794 Evaluating disability in adult burn injury patients treated at a tertiary-care burn unit in Karachi, Pakistan: a longitudinal study using who disability assessment schedule II

Abstract Background Disability after burn injury is not assessed in the context of Pakistan. This study assesses disability among adult burn injury patients presenting to a burn unit in Karachi, Pakistan. Methods This longitudinal study was conducted at a burn centre is Karachi, Pakistan. Adult patients(\u3e18 years) who were discharge after 24-hour admission were enrolled from August 2014–March 2015. Baseline assessment before discharge and follow-up at 2,6 and 12 weeks after discharge via telephone was done using 12-item WHODAS 2.0 (5 -point likert-scale; 1 = none; 2 = mild; 3 = moderate; 4 = severe; and 5 = extreme) related to cognition, mobility, self-care, getting along, life activities and participation. The score range was 12–60 with higher score being worse. Ethical approval was taken from collaborating and participating sites. Results Of the 59 eligible patients, 53 completed all follow-ups. There were 69.8% males. Mean age of all patients was 36.8 ± 14.0 years, 71.7% were married and 17.0% had no/informal education. About half the patients were breadwinners. More than half of burn incidents occurred at home. Flame burns (50.9%) and scalds (17%) were the most common type of burns. The average surface area burnt was 43.0 ± 14.2%. The mean-scores for all patients at baseline, 2-week, 6-week and 12-week were 13.9 ± 4.9, 35.3 ± 13.8, 26.8 ± 11.9 and 20.1 ± 9.1, respectively. The mean-scores for males were lower than that of females for the four assessments (Males: 13.5 ± 1.8, 34.2 ± 14.1, 25.3 ± 10.7, 19.2 ± 8.4 and females: 16.1 ± 8.5, 37.3 ± 13.3, 30.5 ± 14.4, 22.1 ± 10.6). The two-week score was higher for those with \u3e15% burn(36.7 ± 13.9) compared to those with ≤15% burn(34.6 ± 14.2) while the score were similar at 12-week follow-up. Conclusions This analysis shows that the burn injury patients tend to recover from their injury over a period of 12 weeks after discharge. Future work should focus on larger group of patients and long term follow-up at one and two years after burn injury

THERAPEUTIC DRUG MONITORING OF BROAD SPECTRUM ANTIFUNGAL, VORICONAZOLE- A REVIEW

Voriconazole is a broad-spectrum antifungal drug. It belongs to triazole group, and is available in market as oral as well as intravenous (IV) forms. It is highly effective against a number of clinically important fungi causing invasive infections. Its pharmacokinetic profile is non-linear with extensive inter-individual and intra-individual variability. Various factors contribute towards this variability including age, race, gender, genotype, hepatic functions, administration with or without food, and concomitant administration of other drugs causing drug interactions. Variability in plasma concentrations of the drug, arising from these factors, may result in variations in efficacy of the drug or may contribute towards potential toxicity. Voriconazole therapeutic drug monitoring is mandatory considering bad prognosis of patients suffering from invasive fungal infections, especially ones who are immunosuppressed, and prolonged period of treatment needed, in order to optimize antifungal treatment and to prevent the adverse events.&nbsp

COMPARISON AND EVALUATION OF ONE-STEP REVERSE TRANSCRIPTASE-POLYMERASE CHAIN REACTION (RT-PCR) AND REVERSE TRANSCRIPTASE LOOP-MEDIATED ISOTHERMAL AMPLIFICATION ASSAY(RT-LAMP) FOR RAPID DETECTION OF FOOT-AND-MOUTH DISEASE VIRUS (FMDV)

