Sepsis management: An evidence-based approach.

The Surviving Sepsis Campaign (SSC) guidelines have outlined an early goal directed therapy (EGDT) which demonstrates a standardized approach to ensure prompt and effective management of sepsis. Having said that, there are barriers associated with the application of evidence-based practice, which often lead to an overall poorer adherence to guidelines. Considering the global burden of disease, data from low- to middle-income countries is scarce. Asia is the largest continent but most Asian countries do not have a well-developed healthcare system and compliance rates to resuscitation and management bundles are as low as 7.6% and 3.5%, respectively. Intensive care units are not adequately equipped and financial concerns limit implementation of expensive treatment strategies. Healthcare policy-makers should be notified in order to alleviate financial restrictions and ensure delivery of standard care to septic patients.

Clinical outcomes of pneumocystis pneumonia from a tertiary care centre in Pakistan.

OBJECTIVE: To assess the predisposing immunocompromised states, administration of pneumocystis jirovecii pneumonia prophylaxis, the disease course and outcomes of patients with pneumocystis jirovecii pneumonia. METHODS: The retrospective study was conducted at the Aga Khan University Hospital in Karachi. The medical records of patients diagnosed with pneumocystis jirovecii pneumonia from January 1995 to October 2015 were retrieved. Baseline characteristics, clinical course, treatment, and mortality rates were noted. SPSS 19 was used for data analysis. RESULTS: Of the 37 patients, 24(64.9%) were men and 13(35.1%) were women. The overall mean presenting age was 47.08±16.21 years (range: 19-83 years). Ten (27%) patients were positive for human immunodeficiency virus; 12(32.4%) had an underlying autoimmune disease; 3(8.1%) were transplant recipients; 10(27%) had an underlying malignancy, and 19(51.3%) were on long-term corticosteroid therapy. Only 2(5.4%) patients had received pneumocystis jirovecii pneumonia prophylaxis with trimethoprim-sulfamethoxazole. Moreover, 8(21.6%) patients required intensive care unit admission with a mean stay of 2.03±4.91 days (range: 1-22 days).The overall mortality rate was 7(18.9%). CONCLUSIONS: Pneumonia due to pneumocystis jirovecii was found to be a life-threatening disease in the immunocompromised population. The high mortality burden and resource intensive management of the disease emphasizes the need for PCP prophylaxis in immunosuppressed individuals.

Ambulance use in Pakistan: an analysis of surveillance data from emergency departments in Pakistan.

BACKGROUND: The utilization of ambulances in low- and middle-income countries is limited. The aim of this study was to ascertain frequency of ambulance use and characteristics of patients brought into emergency departments (EDs) through ambulance and non-ambulance modes of transportation. METHODS: The Pakistan National Emergency Departments Surveillance (Pak-NEDS) was a pilot active surveillance conducted in seven major tertiary-care EDs in six main cities of Pakistan between November 2010 and March 2011. Univariate and multivariate logistic regression was performed to investigate the factors associated with ambulance use. RESULTS: Out of 274,436 patients enrolled in Pak-NEDS, the mode of arrival to the ED was documented for 94. 9% (n = 260,378) patients, of which 4.1% (n = 10,546) came to EDs via ambulances. The mean age of patients in the ambulance group was significantly higher compared to the mean age of the non-ambulance group (38 ± 18.4 years versus 32.8 ± 14.9 years, p-value < 0.001). The most common presenting complaint in the ambulance group was head injury (12%) while among non-ambulance users it was fever (12%). Patients of all age groups were less likely to use an ambulance compared to those >45 years of age (p-value < 0.001) adjusted for gender, cities, hospital type, presenting complaint group and disposition. The adjusted odds ratio of utilizing ambulances for those with injuries was 3.5 times higher than those with non-injury complaints (p-value < 0.001). Patients brought to the ED by ambulance were 7.2 times more likely to die in the ED than non-ambulance patients after adjustment for other variables in the model. CONCLUSION: Utilization of ambulances is very low in Pakistan. Ambulance use was found to be more among the elderly and those presenting with injuries. Patients presenting via ambulances were more likely to die in the ED.

