Effect of routine pre-operative urethral catheterization of women undergoing minor gynaecological surgeries on urinary symptoms and urinary infections: a randomized control study

Background: The prevalence of urinary tract infection increases in young sexually active women, and women with previous UTI. Routine urethral catheterization performed for bladder evacuation before minor gynecological procedures and it is not clear whether this routine urethral catheterization associated with increased incidence of bacteriuria or UTIs or not. This study designed to detect the effect of routine uretheral catheterization for women undergoing minor gynecological surgeries on urinary symptoms and urinary infections.Methods: Two hundred and forty women infertile women scheduled for uterine assessment by diagnostic hysteroscopy before in-vitro fertilization in assisted reproduction unit of Ahmadi Hospital, Kuwait Oil Company were included in this study. Participants were randomized into; group I (catheterized group) and group II (non-catheterized group). Participants’ urine samples compared pre-operatively and post-operatively and they asked to complete about their pre and post-operative urinary symptoms.Results: Post-operative dysuria, frequency and urgency were significantly higher in catheterized group (22 (18.33%), 26 (21.66%) and 18 (15%); respectively) compared to non- catheterized group [5 (4.16%), 7 (5.83%) and 4 (3.33%); respectively]. Relative risk of dysuria, frequency and urgency after catheterization were 4.4, 3.7 and 4.5; respectively (95% CI; 1.7-11.2, 1.67-8.22 and 1.56-12.9; respectively). Asymptomatic bacteriuria, UTIs and subsequent need for antimicrobial therapy were also significantly high in catheterized group [15 (12.5%), 18 (15%) and 18 (15%); respectively) compared to non-catheterized group (3 (2.5%), 2 (1.96%) and 2 (1.96%); respectively]. Relative risk of asymptomatic bacteriuria and UTIs after catheterization in women undergoing minor gynecological procedures were 5 and 9; respectively (95%CI; 1.48-16.8 and 2.1-37.9).Conclusions: Catheterization in women undergoing minor gynecological surgery was associated with increased risk of dysuria, frequency, urgency, ASB, UTIs and subsequent antimicrobial therapy. Surgeons should revise the practice of routine preoperative catheterization for women undergoing minor gynecological procedures

Accuracy of Gray‑scale and Three‑dimensional Power Doppler Ultrasound Parameters in the Diagnosis of Morbidly Adherent Placenta

Background: Morbidly adherent placenta (MAP) is usually associated with excess blood loss, bladder injuries, and hysterectomies.Aim: This study was designed to evaluate the accuracy of grayscale and three-dimensional (3D) power Doppler ultrasound parameters in the diagnosis of MAP. Subjects and Methods: Fifty pregnant women ≥28 weeks’ gestation with suspected MAP were included randomly in this prospective study. Two-dimensional (2D) transabdominal gray-scale ultrasound and 3D power Doppler scans were done for studied women to confirm placental location and findings suggestive of MAP. Intraoperative findings and histopathology results of removed uteri in the cases were managed by hysterectomies compared to preoperative sonographic findings using Student’s t-test and Mann–Whitney U-test for quantitative data, Chi-square test for qualitative data to detect the accuracy of 2D transabdominal gray-scale ultrasound and 3D power Doppler parameters in the diagnosis of MAP. Results: Best 2D gray scale ultrasound parameters for the detection of emergency hysterectomies in the studied cases were disruption of uterine serosa– bladder interface (81.8% sensitivity) and exophytic mass invading bladder (94.9% specificity, 66.7% positive predictive value (PPV), and 84.1% negative predictive value [NPV]). Best 3D power Doppler parameters for the detection of emergency hysterectomies in the studied cases were disruption of uterine serosa–bladder interface (90.9% sensitivity, 68.8% specificity, and 47% PPV) and crowded vessels over peripheral subplacental zone (93.2% NPV). Conclusion: 3D power Doppler is a useful complementary tool to 2D gray-scale ultrasound for antenatal diagnosis of MAP. Crowded vessels over peripheral sub-placental zone and disruption of uterine serosa–bladder interface were the best 3D power Doppler parameters for the detection of difficult placental separation, considerable intraoperative blood loss, and emergency hysterectomies in the studied cases.KEY WORDS: Three‑dimensional power Doppler, gray-scale, morbidly adherent placent