Foot-and-mouth disease (FMD) is endemic in Pakistan and cause severe economic losses. Serotype O, A and Asia 1 is prevalent and their rapid detection for Pakistaniisolates is needed to determine the serotype prevalence in different areas of the country. One step reversetranscriptase-polymerase chain reaction (RT-PCR) and reverse transcriptase loop-mediated isothermal amplification (RT- LAMP) was compared for the rapid and sensitive detection of FMDV genome. FMDV genome was confirmed in 19/25clinically affected animals by sequencing. These positive samples (n=19) were also confirmed in both RT-PCR and RT-LAMP consensus assay.In theserotyping assay, RT-PCR detection rate was16.67%, 80%, and 50% and RT-LAMP detection rate was 50%, 60% and 50%for serotype Asia 1, O and type A respectively. In general detection of FMDV, RT-PCR assay and the RT-LAMP assay showed high concordance (k = 1.0). However, in serotype detection, RT-LAMP was found more sensitive as compared to RT-PCR for the detection of the FMDV serotype Asia1 and Vice Versa in the detection of serotype O. To the best of the author’s knowledge, this is thefirst document on thecomparison of RT-LAMP and one-step RT- PCR for FMDV using ESE-Quant Tube Scanner in Pakistan.The RT-LAMP assay has the potential for early and rapid clinical diagnosis, surveillance and serotyping of FMDV infection in endemic countries

Baseline Expression of Immune Gene Modules in Blood is Associated With Primary Response to Anti-TNF Therapy in Crohn’s Disease Patients

Background and Aims: Anti-tumour necrosis factor [anti-TNF] therapy is widely used for the treatment of inflammatory bowel disease, yet many patients are primary non-responders, failing to respond to induction therapy. We aimed to identify blood gene expression differences between primary responders and primary non-responders to anti-TNF monoclonal antibodies [infliximab and adalimumab], and to predict response status from blood gene expression and clinical data. Methods: The Personalised Anti-TNF Therapy in Crohn’s Disease [PANTS] study is a UK-wide prospective observational cohort study of anti-TNF therapy outcome in anti-TNF-naive Crohn’s disease patients [ClinicalTrials.gov identifier: NCT03088449]. Blood gene expression in 324 unique patients was measured by RNA-sequencing at baseline [week 0], and at weeks 14, 30, and 54 after treatment initiation [total sample size = 814]. Results: After adjusting for clinical covariates and estimated blood cell composition, baseline expression of major histocompatibility complex, antigen presentation, myeloid cell enriched receptor, and other innate immune gene modules was significantly higher in anti-TNF responders vs non-responders. Expression changes from baseline to week 14 were generally of consistent direction but greater magnitude [i.e. amplified] in responders, but interferon-related genes were upregulated uniquely in non-responders. Expression differences between responders and non-responders observed at week 14 were maintained at weeks 30 and 54. Prediction of response status from baseline clinical data, cell composition, and module expression was poor. Conclusions: Baseline gene module expression was associated with primary response to anti-TNF therapy in PANTS patients. However, these baseline expression differences did not predict response with sufficient sensitivity for clinical use.</p

Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease:3-year data from the prospective, multicentre PANTS cohort study