Pattern of fall injuries in Pakistan: the Pakistan National Emergency Department Surveillance (Pak-NEDS) study.

BACKGROUND: We aimed to analyse the frequency and patterns of fall-related injuries presenting to the emergency departments (EDs) across Pakistan. METHODS: Pakistan National Emergency Departments surveillance system collected data from November 2010 to March 2011 on a 24/7 basis using a standardized tool in seven major EDs (five public and two private hospitals) in six major cities of Pakistan. For all patients presenting with fall-related injuries, we analysed data by intent with focus on unintentional falls. Simple frequencies were run for basic patient demographics, mechanism of falls, outcomes of fall injuries, mode of arrival to ED, investigations, and procedures with outcomes. RESULTS: There were 3335 fall-related injuries. In cases where intent was available, two-thirds (n = 1186, 65.3%) of fall injuries were unintentional. Among unintentional fall patients presenting to EDs, the majority (76.9%) were males and between 15-44 years of age (69%). The majority of the unintentional falls (n = 671, 56.6%) were due to slipping, followed by fall from height (n = 338, 28.5%). About two-thirds (n = 675, 66.6%) of fall injuries involved extremities, followed by head/neck (n = 257, 25.4%) and face (n = 99, 9.8%). Most of the patients were discharged from the hospital (n = 1059, 89.3%). There were 17 (1.3%) deaths among unintentional fall cases. CONCLUSION: Falls are an important cause of injury-related visits to EDs in Pakistan. Most of the fall injury patients were men and in a productive age group. Fall injuries pose a burden on the healthcare system, especially emergency services, and future studies should therefore focus on safety measures at home and in workplaces to reduce this burden.

Overcrowding in the emergency departments: Challenges and opportunities for improvement.

With the advent of Emergency Medicine, one can observe an increase in the number of Emergency Departments (ED) across the country. However, most EDs struggle due to an overwhelming number of patients. Overcrowding can lead to delays in patient care. For a city like Karachi which is an active disaster zone, preemptive preparedness is required in the face of terror threats and such overcrowding needs to be decreased to a bare minimum. The most frequent causes of prolonged length of stay (LOS) in the ED include non-availability of in-hospital beds, delays in response to subspecialty consultations and escalating medical expenses. All of these can negatively impact patient care by putting patient safety at risk and patient care in jeopardy. There is an increased risk of unintentional medical errors and a concomitant increase in unwanted lawsuits. A few simple interventions which may help alleviate this situation to some extent have been discussed.

Clinical course and outcome of acute severe asthma (status asthmaticus) in adults.

OBJECTIVE: To evaluate the clinical course and outcomes in patients with acute severe asthma in a tertiary care setting. METHODS: The retrospective cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of patients of age 16 and above who were admitted with a diagnosis of acute severe asthma from January 2000 to December 2013. These patients had undergone clinical evaluation to assess the severity of illness as well as the complications and eventual outcomes. SPSS 16 was used for statistical analysis. RESULTS: Of the 50 patients in the study, 41 (82%) were females. The overall mean age was 53.1±20.3 years. Ventilator support was required by 37(74%) patients. Presence of acidaemia was associated with the need for invasive ventilation (p<0.033) which in turn was associated with increased hospital stay (p<0.043). Complications were observed in 37(74%) patients, the most common being respiratory failure in 35(70%) and arrhythmias in 8(16%). Use of both non-invasive and invasive ventilation was found to be significantly associated with development of complications (p<0.001 and p<0.009). A total of 4(8%) patients died. Presence of acidaemia was found to be significantly associated with mortality (p<0.032). CONCLUSION: Overt acidaemia at initial presentation in patients with acute severe asthma was significantly associated with higher rates of invasive ventilation leading to increased hospital stay, complications and higher mortality rate.

B-type natriuretic peptide versus amino terminal pro-B type natriuretic peptide: selecting the optimal heart failure marker in patients with impaired kidney function.

