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

Synthesis, and anti-malarial screening, of 1-diethylamino-4- (dihydroartemisinin-10-yl)amino pentane

Artemisinin and its derivatives have become antimalarial drugs of choice because they are effective against most stages in the life cycle of  plasmodium and are safe for all, including pregnant women. World Health Organisation (WHO) has nevertheless recommended artemisinin based combination therapy (ACT) to guard against possible development of resistance, as observed with chloroquine. In this study we coupled dihydroartemisinin with 2-amino- 5-diethyl aminopentane (the chloroquine handle) by using the Mitsunobu coupling (an SN2 reaction). This involvesthe use of diisopropylazodicarboxylate (DIAD), triphenyl phosphine (Ph3P), 2-amino-5-diethylaminopentane and dihydroartemisinin (DHA) at room temperature to synthesize the target compound, 1-diethylamino-4-(dihydroartemisinin-10-yl)amino pentane {coded: DHA-CQ; IUPAC Name: N1,N1-diethyl-N4-(3,6,9- trimethyldecahydro- 3,12-epoxy[1,2]dioxepino[4,3-i] isochromen-10-yl) pentane-1,4-diamine}. The structure of DHA-CQ was determined from spectroscopic data (IR, 1H & 13C NMR, MS). The compound was screened at three dose levels of 3 mg/kg, 10 mg/kg and 30 mg/kg, for in vivo curative antimalarial activity against mice infected with Plasmodium berghei berghei. The target  compound also had an LD50 of 330 mg/kg in mice by the oral route. Asingle dose kinetics study was carried out and three different metabolites were identified.Keywords: Artemisinin; Chloroquine; Dihydroartemisinin; Plasmodium berghei berghei; Mitsunobu couplin

Strategies to manage hepatitis C virus infection disease burden-Volume 4

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortalit