An observational study on dapagliflozin as an add-on therapy in type-2 diabetes mellitus patients in a tertiary care teaching hospital

Background: Diabetes mellitus is one of the prevalent morbid conditions all over the world and no exception for India. Day by day, increase in its prevalence is attributed to lifestyle derangements. To treat this condition many drugs and treatment modalities are developed. Dapagliflozin is an oral antidiabetic drug which acts by sodium-glucose cotransport-2 (SGLT-2) inhibition. Its effectiveness seen in type-2 diabetes mellitus makes it an option for Add-On therapy. Methods: This study is a retrospective observational study conducted at tertiary care hospital, GGH, Kurnool. The study proposal has been reviewed and approved by institutional ethics committee. All adult diabetic patients who were prescribed Dapagliflozin during the period of January 2021 to February 2022, total 45 were included in the study. FBG, HbA1c collected through hospital records from General Medicine and Endocrinology. Patients who stopped drug before 3 months period were excluded. Results: Administration of dapagliflozin as an add-on therapy was found 26.63% decrease in base line mean FBG 184 mg/dl to 135 mg/dl after 3mnoths which is significant (p=0.001). Mean HbA1c significantly reduced by 0.96 percentage point after 3 months (p=0.001). Dapagliflozin effectively reduced the FBG and HbA1c when used in combination with other OHAs or insulin within 3 months. Conclusions: Dapagliflozin as an add-on therapy significantly reduced the HbA1c level and fasting blood glucose of Type-2DM patients, in a 3-month treatment period. Due to the frequency of Genitourinary tract infections, caution is indicated while treating the patients

Taxanes induced hypersensitivity reactions in cancer chemotherapy patients reported at adverse drug reaction monitoring centre at a tertiary care hospital

Background: Cancer chemotherapy involves highly complex regimens using antineoplastic agents like taxanes (paclitaxel, docetaxel) etc. Taxanes cause hypersensitivity reactions (HSRs) like redness, rashes, dyspnoea, severe anaphylaxis and death. In this study, adverse drug reactions (ADRs) associated with taxanes are described & analysed on their severity and preventability. The present study aims to analyse and determine the prevalence of ADRs, especially HSRs in patients treated with taxanes.Methods: After getting IEC approval, the present study is done retrospectively by assessing the HSRs in suspected ADR reporting forms from December 2019 to February 2022 in ADR monitoring centre (AMC) in the Department of Pharmacology at Kurnool Medical College, Kurnool. Descriptive statistics used to analyse patient demography, frequency, various carcinomas under treatment & organ involved, causality assessment using WHO-UMC Scale and Naranjo's Algorithm, severity assessment using modified Hartwig & Siegel’s scale and preventability by modified Schumock & Thornton scale.Results: A total of 258 ADRs were recorded, of which 30 cases reported HSRs with taxanes-paclitaxel (22) and docetaxel (8). The most commonly occurred HSR is shortness of breath. Naranjo’s algorithm showed 52.5% possible (score 1-4) HSRs. WHO-UMC causality assessment scale showed 56.4% as probable HSRs. Modified Hartwig & Siegel severity scale showed 46.6% moderate (level 3). Modified Schumock and Thornton scale showed 76.9% as not preventable.Conclusions: Chemotherapy-related ADRs among cancer patients urges the oncologists to be actively involved in ADR reporting, in the need of the hour in order to mitigate, avoid their occurrence and reducing morbidity and mortality, when practiced with diligence

Evaluation of knowledge, attitude and practice towards drug-drug interactions among postgraduates in tertiary care hospital, Kurnool

Background: Drug-drug interactions (DDIs) are changes in a drug’s effects due to concurrent use of another drug. Clinically significant interactions lead to undesired adverse effects, therapeutic failure, toxicity or may even cause death of the patients. The Aim is to evaluate the Knowledge, Attitude and Practice of Postgraduates regarding DDIs and implementation of educational program may enhance patient’s safety.Methods: A cross-sectional study was conducted among postgraduates in all clinical departments of Government general hospital, Kurnool in the month of October 2021. Pre-validated questionnaire was used to assess the KAP. It contains demographic data, knowledge and practice questions related to DDIs and attitude towards the preferable sources of drug interaction information. Data analysis was done by using SPSS version 26.Results: Out of 220 questionnaires distributed, 126 postgraduates submitted with complete answers(n=126). Overall response rate is 57%. By using the Bloom’s cut-off points, most of the respondents (43.5%) had low level of knowledge towards DDIs. Even respondents with high knowledge level (19%) are not practicing the drug interaction screening during the admission of patients. Majority of PGs with low level knowledge agreed to ask doctors than pharmacist about DDIs and prefer to search for DDIs using reference book than online mode as the source of drug information.Conclusions: In my study, most of the respondents had insufficient knowledge to prevent life threatening DDI’s. So, there is a need to increase medical educational program regarding the importance of screening and assessing of DDI’s before prescribing medicines

Multiple Organ System Defects and Transcriptional Dysregulation in the Nipbl+/− Mouse, a Model of Cornelia de Lange Syndrome

Cornelia de Lange Syndrome (CdLS) is a multi-organ system birth defects disorder linked, in at least half of cases, to heterozygous mutations in the NIPBL gene. In animals and fungi, orthologs of NIPBL regulate cohesin, a complex of proteins that is essential for chromosome cohesion and is also implicated in DNA repair and transcriptional regulation. Mice heterozygous for a gene-trap mutation in Nipbl were produced and exhibited defects characteristic of CdLS, including small size, craniofacial anomalies, microbrachycephaly, heart defects, hearing abnormalities, delayed bone maturation, reduced body fat, behavioral disturbances, and high mortality (75–80%) during the first weeks of life. These phenotypes arose despite a decrease in Nipbl transcript levels of only ∼30%, implying extreme sensitivity of development to small changes in Nipbl activity. Gene expression profiling demonstrated that Nipbl deficiency leads to modest but significant transcriptional dysregulation of many genes. Expression changes at the protocadherin beta (Pcdhb) locus, as well as at other loci, support the view that NIPBL influences long-range chromosomal regulatory interactions. In addition, evidence is presented that reduced expression of genes involved in adipogenic differentiation may underlie the low amounts of body fat observed both in Nipbl+/− mice and in individuals with CdLS

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe