthetic joint infection (PJI) are not uncommon particularly when patients have received long term antibiotics. Polymerase chain reaction (PCR) has a lower specificity partly due to detection of residual DNA from dead bacteria. Propidium monoazide (PMA) prevents DNA from dead bacteria from being amplified during the PCR. This study aimed to determine the role of PMA in PCR for diagnosis of PJI. Clinical samples were tested by PCR with and without prior treatment with PMA and compared to conventional microbiological culture. The PCR assay included genus-specific primers for staphylococci and enterococci and species-specific primers for Cutibacterium acnes. The validated conditions of PMA treatment used in this study were 20 µM concentration and 5 and 10 min of dark incubation and photo-activation respectively. 202 periprosthetic tissues and explanted prostheses from 60 episodes in 58 patients undergoing revision arthroplasties for either PJI or non-infective causes were tested, by culture, PCR, and PMA-PCR. 14 of the 60 episodes satisfied the Musculoskeletal Infection Society (MSIS) criteria for PJI and 46 did not. Sensitivity of culture, PCR, and PMA-PCR were 50%, 71%, and 79% respectively. Specificities were 98%, 72%, and 89% respectively. All figures were calculated for episodes rather than samples. PMA-PCR enhanced both the specificity and the sensitivity of PCR. It has the potential to detect residual bacterial viability prior to reimplantation in the two-stage revision for PJI.

Validation and assessment of an antibiotic-based, aseptic decontamination manufacturing protocol for therapeutic, vacuum-dried human amniotic membrane.

Amniotic membrane (AM) is used to treat a range of ophthalmic indications but must be presented in a non-contaminated state. AM from elective caesarean sections contains natural microbial contamination, requiring removal during processing protocols. The aim of this study was to assess the ability of antibiotic decontamination of AM, during processing by innovative low-temperature vacuum-drying. Bioburden of caesarean section AM was assessed, and found to be present in low levels. Subsequently, the process for producing vacuum-dried AM (VDAM) was assessed for decontamination ability, by artificially loading with Staphylococcus epidermidis at different stages of processing. The protocol was highly efficient at removing bioburden introduced at any stage of processing, with antibiotic treatment and drying the most efficacious steps. The antibacterial activity of non-antibiotic treated AM compared to VDAM was evaluated using minimum inhibitory/biocidal concentrations (MIC/MBC), and disc diffusion assays against Meticillin-resistant Staphylococcus aureus, Meticillin-resistant S. epidermidis, Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis. Antibacterial activity without antibiotic was low, confirmed by high MIC/MBC, and a no inhibition on agar lawns. However, VDAM with antibiotic demonstrated effective antibacterial capacity against all bacteria. Therefore, antibiotic decontamination is a reliable method for sterilisation of AM and the resultant antibiotic reservoir is effective against gram-positive and -negative bacteria.

An external ventricular drainage catheter impregnated with rifampicin, trimethoprim and triclosan, with extended activity against MDR Gram-negative bacteria: an in vitro and in vivo study.

BACKGROUND: External ventricular drainage (EVD) carries a high risk of ventriculitis, increasingly caused by MDR Gram-negative bacteria such as Escherichia coli and Acinetobacter baumannii. Existing antimicrobial EVD catheters are not effective against these, and we have developed a catheter with activity against MDR bacteria and demonstrated the safety of the new formulation for use in the brain. OBJECTIVES: Our aim was to determine the ability of a newly formulated impregnated EVD catheters to withstand challenge with MDR Gram-negative bacteria and to obtain information about its safety for use in the CNS. METHODS: Catheters impregnated with three antimicrobials (rifampicin, trimethoprim and triclosan) were challenged in flow conditions at four weekly timepoints with high doses of MDR bacteria, including MRSA and Acinetobacter, and monitored for bacterial colonization. Catheter segments were also inserted intracerebrally into Wistar rats, which were monitored for clinical and behavioural change, and weight loss. Brains were removed after either 1 week or 4 weeks, and examined for evidence of inflammation and toxicity. RESULTS: Control catheters colonized quickly after the first challenge, while no colonization occurred in the impregnated catheters even after the 4 week challenge. Animals receiving the antimicrobial segments behaved normally and gained weight as expected. Neurohistochemistry revealed only surgical trauma and no evidence of neurotoxicity. CONCLUSIONS: The antimicrobial catheter appears to withstand bacterial challenge for at least 4 weeks, suggesting that it might offer protection against infection with MDR Gram-negative bacteria in patients undergoing EVD. It also appears to be safe for use in the CNS.

An antimicrobial impregnated urinary catheter that reduces mineral encrustation and prevents colonisation by multi-drug resistant organisms for up to 12 weeks.