BACKGROUND: The effect of impaired kidney function on B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) is vague. This study was performed to examine the effect of kidney dysfunction on the afore-mentioned markers and determine appropriate cutoffs for systolic heart failure (SHF). METHODS: In this cross sectional study adults with estimated glomerular filtration rate (eGFR) <60 ml/min for ≥3 months were identified in consulting clinics from June 2009 to March 2010. SHF was defined as documented by a cardiologist with ejection fraction of < 40% and assessed by New York Heart Association classification (NYHA). Plasma was assayed for creatinine (Cr), BNP and NT-proBNP. RESULTS: A total of 190 subjects were enrolled in the study, 95 with and 95 without SHF. The mean age of patients was 58 (±15) years, 67.4% being males. Mean BNP levels showed a 2.5 fold and 1.5 fold increase from chronic kidney disease (CKD) stage 3 to stage 5 in patients with and without SHF respectively. NT-proBNP levels in non-heart failure group were 3 fold higher in CKD stage 5 compared to stage 3. Mean NT-proBNP levels were 4 fold higher in CKD stage 5 compared to stage 3 in patients with SHF. Optimal BNP and NT-proBNP cutoffs of SHF diagnosis for the entire CKD group were 300 pg/ml and 4502 pg/ml respectively. CONCLUSION: BNP and NT-proBNP were elevated in kidney dysfunction even in the absence of SHF; however the magnitude of increase in NT-proBNP was greater than that of BNP. BNP and NT-proBNP can be useful in diagnosing SHF, nonetheless, by using higher cutoffs stratified according to kidney dysfunction. NT-proBNP appears to predict heart failure better than BNP.

Phytochemical profiling of antimicrobial and potential antioxidant plant: Nepeta cataria.

Traditional and phytochemical studies have confirmed the richness and diversity of medicinal plants such as Nepeta cataria (N. cataria), but more studies are needed to complete its metabolite profiling. The objective of this research was to enhance the metabolomic picture and bioactivity of N. cataria for better evaluation. Phytochemical analysis was performed by bio-guided protocols and gas chromatography-mass spectrometry (GC/MS). For this, solvents such as methanol, ethanol, water, acetone, and hexane were used to extract a wide number of chemicals. Antibacterial analysis was performed using the 96-well plate test, Kirby Bauer's disk diffusion method, and the resazurin microdilution test. Antioxidant activity was determined by the DPPH assay and radical scavenging capacity was evaluated by the oxygen radical absorbance capacity (ORAC) assay. GC/MS analysis revealed a total of 247 identified and 127 novel metabolites from all extracts of N. cataria. Water and acetone extracts had the highest identified metabolites (n = 79), whereas methanol extract was the highest in unidentified metabolites (n = 48). The most abundant phytochemicals in methanol extract were 1-isopropylcyclohex-1-ene (concentration = 27.376) and bicyclo [2.2.1] heptan-2-one (concentration = 20.437), whereas in ethanol extract, it was 9,12,15-octadecatrienoic acid (concentration = 27.308) and 1-isopropylcyclohex-1-ene (concentration = 25.854). An abundance of 2 methyl indoles, conhydrin, and coumarin was found in water extracts; a good concentration of eucalyptol was found in acetone extract; and 7,9-di-tert-butyl-1-oxaspiro is the most abundant phytochemicals in hexane extracts. The highest concentration of flavonoids and phenols were identified in hexane and methanol extracts, respectively. The highest antioxidant potential (DPPH assay) was observed in acetone extract. The ethanolic extract exhibited a two-fold higher ORAC than the methanol extract. This examination demonstrated the inhibitory effect against a set of microbes and the presence of polar and non-polar constituents of N. cataria. The results of this study provide a safe resource for the development of food, agriculture, pharmaceutical, and other industrial products upon further research validation.

Demographic and Clinical Determinants of Tuberculosis and TB Recurrence: A Double-Edged Retrospective Study from Pakistan.

