Ethnic pharmacokinetic comparison of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) between Asian and Western healthy subjects.

BACKGROUND: The Phase III KRONOS study (NCT02497001) found the fixed-dose combination triple therapy budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) to be efficacious and well tolerated versus corresponding dual therapies in patients with moderate-to-very severe COPD from North America, China and Japan. However, pharmacokinetic (PK) studies of other drugs have shown that ethnic factors (e.g. genetic factors affecting drug metabolism) can affect the bioavailability of drugs which may impact upon efficacy and safety outcomes. METHODS: This was a post-hoc analysis of data from four randomised, double-blind Phase I studies of BGF MDI 320/18/9.6 µg and 160/18/9.6 µg in Chinese (NCT03075267), Japanese (NCT02197975) and Western (NCT01980615, NCT02189304) healthy subjects. PK properties (area under the plasma concentration-time curve 0-12 h post-dose [AUC0-12] and maximum plasma concentration, [Cmax]) were recorded following single and repeated dosing of BGF MDI 320/18/9.6 µg or 160/18/9.6 µg. Potential ethnic differences in the PK properties of budesonide, glycopyrrolate and formoterol in Chinese, Japanese and Western healthy subjects were derived by non-compartmental analysis, and ethnic insensitivity factors evaluated based on criteria from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Guideline E5 Ethnic Factors in the Acceptability of Foreign Clinical Data. RESULTS: The analyses included data from 64 Chinese, 31 Japanese and 169 Western subjects. Overall, PK properties following single or repeated dosing of BGF MDI were similar across Chinese, Japanese and Western subjects. After single dosing at either dose level, AUC0-12 and Cmax for budesonide, glycopyrrolate and formoterol appeared generally similar for Asian (Chinese and Japanese) versus Western subjects, with most geometric least squares mean ratios within the range of 0.92-1.22. The exception was that Cmax for glycopyrrolate was slightly lower in Asian versus Western subjects (0.6-0.7). Of the 10 ethnic insensitivity factors evaluated, six were met for budesonide, nine for glycopyrrolate and nine for formoterol, suggesting that BGF MDI can be classified as an ethnically insensitive drug. CONCLUSIONS: Overall, these analyses suggest no appreciable ethnic differences in the PK of BGF MDI across Chinese, Japanese and Western healthy subjects.

Glycopyrrolate/formoterol fumarate metered dose inhaler for maintenance-naïve patients with chronic obstructive pulmonary disease: a post-hoc analysis of the randomized PINNACLE trials.

BACKGROUND: Glycopyrrolate (GP)/formoterol fumarate (FF; GFF) metered dose inhaler is a fixed-dose combination dual bronchodilator for patients with chronic obstructive pulmonary disease (COPD); however, whether the efficacy in patients without current maintenance treatment is consistent with currently maintenance-treated patients is unclear. METHODS: Data from patients who were not maintenance-treated at screening (NMT) (n = 1943) and patients who were maintenance-treated at screening (MT) patients (n = 3040) receiving GFF, FF, GP, or placebo were pooled from the Phase III PINNACLE studies (NCT01854645, NCT01854658, NCT02343458) for post-hoc analysis. MT patients had received long-acting bronchodilators and/or inhaled corticosteroids in the 30 days prior to screening, and/or prior to randomization. NMT patients had received short-acting bronchodilators or no treatment. Outcomes included forced expiratory volume over 1 s (FEV1), clinically important deterioration (CID), rescue medication use, and safety. RESULTS: GFF provided significant lung function improvements at Week 24 versus placebo, GP, and FF for NMT patients, with pre-dose trough FEV1 treatment differences of 152 (117-188) mL, 73 (45-100) mL, and 56 (29-84) mL, respectively (least squares mean change from baseline versus comparators [95% CI]; all P < 0.0001). GFF reduced the risk of CID by 17-43% in NMT (P ≤ 0.0157) and 18-52% (P ≤ 0.0012) in MT patients compared with monotherapy and placebo, and reduced rescue medication use by 1.5 puffs/day over 24 weeks for both cohorts. Safety profiles for all cohorts were consistent with each other and the parent studies. CONCLUSIONS: NMT patients achieved better lung function with GFF versus monotherapy and placebo, without increased safety risk. Dual bronchodilator therapy may offer better outcomes than monotherapy for COPD patients when administered as first-line treatment.