Background: We sought to report the effectiveness of infliximab and adalimumab over the first 3 years of treatment and to define the factors that predict anti-TNF treatment failure and the strategies that prevent or mitigate loss of response. Methods: Personalised Anti-TNF therapy in Crohn's disease (PANTS) is a UK-wide, multicentre, prospective observational cohort study reporting the rates of effectiveness of infliximab and adalimumab in anti-TNF-naive patients with active luminal Crohn's disease aged 6 years and older. At the end of the first year, sites were invited to enrol participants still receiving study drug into the 2-year PANTS-extension study. We estimated rates of remission across the whole cohort at the end of years 1, 2, and 3 of the study using a modified survival technique with permutation testing. Multivariable regression and survival analyses were used to identify factors associated with loss of response in patients who had initially responded to anti-TNF therapy and with immunogenicity. Loss of response was defined in patients who initially responded to anti-TNF therapy at the end of induction and who subsequently developed symptomatic activity that warranted an escalation of steroid, immunomodulatory, or anti-TNF therapy, resectional surgery, or exit from study due to treatment failure. This study was registered with ClinicalTrials.gov, NCT03088449, and is now complete. Findings: Between March 19, 2014, and Sept 21, 2017, 389 (41%) of 955 patients treated with infliximab and 209 (32%) of 655 treated with adalimumab in the PANTS study entered the PANTS-extension study (median age 32·5 years [IQR 22·1–46·8], 307 [51%] of 598 were female, and 291 [49%] were male). The estimated proportion of patients in remission at the end of years 1, 2, and 3 were, for infliximab 40·2% (95% CI 36·7–43·7), 34·4% (29·9–39·0), and 34·7% (29·8–39·5), and for adalimumab 35·9% (95% CI 31·2–40·5), 32·9% (26·8–39·2), and 28·9% (21·9–36·3), respectively. Optimal drug concentrations at week 14 to predict remission at any later timepoints were 6·1–10·0 mg/L for infliximab and 10·1–12·0 mg/L for adalimumab. After excluding patients who had primary non-response, the estimated proportions of patients who had loss of response by years 1, 2, and 3 were, for infliximab 34·4% (95% CI 30·4–38·2), 54·5% (49·4–59·0), and 60·0% (54·1–65·2), and for adalimumab 32·1% (26·7–37·1), 47·2% (40·2–53·4), and 68·4% (50·9–79·7), respectively. In multivariable analysis, loss of response at year 2 and 3 for patients treated with infliximab and adalimumab was predicted by low anti-TNF drug concentrations at week 14 (infliximab: hazard ratio [HR] for each ten-fold increase in drug concentration 0·45 [95% CI 0·30–0·67], adalimumab: 0·39 [0·22–0·70]). For patients treated with infliximab, loss of response was also associated with female sex (vs male sex; HR 1·47 [95% CI 1·11–1·95]), obesity (vs not obese 1·62 [1·08–2·42]), baseline white cell count (1·06 [1·02–1·11) per 1 × 109 increase in cells per L), and thiopurine dose quartile. Among patients treated with adalimumab, carriage of the HLA-DQA1*05 risk variant was associated with loss of response (HR 1·95 [95% CI 1·17–3·25]). By the end of year 3, the estimated proportion of patients who developed anti-drug antibodies associated with undetectable drug concentrations was 44·0% (95% CI 38·1–49·4) among patients treated with infliximab and 20·3% (13·8–26·2) among those treated with adalimumab. The development of anti-drug antibodies associated with undetectable drug concentrations was significantly associated with treatment without concomitant immunomodulator use for both groups (HR for immunomodulator use: infliximab 0·40 [95% CI 0·31–0·52], adalimumab 0·42 [95% CI 0·24–0·75]), and with carriage of HLA-DQA1*05 risk variant for infliximab (HR for carriage of risk variant: infliximab 1·46 [1·13–1·88]) but not for adalimumab (HR 1·60 [0·92–2·77]). Concomitant use of an immunomodulator before or on the day of starting infliximab was associated with increased time without the development of anti-drug antibodies associated with undetectable drug concentrations compared with use of infliximab alone (HR 2·87 [95% CI 2·20–3·74]) or introduction of an immunomodulator after anti-TNF initiation (1·70 [1·11–2·59]). In years 2 and 3, 16 (4%) of 389 patients treated with infliximab and 11 (5%) of 209 treated with adalimumab had adverse events leading to treatment withdrawal. Nine (2%) patients treated with infliximab and two (1%) of those treated with adalimumab had serious infections in years 2 and 3. Interpretation: Only around a third of patients with active luminal Crohn's disease treated with an anti-TNF drug were in remission at the end of 3 years of treatment. Low drug concentrations at the end of the induction period predict loss of response by year 3 of treatment, suggesting higher drug concentrations during the first year of treatment, particularly during induction, might lead to better long-term outcomes. Anti-drug antibodies associated with undetectable drug concentrations of infliximab, but not adalimumab, can be predicted by carriage of HLA-DQA1*05 and mitigated by concomitant immunomodulator use for both drugs. Funding: Guts UK, Crohn's and Colitis UK, Cure Crohn's Colitis, AbbVie, Merck Sharp and Dohme, Napp Pharmaceuticals, Pfizer, and Celltrion Healthcare.</p

HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn's Disease

Background &amp; Aims: Anti–tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies. Methods: We performed a genome-wide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn's disease starting infliximab or adalimumab therapy. Immunogenicity was defined as an anti-drug antibody titer ≥10 AU/mL using a drug-tolerant enzyme-linked immunosorbent assay. Significant association signals were confirmed in a replication cohort of 178 patients with inflammatory bowel disease. Results: The HLA-DQA1*05 allele, carried by approximately 40% of Europeans, significantly increased the rate of immunogenicity (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60–2.25; P = 5.88 × 10–13). The highest rates of immunogenicity, 92% at 1 year, were observed in patients treated with infliximab monotherapy who carried HLA-DQA1*05; conversely the lowest rates of immunogenicity, 10% at 1 year, were observed in patients treated with adalimumab combination therapy who did not carry HLA-DQA1*05. We confirmed this finding in the replication cohort (HR, 2.00; 95% CI, 1.35–2.98; P = 6.60 × 10–4). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32–2.70) or infliximab (HR, 1.92; 95% CI, 1.57–2.33), and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37–2.22) or in combination with an immunomodulator (HR, 2.01; 95% CI, 1.57–2.58). Conclusions: In an observational study, we found a genome-wide significant association between HLA-DQA1*05 and the development of antibodies against anti-TNF agents. A randomized controlled biomarker trial is required to determine whether pretreatment testing for HLA-DQA1*05 improves patient outcomes by helping physicians select anti-TNF and combination therapies. ClinicalTrials.gov ID: NCT03088449.</p

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Impact of open access endoscopy on early diagnosis, treatment and gastrointestinal radiology service

The objective is to compare the endoscopic findings before and after initiation of open access and its effect on gastrointestinal radiology services. The data of endoscopic findings before open access endoscopy (July, 1989-June, 1992) and after open access endoscopy (July, 1992-June, 1995) was collected from the records of the endoscopy unit. Similarly, data of barium meals for the same periods was collected from the radiology department. An X 2 test was used to compare the endoscopic findings before and after open access policy. It is found that open access endoscopy increased the workload in the endoscopy unit but at the same time reduced the number of gastrointestinal radiological procedures. It reduced the waiting period for endoscopy and this helped in making early diagnosis and initiation of appropriate treatment

Genetic variability in beta-tubulin-1 in benzimidazole resistant haemonchus contortus from sheep in North-East Punjab, Pakistan

Benzimidazole is a synthetic anthelmintic against which nematode resistance especially in Haemonchus contortus, is emerging at a alarming speed. The mechanism of benzimidazole resistance appears to involve mutations in the gene encoding β-tubulin isotype 1 (β-tubulin-1). The present study was carried out to find out the variation existing in β-tubulin-1 which is directly involved with drug binding capacity involving microtubules polymerization. DNA of adult nematode H. contortus was extracted, amplified and sequenced. Out of 50 worms investigated, 37 showed benzimidazole susceptible gene while 13 were resistant indicating single nucleotide mutation at amino acid 200 TTC/TAC. In addition, 12 worms showed several regions of consistent difference indicating single nucleotide polymorphism (SNPs) at various positions in coding region. It has been concluded that resistant alleles conferring anthelmintic resistance is prevalent in the local population of H. contortus of north-east Punjab, Pakistan

Solar Energy Harvesting and Management in Wireless Sensor Networks

Wireless networks comprise of small devices that are typically deployed in environments where paucity of energy seriously restricts essential operations. The energy source of these devices decreases very quickly during continuous operation and it is pivotal to replace or recharge frequently the power sources. Sometimes, it is very difficult to perform these functions through conventional methods. One attractive solution to this problem is the use of the energy, scattered around us in the environment. The availability of energy from the environment is random and uncertain. In this paper, we present a model, schematically and analytically, for solar energy harvesting with appropriate energy management. We provide analysis and simulations for a solar cell for standard and different irradiance levels. The power of the storage device is also simulated for different times of the day. The proposed model not only scavenges the energy but also assures the connectivity of the network by optimizing the energy consumption