Prednisolone does not improve olfactory function after COVID-19: a randomized, double-blind, placebo-controlled trial

1. Following COVID-19 infection with associated olfactory dysfunction, this randomized trial found no difference between a 10-day course of oral prednisolone and placebo.

Evidence Rating Level: 1 (Excellent)

Olfactory disorders are a common feature in COVID-19 patients, occurring in approximately two in three patients. Most patients recover within 4 weeks, but many will continue to suffer from olfactory disorder after many months. Unfortunately, these olfactory symptoms can result in depressive symptoms and nutritional issues, which ultimately lead to lower patient quality of life. The only therapeutic option offered now is olfactory training, though there is limited evidence about its efficacy. The olfactory symptoms are thought to be a result of an inflammatory response – a short course of oral corticosteroids has been hypothesized to improve olfactory symptoms; however, there is limited evidence for this, and there is not yet a consensus for treatment. The Corticosteroids for COVID-19-induced loss of smell (COCOS) trial was a single-center, randomized, double-blinded, placebo-controlled trial in the Netherlands to determine the efficacy of prednisolone on olfactory disorders following COVID-19 infection. Patients with COVID-19 infection and objective hyposmia or anosmia were recruited from November 2021 to February 2022 and randomized to receive a 10-day course of oral prednisolone or placebo. Patients were assessed at baseline and at 12 weeks, and throughout the trial, both groups performed 12 weeks of olfactory training twice a day. The primary outcome was the objective difference between the two groups on the threshold-discrimination-identification (TDI) score, and secondary outcomes included gustatory function and the impact of changes on the quality of life. 115 patients were enrolled and randomized to prednisolone (n = 58) or placebo (n = 57). With respect to the primary outcome, there was similar improvement in olfactory function in both groups after 12 weeks, with a mean TDI of 26.8 in the placebo group, and 28.8 in the prednisolone group with a median difference of 2.0 (95% CI 0.65 – 1.5, p=0.10). With respect to secondary outcomes, self-reported smell function on the visual analogue scale (VAS) for quality of life was 3.2 (IQR 1.8-6.5) in the placebo group and 3.6 (IQR 1.0-5.8) in the prednisolone group with a median difference of 0.45 (p=0.53). In addition, there were no differences between the two groups in objective gustatory function at 12 weeks. Overall, the findings from this study suggest that in patients who suffered a COVID-19 infection with associated olfactory symptoms, there was no difference in olfactory function between a short course of oral prednisolone and a placebo. A major limitation of this study is the timing of the corticosteroid treatment; in this trial, it was given within 4 weeks of COVID-19 infection, which may result in a decreased efficacy of the corticosteroid course. Given the harmful effects of post-COVID-19 olfactory dysfunction, this study is an important first step in exploring possible treatment options. Further research with variable timing of corticosteroid administration and the effect of different COVID-19 strains on olfactory disorder will be instrumental in guiding future therapy.


The effect of preoperative biliary drainage on postoperative complications of pancreaticoduodenectomy: a triple center retrospective study

1. In patients with a pancreatic or periampullary tumour undergoing pancreaticoduodenectomy (PD), this retrospective study found no difference in surgical complications in patients who underwent preoperative biliary draining (PBD) and patients who did not undergo PBD.

2. Bilirubin level >15 mg/dL in patients undergoing PD was correlated with significantly higher overall complications.

Evidence Rating Level: 2 (Good)

A significant complication of pancreatic and periampullary tumours is biliary obstruction, which can lead to cholangitis, coagulopathies, and gastrointestinal symptoms. The standard procedure for resecting these tumours is a pancreaticoduodenectomy (PD), which is associated with high mortality and morbidity. Hyperbilirubinemia was hypothesized to negatively affect the outcome following PD; addressing biliary obstruction with preoperative biliary drainage (PBD) was thought to reduce post-operative complications. However, there has been limited evidence regarding this, and the latest guidelines suggest the use of PBD according to certain criteria. This retrospective study included patients who underwent PD in three medium-volume Iranian centers between September 2012 and February 2022. Patients were further divided into two populations based on biliary obstruction, defined as a report of subjective jaundice or total bilirubin level of >2 mg/dL. With respect to the management of jaundice, most patients underwent endoscopic retrograde cholangiopancreatography (ERCP) and stent placement prior to referral to a pancreatic surgeon, and in cases of unsuccessful ERCP, a percutaneous transhepatic catheter (PTC) was used. During the study period, PD was performed by a total of 12 surgeons with similar techniques. Outcomes included mortality, defined as death within 90 days after surgery, severe post-operative primary surgical complications, as well as secondary surgical complications such as delayed gastric emptying (DGE), postoperative hemorrhage, postoperative pancreatic fistula (POPF), intraabdominal abscess, and wound infection. 147 patients were included in the study, with 73 (49.7%) receiving preoperative biliary stenting. Postoperatively, overall morbidity was 40.7% and mortality was 21.1%. There was no significant difference in postoperative mortality and morbidity between patients who received PBD and patients who did not receive PBD. Interestingly, bilirubin >15 mg/dL was correlated with higher overall complications (63.6% vs 33.0%, p=.008). In addition, surgery duration was significantly longer in patients with wound infection, intra-abdominal abscess, DGE, secondary complications, and overall complications. Of note, in patients with biliary obstruction, postoperative morbidity and mortality were similar between the PBD and no PBD group, with no risk factors significantly impacting outcomes. Overall, the findings from this study suggest no difference between PBD and no PBD in patients undergoing PD for pancreatic and periampullary tumours. A limitation of this study was that it was conducted only in Iran, and the results may not be generalized to populations with differing racial profiles. This study is an addition to the growing body of evidence surrounding preoperative biliary stenting; it is important to consider the potential financial burden of PBD and possible complications in the absence of clear benefits of the intervention.


Opioid-reduced anesthesia based on esketamine in gynecological day surgery: a randomized double-blind controlled study

1. In adult females undergoing day gynecological surgery, this randomized controlled trial found that opioid-reduced analgesia using esketamine did not result in improved postoperative nausea and vomiting (PONV) when compared to opioid analgesia.

2. There was no significant difference in in subjective pain following surgery between patients who had opioid analgesia and opioid-reduced analgesia using esketamine.

Evidence Rating Level: 1 (Excellent)

Opioids are often used for intraoperative and postoperative pain management; however, perioperative opioid use has been associated with significant side effects including nausea, gastrointestinal paralysis, delirium, and hypoxemia. Many nonopioid analgesics are currently available; intravenous ketamine has been established as an effective adjunctive analgesic. Esketamine, a dextroisomer of ketamine, has a strong analgesic effect and has been combined with other drugs in previous studies to implement opioid-free analgesia. Female sex has been previously found to be an independent risk factor that significantly increases the risk of postoperative nausea and vomiting (PONV), and this double-blind parallel randomized controlled trial investigated whether opioid-reduced anesthesia based on esketamine reduces complications and accelerates rehabilitation in patients undergoing gynecologic day surgery. Included in the study were adult women scheduled for hysteroscopy and cervical conization. The primary outcome was the incidence of postoperative nausea within 24 hours following surgery, with secondary endpoints of postoperative vomiting incidence, postoperative length of hospital stay, pain scores evaluated by the visual analogue scale (VAS), length of stay in the post anesthesia care unit (PACU), adverse hemodynamic events, and other adverse reactions. Patients were randomized in a 1:1:1 ratio into three separate groups. During induction, groups C and MO received alfentanil, whereas group LO received a lower dose of alfentanil mixed with esektamine. For anesthetic maintenance, group C received alfentanil, while groups LO and MO received esketamine only. Throughout the surgery, mean arterial pressure (MAP) and heart rate (HR) were recorded at 9 separate time points. In addition, tatients were followed at two postoperative time points – in the PACU and on the first day of discharge. 141 patients were available for primary analysis, with no significant difference found between the three groups with respect to their preoperative PONV risk score. With respect to the primary endpoint, the incidence of nausea within 24 hours was 33.3% in group C, 18.4% in group MO, and 43.2% in group LO. The incidence of nausea within 24 hours was significantly lower in group MO than in group LO (P<.05). With respect to secondary endpoints, the incidence of vomiting within 24 hours after operation was lower in group MO than in group LO (P<.05). Otherwise, the length of stay in PACU was increased in group LO compared to group C (median 60 vs. 42.5, P<.05). The VAS scores for postoperative pain did not significantly differ among the three groups. Interestingly, the number of patients in group LO with bradycardia and hypotension was significantly decreased compared with group C. Overall, the findings from this study suggest that opioid-reduced analgesia using esketamine did not significantly reduce PONV and may have contributed to more serious PONV and longer postoperative rehabilitation. However, esketamine did display a positive analgesic effect comparable to opioids and showed more stable hemodynamics as well. A limitation of this study was the lack of other supplemental medications to completely replace opioids in an opioid-free analgesia group. This is an important trial in exploring opioid-reduced analgesia as an effective alternative, and further research is required to explore ideal combinations of analgesics and sedatives.


Efficacy of surgical skin preparation solutions in hip arthroplasty: a prospective randomized trial

1. In patients undergoing elective total hip arthroplasty, this randomized trial found that the most common bacterial organisms prior to skin preparation were coagulase-negative staph.

2. Following skin preparation, patients randomized to receive DuraPrep had a significantly lower proportion of positive skin cultures when compared to patients who had received Chloraprep.

Evidence Rating Level: 1 (Excellent)

Postoperative infections are relatively uncommon following hip arthroplasty, but when they do occur, they can lead to significant patient morbidity and cost. A possible risk factor for postoperative infection is the amount of bacterial skin flora present at the operative site at the time of surgery. The use of antimicrobial preoperative skin preparation solutions is routine in surgeries; current guidelines as per the Centers of Disease Control and World Health Organization recommend an alcohol-based preparation combining chlorhexidine or iodophors with alcohol; however, these guidelines do not provide consensus on which agent to combine with alcohol. Previous research has investigated bacterial cultures prior to and following orthopedic surgery in many different areas; however, this research is not necessarily applicable to surgery involving the hip, given the adjacent areas. The purpose of this randomized controlled trial was to examine native bacteria present around the hip and to assess the efficacy of two surgical skin preparation solutions, ChloraPrep (2% chlorhexidine gluconate and 70% isopropyl alcohol) and Duraprep (0.7% iodophor and 74% isopropyl alcohol). 105 patients undergoing primary total hip arthroplasty (THA) were recruited from October 2014 to December 2015 at a single center and randomized to receive ChloraPrep or DuraPrep as surgical skin preparation. Patients had their culture specimens collected prior to skin preparation, following skin preparation, and following skin closure. The most common organisms isolated were Staphylococcus epidermidis, Corynebacterium, Micrococcus luteus, S. hominis, and S. capitis. Following skin preparation, the overall proportion of positive culture results was significantly lower in the DuraPrep group compared to the ChloraPrep group (14% [n=7] vs 35% [n=19], adjusted RR 0.40, 95% CI 0.18-0.85). At this stage, the most common bacterial organisms were M. luteus (15 isolates), Corynebacterium (4 isolates), and S epidermidis (3 isolates). After wound closure, there was no significant difference in positive culture rate between the two groups (29% [n=15] vs. 35% [n=19], adjusted RR 2.10, 95% CI 1.12-3.95). With respect to complications, three patients total had complications within 6 weeks of surgery, 1 (2%) patient in the ChloraPrep group and 2 (4%) patients in the DuraPrep group (p=.6). At 3 months, no superficial wound complications were identified, and no deep wound infections were encountered during this study. Overall, the most common skin flora in the hip area from this study was found to be S. epidermidis, Corynebacterium, M. luteus, S. hominis, and S. capitis. The findings from this study suggest that DuraPrep was initially more effective than ChloraPrep following application, though there was no difference after wound closure. In addition, this initial difference is due to isolates of M. luteus, and there is questionable clinical significance of M. luteus as a positive skin culture as it is a rare cause of periprosthetic infections. A major limitation of this study is the small sample size; given that periprosthetic joint infections following elective THA are quite rare, this study is underpowered to show correlation between joint infection and type of skin preparation solution. Further studies with larger samples will be beneficial to identify the most effective type of surgical skin preparation to prevent periprosthetic joint infections.


Cancer surgery cancellation: incidence, outcomes and recovery in a universal health care system

1. This retrospective study found that patients who experienced a same-day cancellation of their cancer surgery had significantly higher wait times and healthcare cost when compared to patients without a prior history of cancellation.

Evidence Rating Level: 2 (Good)

Cancer surgery cancellation can have negative consequences for all parties involved, including the healthcare system. A delay in surgery by even a few weeks may have a negative impact on curability and overall survival, especially with more aggressive malignancies. During the COVID-19 pandemic, many surgeries were cancelled, of which cancer surgeries were relatively protected likely due to the prioritization of oncologic procedures over nononcologic procedures. Previous research has investigated the effect of surgery cancellation on outcomes, but none have focused on cancer surgery specifically. This study aims to determine the incidence of same-day surgery cancellation in a universal healthcare context, and to determine the association of cancellations with outcomes. This study was a population-based retrospective cohort study in Ontario, Canada. Included were patients with a diagnosis of cancer from January 2010 to December 2016 as per the Ontario Cancer Registry (OCR) which boasts a high capture rate, >98% for all noncutaneous malignancies. Two cohorts were identified; a control cohort of patients who underwent cancer surgery with no prior history of cancellation, and a cancelled cohort of patients who underwent cancer surgery but with a prior history of cancellation. The overall cancellation rate was 1.74%; the cancelled cohort had 3539 patients, and the control cohort had 199599 patients. With respect to baseline characteristics, the cancelled patients were more likely to be younger and male, but this was not clinically meaningful. In addition, the cancelled cohort had a clinically and significantly higher comorbidity index than the control cohort. Genitourinary cancer surgeries were more likely to be cancelled, while gastrointestinal and “other” cancers were less likely to be cancelled. With respect to endpoints, wait times were significantly shorter in the control cohort than in the cancelled cohort (median 66.9 vs 25.4 days, p<0.001). Interestingly, patients in the cancelled group had overall higher survival (hazard ratio [HR] 0.921, 95% CI 0.882-0.960, p<.01) than patients in the control group. At 3 years, however, both groups had a similar survival rate. Patients in the cancelled cohort also had higher complication rates while in hospital than the control cohort (7.3% vs 4.9%, p<.01), specifically a higher rate of only myocardial infarctions. On univariable analysis after controlling for confounders, there was no significant difference between the two groups in all-cause hospital readmission and/or ED visit within 30 days (odds ratio [OR] 1.12, p=.76). The cancelled cohort was also found to cost approximately $1100 more than the control cohort (95% CI $3-$2196, p=.049). Overall, this study identified a low rate (1.64%) of same-day cancer surgery cancellation; these cancellations lead to increased wait times and costs of care but do not have an apparent association with 3-year survival, increased surgical complication rates, or postoperative ED use. A major limitation of this study was that only same-day cancellations were identified, which likely underestimates the true cancer surgery cancellation rate. Furthermore, only patients who eventually underwent their procedure were included, which also contributes to underestimation. This is an important study to identify the negative impact of surgical cancellations, specifically within oncology, and further research should investigate factors that contribute to surgical cancellations.

Image: PD

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