Pharmacokinetics and Tolerability of Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate and Glycopyrronium/Formoterol Fumarate Dihydrate Metered Dose Inhalers in Healthy Chinese Adults: A Randomized, Double-blind, Parallel-group Study.

PURPOSE: The objective of this study was to assess pharmacokinetic (PK) and safety profiles of 2 fixed-dose combinations in development for the treatment of chronic obstructive pulmonary disease (COPD): budesonide/glycopyrronium/formoterol fumarate dihydrate metered-dose inhaler (BGF MDI; triple combination) and glycopyrronium/formoterol fumarate dihydrate (GFF MDI; dual combination). The PK and safety profiles of BGF MDI and GFF MDI were assessed for the first time in healthy Chinese adults after single and repeated (7-day) dosing. METHODS: This Phase I, randomized, double-blind, parallel-group study was conducted at a single site in Shanghai, China. Male or female Chinese subjects, 18-45 years of age and in good general health, were randomized 1:1:1 to receive BGF MDI 320/14.4/10 µg, BGF MDI 160/14.4/10 µg, or GFF MDI 14.4/10 µg. PK parameters were assessed after a single dose (day 1) and at steady state (day 8), and included AUC0-12, Cmax, and Tmax. Tolerability was assessed using physical examination findings, adverse events reporting, 12-lead ECG, vital signs, and clinical laboratory values. FINDINGS: Ninety-six subjects (mean age, 25.6 years; 83.3% male) were randomized and received treatment. All randomized subjects were included in the safety and PK populations. After single and repeated dosing, budesonide AUC0-12 and Cmax were increased dose proportionally from BGF MDI 160/14.4/10 µg to BGF MDI 320/14.4/10 µg, respectively (single dose: AUC0-12, 811.8 vs 1748 h · pg/mL; Cmax, 224.3 vs 459.3 pg/mL; repeated dosing: AUC0-12, 1250 vs 2510 h · pg/mL; Cmax, 315.4 vs 626.4 pg/mL). After single and repeated dosing, glycopyrronium AUC0-12 and Cmax were similar across all treatments (single dose: AUC0-12, 27.20-29.40 h · pg/mL; Cmax, 4.884-5.674 pg/mL; repeated dosing: AUC0-12, 69.49-77.08 h · pg/mL; Cmax, 11.30-13.12 pg/mL) and formoterol (single dose: AUC0-12, 46.49-53.58 h · pg/mL; Cmax 9.651-10.62 pg/mL; repeated dosing: AUC0-12, 81.94-85.32 h · pg/mL; Cmax, 16.13-17.71 pg/mL), suggesting that the addition of budesonide did not appreciably alter the PK properties of GFF MDI. All treatment-emergent adverse events were mild in severity and rates were similar across groups (range, 50.0%-56.3%). There were no new or unexpected findings on tolerability. IMPLICATIONS: Overall, all treatments were well tolerated and PK parameters were generally comparable to those previously reported in Western and Japanese healthy subjects, suggesting that the doses of BGF MDI and GFF MDI in development globally for COPD are also appropriate for Chinese patients with COPD. ClinicalTrials.gov identifier: NCT03075267.

Statistical analysis plan for the control of blood pressure and risk attenuation-rural Bangladesh, Pakistan, Sri Lanka (COBRA-BPS) trial: a cluster randomized trial for a multicomponent intervention versus usual care in hypertensive patients.

BACKGROUND: In rural south Asia, hypertension remains a significant public health issue with sub-optimal blood pressure (BP) control rates. The goal of the trial is to evaluate the effectiveness and cost-effectiveness of a multicomponent intervention (MCI) compared to usual care on lowering BP among adults with hypertension in rural south-Asian communities. This article describes the statistical analysis plan for the primary and secondary objectives related to intervention effectiveness based on clinical and patient-reported endpoints. METHODS/DESIGN: The study is a cluster randomized trial which will enroll 2550 participants aged ≥ 40 years with hypertension from rural communities in Bangladesh, Pakistan, and Sri Lanka. The unit of randomization is a cluster defined by 250-300 households. Thirty clusters, 10 from each country, are randomized in a 1:1 ratio to either MCI or usual care, stratified by country and their distance from the clinic. All participants will be assessed every six months over a two-year period after baseline with measurements of systolic and diastolic BP, antihypertensive and statin medication use, medication adherence, physical activity level, anthropometric parameters, smoking status, and dietary habits. The primary objective is to assess the effectiveness of MCI as compared with usual care in terms of mean change in systolic BP from baseline to final follow-up at two years. The primary outcome will be modelled using a generalized linear mixed-model for repeated measures based on a participant-level analysis. The model will include cluster random-effects and will use a non-independence residual correlation matrix to account for repeated measures on the same participant. Sensitivity analyses for the primary endpoint will be based on multiple imputation as well as pattern mixture model tipping point analyses. Secondary outcomes will be analyzed using the same modeling approach as for the primary outcome, with appropriate distributions within the exponential family and corresponding link functions. DISCUSSION: The a priori statistical analysis plan will avoid reporting bias and data-driven analysis for the primary and key secondary outcomes. The results of the study will provide evidence of the benefits and risks of the MCI for BP control in rural communities in south Asian countries with low-resourced public health infrastructure. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02657746 . Registered on 14 January 2016.

Dermatological conditions seen in renal transplant recipients in a Singapore tertiary hospital.

INTRODUCTION: Lifelong immunosuppression after renal transplant exerts effects on the recipients' skin, including skin infections, skin cancers and drug-induced skin disorders. Our study aimed to determine the epidemiology of skin conditions among renal transplant recipients in the largest tertiary hospital in Singapore. METHODS: We reviewed the medical records of kidney transplant recipients at Singapore General Hospital, Singapore, between 1 January 2003 and 31 December 2013. Among these patients, the clinical data of patients who sought skin consultations with either dermatologists or plastic surgeons within the hospital was captured. RESULTS: A total of 178 patients were included in our study. There were 88 (45.6%) skin infections, 23 (11.9%) drug-induced skin conditions, 9 (4.7%) skin cancers and 73 (37.8%) other skin conditions. Skin infection was the predominant reason for consultation, with viral warts (15%, n = 29) being the most common. Of the nine cases in our cohort with skin cancer, there were three cases of basal cell carcinoma, three cases of Bowen's disease, two cases of extramammary Paget's disease and one case of squamous cell carcinoma. Drug-induced skin conditions, mainly attributable to long-term steroids and cyclosporin use, were represented by acne (9.3%, n = 18) and sebaceous hyperplasia (2.6%, n = 5). CONCLUSION: Our study demonstrated the spectrum of skin conditions that can be expected after renal transplantation. We wish to highlight the importance of careful dermatological screening and long-term follow-up for these patients, in order to reduce post-transplant skin complications.

Lofexidine versus diazepam for the treatment of opioid withdrawal syndrome: A double-blind randomized clinical trial in Singapore.

BACKGROUND: Many individuals leave costly inpatient detoxification programs prematurely because of the severity of withdrawal symptoms experienced. In the absence of opioid-assisted detoxification in Singapore, diazepam is used to manage withdrawal. However since diazepam is addictive, there is a need to explore the effectiveness of alternative medications. DESIGN AND PROCEDURES: The study aimed to examine the safety and efficacy of lofexidine, a non-opiate, non-addictive, alpha 2-adrenergic agonist in assisting opioid detoxification in Singapore, using a randomized, double-blind, investigator-initiated placebo-controlled trial comparing lofexidine against diazepam. Opioid dependent patients (n = 111) were randomized to receive a 10-day course of lofexidine (n = 56) or diazepam (n = 55). The primary endpoint was the Objective Opioid Withdrawal Scale (OOWS) score on days 3 and 4 and secondary outcomes were the Short Opioid Withdrawal Scale (SOWS) score, program retention rate, and ratings of opiate craving. MAIN FINDINGS: The OOWS, SOWS and opiate craving scores were consistently lower in the lofexidine group relative to the diazepam group over the 14-day study period; however no statistically significant differences were found on days 3 and 4 (peak withdrawal). Changes in mean pupil size during peak withdrawal were significantly smaller in the lofexidine group and more participants in the lofexidine group remained in treatment and completed detoxification. CONCLUSIONS: Lofexidine was at least as effective as diazepam in reducing the opioid withdrawal syndrome and increased treatment retention. In addition to its non-addictive and non-abuse properties, lofexidine has several clinical advantages over diazepam. The use of lofexidine is recommended when opioid-assisted medications are not available.

Diabetes Control: Is Vinegar a Promising Candidate to Help Achieve Targets?

BACKGROUND: Renewed interest in vinegar as a glucose-lowering agent led to several small trials in the recent past. However, none of the trials could independently provide sufficient evidence. OBJECTIVES: Our review aimed to obtain reliable estimates of effects of vinegar on short-term and long-term blood glucose control. METHODS: Large bibliographic databases were searched from inception to date of search without language and publication date restrictions. All clinical trials evaluating effect of vinegar on diabetes mellitus patients were eligible. Two authors independently extracted data on fasting and 2-hour postprandial blood glucose, insulin, and HbA1c levels at the various time points. MS Excel, SAS® v9.3, and RevMan v5.3 were used for data analysis. RESULTS: Small significant reduction in mean HbA1c was observed after 8 to 12 weeks of vinegar administration: -0.39% (95% confidence interval = -0.59, -0.18; I2 = 0%). Other long-term outcomes favored vinegar but were not significant. Short-term outcomes showed significantly lower pooled mean difference in glucose levels at 30 minutes in the vinegar group. Readings at 60, 90, and 120 minutes were lower in the vinegar group but not statistically significant. Adverse effects profile also favored the vinegar group. CONCLUSIONS: It is worthwhile to carry out carefully planned large trails to determine the efficacy and effectiveness of vinegar as an adjunct treatment modality.

Incidence and association factors for the development of chronic post-hysterectomy pain at 4- and 6-month follow-up: a prospective cohort study.

Chronic pain has major adverse effects on health-related quality of life and contributes to significant socioeconomic burden. Hysterectomy is a very common gynecological surgery, resulting in chronic post-hysterectomy pain (CPHP), an important pain syndrome. We conducted a prospective cohort study in 216 Asian women who underwent abdominal or laparoscopic hysterectomy for benign conditions. Demographic, psychological, and perioperative data were recorded. Postoperative 4- and 6-month phone surveys were conducted to assess the presence of CPHP and functional impairment. The incidence rates of CPHP at 4 and 6 months were 32% (56/175) and 15.7% (25/159), respectively. Women with CPHP at 4 and 6 months had pain that interfered with their activities of daily living. Independent association factors for CPHP at 4 months were higher mechanical temporal summation score, higher intraoperative morphine consumption, higher pain score in the recovery room, higher pain score during coughing and itching at 24 hours postoperatively, and preoperative pain in the lower abdominal region. Independent association factors for CPHP at 6 months were preoperative pain during sexual intercourse, higher mechanical temporal summation score, and higher morphine consumption during postoperative 24 and 48 hours. In a majority of cases, CPHP resolved with time, but may have significant impact on activities of daily living.

A randomised controlled trial investigating the analgesic efficacy of transversus abdominis plane block for adult laparoscopic appendicectomy.

INTRODUCTION: We conducted a single-centre, prospective randomised clinical trial to investigate the analgesic efficacy of transversus abdominis plane (TAP) block in adult patients undergoing laparoscopic appendicectomy. METHODS: Patients undergoing urgent laparoscopic appendicectomy under general anaesthesia alone (control group) and general anaesthesia supplemented by TAP block (TAP intervention group) were compared. All patients received a multimodal analgesia regime, which included postoperative morphine via a patient-controlled analgesia device. The primary endpoints were morphine consumption at 12 hours and 24 hours postoperatively. Secondary endpoints included pain scores, incidence of nausea and vomiting, and time to hospital discharge. A total of 58 patients were recruited, with 29 patients in each group. RESULTS: Mean postoperative morphine consumption at 12 hours (control group: 11.45 ± 7.64 mg, TAP intervention group: 9.79 ± 8.09 mg; p = 0.4264) and 24 hours (control group: 13.38 ± 8.72 mg, TAP intervention group: 11.31 ± 8.66 mg; p = 0.3686) for the control and TAP intervention groups were not statistically different. Secondary outcomes were also not different between the two groups. Length of stay in the post-anaesthesia care unit was significantly shorter for the TAP intervention group, with a trend toward faster hospital discharge being observed. CONCLUSION: TAP block, a regional anaesthetic procedure performed immediately prior to skin incision for laparoscopic appendicectomy, did not significantly improve postoperative analgesia outcomes.

Evaluation of timings and outcomes in category-one caesarean sections: A retrospective cohort study.

BACKGROUND AND AIMS: A decision-to-delivery interval (DDI) of 30 min for category-one caesarean section (CS) deliveries is the standard of practice recommended by clinical guidelines. Our institution established a protocol for category-one ('crash') CS to expedite deliveries. The aim of this study is to evaluate DDI, factors that affect DDI and the mode of anaesthesia for category-one CS. METHODS: This retrospective cohort study evaluated 390 women who underwent category-one CS in a tertiary obstetric centre. We analysed the factors associated with DDI, mode of anaesthesia and perinatal outcomes. Summary statistics were performed for the outcomes. The association factors were considered significant at P < 0.05. RESULTS: The mean (standard deviation) DDI was 9.4 (3.2) min with all deliveries achieved within 30 min. The longest factor in the DDI was time taken to transfer patients. A shorter DDI was not significantly associated with improved perinatal outcomes. The majority (88.9%) of women had general anaesthesia (GA) for category-one CS. Of those who had an epidural catheter already in situ (34.4%), 25.6% had successful epidural extension. GA was associated with shorter DDI, but worse perinatal outcomes than regional anaesthesia (RA). CONCLUSIONS: Our 'crash' CS protocol achieved 100% of deliveries within 30 min. The majority (88.9%) of the patients had GA for category-one CS. GA was found to be associated with shorter anaesthesia and operation times, but poorer perinatal outcomes compared to RA.

Investigating analgesic and psychological factors associated with risk of postpartum depression development: a case-control study.

AIM: The aim of this study was to investigate the role of peripartum analgesic and psychological factors that may be related to postpartum depression (PPD). METHODS: This case-control study was conducted in pregnant females who delivered at KK Women's and Children's Hospital from November 2010 to October 2013 and had postpartum psychological assessment. Demographic, medical, and postpartum psychological status assessments, intrapartum data including method of induction of labor, mode of labor analgesia, duration of first and second stages of labor, mode of delivery, and pain intensity on hospital admission and after delivery were collected. PPD was assessed using the Edinburgh Postnatal Depression Scale and clinical assessment by the psychiatrist. RESULTS: There were 62 cases of PPD and 417 controls after childbirth within 4-8 weeks. The odds of PPD was significantly lower (33 of 329 [10.0%]) in females who received epidural analgesia for labor compared with those who chose nonepidural analgesia (29 of 150 [19.3%]) ([odds ratio] 0.47 (0.27-0.8), P=0.0078). The multivariate analysis showed that absence of labor epidural analgesia, increasing age, family history of depression, history of depression, and previous history of PPD were independent risk factors for development of PPD. CONCLUSION: The absence of labor epidural analgesia remained as an independent risk factor for development of PPD when adjusted for psychiatric predictors of PPD such as history of depression or PPD and family history of depression.

Improving postoperative handover from anaesthetists to non-anaesthetists in a children's intensive care unit: the receiver's perception.

INTRODUCTION: The efficiency of postoperative handover of paediatric patients to the children's intensive care unit (CICU) varies according to institutions, clinical setup and workflow. Reorganisation of handover flow based on findings from observational studies has been shown to improve the efficiency of information transfer. This study aimed to evaluate a new handover process based on recipients' perceptions, focusing on completeness and comprehensiveness of verbal communication, and the usability of a situation, background, assessment and recommendation (SBAR) form. METHODS: This was a prospective interventional study conducted in the CICU of KK Women's and Children's Hospital, Singapore. It comprised four phases: (1) evaluation of the current handover process through an audit and opinion survey; (2) development of a new handover process based on the opinion survey and hospital personnel feedback; (3) implementation; and (4) evaluation of the new handover process. The new handover process was based on a PETS (pre-handover, equipment handover, timeout and sign out) protocol with a 'single traffic communication' flow and a new SBAR handover document. It included relevant patient information, and the options 'not applicable' and 'none', to increase compliance and reduce ambiguity. RESULTS: Significantly more recipients indicated that the new SBAR form was the most important handover tool and provided more useful information. Recipients' perceptions indicated improvement in information sufficiency and clarity; reduction of omission errors; and fewer inconsistencies in patient descriptions in the new process. CONCLUSION: Dual customisation of the handover process, PETS protocol and SBAR form is necessary to meet the workflow and information demands of the receiving team.

Comparison of epidural oxycodone and epidural morphine for post-caesarean section analgesia: A randomised controlled trial.

BACKGROUND AND AIMS: Epidural morphine after caesarean section may cause moderate to severe pruritus in women. Epidural oxycodone has been shown in non-obstetric trials to reduce pruritus when compared to morphine. We hypothesised that epidural oxycodone may reduce pruritus after caesarean section. METHODS: A randomised controlled trial was conducted in pregnant women at term who underwent caesarean section with combined spinal-epidural technique initiated with intrathecal fentanyl 15 µg. Women received either epidural morphine 3 mg or epidural oxycodone 3 mg via the epidural catheter after delivery. The primary outcome was the incidence of pruritus at 24 h after caesarean section. The secondary outcomes were the pruritus scores, treatment for post-operative nausea and vomiting (PONV), pain scores and maternal satisfaction. RESULTS: One hundred women were randomised (group oxycodone O = 50, morphine M = 50). There was no difference between Group O and M in the incidence of pruritus (n [%] 28 [56%] vs. 31 [62%], P = 0.68) and the worst pruritus scores (mean [standard deviation] 2.6 (2.8) vs. 3.3 [3.1], P = 0.23), respectively. Both groups had similar pain scores at rest (2.7 [2.3] vs. 2.0 [2.7], P = 0.16) and sitting up (5.0 [2.3] vs. 4.6 [2.4], P = 0.38) at 24 h. Pruritus scores were lower at 4-8, 8-12 and 12-24 h with oxycodone, but pain scores were higher. Both groups had a similar need for treatment of PONV and maternal satisfaction with analgesia. CONCLUSION: There was no difference in the incidence of pruritus at 24 h between epidural oxycodone and morphine. However, pruritus scores were lower with oxycodone between 4 and 24 h after surgery with higher pain scores in the same period.

A randomised controlled trial evaluating the impact of targeted vitamin D supplementation on endothelial function in type 2 diabetes mellitus: The DIMENSION trial.

We sought to determine if vitamin D supplementation, to target 25(OH)D concentrations of 30-40 ng/mL, improves endothelial function in Singapore's multi-ethnic type 2 diabetes mellitus population. We randomised 64 type 2 diabetes mellitus patients with hypovitaminosis D to cholecalciferol 4000 International Unit/matching placebo [baseline 25(OH)D < 20 ng/mL] or cholecalciferol 2000 International Unit/matching placebo [baseline 25(OH)D: 20-30 ng/mL] daily for 16 weeks with a down titration at 8 weeks if 25(OH)D > 30 ng/mL. Endothelial function was assessed by peripheral tonometry (reactive hyperaemia index-endothelial peripheral arterial tonometry) and vascular biomarkers: E-selectin, von-Willebrand factor and high-sensitivity C-reactive protein. We compared the change from baseline parameters in the two groups using Student's t-test or Kruskal-Wallis test. A log-normal multivariate regression analysis was used to adjust for relevant baseline variables. The median reactive hyperaemia index in the vitamin D group increased from 0.65 (interquartile range: 0.42) to 0.73 (interquartile range: 0.36), whereas it decreased from 0.73 (interquartile range: 0.65) to 0.65 (interquartile range: 0.38) (p = 0.02) in the placebo group. After adjustment for baseline variables, the change was not statistically significant for reactive hyperaemia index (p = 0.07) and for other vascular biomarkers (p > 0.05). Targeted vitamin D supplementation for 16 weeks resulted in a small but non-significant improvement in endothelial function in a type 2 diabetes mellitus cohort.

