Symptom burden guiding invasive electrophysiological study in paroxysmal supraventricular tachycardia: The believe SVT registry.

BACKGROUND AND OBJECTIVE: Patients with palpitations clinically suggestive of paroxysmal supraventricular tachycardia (PSVT) are often managed conservatively until ECG-documentation of the tachycardia, leading to high impact on life quality and healthcare resource utilization. We evaluated results of electrophysiological study (EPS), and ablation when appropriate, among these patients, with special focus on gender differences in management. METHODS: BELIEVE SVT is a European multicenter, retrospective registry in tertiary hospitals performing EPS in patients with palpitations, without ECG-documentation of tachycardia or preexcitation, and considered highly suggestive of PSVT by a cardiologist or cardiac electrophysiologist. We analyzed clinical characteristics, results of EPS and ablation, complications, and clinical outcomes during follow-up. RESULTS: Six-hundred eighty patients from 20 centers were included. EPS showed sustained tachycardia in 60.9% of patients, and substrate potentially enabling AVNRT in 14.7%. No major/permanent complications occurred. Minor/transient complications were reported in 0.84% of patients undergoing diagnostic-only EPS and 1.8% when followed by ablation. During a 3.4-year follow-up, 76.2% of patients remained free of palpitations recurrence. Ablation (OR: 0.34, P < .01) and male gender (OR: 0.58, P = .01) predicted no recurrence. Despite a higher female proportion among patients with recurrence, (77.2% vs 63.5% among those asymptomatic during follow-up, P < .01), 73% of women in this study reported no recurrence of palpitations after EPS. CONCLUSIONS: EPS and ablation are safe and effective in preventing recurrence of nondocumented palpitations clinically suggestive of PSVT. Despite a lower efficacy, this strategy is also highly effective among women and warrants no gender differences in management.

Recent Trends in the Incidence of Gastric Cancer in the United States.

BACKGROUND: Gastric cancer (GC) incidence rates overall in the United States have declined over recent decades and are predicted to continue declining. However, there have been mixed recent findings regarding the potential stabilization of rates and potential divergent trends by age group. We used the most recent cancer data for the United States and examined trends in GC between 1992 and 2019, overall and in important subgroups of the population. METHODS: Age-adjusted GC incidence rates and trends in adults 20 years or older were calculated using data from the Surveillance, Epidemiology, and End Results (SEER) 12 program. Secular trends were examined overall and by age group, sex, race/ethnicity, SEER registry, and tumor location. We used joinpoint regression to compute annual percent changes, average annual percent changes, and associated 95% CI. RESULTS: GC rates decreased by 1.23% annually from 1992 to 2019. Despite overall decreases, GC incidence rates increased for age groups below 50 years, predominately driven by noncardia GC (74.3% of all GCs). Cardia GC (26.7% of GC) rates decreased in all age groups except for 80 to 84 years. Overall GC rates decreased for both sexes, all races, and for all SEER registry regions, with the largest decreases occurring in males, Asians and Pacific Islanders, and in Hawaii. Age-period-cohort analysis revealed that birth cohorts before 1940 and after 1980 both had increased rates of GC compared with the reference birth cohort of 1955. CONCLUSION: GC rates overall have continued to decline through 2019, despite increases in the rate of noncardia GC for younger age groups.

Effect of Caffeine on Colonic Manometry in Children.

OBJECTIVES: Coffee and caffeinated products have been widely consumed for many centuries. Previous adult studies have suggested that both coffee and decaffeinated beverages induce colonic motility. However, no study has been conducted in pediatrics, and the role of caffeine alone in pediatric colonic motility needs to be explored. METHODS: A prospective study of pediatric patients undergoing standard colonic motility testing that were able to consume caffeinated coffee, decaffeinated coffee, and caffeine tablet during colonic manometry. Patients who had a gastrocolonic reflex and high amplitude propagated contractions (HAPCs) in response to intraluminal administration of bisacodyl in the colon were included in the final analyses. RESULTS: Thirty-eight patients were recruited, 22 of which were excluded, 11 due to abnormal studies (no HAPC seen in response to intraluminal response to bisacodyl), and 11 due to inability to consume all study agents or complete the study. Sixteen patients met criteria for final analyses. Intracolonic bisacodyl produced a larger area under the curve (AUC) compared to all other agents. Caffeinated coffee resulted in a higher AUC, motility index (MI), and time to HAPC compared with decaffeinated coffee ( P < 0.05). There was no significant difference between caffeinated coffee and caffeine tablet, or caffeine tablet and decaffeinated coffee. CONCLUSIONS: Caffeine is indeed a colonic stimulant; however, other components of caffeinated and non-caffeinated beverages likely induce colonic response and require further evaluation for possible use as a colonic stimulant.

Effectiveness of gamma knife radiosurgery in the management of trigeminal neuralgia associated with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Trigeminal neuralgia (TN) is a chronic condition characterized by intense facial pain akin to electric shocks, often associated with the trigeminal nerve. It can be either idiopathic or secondary, with multiple sclerosis (Ms) being a significant contributing factor. Non-responsive patients may opt for minimally invasive procedures, such as gamma knife radiosurgery (GKRS), which offers precise, non-invasive treatment and is frequently chosen as a primary approach. This meta-analysis evaluates the long-term efficacy of GKRS in TN management in Ms patients. METHODS: We conducted a focused search across various databases. Inclusion criteria encompassed studies with ≥ 30 patients using GKRS for TN in Ms, reporting pertinent clinical outcomes. Primary outcomes assessed GKRS efficacy through Barrow Neurological Institute Pain scores. Secondary outcomes encompassed bothersome numbness, facial numbness, and recurrence. Data analysis employed OpenMeta, random effect models, and odds ratios with 95% confidence intervals. Heterogeneity was assessed using I2 statistics. RESULTS: Fourteen studies with 752 cases of GKRS for TN were included. Regarding the outcomes, 83% of patients experienced a positive initial pain response, while the overall treatment success rate was 51%. Additionally, 19.6% of patients reported facial numbness, 4.1% experienced bothersome numbness, and 40% faced recurrence. The odds ratio for positive initial pain response was 0.83 (95% CI, 0.76-0.89), while for treatment success, it was 0.51 (95% CI, 0.379-0.639). Facial numbness had an odds ratio of 0.196 (95% CI, 0.130-0.262), bothersome numbness had an odds ratio of 0.041 (95% CI, 0.013-0.069), and recurrence had an odds ratio of 0.403 (95% CI, 0.254-0.551). CONCLUSIONS: In conclusion, treating trigeminal neuralgia in multiple sclerosis patients remains challenging. GKRS shows promise, but customized treatment approaches tailored to individual patient characteristics are urgently needed to address the unique challenges of this condition.

COVID-19 and thrombotic thrombocytopenic purpura: A case report.

The clinical presentation of COVID-19 varies from being asymptomatic to developing acute respiratory distress syndrome and multi-organ dysfunction. The diffuse microvascular thrombi in multiple organs seen in the autopsy of COVID-19 patients are similar to that of thrombotic microangiopathy (TMA). TMA is characterised by thrombus formation in the microvasculature with laboratory findings of microangiopathic haemolytic anaemia (MAHA) and thrombocytopenia. A 49-year-old male presented to the Aga Khan University Hospital, Karachi. with fever, diarrhoea, altered level of consciousness, and a positive nasopharyngeal swab for SARS-CoV-2. He developed severe thrombocytopenia, MAHA with 5.8% schistocytes, and worsening renal function on the sixth day of admission. Diagnosis of thrombotic thrombocytopenic purpura (TTP) was established based on PLASMIC score, and he was successfully treated with intravenous (IV) Methylprednisolone, therapeutic plasma exchange and IV Rituximab. The case emphasises the need to keep TTP in the differential diagnosis when a patient with COVID-19 develops severe thrombocytopenia, acute renal failure, or impaired level of consciousness, since prompt diagnosis and treatment is necessary to gain favourable outcome.

Identifying Mast Cells in Gastrointestinal Biopsies in Pediatric Irritable Bowel Patients.

OBJECTIVES: Mast cells (MCs) have been proposed to be involved in the pathophysiology of irritable bowel syndrome (IBS). Nonetheless, the quantity and distribution of MCs in the gastrointestinal tract of pediatric patients with IBS are not well defined. This study aimed to compare the number of MCs in children with and without IBS and to establish histopathological reference values in pediatrics. METHODS: Forty-nine participants with IBS were prospectively enrolled and classified into IBS with atopy (n = 29) and IBS without atopy (n = 20). As our retrospective control group, we selected 42 individuals with a history of polyposis syndrome or gastroesophageal reflux disease with normal histopathology. Retrospective selection of the control cohort was performed in a manner similar to previously published adult and pediatric studies. MCs were prospectively stained immunohistochemically on specimens from the stomach, duodenum, terminal ileum, and descending colon of both groups. RESULTS: The IBS group showed significantly more MCs per high-power field (MCs/HPF) in the stomach, duodenum, terminal ileum, and descending colon ( P < 0.001), irrespective of their atopic status. Optimal MC cutoff values for IBS are ≥20.5 MCs/HPF in the stomach (area under the curve [AUC] = 0.84); ≥23.0 MCs/HPF in the duodenum (AUC = 0.79); ≥33.5 MCs/HPF in the terminal ileum (AUC = 0.82); and ≥22.5 MCs/HPF in the descending colon (AUC = 0.86). CONCLUSIONS: Pediatric patients with IBS showed increased numbers of MCs in the stomach, duodenum, terminal ileum, and descending colon when compared with controls. Further trials are needed to explain the role of MCs in pediatric IBS, which might facilitate the development of targeted therapeutic interventions.

Low performance of internal medicine senior residents in in-service examinations.

We observed an unprecedented and consistent low performance of senior residents as compared with juniors in monthly examinations. This compelled us to evaluate systematically and compare the scores of senior residents with their junior colleagues. This retrospective observational study was conducted in April 2020 among internal medicine residents. Residents in first and second year of their training were labelled as junior residents. Residents in third or fourth year of their training were labelled as senior residents. Comparison of mean scores of each resident level was done separately both for monthly formative multiple-choice questions tests, and summative yearly end of term examinations. We discussed the possible reasons as well. There were 67 residents in year 2018 and 69 in 2019. There is no significant difference between scores of monthly examinations of years 2018 and 2019 among residents of each level. Rather, in March and December 2018, junior residents perform better than senior residents with p values of 0.01 and 0.04, respectively. In February and September 2019, senior residents performed better than junior residents with p value of 0.02. Similarly, there is no significant difference in scores of residents of each level in end-of-term examinations of years 2018 and 2019 with p values 0.18 and 0.25, respectively. Performance of senior residents in our residency programme in in-service examinations is relatively low as compared with their junior colleagues. There is a need to evaluate reasons for this relatively low performance of senior residents.

A simple discharge criteria for transfer of patients from intermediate care to general care: a prospective observational study.

OBJECTIVE: To develop and apply a simple criterion for transfer of patients from intermediate care to general care. METHODS: The prospective study was conducted in the intermediate care units of Aga Khan University Hospital, Karachi, from July to December 2018. A discharge criterion for transfer of patients from intermediate care to general care was developed according to which patients with vital signs and Glasgow Coma Scale score within a preset range were considered stable enough for transfer from intermediate care to general care. After labelling the patients on the basis of the criterion, it was determined on the following day which patients remained stable enough for transfer to general care, and which patients became unstable. Data was analysed using SPSS 19. RESULTS: Of the 49 patients with mean age 63.0±16.9 years, 28(57.1%) were males. Overall, 43(87.7%) patients remained stable on the next day. Of them, 33(67.3%) patients were transferred out from intermediate care on the subsequent day, while 8(16.3%) were not transferred out due to primary physician's decision, 1(2%) due to heparin infusion, and 1(2%) due to family request. The condition of the remaining 6(12%) patients deteriorated. CONCLUSIONS: A simple discharge criterion is proposed for intermediate care solely based on clinical.

A network analysis of the Internet Disorder Scale-Short Form (IDS9-SF): A large-scale cross-cultural study in Iran, Pakistan, and Bangladesh.

The Internet Disorder Scale-Short Form (IDS9-SF) is a validated instrument assessing internet disorder which modified the internet gaming disorder criteria proposed in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). However, the relationships between the nine items in the IDS9-SF are rarely investigated. The present study used network analysis to investigate the features of the IDS9-SF among three populations in Bangladesh, Iran, and Pakistan. Data were collected (N = 1901; 957 [50.3%] females; 666 [35.0%] Pakistani, 533 [28.1%] Bangladesh, and 702 [36.9%] Iranians) using an online survey platform (e.g., Google Forms). All the participants completed the IDS9-SF. The central-stability-coefficients of the nine IDS9-SF items were 0.71, 0.89, 0.96, 0.98, 0.98, 1.00, 0.67, 0.79, and 0.91, respectively. The node centrality was stable and interpretable in the network. The Network Comparison Test (NCT) showed that the network structure had no significant differences among Pakistani, Bangladeshi, and Iranian participants (p-values = 0.172 to 0.371). Researchers may also use the IDS9-SF to estimate underlying internet addiction for their target participants and further explore and investigate the phenomenon related to internet addiction. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03284-8.

Sociodemographic and Health Belief Model Factors Associated with Nonadherence to COVID-19 Mitigation Strategies in the United States.

BACKGROUND AND PURPOSE: Virus mitigation strategies such as adhering to stay-at-home orders, practicing social distancing, and engaging in personal protective behaviors are central to slowing the spread of COVID-19. This population-based cohort study sought to identify sociodemographic characteristics and Health Belief Model factors that are associated with nonadherence to COVID-19 mitigation strategies with the goal of informing public health messaging campaigns. METHODS: An online population-based survey was distributed via social media over an 8-week period from April 13, 2020, to June 8, 2020. RESULTS: Data were derived from 2,222 adults (57% female; 40% racial/ethnic minorities). Univariate analyses revealed that men, younger aged (18-30 years) and unmarried adults, and noncollege educated individuals had lower levels of perceived threat, control, and knowledge about COVID-19 (p ≤ .001). Multivariable linear regression models further revealed that male gender was significantly associated with reporting lower levels of adherence to COVID-19 mitigation strategies (p < .001), and that higher levels of perceived threat, perceived control, and knowledge about how to keep oneself and others safe from COVID-19 were significantly associated with reporting higher levels of adherence to COVID-19 mitigation strategies (p < .01). CONCLUSIONS: Findings suggest that public health appeals that target men, emphasize individual risk, and provide clear, consistent guidance on what individuals can do to decrease their risk for COVID-19 may be effective in motivating increased mitigation adherence.

Depletion of dietary phytoestrogens reduces hippocampal plasticity and contextual fear memory stability in adult male mouse.

Introduction: Phytoestrogens are non-steroidal estrogen analogues and are found primarily in soy products. They have received increasing attention as dietary supplements for estrogen deficiency and as modulators of endogenous estrogen functions, including cognition and emotion. In addition to modifying the levels of circulating sex hormones, phytoestrogens also exert direct effects on estrogen and androgen receptors in the brain and thus effectively modulate the neural circuit functions.Objective: The aim of this study was to investigate the long-term effects of low phytoestrogen intake (∼6 weeks) on the hippocampal plasticity and hippocampus-dependent memory formation in the adult C57BL/6 male mice.Methods and Results: In comparison to mice on a diet with normal phytoestrogen content, mice on low phytoestrogen diet showed a significant reduction in the phosphorylation of NR2B subunit, a molecular correlate of plasticity in the Schaffer collateral-CA1 synapse. We observed a profound decrease in long-term potentiation (LTP) in the ventral hippocampus, whereas no effect on plasticity was evident in its dorsal portion. Furthermore, we demonstrated that acute perfusion of slices with an estrogen analogue equol, an isoflovane metabolized from daidzein produced by the bacterial flora in the gut, was able to rescue the observed LTP deficit. Examining potential behavioral correlates of the plasticity attenuation, we found that mice on phytoestrogen-free diet display decreased contextual fear memory at remote but not at recent time points after training.Conclusions: Our data suggests that nutritional phytoestrogens have profound effects on the plasticity in the ventral hippocampus and ventral hippocampus-dependent memory.

Energy trilemma based prioritization of waste-to-energy technologies: Implications for post-COVID-19 green economic recovery in Pakistan.

As lockdown eases, economic activities resume in Pakistan. If the country continues to follow business-as-usual (BAU) then it is anticipated that carbon output could surge past pre-COVID-19 levels - that means more disasters in future. Thus, it is an unprecedented opportunity to shift from BAU and achieve carbon-neutral and nature-positive economic recovery - green economic recovery (GER). To fuel the GER, access to modern, equitable, affordable and sustainable energy is paramount. This study explores waste-to-energy (WtE) as an alternative green fuel for GER. Seven WtE technologies are prioritized based on the concept of energy trilemma - energy security, energy equity, and environmental sustainability. For the evaluation, an energy trilemma based decision support framework is developed using most prominent multi-criteria decision-making (MCDM) methods. The fuzzy set theory is integrated with MCDM methods to minimize uncertainty in results. Sixteen experts are engaged to score each WtE technology with respect to every energy trilemma dimension and sub-dimension. Gasification technology is found to be the most feasible option for WtE generation in Pakistan whereas Torrefaction technology is least favorable. It is concluded that the need to shift towards sustainable energy is more than ever to limit the carbon emission and prevent future crisis.

Compliance of checking HbA1c in a tertiary care hospital of Pakistan.

BACKGROUND AND OBJECTIVES: The prevalence of diabetes mellitus worldwide was 171 million one and half decade ago, while the prediction is 366 million patients by 2030 and more than 640 million people by 2040. HbA1c value represents average blood glucose over the past 2-3 months and accounts for both pre-prandial and post-prandial blood glucose levels. A link between HbA1c and diabetic complications has been confirmed. In general, patients with controlled diabetes mellitus should have at least biannual testing, while patients with uncontrolled diabetes mellitus or unmet glycemic targets should be tested every three months. The objective was to see compliance of checking HbA1c in tertiary care hospital of a developing world. METHODS: This was a retrospective observational study done from 1st February 2019 to 31st March 2019 in the Department of Medicine and Surgery, The Aga Khan University Hospital, Karachi. All patients of age 18 years and above, admitted with a diagnosis of diabetes mellitus (DM)from 1st February 2019 to 31st March 2019 were included. If HbA1c was less than 7% the patients were labelled as having controlled DM, otherwise, uncontrolled DM. If HbA1c of patients with controlled DM was not checked in last six months and if HbA1c of patients with uncontrolled DM was not checked in last three months then it was labelled as non-compliance of checking HbA1c. RESULTS: Out of 1732 diabetic patients only 94 patients fulfilled inclusion criteria. Out of these 94 patients 43 (45.7%) were male. Mean HbA1c was 7.90% (1.4) and 69 (73.4%) patients had uncontrolled diabetes mellitus. Overall, the compliance of checking HbA1c was 58.5%. In uncontrolled diabetes mellitus patients, the compliance of checking HbA1c was 45% and in controlled diabetes mellitus patients the compliance was 96%. CONCLUSION: The compliance of checking HbA1c is inadequate in diabetic inpatients. The considerable prevalence of diabetes and the benefits of timely interventions in diagnosed patients to prevent complications suggest the need for a comprehensive awareness among the doctors for checking HbA1c.

SHORT COMMUNICATION-Inappropriate use of proton pump inhibitor for stress ulcer prophylaxis in a tertiary care hospital in Karachi, Pakistan.

The use of proton pump inhibitors (PPI) has been expanded inappropriately. PPI are among the most selling drugs in the world. There is growing evidence that PPI are associated with significant adverse effects along with undue financial burden. Inappropriate prescription of PPI is common in inpatients. The objective is to determine the frequency of inappropriate use of proton pump inhibitors for stress ulcer prophylaxis. This prospective observational study was conducted in the Department of Medicine of The Aga Khan University Hospital Karachi. 151 adult patients admitted in the hospital were included. All those patients who received PPI due to a condition mentioned by American Gastroenterology Association (AGA) as an indication for PPI, were labeled as PPI appropriately indicated. While those patients who received PPI without a condition mentioned by AGA as an indication for PPI, were labeled as PPI inappropriately indicated. Mean age was 57.2±18.2 years. Route of administration was oral in 110 (72.8%) and IV in 41 (27.2%) patients. Out of 151 patients, 100 (66.2%) patients were receiving PPI without any specific indication while 51 (33.8%) patients were receiving PPI with appropriate indications. Our study showed that inappropriate use of PPI is quite common among admitted patients.

Estimating the obstetric co-morbidity burden using administrative data: The impact of the pregnancy-related assessment window.

BACKGROUND: Despite increased research using large administrative databases to identify determinants of maternal morbidity and mortality, the extent to which these databases capture obstetric co-morbidities is unknown. OBJECTIVE: To evaluate the impact that the time window used to assess obstetric co-morbidities has on the completeness of ascertainment of those co-morbidities. METHODS: We conducted a five-year analysis of inpatient hospitalisations of pregnant women from 2010-2014 using the Nationwide Readmissions Database. For each woman, using discharge diagnoses, we identified 24 conditions used to create the Obstetric Comorbidity Index. Using various assessment windows for capturing obstetric co-morbidities, including the delivery hospitalisation only and all weekly windows from 7 to 280 days, we calculated the frequency and rate of each co-morbidity and the degree of underascertainment of the co-morbidity. Under each scenario, and for each co-morbidity, we also calculated the all-cause, 30-day readmission rate. RESULTS: There were over 3 million delivery hospitalisations from 2010 to 2014 included in this analysis. Compared with a full 280-day window, assessment of obstetric co-morbidities using only diagnoses made during the delivery hospitalisation would result in failing to identify over 35% of cases of chronic renal disease, 28.5% cases in which alcohol abuse was documented during pregnancy, and 23.1% of women with pulmonary hypertension. For seven other co-morbidities, at least 1 in 20 women with that condition would have been missed with exclusive reliance on the delivery hospitalisation for co-morbidity diagnoses. Not only would reliance on delivery hospitalisations have resulted in missed cases of co-morbidities, but for many conditions, estimates of readmission rates for women with obstetric co-morbidities would have been underestimated. CONCLUSIONS: An increasing proportion of maternal and child health research is based on large administrative databases. This study provides data that facilitate the assessment of the degree to which important obstetric co-morbidities may be underascertained when using these databases.

Ratings of performance in multisource feedback: comparing performance theories of residents and nurses.

BACKGROUND: Multisource feedback (MSF) is increasingly being used to assess trainee performance, with different assessor groups fulfilling a crucial role in utility of assessment data. However, in health professions education, research on assessor behaviors in MSF is limited. When assessing trainee performance in work settings, assessors use multidimensional conceptualizations of what constitutes effective performance, also called personal performance theories, to distinguish between various behaviors and sub competencies., This may not only explain assessor variability in Multi Source Feedback, but also result in differing acceptance (and use) of assessment data for developmental purposes. The purpose of this study was to explore performance theories of various assessor groups (residents and nurses) when assessing performance of residents. METHODS: A constructivist, inductive qualitative research approach and semi-structured interviews following MSF were used to explore performance theories of 14 nurses and 15 residents in the department of internal medicine at Aga Khan University (AKU). Inductive thematic content analysis of interview transcripts was used to identify and compare key dimensions in residents' and nurses' performance theories used in evaluation of resident performance. RESULTS: Seven major themes, reflecting key dimensions of assessors' performance theories, emerged from the qualitative data, namely; communication skills, patient care, accessibility, teamwork skills, responsibility, medical knowledge and professional attitude. There were considerable overlaps, but also meaningful differences in the performance theories of residents and the nurses, especially with respect to accessibility, teamwork and medical knowledge. CONCLUSION: Residents' and nurses' performance theories for assessing resident performance overlap to some extent, yet also show meaningful differences with respect to the performance dimensions they pay attention to or consider most important. In MSF, different assessor groups may therefore hold different performance theories, depending on their role. Our results further our understanding of assessor source effects in MSF. Implications of our findings are related to implementation of MSF, design of rating scales as well as interpretation and use of MSF data for selection and performance improvement.

Acetaminophen pharmacokinetics in severely obese adolescents and young adults.

