Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Comparative efficacy, safety, and tolerability of diclofenac and aceclofenac in musculoskeletal pain management: A systematic review

Diclofenac and aceclofenac are nonsteroidal antiinflammatory drugs (NSAIDs). Diclofenac is advocated for the treatment of painful and inflammatory rheumatic and certain nonrheumatic conditions such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, and bursitis, and in other inflammatory or painful conditions such as strains and sprains, dysmenorrhea, back pain, sciatica, and postoperative pain. Aceclofenac provides symptomatic relief in a variety of painful conditions such as joint inflammation, and reduces pain intensity and the duration of morning stiffness in the patients with rheumatoid arthritis, improves spinal mobility in the patients with ankylosing spondylitis. Gastrointestinal (GI) problems are the most frequent effects, which are caused by diclofenac and include dyspepsia and abdominal pain. Aceclofenac also has similar adverse effect but they are mild compared to diclofenac. We have reviewed 9 prospective studies that compared efficacy and safety of diclofenac with those of aceclofenac, 5 studies on osteoarthritis patients, 1 study on rheumatoid arthritis patients, 1 study on overall musculoskeletal disorders, 1 study on lower back pain, and 1 study on postextraction dental pain. Western Ontario and McMaster (WOMAC) universities scores, visual analogue scale (VAS), the Ritchie index, Lequesne OA severity index (OSI) were used in assessing the pain intensity and measuring the efficacy of the drug that proved beneficial in assessing the pain intensity and measuring the efficacy of both the drugs. All the studies came to the conclusion that aceclofenac is a better choice of drug in managing pain in case of all the above conditions with better efficacy and tolerability, patients experienced more number of adverse events (AEs) with diclofenac when compared with aceclofenac

A study of prescribing pattern, comorbidities, and cost analysis in elderly hospitalized patients in Pune

Aim: To study prescribing pattern, comorbidities, and cost analysis in elderly hospitalized patients. Materials and Methods: A prospective, observational study was conducted to assess the prescribing pattern, drug utilization, and cost analysis in elderly patients at a tertiary care hospital in Pune. Data of 120 patients were used to carry out the analysis. Result: A total of 120 elderly inpatients were included in the study. Of these 120 patients, 62 were male and 58 were female; among them, maximum number of patients belong to 60-74 years age group. Common comorbidities found were anemia, lower respiratory tract infections (LRTI), urinary tract infection, hypertension, diabetes mellitus, etc. Mostly hospitalized patients were hypertensive (27.5%), diabetic (18.33%), and anemic (15.83%) followed by respiratory tract infections such as pulmonary Koch′s, pneumonia, and LRTI. Two comorbid conditions were found in 33.33% of patients followed by 25% with one comorbid condition and 24.16% had three comorbid conditions; on an average, three comorbidities were found in a total number of patients. Major classes of drugs prescribed for treatment were cardiovascular drugs (22.60%), antibiotic (20.13%), antiplatelet (7.26%), and antidiabetic drugs (6.43%). The average cost per patient was calculated 5016.48 international normalized ratio, which includes physician, nursing, bed charges, and therapy cost. Conclusion: This study concludes that the prescribing pattern of elderly patients with age group 60-74 years were commonly prescribed for cardiovascular drugs and antibiotic, whereas this proportion was low compared to patients with age >74 years and prescribing pattern also resulted in financial burden on patients healthcare cost

Research & Reviews: Journal of Hospital and Clinical Pharmacy Monitoring Of Adverse Drug Reactions in Elderly Patients in an Indian Tertiary Care Hospital

ABSTRACT Aim: Present study was carried out to assess the incidence of adverse drug reactions (ADR) and assessment of causality, severity, preventability and additional financial burden associated with reported suspected ADRs. Methodology: A prospective spontaneous reporting study was conducted over a period of six months in inpatients of medicine wards and medical intensive care unit at Bharati Hospital, Pune. WHO Probability scale was used for causality assessment. Reported ADRs were classified according to Wills & Brown classification and assessed for severity using scale was developed. Average cost incurred in treating an ADR was calculated. Results: A total of 319 suspected ADRs were reported and evaluated from 78 patients showing an overall incidence of 9.17%. Most of the ADRs were augmented type, whose pharmacology is known. 66% ADRs were classified as "POSSIBLE" in view of causality, while 87% were found to be "MILD" in case of severity. Preventability was found to be 22.87%. Average cost incurred in treating an ADR in hospitalized inpatients was found to be Rs.1328.71 (US $21.90) in India. Conclusion: Incidence of ADRs was more in hospitalized patients compared to ADR induced hospital admission. Awareness about ADR reporting is still poor amongst healthcare professionals in India. Average cost incurred for treating ADR leading to hospital admission was higher

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine