Effect of Sodium-Glucose Cotransporter 2 Inhibitors on the 24-Hour Ambulatory Blood Pressure in Patients With Type 2 Diabetes Mellitus and Hypertension: An Updated Meta-Analysis.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed for type 2 diabetes mellitus (DM) treatment, have shown potential benefits beyond glycemic control, including a positive impact on the blood pressure (BP). This meta-analysis aimed to evaluate their effects on patients with type 2 DM and hypertension. METHODS: We searched the PubMed, Google Scholar, and Cochrane databases for relevant randomized controlled trials published until May 31, 2023. Ten randomized controlled trials involving participants with confirmed type 2 DM were selected. The intervention group received SGLT2i, whereas the control group received a placebo or standard care. The primary outcomes were the 24-hour ambulatory systolic BP (SBP) and diastolic BP (DBP). RESULTS: The results showed a significant reduction in the 24-hour ambulatory SBP (weighted mean difference, -5.08 mm Hg; 95% confidence interval, -7.02 to -3.14; P <.00001) and DBP (weighted mean difference, -2.73 mm Hg; 95% confidence interval, -4.25 to -1.20; P =.0005) with the use of SGLT2i compared with that using the placebo. However, a high-heterogeneity level was observed in both analyses (SBP, I2 = 83%; DBP, I2 = 91%). Sensitivity analysis excluding specific studies reduced heterogeneity while maintaining statistically significant and clinically relevant reductions in the BP. CONCLUSION: In conclusion, this meta-analysis proves that SGLT2i significantly reduce the 24-hour ambulatory BP. SGLT2i may be considered an effective treatment option for lowering the BP in addition to standard care in patients with hypertension and type 2 DM.

Comparing pyridoxine with dopaminergic agonists (cabergoline and bromocriptine): Unveiling the strategy for lactation inhibition - A systematic review of clinical trials.

This systematic review aims to evaluate the efficacy and safety of Pyridoxine compared to Dopaminergic agonists (cabergoline and bromocriptine) in post-partum lactation inhibition. Cochrane Central, PubMed/MEDLINE, Cochrane Central, ScienceDirect, ClinicalTrials.gov, Web of Science, CINAHL and Google Scholar, covering the period from inception to November 2023. Additionally, the bibliographies of included articles and previous meta-analyses were screened for any relevant articles. The systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The outcomes of interest encompassed inhibition of lactation, breast pain/tenderness, breast engorgement, milk secretion, fever, mastitis, prolactin level and adverse events related to pyridoxine, cabergoline and bromocriptine. Methodological quality assessment was conducted using the Cochrane risk of bias assessment tool for rigorous evaluation. Three clinical trials assessed the effectiveness of pyridoxine and dopaminergic agents (cabergoline and bromocriptine) for lactation inhibition. It was assessed by using different assessment methods such as a scale for milk secretion, serum prolactin levels, and questionnaires for assessing breast engorgement, breast pain, and milk leakage. On the global assessment of the therapeutic efficacy of dopaminergic agents, it was found that there was significant inhibition of lactation as compared to pyridoxine (p < 0.001). In conclusion, this systematic review contributes significant insights into lactation inhibition interventions. Dopaminergic agonists, specifically cabergoline and bromocriptine, stand out as more effective and tolerable choices compared to Pyridoxine. These findings provide a foundation for informed clinical decisions and underscore the need for careful consideration of lactation inhibition strategies in diverse clinical contexts.

Differential Use of Glycoprotein IIb/IIIa Inhibitors with Bivalirudin in Patients with STEMI Undergoing PCI: A Systematic Review and Meta-Analysis.

AIM: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI. METHODS: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003). CONCLUSION: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.

The use of acetaminophen in pregnancy: a double whammy.

Acetaminophen is the most widely over the counter used analgesic in the world, and the World Health Organization advises using it as first-line treatment for pain issues (WHO).However, various side effects have been documented with its use such as nausea, vomiting, constipation at low doses whereas in large doses, it might even result in hepatoxicity.Recent literature suggests that the use of acetaminophen in pregnancy even in optimal doses could result infant being born with ADHD and autism, so in this short communication we talk about the prevalence of neurodevelopment disorders in infants as a result of its use, as well as shed light to the measures that should be adopted to minimize the adverse effects.

A retrospective comparison of two different immobilization systems for radiotherapy of extremity soft tissue sarcomas and its influence on CTV-PTV margin.

BACKGROUND: On account of extremity wide range of movements and difficulty of reproducibility during irradiation of extremity sarcomas, assorted immobilization strategies are employed to eliminate setup errors. The study purpose was to compare the setup errors of the commonly used immobilization tools and to define planning target volume (PTV) margins for each device. METHODS: A retrospective review comparing Vac-Loc™ and thermoplastic cast (Tcast) was conducted. On radiotherapy treatment, portal imaging was matched with the pre-treatment simulation imaging for both fixation tools. The isocenter shifts and total vector error (TVE) were compared. Random (σ) and systemic errors (Σ) were computed and PTV margins were defined. RESULTS: Three hundred seven shifts in each direction measured in 14 patients. Mean displacements for the Vac-Loc™ and Tcast, respectively, were as follow: vertical; -0.01 cm vs. 0.02 cm, longitudinal; 0.03 cm vs. 0.04; lateral; 0.04 cm vs. 0.00 cm and TVE; 0.15 cm vs. 0.17 cm with no significant statistical difference. Random and systemic errors were comparable for both devices. The lateral displacement and rotational random errors were higher Vac-Loc™ compared to Tcast. Overall measured PTV margins were marginally lower for Tcast compared to Vac-Loc™. CONCLUSION: Vac-Loc™ and Tcast are valid options for immobilization with no clear superiority of either device. The marginal advantage of Tcast warrants further prospective studies.

Survival after therapy for pediatric ependymoma in a tertiary care center in Saudi Arabia.

BACKGROUND: There is limited data from Saudi Arabia on the demographic characteristics, outcomes and effectiveness of different treatment modalities in children with intracranial ependymoma. OBJECTIVE: Study the characteristics of pediatric ependymoma and outcomes of treatment modalities in Saudi Arabia. DESIGN: Retrospective. SETTING: Tertiary care center. PATIENTS AND METHODS: Children with intracranial ependymoma who were younger than 14 years of age and treated between 2006 and 2015 were included in the study. Patients with prior radiation, chemo-therapy, or surgical resection at other centers were excluded. MAIN OUTCOME MEASURES: Kaplan-Meier survival curves were used to estimate the event-free (EFS) and overall survival (OS) rates of the patients. SAMPLE SIZE: 22. RESULTS: Of the 22 children, 4 (18.2%) were less than three years old. All intracranial ependymomas had upfront surgical resection of the primary tumor. Gross total resection was achievable in 9 (42.9%) cases and subtotal resection in another 9 (42.9%). Near-total resection was done in 3 (14.3%) cases. Median time from surgery to start of radiotherapy was 62 days. RT was given to 17 (77.3%) patients. Both mean and median RT dose was 55.8 Gy. Only 5 (22.7%) of the children received chemotherapy. The median duration of follow-up was 5.38 years and the median time for EFS was 2.27 years. The cumulative OS rate of the study was 44.5%. The cumulative EFS survival rate of the study was 18.6%. Among demographic, pathological, radiological features, none had a statistically significant effect on the survival. CONCLUSIONS: The outcomes are comparable to those reported by international investigators for similar populations. Further improvements can be achieved by avoiding delays in radiation therapy and adding molecular staging. LIMITATIONS: The limited number of cases, retrospective nature, lack of molecular biology and size of the tumors. CONFLICT OF INTEREST: None.

Efficacy of 8 Gy Single Fraction Palliative Radiation Therapy in Painful Bone Metastases: A Single Institution Experience.

Introduction Bone metastasis (BM) is a major complication of many solid tumors like breast, prostate, lung and renal cancers. BM leads to serious sequelae of pain, fractures, spinal cord compression and hypercalcemia. Radiotherapy has an established role in relieving pain caused by BM. Worldwide different radiotherapy schedules are being used for BM. The aim of this study is to determine the efficacy of single fraction palliative radiotherapy for painful bone metastases. Methods Between April 2014 and April 2017, single fraction radiotherapy was used to treat 73 patients in our institution. They had pathologically proven breast, prostate, lung or renal cancer with radiological evidence of bone metastases. There were 39 males (53%) and 34 females (47%). The median age was 58 years (range 33-87 years). 39% patients (n = 28) had breast cancer, 35% had prostate cancer (n = 26), 23% had lung cancer (n = 17), and 3% had renal cancer (n = 2). On presentation, all the patients had a pain score of more than five on Brief Pain Inventory (BPI). Results Response assessment to pain after three months from single fraction radiotherapy was found to be complete response (CR) in 23% patients (n = 17), partial response (PR) in 38% patients (n = 28), stable disease (SD) in 26% patients (n = 19) and progressive disease (PD) in 12% patients (n = 9). The overall efficacy of treatment was 62%, with CR 23% and PR 38%. Pre-treatment mean pain score was 8.15 compared to 4.68 post-treatment (p < 0.001). Conclusions Single fraction palliative radiotherapy of 8 Gy showed significant efficacy in painful bone metastases in our setting and merits further investigation in our population.

