Dapagliflozin Pretreatment Prevents Cardiac Electrophysiological Changes in a Diet and Streptozotocin Induction of Type 2 Diabetes in Rats: A Potential New First-Line?

Purpose: Dapagliflozin exerts cardioprotective effects in Type 2 Diabetes Mellitus (T2DM). However, whether these effects prevent electrocardiographic changes associated with T2DM altogether remain unknown. Our aim was to investigate the prophylactic effect of dapagliflozin pretreatment on the rat ECG using a high-fat, high-fructose (HFHf) diet and a low dose streptozotocin (STZ) model of T2DM. Methods: Twenty-five (25) rats were randomized into five (5) groups: normal control receiving a normal diet while the other groups received an 8-week HFHf and 40mg/kg STZ on day 42, and either: saline for the diabetic control (1 mg/kg/d), low dose (1.0 mg/kg/d) and high dose dapagliflozin (1.6 mg/kg/d), or metformin (250 mg/kg/d). Oral glucose tolerance (OGT), electrocardiograms (ECGs), paracardial adipose mass, and left ventricular fibrosis were determined. Data were analyzed using GraphPad version 9.0.0.121, with the level of significance at p < 0.05. Results: Compared to the diabetic control group, a high dose of dapagliflozin preserved the OGT (p = 0.0001), QRS-duration (p = 0.0263), QT-interval (p = 0.0399), and QTc intervals (p = 0.0463). Furthermore, the high dose dapagliflozin group had the lowest paracardial adipose mass (p = 0.0104) and fibrotic area (p = 0.0001). In contrast, while metformin showed favorable effects on OGT (p = 0.0025), paracardial adiposity (p = 0.0153) and ventricular fibrosis (p = 0.0291), it did not demonstrate significant antiarrhythmic effects. Conclusion: Pretreatment with higher doses of Dapagliflozin exhibits prophylactic cardioprotective characteristics against diabetic cardiomyopathy that include antifibrotic and antiarrhythmic qualities. This suggests that higher doses of dapagliflozin could be a more effective initial therapeutic option in T2DM.

Knowledge, attitudes and practices towards COVID-19 among healthcare workers: A cross-sectional survey from Kiambu County, Kenya.

BACKGROUND: The knowledge possessed by healthcare workers (HCWs), along with their attitudes and practices play a vital role in effectively managing a pandemic. This is crucial considering that HCWs are exposed to great risk at the forefront of such crises. We aimed to describe the knowledge, attitude, and practices (KAP) of HCWs during the COVID-19 pandemic in Kiambu county, Kenya. METHODS: A cross-sectional study using a structured questionnaire was conducted from 11th March 2021 to 12th August 2021. Bloom's cutoff points were used to determine KAP scores (>80%: good, 60-79%: medium and <60% poor). Multivariable ordinal logistic regression analyses were conducted, calculating adjusted odds ratios (AOR) at a 95% confidence interval. Spearman's rank correlations were used to examine the relationship between KAP scores. RESULTS: 438 HCWs participated in the study, majority of whom were female (64.5%), had obtained a diploma (59.6%) and were informed through government websites (78.6%). 43.0% had good knowledge, 17.5% good attitudes, and 68.4% good practice. 23.0% had medium knowledge, 35.6% medium attitude, 15.7% medium practice, while 34.0% had poor knowledge, 46.9% poor attitude and 15.9% poor practice. Only 68.9% of the caregivers correctly recognized the county's COVID-19 isolation centre and only 7.9% chose the two correct documents for the entry of data for a suspected COVID-19 case. Furthermore, the general attitude towards their own personal safety and their training regarding PPEs (17.8% and 23.8% strongly agreed with the contrary) were less compelling. There was a significant positive association between obtaining information from international government sites [AOR: 1.382 (1.058-1.807); p = 0.0178)] and good knowledge. Referring to local government sites for information regarding COVID-19 produced better attitudes [AOR: 1.710 (1.194-2.465); p = 0.0036] and produced almost twice the odds of having better practice [AOR: 1.800 (1.181-2.681); p = 0.0048]. There was a significant correlation between knowledge and practice (r = -0.330, p = 2.766×10-11), and knowledge and attitude (r = -0.154, p = 6.538×10-3). CONCLUSION: This study emphasizes the substantial impact that governing bodies have on shaping favorable KAP. As a result, it's crucial for local government platforms to prioritize the dissemination of up-to-date information that aligns with international standards. This information should be tailored to the specific region, focusing on addressing deficiencies in healthcare practices and patient management. The identification of a significant number of HCWs lacking confidence in managing COVID-19 patients and feeling unprotected underscores a clear need for improvement in their understanding and implementation of preventive measures. This gap can be bridged by adequately equipping HCWs with locally manufactured PPEs. This aspect is crucial for pandemic preparedness, and we further advocate for the creation of a locally produced repository of medical equipment. These actions are pivotal in improving future crisis management capabilities.

Comparing labour induction outcomes using misoprostol and dinoprostone in term pregnancies: A retrospective study at Kiambu Level 5 Hospital between 2018 and 2020.

BACKGROUND: The Maternal and Perinatal Death Surveillance and Response (MPDSR) was introduced in Kenya in 2016 and implemented at Kiambu Level 5 Hospital (KL5H) three years later in 2019. During a routine MPDSR meeting at KL5H, committee members identified a possible link between the off-label use of 200mcg misoprostol tablets divided eight times to achieve the necessary dose for labour induction (25mcg) and maternal deaths. Following this, an administrative decision was made to switch from misoprostol to dinoprostone for the induction of labour in June of 2019. This study aimed to assess the overall impact of MPDSR as well as the effect of replacing misoprostol with dinoprostone on uterine rupture, maternal and neonatal deaths at KL5H. METHODS: We conducted a retrospective cohort study of women who gave birth at KL5H between January 2018 and December 2020. We defined the pre-intervention period as January 2018-June 2019, and the intervention period as July 2019-December 2020. We randomly selected the records of 411 mothers, 167 from the pre-intervention period and 208 from the intervention period, all of whom were induced. We used Bayes-Poisson Generalised Linear Models to fit the risk of uterine rupture, maternal and perinatal death. 12 semi-structured key person questionnaires was used to describe staff perspectives regarding the switch from misoprostol to dinoprostone. Inductive and deductive data analysis was done to capture the salient emerging themes. RESULTS: We reviewed 411 patient records and carried out 12 key informant interviews. Mothers induced with misoprostol (IRR = 3.89; CI = 0.21-71.6) had an increased risk of death while mothers were less likely to die if they were induced with dinoprostone (IRR = 0.23; CI = 0.01-7.12) or had uterine rupture (IRR = 0.56; CI = 0.02-18.2). The risk of dying during childbearing increased during Jul 2019-Dec 2020 (IRR = 5.43, CI = 0.68-43.2) when the MPDSR activities were strengthened. Induction of labour (IRR = 1.01; CI = 0.06-17.1) had no effect on the risk of dying from childbirth in our setting. The qualitative results exposed that maternity unit staff preferred dinoprostone to misoprostol as it was thought to be more effective (fewer failed inductions) and safer, regardless of being more expensive compared to misoprostol. CONCLUSION: While the period immediately following the implementation of MPDSR at KL5H was associated with an increased risk of death, the switch to dinoprostone for labour induction was associated with a lower risk of maternal and perinatal death. The use of dinoprostone, however, was linked to an increased risk of uterine rupture, possibly attributed to reduced labour monitoring given that staff held the belief that it is inherently safer than misoprostol. Consequently, even though the changeover was warranted, further investigation is needed to determine the reasons behind the rise in maternal mortalities, even though the MPDSR framework appeared to have been put in place to quell such an increase.