Impact of Asia-Pacific guidelines on gastric cancer and Helicobacter pylori infection on prevailing clinical practices.

OBJECTIVE: To determine the impact of the Asia-Pacific guidelines on gastric cancer prevention and Helicobacter pylori (H. pylori) infection on clinical practice. METHODS: An electronic survey was carried out among Asian Pacific Digestive Week (APDW) medical delegates in 2012. The survey questionnaire captured details such as participants' characteristics, their awareness of the guidelines and knowledge of the key guideline recommendations, the impact of the guidelines on individual practice and on national policies and the sources of medical information that the individual used to make clinical decisions. A total of 1372 APDW medical delegates were invited via email to participate in the electronic survey and 432 (31.5%) responded. RESULTS: Among the respondents, 57.6% were familiar with at least one of the guidelines. Among those familiar with the guidelines, 85.9% believed that they influenced their clinical practice. More than half (64.9%) reported that the guidelines clarified treatment indications for them. In terms of knowledge content, 85.0% of the participants provided correct responses to at least four of the six questions on understanding. More than half (52.7%) of the participants felt that the guidelines had made an impact on national policies. CONCLUSION: The Asia-Pacific guidelines on gastric cancer and H. pylori had a positive impact on individual clinical practice and national policies.

Cognitive Impairment after Mild Stroke: Development and Validation of the SIGNAL2 Risk Score.

BACKGROUND: Post stroke cognitive impairment (PSCI), an important complication of strokes, has numerous risk factors. A scale adequately classifying risk of cognitive impairment 3-6 months after mild stroke will be useful for clinicians. OBJECTIVE: To develop a risk score based on clinical and neuroimaging variables that will be useful in identifying mild ischemic stroke patients at high risk for PSCI. METHODS: The risk score development cohort comprised of a retrospective dataset of 209 mild stroke patients with MRI confirmed infarcts, without pre-stroke cognitive impairment, and evaluated within 6 months post-stroke for PSCI. Logistic regression identified factors predictive of PSCI and a risk score was developed based on regression coefficients. The risk score was checked for stability using 10-fold cross-validation and validated in an independent prospective cohort of 185 ischemic mild stroke patients. RESULTS: Within 6 months post-stroke, 37.32% developed PSCI in the retrospective dataset. A 15-point risk score based on age, education, acute cortical infarcts, white matter hyperintensity, chronic lacunes, global cortical atrophy, and intracranial large vessel stenosis was highly predictive of PSCI with an AUC of 0.829. 10.11% with low scores, 52.69% with moderate scores, and 74.07% with high scores developed PSCI. In the prospective validation cohort, the model had an AUC of 0.776, and exhibited similar accuracy and stability statistics at both 6 and 12 months. CONCLUSION: The seven item risk score adequately identified mild stroke patients who are at an increased risk of developing PSCI.

Medication discrepancies and associated risk factors identified among elderly patients discharged from a tertiary hospital in Singapore.

INTRODUCTION: Medication discrepancies and poor documentation of medication changes (e.g. lack of justification for medication change) in physician discharge summaries can lead to preventable medication errors and adverse outcomes. This study aimed to identify and characterise discrepancies between preadmission and discharge medication lists, to identify associated risk factors, and in cases of intentional medication discrepancies, to determine the adequacy of the physician discharge summaries in documenting reasons for the changes. METHODS: A retrospective clinical record review of 150 consecutive elderly patients was done to estimate the number of medication discrepancies between preadmission and discharge medication lists. The two lists were compared for discrepancies (addition, omission or duplication of medications, and/or a change in dosage, frequency or formulation of medication). The patients' clinical records and physician discharge summaries were reviewed to determine whether the discrepancies found were intentional or unintentional. Physician discharge summaries were reviewed to determine if the physicians endorsed and documented reasons for all intentional medication changes. RESULTS: A total of 279 medication discrepancies were identified, of which 42 were unintentional medication discrepancies (35 were related to omission/addition of a medication and seven were related to a change in medication dosage/frequency) and 237 were documented intentional discrepancies. Omission of the baseline medication was the most common unintentional discrepancy. No reasons were provided in the physician discharge summaries for 54 (22.8%) of the intentional discrepancies. CONCLUSION: Unintentional medication discrepancies are a common occurrence at hospital discharge. Physician discharge summaries often do not have adequate information on the reasons for medication changes.