Effect of Progesterone Therapy versus Diet Modification on Constipation during Pregnancy

Background: Pregnant women may experience constipation for the first time or their existing constipation symptoms increase in severity during pregnancy.Aim: To compare the effect of progesterone versus diet modification in the treatment of constipation during pregnancy.Subjects and Methods: Women aged ≥18 years with functional constipation according to the Rome III criteria from obstetrics outpatients’ clinic and midwife practices included in this study. Participants divided into two groups; control group managed with diet modifications and study group pregnant women with threatened miscarriage and advised to take vaginal progesterone ≥1 week. Participants completed a nonvalidated questionnaire created by the authors during the whole week before intake of progesterone or diet modifications and after treatment phase. Independent Student’s t‑test and Chi‑square (X2) test were used for statistical analysis to compare between two studied groups. Primary outcome measures; change in defecation frequency.Results: Sensation of anorectal obstruction and sensation of incomplete evacuation were significantly less in Group B (progesterone therapy) compared to Group A (diet modification) (54% [154/281] and 62.98% [177/281] vs. 89.76% [614/684] and 91.08% [623/684], respectively) (P = 0.04 and 0.03, respectively). Straining during defecation and manual maneuvers to facilitate evacuation were significantly less in Group B compared to Group A (63.7% [179/281] and 19.9% [56/281] vs. 94.59% [647/684] and 86.54% [592/684], respectively) (P < 0.01 and 0.02, respectively). Episodes of abdominal pain and presence of reflux episodes were also significantly less in Group B compared to Group A (18.5% [52/281] and 17.43% [49/281] vs. 84.11% [589/684] and 75% [513/684], respectively) (P = 0.01 and 0.03, respectively). Conclusions: Estrogen, rather than progesterone, may be a detrimental factor of constipation during pregnancy via decreased bowel movement. Progesterone therapy seems to be effective in the treatment of functional constipation during pregnancy. A randomized placebo controlled trial is required to confirm the data of this study.KEY WORDS: Constipation, diet modification, pregnancy, progesteron

Identification of new FK866 analogues with potent anticancer activity against pancreatic cancer

11 p.- 2 fig.-4 tab.-8 schem.-1 graph. abst.Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases for which chemotherapy has not been very successful yet. FK866 ((E)-N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide) is a well-known NAMPT (nicotinamide phosphoribosyltransferase) inhibitor with anti-cancer activities, but it failed in phase II clinical trials. We found that FK866 shows anti-proliferative activity in three PDAC cell lines, as well as in Jurkat T-cell leukemia cells. More than 50 FK866 analogues were synthesized that introduce substituents on the phenyl ring of the piperidine benzamide group of FK866 and exchange its buta-1,4-diyl tether for 1-oxyprop-3-yl, (E)-but-2-en-1,4-diyl and 2- and 3-carbon tethers. The pyridin-3-yl moiety of FK866 was exchanged for chlorinated and fluorinated analogues and for pyrazin-2-yl and pyridazin-4-yl groups. Several compounds showed low nanomolar or sub-nanomolar cell growth inhibitory activity. Our best cell anti-proliferative compounds were the 2,4,6-trimethoxybenzamide analogue of FK866 ((E)-N-(4-(1-(2,4,6-trimethoxybenzoyl)piperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide) (9), the 2,6-dimethoxybenzamide (8) and 2-methoxybenzamide (4), which exhibited an IC50 of 0.16 nM, 0.004 nM and 0.08 nM toward PDAC cells, respectively.The research leading to these results has received funding from the European Community's Seventh Framework Programme [FP7-2007-2013] under grant agreement no. 256986 (PANACREAS), from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 813284 (INTEGRATA), by the Spanish Ministry of Science, Innovation, and Universities (SAF2017-89672-R) and by the Associazione Italiana per la Ricerca sul Cancro (AIRC), IG#22098.Peer reviewe

