Assertive community treatment for high-utilizing alcohol misuse patients: a before-and-after cohort study protocol.

BACKGROUND: The challenge posed by Alcohol-Related Frequent Attenders (ARFAs) in Emergency Departments (EDs) is growing in Singapore, marked by limited engagement with conventional addiction treatment pathways. Recognizing this gap, this study aims to explore the potential benefits of Assertive Community Treatment (ACT) - an innovative, community-centered, harm-reduction strategy-in mitigating the frequency of ED visits, curbing Emergency Medical Services (EMS) calls, and uplifting health outcomes across a quartet of Singaporean healthcare institutions. METHODS: Employing a prospective before-and-after cohort design, this investigation targeted ARFAs aged 21 years and above, fluent in English or Mandarin. Eligibility was determined by a history of at least five ED visits in the preceding year, with no fewer than two due to alcohol-related issues. The study contrasted health outcomes of patients integrated into the ACT care model versus their experiences under the exclusive provision of standard emergency care across Hospitals A, B, C and D. Following participants for half a year post-initial assessment, the evaluation metrics encompassed socio-demographic factors, ED, and EMS engagement frequencies, along with validated health assessment tools, namely Christo Inventory for Substance-misuse Services (CISS) scores, University of California, Los Angeles (UCLA) Loneliness scores, and Centre for Epidemiologic Studies Depression Scale Revised (CESD-R-10) scores. DISCUSSION: Confronted with intricate socio-economic and medical challenges, the ARFA cohort often grapples with heightened vulnerabilities in relation to alcohol misuse. Pioneering the exploration of ACT's efficacy with ARFAs in a Singaporean context, our research is anchored in a patient-centered approach, designed to comprehensively address these multifaceted clinical profiles. While challenges, like potential high attrition rates and sporadic data collection, are anticipated, the model's prospective contribution towards enhancing patient well-being and driving healthcare efficiencies in Singapore is substantial. Our findings have the potential to reshape healthcare strategies and policy recommendations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04447079. Initiated on 25 June 2020.

Implementation of Prediction Models in the Emergency Department from an Implementation Science Perspective-Determinants, Outcomes, and Real-World Impact: A Scoping Review.

STUDY OBJECTIVE: Prediction models offer a promising form of clinical decision support in the complex and fast-paced environment of the emergency department (ED). Despite significant advancements in model development and validation, implementation of such models in routine clinical practice remains elusive. This scoping review aims to survey the current state of prediction model implementation in the ED and to provide insights on contributing factors and outcomes from an implementation science perspective. METHODS: We searched 4 databases from their inception to May 20, 2022: MEDLINE (through PubMed), Embase, Scopus, and CINAHL. Articles that reported implementation outcomes and/or contextual determinants under the Reach, Effectiveness, Adoption, Implementation Maintenance (RE-AIM)/Practical, Robust, Implementation, and Sustainability Model (PRISM) framework were included. Characteristics of studies, models, and results of the RE-AIM/PRISM domains were summarized narratively. RESULTS: Thirty-six reports on 31 implementations were included. The most common prediction models implemented were early warning scores. The most common implementation strategies used were training stakeholders, infrastructural changes, and using evaluative or iterative strategies. Only one report examined ED patients' perspectives, whereas the rest were focused on the experience of health care workers or organizational stakeholders. Key determinants of successful implementation include strong stakeholder engagement, codevelopment of workflows and implementation strategies, education, and usability. CONCLUSION: Examining ED prediction models from an implementation science perspective can provide valuable insights and help guide future implementations.

Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Epidural analgesia is often used for pain relief during labour and childbirth, and involves administration of local anaesthetics (LA) into the epidural space resulting in sensory blockade of the abdomen, pelvis, and perineum. Epidural opioids are often co-administered to improve analgesia. Administration of epidural medications can be accomplished by basal infusion (BI) or automated mandatory bolus (AMB). With BI, medications are administered continuously, while AMB involves injecting medications at set time intervals. Patient-controlled epidural analgesia (PCEA) on top of AMB or BI enables patients to initiate additional boluses of epidural medications.  The superior method of delivering epidural medications would result in lower incidence of pain requiring anaesthesiologist intervention (breakthrough pain). Also, it should be associated with lower incidence of epidural-related adverse effects including caesarean delivery, instrumental delivery (use of forceps or vacuum devices), prolonged duration of labour analgesia, and LA consumption. However, clear evidence of the superiority of one technique over the other is lacking. Also, differences in the initiation of epidural analgesia such as combined spinal-epidural (CSE) (medications given into the intrathecal space in addition to the epidural space) compared to epidural only, and medications used (types and doses of LA or opioids) may not have been accounted for in previous reviews.  Our prior systematic review suggested that AMB reduces the incidence of breakthrough pain compared to BI with no significant difference in the incidence of caesarean delivery or instrumental delivery, duration of labour analgesia, and LA consumption. However, several studies comparing AMB and BI have been performed since then, and inclusion of their data may improve the precision of our effect estimates. OBJECTIVES: To assess the benefits and harms of AMB versus BI for maintaining labour epidural analgesia in women at term. SEARCH METHODS: We searched CENTRAL, Wiley Cochrane Library), MEDLINE, (National Library of Medicine), Embase(Elseiver), Web of Science (Clarivate), the WHO-ICTRP (World Health Organization) and ClinicalTrials.gov (National Library of Medicine) on 31 December 2022. Additionally, we screened the reference lists of relevant trials and reviews for eligible citations, and we contacted authors of included studies to identify unpublished research and ongoing trials. SELECTION CRITERIA: We included all randomised controlled studies that compared bolus dosing AMB with continuous BI during epidural analgesia. We excluded studies of women in preterm labour, with multiple pregnancies, with fetal malposition, intrathecal catheters, those that did not use automated delivery of medications, and those where AMB and BI were combined. DATA COLLECTION AND ANALYSIS: We used standard methodology for systematic review and meta-analysis described by Cochrane. Primary outcomes included: incidence of breakthrough pain requiring anaesthesiologist intervention; incidence of caesarean delivery; and incidence of instrumental delivery. Secondly, we assessed the duration of labour; hourly LA consumption in bupivacaine equivalents, maternal satisfaction after fetal delivery, and neonatal Apgar scores.  The following subgroup analyses were chosen a priori: epidural alone versus CSE technique; regimens that used PCEA versus those that did not; and nulliparous versus combination of nulli- and multi-parous women. We used the GRADE system to assess the certainty of evidence associated with our outcome measures. MAIN RESULTS: We included 18 studies of 4590 women, of which 13 enrolled healthy nulliparous women and five included healthy nulli- and multiparous women. All studies excluded women with preterm or complicated pregnancies. Techniques used to initiate epidural analgesia differed between the studies: seven used combined spinal epidural, 10 used epidural, and one used dural puncture epidural (DPE). There was also variation in analgesics used. Eight studies utilised ropivacaine with fentanyl, three used ropivacaine with sufentanil, two utilised levobupivacaine with sufentanil, one used levobupivacaine with fentanyl, and four utilised bupivacaine with fentanyl. Most of the studies were assessed to have low risk of randomisation, blinding, attrition, and reporting biases, except for allocation concealment where eight studies were assessed to have uncertain risk and three with high risk. Our results showed that AMB was associated with lower incidence of breakthrough pain compared to BI (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.55 to 0.91; I2 = 57%) (16 studies, 1528 participants), and lower hourly LA consumption in bupivacaine equivalents (mean difference (MD) -0.84 mg/h; 95% CI -1.29 to -0.38, I2 = 87%) (16 studies, 1642 participants), both with moderate certainty. AMB was associated with an estimated reduction in breakthrough pain incidence of 29.1% (incidence 202 per 1000, 95% CI 157 to 259), and was therefore considered clinically significant. The incidence of caesarean delivery (RR 0.85; 95% CI 0.69 to 1.06; I2 = 0%) (16 studies, 1735 participants) and instrumental delivery (RR 0.85; 95% CI 0.71 to 1.01; I2 = 0%) (17 studies, 4550 participants) were not significantly, both with moderate certainty. There was no significant difference in duration of labour analgesia (MD -8.81 min; 95% CI -19.38 to 1.77; I2 = 50%) (17 studies, 4544 participants) with moderate certainty. Due to differences in the methods and timing of outcome measurements, we did not pool data for maternal satisfaction and Apgar scores. Results reported narratively suggest AMB may be associated with increased maternal satisfaction (eight studies reported increased satisfaction and six reported no difference), and all studies showed no difference in Apgar scores. WIth the exception of epidural alone versus CSE which found significant subgroup differences in LA consumption between AMB and BI, no significant differences were detected in the remaining subgroup analyses. AUTHORS' CONCLUSIONS: Overall, AMB is associated with lower incidence of breakthrough pain, reduced LA consumption, and may improve maternal satisfaction. There were no significant differences between AMB and BI in the incidence of caesarean delivery, instrumental delivery, duration of labour analgesia, and Apgar scores. Larger studies assessing the incidence of caesarean and instrumental delivery are required.

Comparative efficacy of anaesthetic methods for closed reduction of paediatric forearm fractures: a systematic review.