Incidence and characteristics of breakthrough pain in parturients using computer-integrated patient-controlled epidural analgesia.

INTRODUCTION: The computer-integrated patient-controlled epidural analgesia (CIPCEA) system can automatically adjust the background infusion rate during combined spinal-epidural analgesia based on the parturient's need, as labor progresses. OBJECTIVES: The objective is to identify risk factors associated with breakthrough pain during labor as well as identify obstetric and fetal outcomes that are affected by breakthrough pain. DESIGN: This is a retrospective review of prospectively collected data. SETTING: The setting is in a delivery room. PARTICIPANTS: The participants are 280 nulliparous women in early labor (≤5 cm cervical dilatation) who received combined spinal-epidural analgesia with CIPCEA. INTERVENTIONS: The intervention is CIPCEA. MEASUREMENTS: The primary outcome is the incidence of breakthrough pain (≥1 episodes of pain or pressure that required supplemental epidural medications) during labor. Relevant demographic, anesthetic, obstetric, and fetal characteristics were also measured. Univariate and multivariate analyses were performed to identify obstetric and anesthetic factors that were associated with increased incidence of breakthrough pain as well as to evaluate the impact of breakthrough pain on obstetric and fetal outcomes. RESULTS: The incidence of breakthrough pain was 9.6%. Independent factors associated with incidence of breakthrough pain are the presence of dysfunctional labor, increased maternal body mass index, and decreased successful-to-total-bolus-demand ratio. The postlabor characteristics independently associated with breakthrough pain were increased duration of labor, decreased duration of effective analgesia, increased total local anesthetic consumption, and decreased maternal satisfaction. CONCLUSIONS: Low successful to total patient demand bolus ratio was the factor with the strongest association with breakthrough pain. Breakthrough pain was also associated with dysfunctional labor and poorer maternal satisfaction.

Rationale, Methodology, and Implementation of a Dispatcher-assisted Cardiopulmonary Resuscitation Trial in the Asia-Pacific (Pan-Asian Resuscitation Outcomes Study Phase 2).

Abstract Background. Survival outcomes from out-of-hospital cardiac arrest (OHCA) in Asia are poor (2-11%). Bystander cardiopulmonary resuscitation (CPR) rates are relatively low in Asia. Dispatcher-assisted CPR (DA-CPR) has recently emerged as a potentially cost-effective intervention to increase bystander CPR and survival from OHCA. The Pan-Asian Resuscitation Outcomes Study (PAROS), an Asia-Pacific cardiac arrest registry, was set up in 2009, with the aim of understanding OHCA as a disease in Asia and improving OHCA survival. The network has adopted DA-CPR as part of its strategy to improve OHCA survival. Objective. This article aims to describe the conceptualization, study design, potential benefits, and difficulties for implementation of DA-CPR trial in the Asia-Pacific. Methods. Two levels of intervention, basic and comprehensive, will be offered to PAROS participating sites. The basic level consists of implementation of a DA-CPR protocol and training program, while the comprehensive level consists of implementation of the basic level, with the addition of a dispatch quality measurement tool, quality improvement program, and community education program. Sites that are not able to implement the package will contribute control data. The primary outcome of the study is survival to hospital discharge or survival to 30 days post cardiac arrest. DA-CPR and bystander CPR are secondary outcomes. Conclusion. Implementation of DA-CPR requires concerted efforts by EMS leaders and supervisors, dispatchers, hospital stakeholders, policy makers, and the general public. The DA-CPR trial implemented by the PAROS sites, if successful, can serve as a model for other countries considering such an intervention in their EMS systems.