Two major complications of indwelling urinary catheterisation include infection and mineral encrustation of the catheter. Our antimicrobial urinary catheter (AUC) impregnated with rifampicin, triclosan, and sparfloxacin has demonstrated long-term protective activity against major uropathogens. This study aimed to firstly assess the ability of the AUC to resist mineral encrustation in the presence and absence of bacteria. Secondly, it aimed to investigate the AUC's anti-biofilm activity against multi-drug resistant organisms. There was no difference in surface roughness between AUC and control segments. In a static and a perfusion model, phosphate deposition was significantly reduced on AUCs challenged with P. mirabilis. Furthermore, none of the AUCs blocked during the 28 day test period, unlike controls. The AUC prevented colonisation by methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, extended-spectrum beta-lactamase producing E. coli, and carbapenemase-producing E. coli for 12 consecutive weekly challenges. All three drugs impregnated into the catheter continued to exert protective activity throughout 12 weeks of constant perfusion. The drugs appear to migrate into the crystalline biofilm to continually protect against bacteria not it direct contact with the catheter surface. In conclusion, the AUC reduces mineral encrustation and may increase time to blockage in the presence of P. mirabilis, and does not predispose to mineral deposition under other conditions. It also offers 12 weeks of protection against multi-drug resistant bacteria. STATEMENT OF SIGNIFICANCE: Infection and associated mineral encrustation of urinary catheters are two serious complications of indwelling urinary catheters. Others have attempted to address this through various technologies such as coatings, dips, and surface modifications to prevent infection and/or encrustation. However, all current 'anti-infective' urinary catheter technologies are limited to short-term use. Some patients with spinal injuries, multiple sclerosis, stroke survivors and others use long-term catheters for 4-12 weeks at a time with multiple catheterisation possibly throughout the rest of their life. We present a urinary catheter for long-term use that is impregnated with three antimicrobials by a patient-protected process to prevent infection and encrustation for up to 12 weeks, the maximum lifetime of a long-term catheter before it is changed.

Comparison of different human tissue processing methods for maximization of bacterial recovery.

Tissues are valuable microbiological samples that have proved superiority over swabs. Culture of tissue samples is used in the diagnosis of a variety of infections. However, as well as factors such as the site of obtaining the sample, the number of samples, and previous antibiotic use, the method of tissue processing may have an important effect on sensitivity. Data from the literature comparing different tissue processing methods is very limited. This study aimed to compare different mechanical and chemical methods of tissue processing in terms of efficacy and retaining the viability of the bacteria in the tissues. Standard suspensions of Staphylococcus aureus and Escherichia coli were prepared and treated differently to test the effect of that treatment on bacterial viability. Artificially inoculated pork tissue and known infected human tissue samples were then processed by different methods prior to culture, and results were compared. Percentages of reduction in the number of viable bacteria compared to the control by homogenization was similar to 5-min dithiothreitol treatment but significantly lower than bead beating. Bacterial recovery from homogenized human tissues was significantly higher than from any other method of treatment. Although bead beating could be the most efficient method in obtaining a homogeneous tissue product, it significantly reduces the number of viable bacteria within tissues. Homogenization offers the most effective easily controllable retrieval of bacteria from tissue and retains their viability. Guidelines for diagnosing infections using tissue samples should include a standardized processing method.

Does release of antimicrobial agents from impregnated external ventricular drainage catheters affect the diagnosis of ventriculitis?

OBJECTIVE: Recently concern has arisen over the effect of released antimicrobial agents from antibiotic-impregnated external ventricular drainage (EVD) catheters on the reliability of CSF culture for diagnosis of ventriculitis. The authors designed a laboratory study to investigate this possibility, and to determine whether there was also a risk of loss of bacterial viability when CSF samples were delayed in transport to the laboratory. METHODS: Three types of commercially available antibiotic-impregnated EVD catheters were perfused with a suspension of bacteria (Staphylococcus epidermidis) over 21 days. Samples were analyzed for bacterial viability and for concentrations of antibiotics released from the catheters. The authors also investigated the effect on bacterial viability in samples stored at 18°C and 4°C to simulate delay in CSF samples reaching the laboratory for analysis. RESULTS: Bacterial viability was significantly reduced in all 3 catheter types when sampled on Day 1, but this effect was not observed in later samples. The results were reflected in stored samples, with significant loss of viability in Day 1 samples but with little further loss of viable bacteria in samples obtained after this time point. All samples stored for 18 hours showed significant loss of viable bacteria. CONCLUSIONS: While there were differences between the catheters, only samples taken on Day 1 showed a significant reduction in the numbers of viable bacteria after passing through the catheters. This reduction coincided with higher concentrations of antimicrobial agents in the first few hours after perfusion began. Similarly, bacterial viability declined significantly after storage of Day 1 samples, but only slightly in samples obtained thereafter. The results indicate that drugs released from these antimicrobial catheters are unlikely to affect the diagnosis of ventriculitis, as sampling for this purpose is not usually conducted in the first 24 hours of EVD.

