Pain after oocyte retrieval in women with endometriosis undergoing fertility preservation or IVF.

RESEARCH QUESTION: Do women with endometriosis undergoing oocyte retrieval for fertility preservation experience the same level of pain as women undergoing oocyte retrieval for IVF? DESIGN: This retrospective cohort study included 796 cycles in women with endometriosis undergoing oocyte retrieval for fertility preservation (n = 401) or IVF (n = 395) between January 2020 and October 2022. Post-operative pain assessments were compared between the two groups using a numeric rating scale (NRS). RESULTS: Women in the fertility preservation group were younger (32.1 ± 4.2 years versus 35.1 ± 4.1 years; P < 0.001), had a lower body mass index (22.8 ± 3.9 kg/m2 versus 24.6 ± 4.4 kg/m2; P < 0.001) and had a lower concentration of anti-Müllerian hormone (1.8 ± 1.5 ng/ml versus 2.15 ± 2.11 ng/ml; P = 0.026) in comparison with women in the IVF group. The oestrogen concentration on the day of ovulation trigger was higher in women in the fertility preservation group (2188 ± 1152 pg/ml versus 2081 ± 995 pg/ml; P = 0.004), and the prevalence rates of adenomyosis and digestive endometrial lesions were lower in women in the fertility preservation group (14% versus 29%, P < 0.001; 16% versus 25%, P = 0.003, respectively) compared with women in the IVF group. After oocyte puncture, more women in the fertility preservation group had an NRS pain score >3 (moderate to severe pain) compared with women in the IVF group (20% versus 14%; P = 0.018). The progestin-primed ovarian stimulation (PPOS) protocol was identified as an independent predictive factor of greater post-operative pain (adjusted OR 2.30, 95% CI 1.06-5.15; P = 0.039). CONCLUSION: Women with endometriosis undergoing fertility preservation reported more intense post-operative pain in the recovery room than women undergoing IVF. The PPOS protocol was an independent risk factor of intense pain (NRS pain score >3) in women with endometriosis, but further studies are needed to confirm this result.

Acute pain management after vaginal delivery with perineal tears or episiotomy.

BACKGROUND: A vaginal delivery may be associated with acute postpartum pain, particularly after perineal trauma. However, pain management in this setting remains poorly explored. OBJECTIVE: The aim of this systematic review was to evaluate the literature and to develop recommendations for pain management after a vaginal delivery with perineal trauma. EVIDENCE REVIEW: MEDLINE, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) and systematic reviews assessing pain after a vaginal delivery with perineal tears or episiotomy until March 2023. Cochrane Covidence quality assessment generic tool and the RoB Vis 2 tool were used to grade the quality of evidence. FINDINGS: Overall, 79 studies (69 RCTs and 10 systematic reviews and meta-analyses) of good quality of evidence were included. Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line treatment. Epidural morphine (≤2 mg) is recommended among women with labor epidural analgesia and severe perineal tears, with adequate respiratory monitoring. Local anesthetic infiltration, topical local anesthetic, ointment application, and pudendal nerve block are not recommended due to insufficient or lack of evidence. Ice or chemical cold packs are recommended for postpartum pain first-line treatment due to their simplicity of use. Transcutaneous nerve stimulation and acupuncture are recommended as adjuvants. When a perineal suture is indicated, a continuous suture compared with an interrupted suture for the repair of episiotomy or second-degree perineal tears is recommended for the outcome of pain. For women with first-degree or second-degree perineal tears, no suturing or glue compared with suturing is recommended for the outcome of pain. CONCLUSIONS: Postpartum pain management after a vaginal delivery with perineal trauma should include acetaminophen, NSAIDs, and ice or chemical cold packs. Epidural morphine should be reserved for severe perineal tears. A surgical repair technique should depend on perineal tear severity.

Pain management after thoracic surgery or chest trauma.

Accidental or surgically induced thoracic trauma is responsible for significant pain that can impact patient outcomes. One of the main objectives of its pain management is to promote effective coughing and early mobilization to reduce atelectasis and ventilation disorders induced by pulmonary contusion. The incidence of chronic pain can affect more than 35% of patients after both thoracotomy and thoracoscopy as well as after chest trauma. As the severity of acute pain is associated with the incidence of chronic pain, early and effective pain management is very important. In this narrative review, we propose to detail systemic and regional analgesia techniques to minimize postoperative pain, while reducing transitional pain, surgical stress response and opioid side effects. We provide the reader with practical recommendations based on both literature and clinical practice experience in a referral level III thoracic trauma center.

PROSPECT guidelines update for evidence-based pain management after prostatectomy for cancer.

The aim of this review was to update the recommendations for optimal pain management after open and laparoscopic or robotic prostatectomy. Optimal pain management is known to influence postoperative recovery, but patients undergoing open radical prostatectomy typically experience moderate dynamic pain in the immediate postoperative day. Robot-assisted and laparoscopic surgery may be associated with decreased pain levels as opposed to open surgery. We performed a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) with PROcedure SPECific Postoperative Pain ManagemenT (PROSPECT) methodology. Randomised controlled trials (RCTs) published in English language, from January 2015 until March 2020, assessing postoperative pain, using analgesic, anaesthetic and surgical interventions, were identified from MEDLINE, EMBASE and Cochrane Databases. Of the 1797 studies identified, 35 RCTs and 3 meta-analyses met our inclusion criteria. NSAIDs and COX-2 selective inhibitors proved to lower postoperative pain scores. Continuous intravenous lidocaine reduced postoperative pain scores during open surgery. Local wound infiltration showed positive results in open surgery. Bilateral transversus abdominis plane (TAP) block was performed at the end of surgery and lowered pain scores in robot-assisted procedures, but results were conflicting for open procedures. Basic analgesia for prostatic surgery should include paracetamol and NSAIDs or COX-2 selective inhibitors. TAP block should be recommended as the first-choice regional analgesic technique for laparoscopic/robotic radical prostatectomy. Intravenous lidocaine should be considered for open surgeries.

