Colonoscopic cancer detection rate: a new performance measure - is it FIT for purpose?

Introduction: Gastrointestinal symptoms correlate poorly with cancer diagnosis. A faecal immunochemical test (FIT) result of ≥10 µg has high sensitivity and negative predictive value for colorectal cancer (CRC) detection. An FIT-based diagnostic pathway may lead to more effective resource utilisation. We aimed to use National Endoscopy Database (NED) data to create a new colonoscopy performance measure, cancer detection rate (CDR) to assess the appropriate identification of target populations for colonoscopy; then to use CDR to assess the impact of implementing an FIT-based referral pathway locally. Methods: NED data were analysed to compare local diagnostic colonoscopic CDR in 2019 (prepathway revision) and 2021 (postpathway revision), benchmarked against overall national CDR for the same time frames. Results: 1, 123, 624 NED diagnostic colonoscopies were analysed. Locally, there was a significant increase in CDR between 2019 and 2021, from 3.01% (2.45%-3.47%) to 4.32% (3.69%-4.95%), p=0.003. The CDR increase was due to both a 10% increase in the number of CRCs detected and a 25% reduction in the number of diagnostic colonoscopies performed. Nationally, there was a smaller, but significant, increase in CDR from 2.02% (1.99%-2.07%) to 2.33% (2.29%-2.37%), p<0.001. The rate of increase in CDR% between 2019 and 2021 was significantly different locally compared with nationally. Conclusion: Our study indicates that the introduction of a robustly vetted FIT-based algorithm to determine whether diagnostic colonoscopy is required, is effective in increasing the colonoscopic CDR. Moreover, CDR appears to be a meaningful performance metric that can be automatically calculated through NED, enabling monitoring of the quality of referral and vetting pathways.

Benign Paroxysmal Positional Vertigo After Joint Replacement Surgeries: Case Series.

Benign paroxysmal positional vertigo (BPPV) is characterized by brief episodes of vertigo triggered by changes in head position caused by the displacement of otoliths from the utricle to the semicircular canals, particularly the posterior canal. This study explored the potential link between BPPV, the patient's preexisting conditions, and surgery-related factors including surgical positioning, duration of the procedure, exposure to vibratory forces, and anesthesia effects. This report presents two cases of BPPV following major joint replacement surgery. The first case involved a 65-year-old male with a history of diet-controlled diabetes who had undergone right-sided total hip replacement. The second case was that of a 60-year-old female with a history of osteoporosis managed with bisphosphonate therapy and left-sided knee replacement. Both patients developed vertigo symptoms one day postoperatively and were diagnosed with BPPV. In both cases, the Dix-Hallpike test confirmed the right-sided posterior canal BPPV diagnosis, and the patients were successfully treated using the Epley maneuver. Notably, there was no recurrence of vertigo at the four-week follow-up. These cases highlight the importance of considering BPPV in patients presenting with vertigo symptoms after joint replacement surgery, especially in the presence of comorbidities like diabetes and osteoporosis which possibly increase susceptibility to BPPV. This article presents two cases of benign paroxysmal positional vertigo (BPPV) following non-otologic surgery. It explores the pathophysiological mechanism underlying BPPV after such surgeries and also discusses the diagnosis and treatment approaches. This underscores the need for prompt diagnosis and treatment of BPPV to improve postoperative outcomes.

Accuracy of procalcitonin for diagnosing sepsis in adult patients admitted to the emergency department: a systematic review and meta-analysis.