BACKGROUND: Forearm fractures in children often require closed reduction in the emergency setting. The choice of anaesthesia influences the degree of pain relief, which determines the success of reduction. Main methods of anaesthesia include procedural sedation and analgesia, haematoma block, intravenous regional anaesthesia (IVRA) and regional nerve blocks. However, their comparative effectiveness is unclear. This study aims to synthesise peer-reviewed evidence and identify the most effective, in terms of pain reduction, and safest anaesthetic method. METHODS: MEDLINE, Embase and the Cochrane Library were searched from inception to 15 June 2021. Randomised controlled trials comparing anaesthetic methods for the closed reduction of paediatric forearm fractures in the emergency setting were included. Two reviewers independently screened, collected data and assessed the risk of bias for the selected outcomes. The primary outcome was pain during reduction. Secondary outcomes included pain after reduction, adverse effects, satisfaction, adequacy of sedation/anaesthesia, success of reduction and resource use. RESULTS: 1288 records were screened and 9 trials, which studied 936 patients in total, were included. Four trials compared the main methods of anaesthesia. Within the same method of anaesthesia, one compared administrative routes, one compared procedural techniques, one compared different drugs, one compared the use of adjuncts and one compared different doses of the same drug. One study found better pain outcomes with infraclavicular blocks compared with procedural sedation and analgesia. Lidocaine was superior in analgesic effect to prilocaine in IVRA in one study. One study found lower pain scores with moderate-dose than low-dose lidocaine in IVRA. CONCLUSION: Few randomised controlled trials compared anaesthetic methods in the closed reduction of paediatric forearm fractures. High heterogeneity precluded meta-analysis. Overall, current data are insufficient to guide the choice of anaesthetic method in emergency settings. More adequately powered trials, conducted using standardised methods, are required.

Trends of chronic illness in emergency department admissions among elderly adults in a tertiary hospital over ten years.

BACKGROUND: This study aimed to determine to what extent an aging population and shift to chronic illness has contributed to emergency admissions at a tertiary care hospital over ten years. METHODS: This was a retrospective observational study performed using a database of all emergency admissions from the Emergency Department (ED) at a single tertiary hospital in Singapore during a ten-year period (January 1st, 2008 to December 31st, 2017). Emergency admissions were defined as ED visits with inpatient admission as the disposition. This study analyzed the trends of demographics, pre-existing comorbidities, chronic conditions or ambulatory care sensitive conditions (ACSC) of all patients who underwent emergency admissions in Singapore General Hospital. RESULTS: A total of 446,484 emergency records were included. For elderly patients, the proportions of them had pre-existing multimorbidity at the time of undergoing emergency admissions were found to be lower at the end the 10-year study period relative to the beginning of the study period. The proportions of emergency admissions whose ED primary diagnoses were categorized as chronic conditions and certain chronic ACSC including chronic obstructive pulmonary disease, congestive heart failure, diabetes complications, and epilepsy also decreased for elderly patients over the 10-year study period. CONCLUSIONS: In Singapore, despite a rapidly aging population, there have been surprisingly lower proportions of chronic conditions, pre-existing comorbidities, and chronic ACSC among the elderly emergency admissions. This is possibly consistent with an overall improved management of the chronic conditions among the elderly population. Future studies should include similar studies at the national level and comparison with other healthcare settings in different countries.

Modification and validation of liquid chromatographic method for the quantification of ciprofloxacin in human plasma and its application to a bioavailability study.

A new simple, accurate, precise and sensitive liquid chromatographic method for the analysis of Ciprofloxacin in human plasma, suitable for quantification of drug was developed and validated using HPLC-UV method. The analyte was chromatographically separated from endogenous plasma components on a C-18 reversed phase column (5µm, 25cm × 0.46cm) and detected at 278nm. The sample pretreatment was carried out with acetonitrile on 200µl of plasma. The Lower limit of quantification (LLOQ) was 0.04 µg/ml with linearity in the range 0.04-4 µg/ml and coefficient of correlation value (R2)>0.995. The method was successfully validated as per current FDA guidance for necessary parameters and applied to a pilot bioavailability study conducted on six healthy volunteers with marketed Ciprofloxacin 250mg immediate release tablets. The plasma concentrations were subjected to non-compartmental analysis for calculation of pharmacokinetic parameters like Cmax, Tmax, AUCo-t, AUC 0-∞ and t½ etc. The mean values of Cmax and Tmax were found to be 1.35±0.09µg/ml and 1.25±0.27h respectively while for other pharmacokinetic parameters including AUCo-t, AUC0-∞ were found to be 5.98±0.96 µg/ml×h and 6.34±1.07µg/ml×h. The drug exhibited half-life (t½) of 3.94±0.33h. The obtained results proved the suitability of the method for routine pharmacokinetic studies of Ciprofloxacin.

Coronavirus disease 2019 (COVID-19): an evidence map of medical literature.

