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

Number needed to treat and costs per responder among biologic treatments for moderate-to-severe plaque psoriasis in Japan

<p><b>Background:</b> Biologics have been shown to improve the outcomes of patients with psoriasis but their cost is an issue.</p> <p><b>Objective:</b> Determine the number needed to treat (NNT) to achieve a 75%/90% reduction in the Psoriasis Area and Severity Index (PASI-75/90) and evaluate the incremental cost per PASI-75/90 responder (CPR) relative to placebo in Japan.</p> <p><b>Methods:</b> A network meta-analysis was conducted to estimate the relative probabilities of achieving PASI-75/90 and NNTs. Drug costs were assessed based on Pharmaceutical and Medical Device Agency-approved dosing. The CPR was estimated for a short-term induction period and first year of treatment.</p> <p><b>Results:</b> Compared with placebo, the PASI-75 NNT was 1.27 for adalimumab 80 mg, 1.29 for secukinumab 150 mg, 1.36 for secukinumab 300 mg, 1.57 for adalimumab 40 mg, 1.68 for ustekinumab 90 mg, 1.97 for ustekinumab 45 mg and 2.00 for infliximab 5 mg/kg. The short-term PASI-75 CPR relative to placebo was $5,062 for secukinumab 150 mg,$8209 for adalimumab 40 mg, $10,654 for secukinumab 300 mg,$11,754 for adalimumab 80 mg, $15,407 for ustekinumab 45 mg,$19,147 for infliximab 5 mg/kg and $26,257 for ustekinumab 90 mg. A similar ranking was observed for one-year PASI-75 CPRs and PASI-90 NNTs and CPRs.</p> <p><b>Conclusion:</b> Adalimumab 40 mg/80 mg and secukinumab 150 mg/300 mg were the most efficacious and cost-efficient for patients with psoriasis in Japan.</p

Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers

How HIV controllers (HICs) maintain undetectable viremia without therapy is unknown. The strong CD8+ T-cell HIV suppressive capacity found in many, but not all, HICs may contribute to long-lasting viral control. However, other earlier defense mechanisms may be involved. Here, we examined intrinsic HIC cell resistance to HIV-1 infection. After in vitro challenge, monocyte-derived macrophages and anti–CD3-activated CD4+ T cells from HICs showed low HIV-1 susceptibility. CD4 T-cell resistance was independent of HIV-1 coreceptors and affected also SIVmac infection. CD4+ T cells from HICs expressed ex vivo higher levels of p21Waf1/Cip1, which has been involved in the control of HIV-1 replication, than cells from control subjects. However, HIV restriction in anti–CD3-activated CD4+ T cells and macrophages was not associated with p21 expression. Restriction inhibited accumulation of reverse transcripts, leading to reduction of HIV-1 integrated proviruses. The block could be overcome by high viral inocula, suggesting the action of a saturable mechanism. Importantly, cell-associated HIV-1 DNA load was extremely low in HICs and correlated with CD4+ T-cell permissiveness to infection. These results point to a contribution of intrinsic cell resistance to the control of infection and the containment of viral reservoir in HICs