A roadmap toward implementing health technology assessment in Egypt

BackgroundThe Egyptian healthcare system is currently in the early phase of health technology assessment (HTA) implementation. The aim of this study is to propose an implementation roadmap based on the national healthcare system status.MethodsA survey was conducted among Egyptian healthcare sector decision-makers to assess the current and future (preferred) HTA implementation status in Egypt based on a widely used international scorecard methodology. Subsequently, interviews were conducted with experts representing middle- and top-tier management in the Egyptian healthcare system to interpret the survey results and recommend specific actions.ResultsExperts recommended more capacity-building programs for HTA and health economics. Additionally, they proposed establishing HTA units in separate healthcare authorities and merging them into a single central HTA unit in the long term. Regarding the scope of implementation, experts recommended commencing with the assessment of innovative pharmaceuticals, and thereafter, expanding the scope to cover all health technologies in the long term. Additionally, they recommended using innovative tools such as “multi-criteria decision analysis (MCDA)” for tendering, and “managed entry agreements” for reimbursement decisions. Local burden of diseases and costing studies were also recommended to facilitate the implementation of HTA.ConclusionExperts agreed that several actions are required for successful HTA implementation in Egypt, including coordination between HTA bodies, application of an explicit MCDA framework, and strengthening of local evidence generation. To implement these actions, investment in technical capacity-building is indispensable. Most experts favored using multiple and soft cost-effectiveness thresholds. Efforts should be made to publish HTA submission guidelines and timelines of the processes

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Beyond Toxic Leaders : Follower-centered Approach

Rethinking the possible borders of leadership, requires an investigative work which problematizes the principal assumptions upon which leadership discourse is built. From follower-centered approach, this research examines the relational factors that might accelerate the wheel of toxic behaviour in organizations, with a brief critique of the out- dated themes which continue to occupy fair amount of the discourse of leadership, this critique is based on problematizing the perspectives, commonly referred to, as The Romance of Leadership. after doing so, I try to create a counterweight body of work in which I disregard some of leaders domination by focusing on followers instead, consequently, I attempt to introduce possible breakthrough in term of language as an approach to replace old and depreciated terms, as well as, recommendations for countering the radical views toward followers. In addition, I did an empirical investigation to the abovementioned themes by conducting a study in my workplace in order to check the plausibility of the conceptualization I done before, through, and after the empirical phase of this thesis, finally, I presented some personal reflections in regard with the course of study and suggested some ideas concerning the methodology within which this research has functioned.  

PERIODIC FASTING AS A TOOL FOR DRUG REPURPOSING: ENHANCEMENT OF CHOLESTEROL BIOSYNTHESIS INHIBITORS ANTITUMOR EFFECTS VIA DIETARY RESTRICTION

Drug repurposing through fasting could pinpoint new cancer cell liabilities and define new treatment options. By screening over 800 approved drugs in PK9 pancreatic ductal adenocarcinoma (PDAC) cells, we identified azoles, inhibitors of cholesterol biosynthesis, as agents whose cytotoxic activity against cancer cells was synergistically enhanced by starvation conditions. We hypothesized that starvation and azoles would cooperate by blunting cholesterol production in PDAC cells. Interestingly, we found other cholesterol inhibitors had their antitumor effects strongly enhanced by starvation. In addition, combined starvation and cholesterol inhibitors reduced tumor growth in gastrointestinal mouse models and intracellular cholesterol levels both in vitro and in vivo. Furthermore, methyl-beta-cyclodextrin, which depletes intracellular cholesterol, and starvation showed a synergistic cytotoxic effect against Capan-1 and MIA PaCa-2 cells (another PDAC cell line). Adding back cholesterol or LDL in gastrointestinal tumor cells/xenografts prevented the synergistic interaction between starvation and cholesterol inhibitors. Combined therapy inhibited pAKT (partially restored with LDL add-back) whereas, its antitumor activity was abolished by the simultaneous supplementation with circulating growth-promoting factors (IGF1, insulin, and leptin). In addition, combined therapy reduced mitochondrial oxidative phosphorylation (OXPHOS) and energy status in gastrointestinal tumor xenografts, whereas cholesterol restoration abolishes this effect. Taken together, these findings support the rationale for conducting clinical studies to assess the safety, feasibility, and activity of combining periodic cycles of fasting with inhibitors of cholesterol biosynthesis in cancer patients