BACKGROUND: Since the beginning of the COVID-19 outbreak in December 2019, a substantial body of COVID-19 medical literature has been generated. As of June 2020, gaps and longitudinal trends in the COVID-19 medical literature remain unidentified, despite potential benefits for research prioritisation and policy setting in both the COVID-19 pandemic and future large-scale public health crises. METHODS: In this paper, we searched PubMed and Embase for medical literature on COVID-19 between 1 January and 24 March 2020. We characterised the growth of the early COVID-19 medical literature using evidence maps and bibliometric analyses to elicit cross-sectional and longitudinal trends and systematically identify gaps. RESULTS: The early COVID-19 medical literature originated primarily from Asia and focused mainly on clinical features and diagnosis of the disease. Many areas of potential research remain underexplored, such as mental health, the use of novel technologies and artificial intelligence, pathophysiology of COVID-19 within different body systems, and indirect effects of COVID-19 on the care of non-COVID-19 patients. Few articles involved research collaboration at the international level (24.7%). The median submission-to-publication duration was 8 days (interquartile range: 4-16). CONCLUSIONS: Although in its early phase, COVID-19 research has generated a large volume of publications. However, there are still knowledge gaps yet to be filled and areas for improvement for the global research community. Our analysis of early COVID-19 research may be valuable in informing research prioritisation and policy planning both in the current COVID-19 pandemic and similar global health crises.

HPLC-UV method for simultaneous quantitation of artemether and lumefantrine in fixed dose combination orodispersible tablet formulation.

This paper describes the development and validation of a high performance liquid chromatography (HPLC-UV) method for the simultaneous quantitative determination of artemether and lumefantrine in fixed dose combination tablets. Chromatographic quantitation was carried out on a C-18 column Mediterrania Sea 18 (250×4.6 mm i.d.; 5 µm particle size) using a mobile phase consisting of 80:20 v/v mixture of acetonitrile and 0.05 % trifluoroacetic acid with final pH adjusted to 2.35 at flow rate of 1 ml/minute. The eluents was detected using photo diode array detector at wavelength of 210nm for artemether and 286 nm for lumefantrine. The retention times were ~5.8 mins for artemether and ~7.3 mins for lumefantrine. The newly developed method was validated and was found linear (r2 >0.99), precise (R.S.D. <2.0%), accurate, specific and robust. The artemether contents in the tablet formulation varied from 99.026 % to 99.347%, while lumefantrine contents were 99.546-99.728 %.

Comparative pharmacokinetic evaluation of extended release itopride HCl pellets with once daily tablet formulation in healthy human subjects: a two treatment, four period crossover study in fasted and fed condition.

OBJECTIVE: In this study, pharmacokinetics (PKs) and bioavailability of newly developed extended release (ER) Itopride HCl 150 mg encapsulated ER pellets (test) and 150 mg Ganaton ER once-daily (OD) tablets (reference) were compared and evaluated under fasted and fed conditions. METHODS: Twelve healthy human subjects were enrolled in a single dose, randomized; two treatments, two sequences, four period crossover study. A modified and validated liquid chromatographic method was used for the estimation of Itopride HCl in plasma samples. The data were analyzed through non-compartmental model using PK software Phoenix Winnonlin version 7. The outcome was measured on logarithmically transformed data, where p > 0.05 was considered as non-significant with 90% CI limit of 0.8-1.25. RESULTS: The Cmax, AUC0-t, and AUC0-∞ values of Itopride HCl 150 mg ER pellets versus that of OD 150 mg tablets, in fed and fasted states, were within the limits specified by FDA to establish bioequivalence. The relative bioavailability of Itopride HCl 150 mg ER pellets were 1.019 (fed) and 1.081(fasted). The 90% CIs of AUC values for Itopride HCl 150 mg ER pellets and OD 150 mg tablets in fed versus fast were significantly greater and were not within 80-125% limit. CONCLUSION: The test and reference formulations had similar pharmacokinetic parameters in each condition studied. However, an increase in the amount of drug was observed in the fed state.

Modifiable Factors Associated With Survival After Out-of-Hospital Cardiac Arrest in the Pan-Asian Resuscitation Outcomes Study.