Bleeding in Locally Invasive Pelvic Malignancies: Is Hypofractionated Radiation Therapy a Safe and Effective Non-Invasive Option for Securing Hemostasis? A Single Institution Perspective.

INTRODUCTION:  Control of bleeding due to locally invasive disease is of paramount importance in the management of cancer patients. This study was undertaken to explore the outcomes of palliative intent hypofractionated radiation therapy (HRT) in advanced stage pelvic malignancies that presented with bleeding. METHODS:  This study enrolled patients treated with palliative intent hypofractionated radiation therapy from July 2015 to November 2017. In the inclusion criteria, all these patients had the common presenting complaint of bleeding from the tumor. These patients were not treated with radiation therapy before for the same indication. Patients with known bleeding disorders and those undergoing parallel interventions for bleeding control were excluded from the study. Bleeding was categorized based on the World Health Organization (WHO) scale for the classification of bleeding. Response assessment was classified into a complete response, partial response and no response. A comparison was made for the bleeding scale before and after HRT using the Wilcoxon signed rank test. The comparison of mean hemoglobin levels before and after the HRT was calculated by paired t-test. RESULTS:  Forty-two patients with advanced pelvic malignancies qualified for inclusion in the study after applying the inclusion/exclusion criteria. Among those analyzed, the median age was 67 years (range 37 - 95 years). The male and female proportion was 38% and 62% respectively. Different cancers included uterine cancer 31%, cervical cancer 24%, bladder cancer 21%, rectal cancer 17% and vulvar cancer in 7%. The baseline bleeding scale in these cases was found to be grade 1 in 12%, grade 2 in 55% and grade 3 in 33% cases. The median dose in our cohort was 20 Gy in five fractions over one week (range was 8 Gy to 40 Gy). Following HRT, the WHO bleeding score at one month was recorded as grade 0 in 57%, grade 1 in 31%, grade 2 in 7%, grade 3 in 5% and grade 4 in none. Toxicity profile did not show any grade 3 or above acute toxicity in the study. Response rates were 57% complete response, 36% partial response and 7% no response. The mean hemoglobin level post-treatment versus pre-treatment was found to be 9.6 g/dL versus 7.3 g/dL. CONCLUSIONS:  Hypofractionated radiotherapy was found to be a safe and effective non-invasive palliative treatment modality for securing hemostasis in advanced pelvic malignancies that presented with bleeding.

Outcomes of Early-stage Glottic Carcinoma Treated with Radiation Therapy: A Single Institution Experience.

OBJECTIVE:  To evaluate the outcomes of radical intent radiation therapy in early glottic carcinoma (EGC), including local control rate (LCR), disease-free survival (DFS), death specific free survival (DSFS), and overall survival (OS) rates, in Saudi patients treated at a single institution.  Materials and methods: This is an institutional review board (IRB) approved, retrospective study of 27 patients with T1-2 N0 M0, early glottic carcinoma (EGC) who were treated from 2010 to 2015 at our institution with different radiotherapy (RT) fractionation regimens. The regimens included six different fractionation schedules of radiotherapy (RT): 50 Gy (20 x 2.5 Gy) dose prescribed to 95% isodose line, 52.4 Gy (20 x 2.52 Gy), 63 Gy (28 x 2.25 Gy), 66 Gy (33 x 2 Gy), and 70 Gy (35 x 2 Gy). The cohort was stratified into two groups, ≤ 52.5 Gy (n=15) and > 52.5 Gy (n=12). The median follow-up of all patients was 31.7 months (range 7-82). RESULTS: The mean age of the cohort was 64.5 years (median 65, range: 41-83). Eleven patients (40.7%) had a history of smoking. The majority of the cohort was with T1a EGC (70.4%, n=19), and anterior commissure invasion was seen in three patients (11.1%). The mean RT doses were 55.6 Gy (range: 50-70). The five-year LCR, DFS, DSFS, and OS rates were 83.1%, 80.0%, 96.2%, and 92.6%, respectively. The LCR rates for those receiving a dose of 52.5 Gy or less were 61.3 months compared to 89.5 months for those who received more than 52.5 Gy (p=0.994). Non-smokers and patients with an unknown smoking history achieved a five-year LCR of 100%, while patients with a positive smoking history achieved a five-year LCR of 60.6% (p=0.044). CONCLUSION:  Radiation therapy for EGC in our patients showed reasonable five-year LCR with larynx preservation at 83.1%, DFS 80.0%, five-year OS rate 92.6%, and DSFS rate 96.2%. We found that smoking had a significant correlation with LCR. However, large prospective trials are warranted to evaluate the efficacy of overall treatment time, dose per fraction of above 2 Gy, and smoking effect.