Biomaterial modification of urinary catheters with antimicrobials to give long-term broadspectrum antibiofilm activity.

Catheter-associated urinary tract infection (CAUTI) is the commonest hospital-acquired infection, accounting for over 100,000 hospital admissions within the USA annually. Biomaterials and processes intended to reduce the risk of bacterial colonization of the catheters for long-term users have not been successful, mainly because of the need for long duration of activity in flow conditions. Here we report the results of impregnation of urinary catheters with a combination of rifampicin, sparfloxacin and triclosan. In flow experiments, the antimicrobial catheters were able to prevent colonization by common uropathogens Proteus mirabilis, Staphylococcus aureus and Escherichia coli for 7 to 12weeks in vitro compared with 1-3days for other, commercially available antimicrobial catheters currently used clinically. Resistance development was minimized by careful choice of antimicrobial combinations. Drug release profiles and distribution in the polymer, and surface analysis were also carried out and the process had no deleterious effect on the mechanical performance of the catheter or its balloon. The antimicrobial catheter therefore offers for the first time a means of reducing infection and its complications in long-term urinary catheter users.

Biofilm eradication with biodegradable modified-release antibiotic pellets: a potential treatment for glue ear.

OBJECTIVE: To develop a biodegradable, modified-release antibiotic pellet capable of eradicating biofilms as a potential novel treatment for biofilm infections. DESIGN: Pellets containing poly(DL-lactic-co-glycolic acid) microparticles, rifampin and clindamycin hydrochloride (3.5%, 7%, or 28% antibiotic by weight), and carrier gel (carboxymethylcellulose or poloxamer 407) were tested in vitro. Drug release was assessed using serial plate transfer testing and high-performance liquid chromatography, and pellets were tested against biofilms in an in vitro model of Staphylococcus aureus biofilm grown on silicone. RESULTS: Serial plate transfer testing demonstrated continuing bacterial inhibition for up to 21 days for all pellets studied. High-performance liquid chromatography showed high levels of drug release for 2 to 4 days, with greatly reduced levels subsequently; continued measurable clindamycin (but not rifampin) release for up to 21 days was achieved. Pellets made with poloxamer released higher drug levels for a longer period. Irrespective of the carrier gel used, pellets containing 7% and 28% (but not 3.5%) antibiotic eradicated biofilms successfully. CONCLUSIONS: Antibiotic pellets can release antibiotics for up to 21 days and are able to eradicate biofilms in an in vitro model. Use of modified-release antibiotic formulations in the middle ear as a treatment for biofilms appears to be a potentially promising new therapy for otitis media with effusion.

Action of linezolid or vancomycin on biofilms in ventriculoperitoneal shunts in vitro.

Cerebrospinal fluid (CSF) shunts used to treat hydrocephalus have an overall infection rate of about 10% of operations. The commonest causative bacteria are Staphylococcus epidermidis, followed by Staphylococcus aureus and enterococci. Major difficulties are encountered with nonsurgical treatment due to biofilm development in the shunt tubing and inability to achieve sufficiently high CSF drug levels by intravenous administration. Recently, three cases of S. epidermidis CSF shunt infection have been treated by intravenous linezolid without surgical shunt removal, and we therefore investigated vancomycin and linezolid against biofilms of these bacteria in vitro. A continuous-perfusion model of shunt catheter biofilms was used to establish mature (1-week) biofilms of Staphylococcus aureus, Staphylococcus epidermidis (both methicillin resistant [MRSA and MRSE]), Enterococcus faecalis, and Enterococcus faecium. They were then "treated" with either vancomycin or linezolid in concentrations achievable in CSF for 14 days. The biofilms were then monitored for 1 week for eradication and for regrowth. Enterococcal biofilms were not eradicated by either vancomycin or linezolid. Staphylococcal biofilms were eradicated by both antibiotics after 2 days and did not regrow. No resistance was seen. Linezolid at concentrations achievable by intravenous or oral administration was able to eradicate biofilms of both S. epidermidis (MRSE) and S. aureus (MRSA). Neither vancomycin at concentrations achievable by intrathecal administration nor linezolid was able to eradicate enterococcal biofilms. It is hoped that these in vitro results will stimulate further clinical trials with linezolid, avoiding surgical shunt removal.