STUDY OBJECTIVE: The study aims to identify modifiable factors associated with improved out-of-hospital cardiac arrest survival among communities in the Pan-Asian Resuscitation Outcomes Study (PAROS) Clinical Research Network: Japan, Singapore, South Korea, Malaysia, Taiwan, Thailand, and the United Arab Emirates (Dubai). METHODS: This was a prospective, international, multicenter cohort study of out-of-hospital cardiac arrest in the Asia-Pacific. Arrests caused by trauma, patients who were not transported by emergency medical services (EMS), and pediatric out-of-hospital cardiac arrest cases (<18 years) were excluded from the analysis. Modifiable out-of-hospital factors (bystander cardiopulmonary resuscitation [CPR] and defibrillation, out-of-hospital defibrillation, advanced airway, and drug administration) were compared for all out-of-hospital cardiac arrest patients presenting to EMS and participating hospitals. The primary outcome measure was survival to hospital discharge or 30 days of hospitalization (if not discharged). We used multilevel mixed-effects logistic regression models to identify factors independently associated with out-of-hospital cardiac arrest survival, accounting for clustering within each community. RESULTS: Of 66,780 out-of-hospital cardiac arrest cases reported between January 2009 and December 2012, we included 56,765 in the analysis. In the adjusted model, modifiable factors associated with improved out-of-hospital cardiac arrest outcomes included bystander CPR (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.31 to 1.55), response time less than or equal to 8 minutes (OR 1.52; 95% CI 1.35 to 1.71), and out-of-hospital defibrillation (OR 2.31; 95% CI 1.96 to 2.72). Out-of-hospital advanced airway (OR 0.73; 95% CI 0.67 to 0.80) was negatively associated with out-of-hospital cardiac arrest survival. CONCLUSION: In the PAROS cohort, bystander CPR, out-of-hospital defibrillation, and response time less than or equal to 8 minutes were positively associated with increased out-of-hospital cardiac arrest survival, whereas out-of-hospital advanced airway was associated with decreased out-of-hospital cardiac arrest survival. Developing EMS systems should focus on basic life support interventions in out-of-hospital cardiac arrest resuscitation.

Omega-3 fatty acids for dialysis vascular access outcomes in patients with chronic kidney disease.

BACKGROUND: Maintaining long-term vascular access patency is necessary for high quality haemodialysis (HD) treatment of patients with the terminal and most serious stage of chronic kidney disease (CKD) - end-stage kidney disease (ESKD). Oral supplementation with omega-3 fatty acids (ω-3FA) may help to prevent blockage of the vascular access by reducing the risk of thrombosis and stenosis. OBJECTIVES: To evaluate the efficacy and safety of ω-3FA supplementation versus placebo or no treatment for maintaining vascular access patency in ESKD patients undergoing HD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 23 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) of omega-3 fatty acids versus placebo that assessed the patency of arteriovenous fistula (AVF) or arteriovenous graft (AVG) types of vascular access in ESKD patients. DATA COLLECTION AND ANALYSIS: We assessed the risk of bias of each eligible study using the Cochrane Risk of Bias tool and made separate overall risk of bias judgments for the efficacy and safety outcomes. The certainty of evidence was assessed using the GRADE approach. The primary efficacy outcome was loss of vascular patency and the primary safety outcomes were occurrences of serious adverse events (e.g. death, hospitalisation, cardiovascular events, major bleeding). Secondary outcomes were the occurrence of non-serious adverse events (e.g. minor bleeding, gastrointestinal events and other adverse events). Efficacy effects were reported as risk ratios (RR) and safety effects as risk differences (RD) with 95% confidence intervals (CI). Studies were pooled separately by type of vascular access using a random-effects model. MAIN RESULTS: Five studies (833 participants) were included; one was a very small pilot study of 7 participants. All studies compared oral ω-3FA supplements against placebo. Four studies enrolled participants with arteriovenous grafts (AVGs), and the other had participants with arteriovenous fistulas (AVFs). The risk of bias for both efficacy and safety outcomes was unclear for all studies, due mainly to incomplete reporting for allocation concealment and incompleteness of study follow-up.In AVF patients, ω-3FA supplementation probably makes little or no difference to the 12-month risk of patency loss (1 study, 536 participants: RR 1.01, 95% CI 0.84 to 1.21; moderate certainty evidence), risk of death (1 study, 567 participants: RD 0.00, 95% CI -0.03 to 0.02; moderate certainty evidence) and risk of hospitalisation (1 study, 567 participants: RD 0.00, 95% CI -0.08 to 0.08; low certainty evidence). There was no information on cardiovascular events and major bleeding.In AVG patients, it is very uncertain whether ω-3FA supplementation reduces the risk of patency loss within 6 months (2 studies, 41 participants: RR 0.91, 95% CI 0.36 to 2.28; very low certainty evidence) or 12 months (2 studies, 220 participants: RR 0.59, 95% CI 0.27 to 1.31; very low certainty evidence). ω-3FA supplementation may make little or no difference to the risk of death within 6 to 12 months in AVG patients (4 studies, 261 participants: RD 0.01, 95% CI -0.05 to 0.07; low certainty evidence). It is very uncertain if ω-3FA supplementation increases the risk of hospitalisation (3 studies, 65 participants: RD 0.08, 95% CI -0.11 to 0.28; very low certainty evidence), changes the risk of cardiovascular events (4 studies, 261 participants: RD -0.02, 95% CI -0.11 to 0.07; very low certainty evidence), or increases the risk of major bleeding (3 studies, 65 participants: RD 0.08, 95% CI -0.11 to 0.28; very low certainty evidence) within 6 to 12 months in AVG patients. There may be an increase in the risk of mild gastrointestinal adverse reactions (3 studies, 65 participants: RD 0.25, 95% CI 0.07 to 0.43; low certainty evidence) such as a sensation of bloatedness, gas or a fishy aftertaste. AUTHORS' CONCLUSIONS: In CKD patients with an AVF, there is moderate certainty that ω-3FA supplementation makes little or no difference to preventing patency loss; and in patients with an AVG, it is very uncertain that ω-3FA supplementation prevents patency loss within 12 months.

Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Childbirth may cause the most severe pain some women experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour and is considered to be the reference standard. Traditionally epidural analgesia has been delivered as a continuous infusion via a catheter in the epidural space, with or without the ability for the patient to supplement the analgesia received by activating a programmable pump to deliver additional top-up doses, known as patient-controlled epidural analgesia (PCEA). There has been interest in delivering maintenance analgesic medication via bolus dosing (automated mandatory bolus - AMB) instead of the traditional continuous basal infusion (BI); recent randomized controlled trials (RCTs) have shown that the AMB technique leads to improved analgesia and maternal satisfaction. OBJECTIVES: To assess the effects of automated mandatory bolus versus basal infusion for maintaining epidural analgesia in labour. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the World Health Organization International Clinial Trials Registry Platform (WHO-ICTRP) and ClinicalTrials.gov on 16 January 2018. We screened the reference lists of all eligible trials and reviews. We also contacted authors of included studies in this field in order to identify unpublished research and trials still underway, and we screened the reference lists of the included articles for potentially relevant articles. SELECTION CRITERIA: We included all RCTs that compared the use of bolus dosing AMB with continuous BI for providing pain relief during epidural analgesia for labour in women. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: risk of breakthrough pain with the need for anaesthetic intervention; risk of caesarean delivery; risk of instrumental delivery. Secondary outcomes included: duration of labour; local anaesthetic consumption. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 12 studies with a total of 1121 women. Ten studies enrolled healthy nulliparous women only and two studies enrolled healthy parous women at term as well. All studies excluded women with complicated pregnancies. There were variations in the technique of initiation of epidural analgesia. Seven studies utilized the combined spinal epidural (CSE) technique, and the other five studies only placed an epidural catheter without any intrathecal injection. Seven studies utilized ropivacaine: six with fentanyl and one with sufentanil. Two studies used levobupivacaine: one with sufentanil and one with fentanyl. Three used bupivacaine with or without fentanyl. The overall risk of bias of the studies was low.AMB probably reduces the risk of breakthrough pain compared with BI for maintaining epidural analgesia for labour (from 33% to 20%; risk ratio (RR) 0.60; 95% confidence interval (CI) 0.39 to 0.92, 10 studies, 797 women, moderate-certainty evidence). AMB may make little or no difference to the risk of caesarean delivery compared to BI (15% and 16% respectively; RR 0.92; 95% CI 0.70 to 1.21, 11 studies, 1079 women, low-certainty evidence).AMB may make little or no difference in the risk of instrumental delivery compared to BI (12% and 9% respectively; RR 0.75; 95% CI 0.54 to 1.06, 11 studies, 1079 women, low-certainty evidence). There is probably little or no difference in the mean duration of labour with AMB compared to BI (mean difference (MD) -10.38 min; 95% CI -26.73 to 5.96, 11 studies, 1079 women, moderate-certainty evidence). There is probably a reduction in the hourly consumption of local anaesthetic with AMB compared to BI for maintaining epidural analgesia during labour (MD -1.08 mg/h; 95% CI -1.78 to -0.38, 12 studies, 1121 women, moderate-certainty evidence). Five out of seven studies reported an increase in maternal satisfaction with AMB compared to BI for maintaining epidural analgesia for labour; however, we did not pool these data due to their ordinal nature. Seven studies reported Apgar scores, though there was significant heterogeneity in reporting. None of the studies showed any significant difference between Apgar scores between groups. AUTHORS' CONCLUSIONS: There is predominantly moderate-certainty evidence that AMB is similar to BI for maintaining epidural analgesia for labour for all measured outcomes and may have the benefit of decreasing the risk of breakthrough pain and improving maternal satisfaction while decreasing the amount of local anaesthetic needed.

Development and validation of liquidchromatographic method for quantitative determination of Loxoprofen in mobilephase and in human plasma.