BACKGROUND: Intravenous acetaminophen is commonly administered as an adjunctive to opioids during major surgical procedures, but neither the correct pharmacokinetic size descriptor nor the dose is certain in severely obese adolescents undergoing bariatric surgery. METHODS: Adolescents, 14-20 years of age, with a body mass index (BMI) ≥95th percentile for age and sex or BMI ≥40 kg·m-2 , presenting for laparoscopic or robotic assisted or vertical sleeve gastrectomy were administered intravenous acetaminophen (1000 mg) following completion of the surgical procedure. Venous blood was drawn for acetaminophen assay at eight time points, starting 15 minutes after completion of the infusion and up to 12 hours afterward. Time-concentration data profiles were analyzed using nonlinear mixed effects models. Parameter estimates were scaled to a 70-kg person using allometry. Normal fat mass was used to assess the impact of obesity on pharmacokinetic parameters. RESULTS: The study cohort comprised 11 female patients, age 17 SD 2 years with a weight of 125 SD 19 kg and a mean BMI of 46 SD 5 kg·m-2 . The plasma acetaminophen serum concentration was 17 (SD 4) µg·mL-1 at 10-20 minutes after completion of the infusion and 5 (SD 6) µg·mL-1 at 80-100 minutes. A two-compartment model, used to investigate pharmacokinetics, estimated clearance 10.6 (CV 72%) L·h·70 kg-1 , intercompartment clearance 37.3 (CV 63%) L·h·70 kg-1 , central volume of distribution 20.4 (CV 46%) L·70 kg-1 , and peripheral volume of distribution 16.8 (CV 42%) L·70 kg-1 . Clearance was best described using total body weight. Normal fat mass with a parameter that accounts for fat mass contribution (Ffat) of 0.88 best described volumes. CONCLUSION: Current recommendations of acetaminophen to a maximum dose of 1000 mg resulted in serum concentrations below detection limits in all patients within 2 hours after administration. Dose is better predicted using total body mass with allometric scaling.

Barriers and perceptions regarding code status discussion with families of critically ill patients in a tertiary care hospital of a developing country: A cross-sectional study.

BACKGROUND: In Asian societies including Pakistan, a complex background of illiteracy, different familial dynamics, lack of patient's autonomy, religious beliefs, and financial constraints give new dimensions to code status discussion. Barriers faced by physicians during code status discussion in these societies are largely unknown. AIM: To determine the barriers and perceptions in discussion of code status by physicians. DESIGN: Questionnaire-based cross-sectional study. SETTING AND PARTICIPANTS: This study was conducted in the Department of Medicine of The Aga Khan University Hospital, Karachi, Pakistan. A total of 134 physicians who had discussed at least five code statuses in their lifetime were included. RESULTS: A total of 77 (57.4%) physicians responded. Family-related barriers were found to be the most common barriers. They include family denial (74.0%), level of education of family (66.2%), and conflict between individual family members (66.2%). Regarding personal barriers, lack of knowledge regarding prognosis (44.1%), personal discomfort in discussing death (29.8%), and fear of legal consequences (28.5%) were the top most barriers. In hospital-related barriers, time constraint (57.1%), lack of hospital administration support (48.0%), and suboptimal nursing care after do not resuscitate (48.0%) were the most frequent. There were significant differences among opinions of trainees when compared to those of attending physicians. CONCLUSION: Family-related barriers are the most frequent roadblocks in the end-of-life care discussions for physicians in Pakistan. Strengthening communication skills of physicians and family education are the potential strategies to improve end-of-life care. Large multi-center studies are needed to better understand the barriers of code status discussion in developing countries.

Frequency of worsening liver function in severe dengue hepatitis patients receiving paracetamol: A retrospective analysis of hospital data.

OBJECTIVE: To determine the frequency of worsening liver function among hospital in-patients with severe dengue hepatitis receiving paracetamol. METHODS: This retrospective study was conducted at the Department of Medicine, Aga Khan University Hospital, Karachi, and comprised records of dengue patients with severe hepatitis who received paracetamol for control of fever between June 2007 and December 2014. Alanine aminotransferase at baseline and following paracetamol administration was noted, as well as dosage and duration of paracetamol, along with participants' demographic details. Frequency of patients who developed worsening or improvement of alanine aminotransferase was also noted. SPSS 19 was used for data analysis. RESULTS: Of the 113 subjects, 73(64.6%) were male and 40(35.4%) were female. Overall improvement was observed in subsequent alanine aminotransferase levels (491 units per litre, IQR 356.5 TO 775 vs 151 units per litre, IQR 49.5 to 299.5). Most commonly prescribed dose of paracetamol was 2g (IQR 1 to 5 grams), which was taken for a median duration of 1 day (IQR 1 to 3 days). Moreover, 100(88.5 %) patients showed improvement in alanine aminotransferase. Only 13(11.5 %) patients developed worsening of alanine aminotransferase. Of those with worsening liver function, 8(61.5 %) were discharged home with no clinical deterioration and 5(38.5 %) deaths were observed. However, causes of deaths were unrelated to liver dysfunction. CONCLUSIONS: The frequency of worsening liver function following paracetamol administration in patients with severe dengue hepatitis was relatively low.