Objective: TB recurrence is the second episode of TB after initial treatment bringing about an additional 7% load in TB burden intensified by 17.7% of multidrug-resistant recurrent cases. It is necessary to curb recurrence so that attempts to deal with active disease can be made more effective. This study aimed to characterize sociodemographic and clinical factors associated with recurrent TB in a high-burden setting. Methodology. A retrospective case-control study was carried out at two hospitals in Rawalpindi, Pakistan. TB patients and controls were included in the study. Sociodemographic and clinical data were collected by questionnaire from all subjects. Multivariate regression analysis was performed to determine factors associated with TB and TB recurrence respectively. Results: In our study cohort, factors significantly associated with TB were low BMI (OR: 0.961 (CI 0.954-0.968), p < 0.001), female gender (OR: 2.065 (CI 1.922-2.219), p < 0.001), being single/unmarried (OR: 1.214 (CI 1.109-1.328), p=0.003), middle-income status (OR: 1.935 (CI 1.616-2.323), p < 0.001), smoking (OR: 1.567 (CI 1.435-1.710), p < 0.001), and diabetes mellitus (OR: 1.142 (CI 1.017-1.278), p=0.023). TB recurrence constituted 11.2% of patients presenting to the hospital. Compared with the first episode of TB, cases with recurrence were more likely to be older (OR: 1.011 (CI 1.004-1.017), p < 0.001), have disease awareness (OR: 1.906 (CI 1.486-2.437), p < 0.001), smear positive (OR: 2.384 (CI 1.650-3.536), p < 0.001), and be drug-resistant (OR: 5.615 (CI 4.265-7.386), p < 0.001). Conclusion: In the present study cohort, low BMI, female gender, being single, middle-income status, being unemployed, smoking, and being diabetic came out to be the sociodemographic and clinical risk factors for TB. Further exploring the TB cases increasing age, drug resistance and smear positivity stood out to be the major sociodemographic and clinical factors of TB recurrence despite high disease awareness.

Nanomaterials as nanocarriers: a critical assessment why these are multi-chore vanquisher in breast cancer treatment.

Breast cancer is a group of diseases with various subtypes and leads to high mortality throughout the globe. Various conventional techniques are in practice to cure breast cancer but these techniques are linked with various shortcomings. Mostly these treatments are not site directed and cause toxicity towards normal cells. In order to overcome these issues, we need smart system that can deliver anticancer drugs to specific sites. Targeted drug delivery can be achieved via passive or active drug delivery using nanocarriers. This mode of drug delivery is more effective against breast cancer and may help in the reduction of mortality rate. Potentially used nanocarriers for targeted drug delivery belong to organic and inorganic molecules. Various FDA approved nano products are in use to cure breast cancer. However, body's defense system is main limitation for potential use of nano systems. However, this can be overcome by surface modification of nanocarriers. In this review, breast cancer and its types, targeted drug delivery and nanocarriers used to cure breast cancer are discussed. By progressing nanotechnology, we will be able to fight against this life threatening issue and serve the humanity, which is the basic aim of scientific knowledge.

Validating a point of care lactate meter in adult patients with sepsis presenting to the emergency department of a tertiary care hospital of a low- to middle-income country.

BACKGROUND: Timely identification of high blood lactate levels in septic patients may allow faster detection of those patients requiring immediate resuscitation. Point-of-care (POC) testing is being increasingly utilized in the emergency department (ED). We examined the accuracy and time-saving effect of a handheld POC lactate device for the measurement of fingertip and whole blood lactate as compared with reference laboratory blood testing in septic ED patients. METHODS: A convenience sample of adult ED patients receiving serum lactate testing were enrolled prospectively in the ED of a multidisciplinary tertiary care hospital serving the population of one of the major cities of Pakistan. Participants underwent fingertip POC lactate measurement with a portable device simultaneous whole blood sampling for analysis by both the POC lactate device and standard laboratory method. Lactate measurements were compared by intraclass correlation (ICC) and Bland and Altman plots. RESULTS: Forty-three septic patients were included in the study. The fingertip POC & whole blood POC lactate measurements each correlated tightly with the reference method (ICC=0.93 & ICC=0.92, respectively). Similarly at 6 hours, the fingertip POC & whole blood POC lactate measurements demonstrated satisfactory correlation with the reference method (ICC=0.95 & ICC=0.97, respectively). CONCLUSION: Fingertip POC lactate measurement is an accurate method to determine lactate levels in septic ED patients.