A Simple, sensitive and accurate high-performance liquid chromatographic (HPLC) method for effective and specific analysis of Loxoprofen (LXP) in the mobilephase and human plasma was developed. Effective chromatographic separation was attained on a Mediterranean Sea C18 column (250×4.6mm, 5um) with mobilephase containing acetonitrile and 0.01 M NaH2PO4 buffer (55:45) by adjusting pH 6.5 with sodium dihydrogen phosphate buffer at a flow rate of 1ml/min. Calibration ranges from 0.1ppm to 10 ppm with a coefficient of relation value (R2=0.999) by using a linear regression method and lower limit of quantification was 0.1ppm. The current method showed inter-day and intra-day accuracy and precision within the range of ±10%. % RSD was found to be less than 5 %. Analytical recovery was more than 90% which confirmed the reliability of current method. The proposed method was found appropriate for assessment of LXP in pharmacokinetic and bioequivalence study.

Effect of bisphosphonates on root resorption after tooth replantation - a systematic review.

BACKGROUND/AIM: Replantation of avulsed teeth may lead to root resorption. Bisphosphonates (BPs), a class of drugs of used to treat resorptive diseases of the bone such as osteoporosis and Paget's disease, have been observed to exert an antiresorptive effect on periodontal bone as well. The antiresorptive properties of BPs could prove them useful in preventing root resorption of replanted avulsed teeth. The aim of this systematic review was to analyze and summarize the currently available literature concerning the use of BPs in preventing root resorption of avulsed teeth. MATERIALS AND METHODS: PubMed/MEDLINE, Google Scholar, ISI Web of Knowledge, and Embase databases were searched using keywords 'bisphosphonate', 'replantation', and 'tooth'. Quality assessment of each study was carried out. In addition, general characteristics and outcomes of each study were summarized. RESULTS: After exclusion of 116 irrelevant articles, 10 animal studies were included in this review. The majority of the studies suggest that surface application of zoledronate or alendronate reduces root resorption of replanted teeth in animal models. Surface treatment with etidronate had no significant effect on root resorption, and intracanal etidronate accelerated resorption. CONCLUSION: Surface application of zoledronate and alendronate reduces root resorption of replanted teeth in animal models. However, the efficacy of intracanal usage of BPs is still debatable.

Development & validation of reversed phase HPLC method for quantification of water insoluble API.

In the present work a specific, accurate, precise, and reproducible UV-HPLC method was developed and validated for the analysis of Aceclofenac. This method involved elution of Aceclofenac in a mobile phase which is composed of buffer pH 6.8 (i.e. using 0.01N KH2PO4) and HPLC grade Acetonitrile (60:40). Separation of the analyte was achieved using HPLC isocratic pump attached to the UV-VIS detectorC18, guard column and C18 column. The injection volume was 20µL, detected at 274 nm; flow rate: 1mL/min. Standard calibration curve was measured and found linear from 0.1 to 40µg/ml. The validation parameters were measured according to FDA guidelines and successful results were obtained. The presented analytical method could be employed for pharmacokinetic studies.

Development and validation of HPLC method for the determination of Cefpodoxime Proxetil in human plasma.

A new, simple, accurate, precise and specific method has been developed for the analysis of Cefpodoxime Proxetil in human plasma. The proposed method was developed and validated with the aim to be used in Bioavailability/Bioequivalence studies for quantification of drug in human plasma. The mobile phase components were acetonitrile, methanol, and water in the ratio of 20:50:30. Ortho phosphoric acid was used to adjust at pH5.0. Flow rate and wavelength were kept 1ml/min and 247nm respectively. The column was C-18 HPLC column 5um particle size, L x 1.d. 25cm x4.6mm. (Supelcosil). Retention time of Cefpodoxime Proxetil was found to be 10.967min. The developed method was validated for selectivity, recovery, accuracy, precision, repeatability, reproducibility, stability and linearity in the range of 0.195mcg/ml to 50mcg/ml. The accuracy and Precision of the proposed method were well within the predefined limits i.e. ±15% for all the calibration standards other than LLOQ (Lower Limit of Quantification) where it was well within ±20% of the nominal value. The analytical recovery was always above 89% showing satisfactory recovery. The coefficient of correlation (R2 ) was 0.999. The developed method was found suitable for the estimation of Cefpodoxime Proxetil in plasma.

HPLC method development and validation for the determination of Cefaclor in human plasma.