Pain measurement and critical review of analgesic trials: pain scores, functional pain measurements, limits and bias of clinical trials.

Randomized clinical trials designed to assess analgesic agents and/or techniques used for postoperative pain control have several limitations, which are addressed in this article. Efficacy of analgesics cannot be limited to the evaluation of pain intensity or the amount of opioid rescue medication, but it also means to evaluate parameters such as the delay and duration of the effect, the number of patients with satisfactory pain control, and side effects. Because combination of analgesics is the standard of care in clinical practice, its value also needs to be documented. Eventually, analgesic treatments have to be considered in the settings of postoperative supportive care and enhanced recovery programmes after surgery.

[Management of epithelial ovarian cancer. Short text drafted from the French joint recommendations of FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa]. / Texte court rédigé à partir de la recommandation nationale de bonnes pratiques cliniques « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa ¼.

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). In case of ovarian, Fallopian tube or primitive peritoneal cancer of FIGO III-IV stages, thoraco-abdomino-pelvic CT scan with injection (grade B) is recommended. Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A).

Modelling of the optimal bupivacaine dose for spinal anaesthesia in ambulatory surgery based on data from systematic review.

BACKGROUND: Spinal bupivacaine is used for day-case surgery but the appropriate dose that guarantees hospital discharge is unknown. OBJECTIVE: We sought to determine the spinal bupivacaine dose that prevents delayed hospital discharge in ambulatory surgery. DESIGN: Systematic review of clinical trials. DATA SOURCES: Comprehensive search in electronic databases of studies published between 1996 and 2014 reporting the use of spinal bupivacaine in ambulatory patients. Additional articles were retrieved through hyperlinks and by manually searching reference lists in original articles, review articles and correspondence published in English and French. MAIN OUTCOME MEASURES: Data were used to calculate, motor block duration and discharge time, an estimated maximal effect (Emax: maximum theoretical time of motor block) and the effective dose to obtain half of Emax (D50) with 95% confidence intervals (CIs). A simulation was performed to determine the dose corresponding to a time to recovery of 300 min for motor function, and 360 min for discharge, in 95% of the patients. RESULTS: In total, 23 studies (1062 patients) were included for analysis of the time to recovery of motor function, and 12 studies (618 patients) for the time to hospital discharge. The Emax for recovery of motor function was 268 min [95% CI (189 to 433 min)] and the D50 was 3.9 mg [95% CI (2.3 to 6.2 mg)]. A 7.5-mg dose of bupivacaine enables resolution of motor block and ambulation within 300 min in 95% of the patients. A 5-mg dose or less was associated with an unacceptable failure rate. CONCLUSION: Ambulatory surgery is possible under spinal anaesthesia with bupivacaine although the dose range that ensures reliable anaesthesia with duration short enough to guarantee ambulatory management is narrow.

Sustainable rare diseases business and drug access: no time for misconceptions.

Legislative incentives enacted in Europe through the Regulation (EC) No. 141/2000 to incentivize orphan drug development have over the last 12 years constituted a powerful impetus toward R&D directed at the rare diseases population. However, despite therapeutic promises contained in these projects and significant economic impact linked to burgeoning R&D expenditures, the affordability and value of OMPs has become a topic of health policy debate in Europe fueled by the perception that OMPs have high acquisition costs, and by misconceptions around pricing dynamics and rare-diseases business models. In order to maintain sustainable patient access to new and innovative therapies, it is essential to address these misconceptions, and to ensure the successful continuation of a dynamic OMPs R&D within rare-diseases public health policy. Misconceptions abound regarding the pricing of rare diseases drugs and reflect a poor appreciation of the R&D model and the affordability and value of OMPs. Simulation of potential financial returns of small medium sized rare diseases companies focusing on high priced drugs show that their economic returns are likely to be close to their cost of capital. Research in rare diseases is a challenging endeavour characterised by high fixed costs in which companies accrue substantial costs for several years before potentially generating returns from the fruits of their investments. Although heavily dependent upon R&D capabilities of each individual company or R&D organization, continuous flow of R&D financial investment should allow industry to increasingly include efficiencies in research and development in cost considerations to its customers. Industry should also pro-actively work on facilitating development of a specific value based pricing approach to help understanding what constitute value in rare diseases. Policy makers must reward innovation based upon unmet need and patient outcome. Broader understanding by clinicians, the public, and policy makers of the complexity of clinical programs to deliver OMPs to market is required to better comprehend the decisions needed and made by industry. In parallel, an overt effort to consider the impact of public policies on R&D investments is key to enable policy makers to better reconcile the incentives provided by public policy decisions and companies investments decisions in a more positive manner.