Pneumoperitoneum, pneumoretroperitoneum, pneumomediastinum and extensive subcutaneous emphysema in a patient with ulcerative colitis: A case report.

INTRODUCTION: Pneumo-mediastinum and subcutaneous emphysema are rare presentations of lower gastrointestinal tract perforation. PRESENTATION OF CASE: We are presenting the case of a middle aged man diagnosed with UC who presented with dyspnea and subcutaneous emphysema, attributed to multiple perforations including the stomach and colon. CASE DISCUSSION: Patients with ulcerative colitis (UC) are at an increased risk of perforations due to friability of colonic mucosa given the chronic inflammation and relapsing flares. Chronic use of steroids further predisposes to stress ulcers. These pathologies sometimes coexist and identification of each is crucial for the appropriate treatment plan. CONCLUSION: The case allows for a learning opportunity focusing on coexisting pathologies which may be differentiated based on anatomical knowledge and patient presentation.

Case series and literature review of multiple nodular sarcoidosis.

BACKGROUND: Nodular lung disease is a rare presentation of sarcoidosis. Radiologically it can present as multiple pulmonary masses or solitary lung nodule. CASE PRESENTATION: We report three cases of nodular sarcoidosis in young females of Asian origin who had initially presented with dry cough and worsening dyspnea non-responsive to initially administered antibiotics. Pulmonary nodules were discovered upon radiographic imaging in all three cases which raised concern for the possibility of neoplastic processes. Subsequent biopsies revealed granulomatous inflammation indicative of sarcoidosis. All cases responded very well to systemic corticosteroids. CONCLUSION: Sarcoidosis may present as nodular infiltrates which alerts the treating physician to other neoplastic and infectious diseases of the lungs. Appropriate workup may reveal the true nature of this disease and hence, simplify treatment.

Trends in antibiotic susceptibility and incidence of late-onset Klebsiella pneumoniae neonatal sepsis over a six-year period in a neonatal intensive care unit in Karachi, Pakistan.

INTRODUCTION: The incidence, change in antibiotic susceptibility, and risk factors associated with mortality of late-onset Klebsiella pneumoniae sepsis during 2006-2011, in a neonatal intensive care unit (NICU) of a developing country, were analyzed. METHODS: The medical records of neonates with a discharge diagnosis of sepsis due to late-onset K. pneumoniae were retrieved. Demographic features, gestational age, date and year of admission, antibiotic susceptibility of isolates, and discharge status were recorded. The late-onset K. pneumoniae incidence per 1000 NICU admissions and risk factors for mortality due to late-onset K. pneumoniae sepsis are reported. RESULTS: During the period 2006-2011, 104 of 2768 neonates developed late-onset K. pneumoniae sepsis. The overall incidence of late-onset K. pneumoniae sepsis was 3.7% (37/1000 NICU admissions), with the highest annual incidence being 53/1000 in 2010. Most cases were males (n = 64; 62%) and most were premature and very low birth weight (n = 68; 65%). More than 80% of isolates were resistant to ampicillin + clavulanic acid, gentamicin, aztreonam, and cephalosporins. An increasing trend of resistance to amikacin, fluoroquinolones, piperacillin/tazobactam, and imipenem was observed. In 2011, three-quarters (72%; n=13) of late-onset K. pneumoniae were CR K. pneumoniae. Seventeen (16%) neonates died. Being male (p = 0.06, adjusted odds ratio (AOR) 9.2, 95% confidence interval (CI) 1.3-66.9), having an extremely low birth weight (p = 0.01, AOR 6.1, 95% CI 0.8-44.4), having severe thrombocytopenia (p = 0.07, AOR 3.9, 95% CI 1.2-13.0), and failure to achieve microbiological clearance (p < 0.001, AOR 19.6, 95% CI 4.0-98.0) were significantly associated with mortality due to late-onset K. pneumoniae sepsis. CONCLUSION: There has been a rise in carbapenem-resistant strains of late-onset K. pneumoniae, associated with an increased mortality and limited antibacterial choices. Antimicrobial stewardship and rigorous infection control measures seem to be the only way to limit the spread of these strains.