Cefaclor was analyzed in the human plasma by developing a simple, precise and accurate assay method which was then validated for its accuracy, specificity and precision. The mobile phase comprised of a mixture of sodium 1-pentanesulfonate, water, triethylamine and methanol. Phosphoric acid was used to adjust the pH to 2.5±0.1. The flow rate was maintained at 1.5ml/min and the wavelength was set at 265 nm. A C-18 HPLC, column 5um particle size, L x 1.D. 25cm x 4.6mm (Supelcosil) was utilized for chromatographic separation. The retention time of Cefaclor was found to be 17min. This method was validated for selectivity, accuracy, precision, repeatability, reproducibility, recovery, linearity, and stability. Calibration curves were found linear were in the range of 0.39µg/ml to50µg/mland the coefficient of correlation (R2) was found to be 0.999. Hence, this method has been found useful for the determination of Cefaclor in plasma.

Chromatographic method development and validation for the determination of valsartan in biological fluid.

A swift, precise and simple HPLC bioanalytical technique with UV detection was established and validated for quantitative estimation of valsartan in human plasma. The analyte was separated from plasma by protein precipitation with acetonitrile and chromatographically separated on Zorbax SB-C18 (5µm, 4.6mm × 15cm) column. The solvent mixture system consisting of acetonitrile, water and glacial acetic acid (40:59:1 v/v), was pumped using isocratic mode at 1mL/min flow rate. Samples' detection of drug was made spectrophotometrically at a wavelength of 264nm. The analyte response was instituted to be linear from 0.06 to 8µg/mL with a regression value of 0.999. The accuracy of the proposed method was ranged between 97.2-100.3% with 5% RSD. The analytical recovery (>95%) was consistently observed and satisfactory sample stability was also found at different environmental conditions. In conclusion the reported bio-analytical method is easy and robust that was successfully utilized in estimation of valsartan in a pharmacokinetic study.

Outcomes of Dental Implant Therapy in Patients With Down Syndrome: A Systematic Review.

OBJECTIVES: Patients with Down syndrome (DS) require an earlier and more frequent tooth replacement than rest of the population. The objective of this systematic review is to critically analyze and summarize studies to ascertain the outcomes and survival of dental implants placed in jaws of DS patients. METHODS: Using the key words "dental implants," "Down syndrome," and "prosthodontics," an electronic search was conducted via PubMed/MEDLINE, ISI Web of Science, Google Scholar, Embase, and Central Register of Controlled Trials (CENTRAL) databases by 2 authors, S.N. and Z.K., independently. Retrieved studies were screened against the predefined exclusion and inclusion criteria. To estimate the risk of bias, quality assessment of included studies was carried using the 'Case Reports (CARE) guidelines'. RESULTS: Primary search resulted in 156 studies. Eight studies met the inclusion criteria and reporting a total of 81 dental implants placed in 36 DS patients. The type of implant loading ranged from immediate to a delay of 1 year after placement of the implant. Implant diameter ranged from 3.3 to 4.5 mm, and height ranged from 8.5 to 18 mm. The follow-up ranged from 1 to 6 years. Of 81 implants placed, 21 implants (26%) were reported as failed. CONCLUSIONS: Patients with DS have a higher risk of implant failure. However, the reason for the failure is not very well understood. Although case reports and case series suggest that implant survival is diminished in DS patients, large-scale randomized controlled trials are required to determine the exact mechanism associated with risks of implant failure.

Cost-effectiveness analysis of liver resection versus transplantation for early hepatocellular carcinoma within the Milan criteria.

UNLABELLED: Both liver resection (LR) and cadaveric liver transplantation (CLT) are potentially curative treatments for patients with hepatocellular carcinoma (HCC) within the Milan criteria and with adequate liver function. Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of LR against CLT for patients with HCC within the Milan criteria using a decision analytic model. A Markov cohort model was developed to simulate a cohort of patients aged 55 years with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, undergoing LR or CLT, and followed up over their remaining life expectancy. Analysis was performed in different geographical cost settings: the USA, Switzerland and Singapore. Transition probabilities were obtained from systematic literature reviews, supplemented by databases from Singapore and the Organ Procurement and Transplantation Network (USA). Utility and cost data were obtained from open sources. LR produced 3.9 quality-adjusted life years (QALYs) while CLT had an additional 1.4 QALYs. The incremental cost-effectiveness ratio (ICER) of CLT versus LR ranged from $111,821/QALY in Singapore to $156,300/QALY in Switzerland, and was above thresholds for cost-effectiveness in all three countries. Sensitivity analysis revealed that CLT-related 5-year cumulative survival, one-time cost of CLT, and post-LR 5-year cumulative recurrence rates were the most sensitive parameters in all cost scenarios. ICERs were reduced below threshold when CLT-related 5-year cumulative survival exceeded 84.9% and 87.6% in Singapore and the USA, respectively. For Switzerland, the ICER remained above the cost-effectiveness threshold regardless of the variations. CONCLUSION: In patients with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, LR is more cost-effective than CLT across three different costing scenarios: the USA, Switzerland, Singapore.