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

Screening and Characterization of RAPD Markers in Viscerotropic <i>Leishmania</i> Parasites

<div><p>Visceral leishmaniasis (VL) is mainly due to the <i>Leishmania donovani</i> complex. VL is endemic in many countries worldwide including East Africa and the Mediterranean region where the epidemiology is complex. Taxonomy of these pathogens is under controversy but there is a correlation between their genetic diversity and geographical origin. With steady increase in genome knowledge, RAPD is still a useful approach to identify and characterize novel DNA markers. Our aim was to identify and characterize polymorphic DNA markers in VL <i>Leishmania</i> parasites in diverse geographic regions using RAPD in order to constitute a pool of PCR targets having the potential to differentiate among the VL parasites. 100 different oligonucleotide decamers having arbitrary DNA sequences were screened for reproducible amplification and a selection of 28 was used to amplify DNA from 12 <i>L. donovani</i>, <i>L. archibaldi</i> and <i>L. infantum</i> strains having diverse origins. A total of 155 bands were amplified of which 60.65% appeared polymorphic. 7 out of 28 primers provided monomorphic patterns. Phenetic analysis allowed clustering the parasites according to their geographical origin. Differentially amplified bands were selected, among them 22 RAPD products were successfully cloned and sequenced. Bioinformatic analysis allowed mapping of the markers and sequences and priming sites analysis. This study was complemented with Southern-blot to confirm assignment of markers to the kDNA. The bioinformatic analysis identified 16 nuclear and 3 minicircle markers. Analysis of these markers highlighted polymorphisms at RAPD priming sites with mainly 5′ end transversions, and presence of inter– and intra– taxonomic complex sequence and microsatellites variations; a bias in transitions over transversions and indels between the different sequences compared is observed, which is however less marked between <i>L. infantum</i> and <i>L. donovani</i>. The study delivers a pool of well-documented polymorphic DNA markers, to develop molecular diagnostics assays to characterize and differentiate VL causing agents.</p></div

RAPD profiles obtained with primers OP-O7 (A) and OP-O13 (B) to illustrate examples of monomorphic and polymorphic profiles.

<p>Laboratory codes of the strains are indicated for each lane. SD: Sudan; TN: Tunisia; M: 100 bp DNA size marker. Indicated sizes are in bp.</p

Comparative inter-species analysis of mutations within the RAPD priming sites.

<p>Comparative inter-species analysis of mutations within the RAPD priming sites.</p

Panel of <i>Leishmania</i> strains used for screening of RAPD markers.

<p>WHO that summarizes Host, geographical origin, year of isolation and laboratory code is presented together with pathology and zymodeme code whenever available. MON– corresponds to zymodeme code attributed by the reference center in Montpellier. The table also gathers study codes assigned to some of the isolates in other studies: D21, D28, D29, D31 and D32: strains used in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109773#pone.0109773-Mauricio1" target="_blank">[20]</a>; DON-39 and ARC-43: strains used in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109773#pone.0109773-Kuhls1" target="_blank">[21]</a>; Devi, H9, LRC-L57, ADDIS 164: strains used in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109773#pone.0109773-Jamjoom1" target="_blank">[18]</a>; Devi, GEBRE1 and KA-Jeddah: strains used in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109773#pone.0109773-Thiel1" target="_blank">[53]</a>; DON-81and ARC-43 (LG11): strains used in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109773#pone.0109773-Kuhls2" target="_blank">[28]</a>; DON-09, DON-31, DON-39 and ARC-11: strains used in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109773#pone.0109773-Chocholov1" target="_blank">[25]</a>. Country abbreviations are shown as specified by WHO recommendations (SD: Sudan; TN: Tunisia; ET: Ethiopia; SA: Saudi Arabia; KE: Kenya; IN: India). ND: Not Determined; CL: cutaneous leishmaniasis; VL: visceral leishmaniasis; PKDL: Post Kala azar Dermal Leishmaniasis.</p><p>Panel of <i>Leishmania</i> strains used for screening of RAPD markers.</p

Selected features characterizing the cloned RAPD markers.

a<p>: Non coding Sequence;</p>b<p>: Overlap with a coding sequence;</p>c<p>: Matching with a coding sequence;</p>d<p>: Minicircle sequence;</p><p>* Imperfect Microsatellite: one mutation in one repeat;</p><p>**Imperfect Microsatellite: one mutation in two repeats;</p><p>*** Imperfect Microsatellite: one mutation in three repeats; (d): a 58 bp deletion associated to the microsatellite; NA: not applicable; −: no microsatellite observed or no mutations at priming site; +: presence of mismatch at priming site.</p><p>Selected features characterizing the cloned RAPD markers.</p