BACKGROUND: Differentiating sepsis from non-infectious systemic inflammatory response syndrome (SIRS) is challenging. Biomarkers like procalcitonin (PCT) aid early risk assessment and guide antibiotic use. This study aims to ascertain PCT's accuracy as a sepsis biomarker among adult emergency department admissions. METHOD: The PRISMA guidelines were followed to search for relevant articles in five electronic databases between April 14th and August 4th, 2023: PubMed, Cochrane Library, ProQuest, EMBASEs, and ScienceDirect. Studies had to be published in English to avoid directly translating scientific terms. Besides, the inclusion criteria were based on the diagnosis of sepsis in adult patients admitted to an emergency department. QUADAS-2 tool provided by the Review Manager version 5.4.1 was utilized to assess the risk of bias in included studies. STATA (v. 16) software was used to perform the meta-analysis. RESULTS: Ten of 2457 studies were included. We sampled 2980 adult sepsis patients for the under-investigated role of PCT in ED sepsis diagnosis. PCT emerged as the primary early diagnostic biomarker with high levels (29.3 ± 85.3 ng/mL) in sepsis patients. Heterogeneity in outcomes, possibly due to bias in cohort and observational studies, was observed. CONCLUSION: PCT tests offer moderate accuracy in diagnosing sepsis and stand out for rapidly and precisely distinguishing between viral and bacterial inflammations.

Repurposing AZD5438 and Dabrafenib for Cisplatin-Induced AKI.

SIGNIFICANCE STATEMENT: To combat both untoward effects of nephrotoxicity and ototoxicity in cisplatin-treated patients, two potential therapeutic oral anticancer drugs AZD5438 and dabrafenib, a phase-2 clinical trial protein kinase CDK2 inhibitor and an US Food and Drug Administration-approved drug BRAF inhibitor, respectively, were tested in an established mouse AKI model. Both drugs have previously been shown to protect significantly against cisplatin-induced hearing loss in mice. Each drug ameliorated cisplatin-induced increases in the serum biomarkers BUN, creatinine, and neutrophil gelatinase-associated lipocalin. Drugs also improved renal histopathology and inflammation, mitigated cell death by pyroptosis and necroptosis, and significantly enhanced overall survival of cisplatin-treated mice. BACKGROUND: Cisplatin is an effective chemotherapy agent for a wide variety of solid tumors, but its use is dose-limited by serious side effects, including AKI and hearing loss. There are no US Food and Drug Administration-approved drugs to treat both side effects. Recently, two anticancer oral drugs, AZD5438 and dabrafenib, were identified as protective against cisplatin-induced hearing loss in mice. We hypothesize that similar cell stress and death pathways are activated in kidney and inner ear cells when exposed to cisplatin and tested whether these drugs alleviate cisplatin-induced AKI. METHODS: The HK-2 cell line and adult FVB mice were used to measure the protection from cisplatin-induced cell death and AKI by these drugs. Serum markers of kidney injury, BUN, creatinine, and neutrophil gelatinase-associated lipocalin as well as histology of kidneys were analyzed. The levels of markers of kidney cell death, including necroptosis and pyroptosis, pERK, and proliferating cell nuclear antigen, were also examined by Western blotting and immunofluorescence. In addition, CDK2 knockout (KO) mice were used to confirm AZD5438 protective effect is through CDK2 inhibition. RESULTS: The drugs reduced cisplatin-induced cell death in the HK-2 cell line and attenuated cisplatin-induced AKI in mice. The drugs reduced serum kidney injury markers, inhibited cell death, and reduced the levels of pERK and proliferating cell nuclear antigen, all of which correlated with prolonged animal survival. CDK2 KO mice were resistant to cisplatin-induced AKI, and AZD5438 conferred no additional protection in the KO mice. CONCLUSIONS: Cisplatin-induced damage to the inner ear and kidneys shares similar cellular beneficial responses to AZD5438 and dabrafenib, highlighting the potential therapeutic use of these agents to treat both cisplatin-mediated kidney damage and hearing loss.

Prevalence of chronic pain in Pakistan - a national survey.

OBJECTIVE: To assess the prevalence of chronic pain, its physical and psychosocial impact on daily life, and the various therapies adopted to alleviate pain. METHODS: The cross-sectional population-based telephonic survey was conducted from May to July 2021 at Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, and comprised patients of either gender aged at least 18 years suffering from chronic pain who visited the institutional laboratory collection centres. In the first phase, people who were suffering from chronic pain were screened, while in the second phase, data was collected using a detailed questionnaire exploring pain history, treatment and its effects. The data was compiled and analysed using Antlere's AI based software. RESULTS: Of the 4,801 patients contacted, 757(15.75%) were suffering from chronic pain. A total of 201(20%) subjects reported that their pain score was 5/10 on the numerical rating scale. Back pain was the major complaint (183, 18%) among the subjects. Of the total, 335(44.25%) were having active treatment, and 226 (67%) of them said the medication was effective. Overall, 706 (93%) patients had never visited a pain management specialist. Furthermore, 252 (33%) participants were diagnosed with depression, and 106 (14%) patients said that they were suicidal at some point in life. CONCLUSIONS: .The survey observed that a high percentage of unawareness existed on pain management among the Pakistani citizens.

High flow nasal oxygen (HFNO) in the treatment of COVID-19 infection of adult patients from - An emergency perspective: A systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2, which was first discovered in Wuhan, China. The disease has grown into a global pandemic causing mild to moderate symptoms in most people. The disease can also exhibit serious illnesses, especially for patients with other chronic diseases such as cardiovascular diseases, diabetes, chronic respiratory disease, or cancer. In such cases of severe illness, high flow nasal oxygen (HFNO) has been used to provide oxygenation to COVID-19 patients. However, the efficiency of HFNO remains uncertain, prompting the conduction of this systematic review to evaluate the effectiveness of the therapy. A thorough search for relevant and original articles was carried out on five electronic databases, including ScienceDirect, PubMed, Cochrane Library, Embase, and Google Scholar. No time limitation was placed during the search as it included all the articles related to COVID-19 from 2019 to 2022. The search strategy utilized in this systematic review yielded 504 articles, of which only 10 met the eligibility criteria and were included. Our meta-analysis reveals that HFNO success rate was higher than HFNO failure rates (0.52 (95% CI; 0.47, 0.56) and 0.48 (95% CI; 0.44, 0.53), respectively), however, the difference was statistically insignificant. HFNO was associated with a significant decrease in mortality and intubation rates (0.28 (95% CI; 0.19, 0.39) and 0.28 (95% CI; 0.18, 0.41), respectively). Our statistical analysis has shown that significantly lower ROX index (5.07 ± 1.66, p = 0.028) and PaO2/FiO2 (100 ± 27.51, p = 0.031) are associated with HFNO failure, while a significantly lower respiratory rate (RR) (23.17 ± 4.167, p = 0.006) is associated with HFNO success. No statistically significant difference was observed in SpO2/FiO2 ratio between the HFNO success and failure groups (154.23 ± 42.74 vs. 124.025 ± 28.50, p = 0.62, respectively). Based on the results from our meta-analysis, the success or failure of HFNO in treating COVID-19 adult patients remains uncertain. However, HFNO has been shown to be an effective treatment in reducing mortality and intubation rates. Therefore, HFNO can be recommended for COVID-19 patients but with close monitoring and should be carried out by experienced healthcare workers.

An Analytical Comparison Between Ketamine Alone and a Combination of Ketamine and Propofol (Ketofol) for Procedural Sedation and Analgesia From an Emergency Perspective: A Systematic Review and Meta-Analysis.

Procedural sedation and analgesia (PSA) is a treatment approach involving treating patients with agents with dissociative, sedative, or analgesic properties to suppress their consciousness to variable levels. Ketamine and propofol have been used historically for PSA. Because they each have their demerits, it was postulated that combining both drugs (ketofol) would result in a mixture with additive properties and lessen or eliminate the demerits attributed to each drug. The primary objective of this systematic review and meta-analysis is to compare ketamine alone and a combination of ketamine and propofol (ketofol) for procedural sedation and analgesia from an emergency perspective. A systematic search was conducted on published studies from the databases of Scopus, ScienceDirect, PubMed, Google Scholar, APA PsycInfo, and the Cochrane Central Register of Controlled Trial (CENTRAL) until July 2022. The articles that were published on the online databases were authored between January 2007 and 2018. The selected papers were scanned and examined to check whether they met the eligibility criteria for the study. The search produced six articles that were included in the systematic review and meta-analysis. All six articles that passed the eligibility criteria were viable for the analysis. All the trials focused on the effectiveness of ketofol versus ketamine for PSA from an emergency perspective. Ketofol was found to be safe and more effective in comparison to ketamine for PTA.

Evaluating the Effectiveness of Pretreatment With Intravenous Fluid in Reducing the Risk of Developing Contrast-Induced Nephropathy: A Systematic Review and Meta-Analysis.

Contrast media administration to patients during cardiac events increases the risk of developing contrast-induced nephropathy (CIN). CIN is among some complications usually associated with the percutaneous coronary intervention and may result in acute renal failure. Several risk factors are associated with CIN. These risk factors include; age (elderly patients), pre-existing renal impairment, diabetes mellitus, and the use of high osmolar contrast media. Studies have shown that several measures such as using low osmolar contrast media, N-acetylcysteine, intravenous sodium bicarbonate, and hydration through oral or intravenous fluid administration play a significant role in CIN incidence reduction. Hydration using intravenous fluid, especially saline solution, has been critical in preventing CIN. Prehydration using the intravenous fluid before contrast media administration is vital. A systematic literature search with meta-analysis for relevant and original articles was carried out from 2000 to 2022 on databases such as PubMed, Cochrane Library, Google Scholar, ScienceDirect, Web of Science, and Embase. The search on the databases was based on various keywords related to intravenous fluid and CIN. The studies that met the inclusion criteria were critically analyzed, and data such as study design, interventions, participants, and outcomes of the research were retrieved. Out of the 784 results yielded during the initial search, ten articles met the eligibility criteria and were included in the study. The data analysis obtained from the included studies showed that pretreatment using intravenous fluid has conflicting results. Some studies showed that hydrating patients using intravenous fluid before contrast media administration significantly reduces the risk of CIN. In contrast, others claimed that intravenous fluid has minimal impact on preventing CIN. Despite the different investigations conducted on CIN, it remains insufficiently understood. From the analysis, most of the studies support that intravenous fluid administration decreases the occurrence of CIN in patients that receive contrast media. The analysis also has established that oral hydration is similar to intravenous fluid administration in reducing CIN incidence.

Benign Paroxysmal Positional Vertigo After Mandibular Fractures.

Benign paroxysmal position vertigo (BPPV) is a debilitating condition. BPPV is a peripheral vestibular disorder, and people with this condition experience varying levels of dizziness. BPPV, in most patients, is often overlooked as vertigo and dizziness may be triggered by an underlying chronic disease and disorder. Patients may be misdiagnosed or have delayed diagnosis, resulting in unnecessary health procedures. In this study, we present two cases of BPPV in a 29-year-old female and a 32-year-old male, who presented initially with fracture of the angle of left mandibles, which were treated surgically. Both patients developed BPPV secondary to head trauma leading to mandibular fracture. It is important to diagnose and treat BPPV early to prevent long-term disability.

Perceptions and practices regarding the process of obtaining informed consent from surgical patients at a tertiary care hospital.

BACKGROUND: Proper informed consent is essential for patients to have sound knowledge about the indication, risks, and benefits of a proposed surgical procedure. The study aim was to assess the perceptions of postoperative patients about the informed consent process and identify various influential factors in a tertiary care hospital. METHODS: A cross-sectional study was conducted from February to August 2018 at a tertiary care hospital in Lahore, Pakistan. A validated questionnaire was used to conduct interviews of 101 patients planning to undergo elective surgery after fulfilling all ethical considerations. A purposive sampling technique was employed to enroll and the data analysis was performed by using SPSS version 23. RESULTS: Out of total 101 patients, 50 (49.5%) of them were males and the mean age of total sample was 36.98 ± 14.23 years. The majority 92 (91.1%) considered informed consent to be important and that it did not influence their surgical decision 85 (84.2%). Consent was obtained by the consulting surgeon from 41 (40.6%) patients and by the residents/house officer from 60 (59.4%) patients. Fifteen (14.8%) patients signed the consent form themselves, and 86 (85.1%) relatives of patients signed. Ninety-eight (97.0) patients were told about indications of the surgery, and 54 (53.5%) were told about possible complications. Seventy-five (74.3%) patients were informed about alternatives to surgery. Significant reasons for not signing were language (p = 0.03), educational status (p = 0.002), and not being informed by relatives before signing (p = 0.02). CONCLUSION: The patients had adequate knowledge about the process of informed consent and considered it important. Factors identified as barriers to signing the consent form by the patients themselves included language, better educational status, and not being asked by relatives. It is imperative to involve the patients in the process of consent, especially in signing by them or in their presence by their surrogate.

Rhabdomyolysis After Total Abdominal Hysterectomy Requiring Urgent Hemodialysis Due to Hyperkalemia.

A 63-year-old woman with a past medical history of invasive ductal carcinoma of the breast, status post lumpectomy and chemoradiation, 15 cm left inguinal-femoral enlarged lymph node consistent with high-grade serous carcinoma of the ovary and 4.7 cm right adnexal mass underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymph node dissection with cystoscopy and bilateral ureteral catheter placement. There was no intraoperative complication. After surgery, patient's urine output decreased, and she developed acute kidney injury (AKI). Initially, it was thought that her reduced output might be due to surgery/anesthesia. She also developed arm and leg weakness raising suspicion for stroke. The neurological workup was unremarkable for any acute abnormality. Her creatinine kinase (CK) level was >20,000 u/l consistent with rhabdomyolysis. She was hydrated aggressively and required hemodialysis due to hyperkalemia. During the hospital course, her kidney function improved, and rhabdomyolysis resolved, and she did not require dialysis after discharge.

Curing Benign Paroxysmal Positional Vertigo in Patients With Brain Tumor: Case Series and Literature Review.

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder. It accounts for a third of all vestibular disorders diagnosed in the general population and is usually diagnosed and treated successfully. This article presents two cases of BPPV in a 52-year-old man and a 45-year-old patient, respectively. Both patients presented with recurrent episodes of vertigo associated with certain head movements. Medical history for the first patient included surgery for acoustic neuroma 12 months before developing the vertigo episodes. The second patient underwent a neurosurgical operation for glioblastoma multiforme (GBM) followed by radiotherapy three months before this presentation. Both patients were diagnosed with right-sided posterior canal BPPV after the Dix-Hallpike test. Their symptoms completely resolved within few minutes of the Epley maneuver. These cases highlight the importance of diagnosing and treating a potentially curable condition that can coexist in some patients with brain tumors.

Ruptured functioning adrenal tumour, atypical presentation with renal colic and hypertension.

Pheochromocytomas are uncommon tumours that originate in chromaffin cells. They are a representation of 0.1%-1% of all cases of secondary hypertension. Most pheochromocytomas are unilateral and benign, featuring catecholamine production, as well as the production of other neuropeptides. Pheochromocytomas are mostly located in the adrenal gland; the frequency of occurrence is highest between 30 and 50 years of age; however, up to 25% of cases may be linked to multiple endocrine neoplasia type 2, Von-Hippel-Landau disease and type 1 neurofibromatosis in the young.We present a case of ruptured left adrenal pheochromocytoma with an atypical presentation. A 30-year-old male patient presented with severe left flank pain and hypertension. The CT scan of the abdomen showed bleeding from the left adrenal mass, where resuscitation and angioembolisation were done. Embolisation of the inferior and superior arteries was done, but the middle failed. The patient experienced a significant drop in haemoglobin and a haemorrhagic shock post angioembolisation, which called for emergency laparotomy. The patient is currently doing well with an uneventful postoperative course.

Subcutaneous emphysema, pneumothorax, pneumomediastinum and pneumoperitoneum after upper gastrointestinal endoscopy.

Upper gastrointestinal (GI) endoscopies are performed for several reasons. The overuse of endoscopy has negative effects on the quality of healthcare and pressurises endoscopy services. It also results in the complications. These complications include pneumoperitoneum, pneumomediastinum and subcutaneous pneumomediastinum. However, it is worth noting that these complications rarely occur during endoscopy of the upper GI tract. These complications, when they occur, indicate perforation of the retroperitoneal space or peritoneal cavity. In this article, we discuss a case of pneumoperitoneum, pneumomediastinum and subcutaneous emphysema after upper GI endoscopy.

Acute Spontaneous Spinal Subdural Hematoma: A Case Report.

BACKGROUND Spontaneous spinal subdural hematoma is a rare condition that can lead to devastating neurologic deficits, usually caused by coagulation abnormalities, trauma, underlying neoplasm, or arteriovenous malformation. The patient presents with local and/or radicular pain, followed by loss of sensory, motor, bladder, and bowel function. CASE REPORT A 25-year-old patient presented with left-sided weakness preceded by nontraumatic upper back pain. He denied any past medical illness and being on any regular medications. He had decreased strength in the left lower limb, left upper limb, and right lower limb, with intact strength in the right upper limb. The patient exhibited decreased sensation of pain and touch on the right side of the lower limb, bilateral loss of proprioception, and intact reflexes and anal tone. He had weakness on the left side of the body and contralateral decreased sensation of pain and touch on the right side. These symptoms were suggestive of Brown-Sequard syndrome, while the bilateral loss of proprioception suggested posterior cord syndrome. Magnetic resonance imaging showed an acute spinal subdural canal hematoma producing cord compression. The patient had an urgent laminectomy and hematoma evacuation. Afterward, his neurological function improved. CONCLUSIONS Spontaneous spinal subdural hematoma can occur without any known pathology or remarkable trauma. It can compress the spinal cord and produce cerebral stroke-like symptoms. Hence, spinal hematoma should be ruled out in any patient presenting with a neurological deficit.

Follicular Lymphoma Recurrence Presenting as Unilateral Leg Swelling and Ipsilateral Hydronephrosis.

A 73-year-old man with a history of follicular lymphoma ten years ago with complete remission presented to the emergency room with a large unilateral left-leg swelling as the only symptom. Doppler ultrasonography ruled out deep vein thrombosis. Bedside point-of-care ultrasound (PoCUS) revealed left moderate hydronephrosis. A CT of the abdomen showed a bulky soft tissue mass in the region of the distal left psoas muscle. The mass was generating an extrinsic compression of the left ureter and venous system. The histological study of the lesion established the diagnosis of follicular lymphoma recurrence. The patient subsequently received immunochemotherapeutic treatment in the oncological treatment center. This case report is intended to promote awareness about a possible clinical correlation between unilateral leg swelling and hydronephrosis with a compressive intra-abdominal mass.

Vitamin D microencapsulation and fortification: Trends and technologies.

Today, as per the latest medical reports available, majority of the population throughout globe is facing vitamin D (Vit D) deficiency. Even in sub-tropical countries like India and many others Vit D deficiency is highly prevalent despite the exuberant available sunshine (a major source of Vit D) throughtout the year. The reason could be attributed to an array of factors including socioeconomical, cultural and religious. Further, other than the sunlight, there are very limited sources of Vit D to fulfil the recommended dietary allowance of Vit D (RDA: 400-800 IU per day). A large proportion of Vit D is lost during food processing and storage due to environmental stress conditions such as temperature, pH, salt, oxygen and light. Vita D, an important micronutrient, is essentially required for the prevention of disorders such as neurodegenerative diseases, cardiovascular diseases, cancer etc. in addition to its traditional role in bone metabolism. Therefore, in order to meet the daily requirements of Vit D for human body, WHO has recognized fortification as the most efficient and safest method to address malnutrition. But there are innumerable chellenges involved during food fortification using Vit D as fortificants such as homogeneity into the food matrix, physico-chemical/photochemical degradation, loss during processing and storage, interactions with other components of food matrix resulting into change in taste, texture and appearance thus affecting acceptability, palatability and marketability. Fortification of Vit D into food products especially the ones which have an aqueous portion, is not simple for food technologist. Recent advances in nanotechnology offer various microencapsulation techniques such as liposome, solid-lipid particles, nanostructured lipid carriers, emulsion, spray drying etc. which have been used to design efficient nanomaterials with desired functionality and have great potential for fortification of fortificants like Vit D. The present review is an undate on Vit D, in light of its fortification level, RDA, factors affecting its bioavailability and various microencapsulation techniques adopted to develop Vit D-nanomaterials and their fate in food fortification.

Sore throat turned to be a bronchogenic carcinoma with superior vena cava syndrome.

Superior vena cava (SVC) syndrome is a group of symptoms caused by complete or partial obstruction of the flow of blood through the SVC. The obstruction is, in most cases, caused by the formation of thrombus or infiltration of a tumour through the vessel wall. The result is venous congestion that creates a clinical situation relating to increase in the venous pressure in the upper part of the body. Symptoms commonly associated with vena cava syndrome include cough, dyspnoea, swelling of the neck, face and the upper extremities and dilation of the chest vein collaterals. In this paper, we examine the case of a 50-year-old man who presented to the emergency department with 'sore throat' which can be easily misdiagnosed as a case of uncomplicated acute pharyngitis. It was a real challenge to diagnose our patient as SVC syndrome caused by bronchogenic carcinoma.

Combination of TLR2 and TLR3 agonists derepress infectious bursal disease virus vaccine-induced immunosuppression in the chicken.

Live intermediate plus infectious bursal disease virus (IBDV) vaccines (hot vaccines) are used for protection against the virulent IBDV strains in young chickens. We evaluated the potential of Toll-like receptor (TLR) agonists to alleviate hot vaccine-induced immunosuppression. The combination of Pam3CSK4 and poly I:C synergistically upregulated IFN-ß, IFN-γ, IL-12, IL-4, and IL-13 transcripts and cross-inhibited IL-1ß, IL-10, and iNOS transcripts in the chicken peripheral blood mononuclear cells (PBMCs) as analyzed by quantitative real-time PCR. Further, four-week old specific pathogen free White Leghorn chickens (n = 60) were randomly divided into six groups and either immunized with hot IBDV vaccine with or without Pam3CSK4 and/or poly I:C or not vaccinated to serve as controls. The results indicated that poly I:C alone and in combination with Pam3CSK4 alleviated vaccine-induced immunosuppression, as evidenced by greater weight gain, increased overall antibody responses to both sheep erythrocytes and live infectious bronchitis virus vaccine, upregulated IFN-γ transcripts and nitric oxide production by PBMCs (P < 0.05), and lower bursal lesion score in the experimental birds. In conclusion, poly I:C alone and its combination with Pam3CSK4 reduced the destruction of B cells as well as bursal damage with restoration of function of T cells and macrophages when used with a hot IBDV vaccine.

Tramadol: a valuable treatment for pain in Southeast Asian countries.

BACKGROUND: The supply of controlled drugs is limited in the Far East, despite the prevalence of health disorders that warrant their prescription. Reasons for this include strict regulatory frameworks, limited financial resources, lack of appropriate training amongst the medical profession and fear of addiction in both general practitioners and the wider population. Consequently, the weak opioid tramadol has become the analgesic most frequently used in the region to treat moderate to severe pain. METHODS: To obtain a clearer picture of the current role and clinical use of tramadol in Southeast Asia, pain specialists from 7 countries in the region were invited to participate in a survey, using a questionnaire to gather information about their individual use and experience of this analgesic. RESULTS: Fifteen completed questionnaires were returned and the responses analyzed. Tramadol is used to manage acute and chronic pain caused by a wide range of conditions. Almost all the specialists treat moderate cancer pain with tramadol, and every one considers it to be significant or highly significant in the treatment of moderate to severe non-cancer pain. The reasons for choosing tramadol include efficacy, safety and tolerability, ready availability, reasonable cost, multiple formulations and patient compliance. Its safety profile makes tramadol particularly appropriate for use in elderly patients, outpatients, and for long-term treatment. The respondents strongly agreed that tighter regulation of tramadol would reduce its medical availability and adversely affect the quality of pain management. In some countries, there would no longer be any appropriate medication for cancer pain or the long-term treatment of chronic pain. CONCLUSIONS: In Southeast Asia, tramadol plays an important part in the pharmacological management of moderate to severe pain, and may be the only available treatment option. If it were to become a controlled substance, the standard of pain management in the region would decline.