Time to surgery after completion of neoadjuvant chemotherapy does not negatively impact recurrence and survival outcomes in breast cancer patients.

BACKGROUND: The effect of time to surgery after completion of neoadjuvant chemotherapy and outcomes in breast cancer patients remains poorly defined. Acceptable time to surgery has frequently been arbitrarily defined as between four to eight weeks. This study aims to ascertain if time to surgery after completion of neoadjuvant chemotherapy impacts disease-free survival (DFS) and overall survival (OS). MATERIALS AND METHODS: This single-institution retrospective study included patients who underwent neoadjuvant therapy and subsequent surgery from 2006 to 2017. Demographic, clinicopathological factors, and surgical data from 259 patients were analyzed. 105 patients received surgery within 28 days (group 1). 128 patients received surgery within 29-56 days (group 2), and 26 patients received surgery after 57 days or more (group 3). DFS and OS among the three groups were compared. RESULTS: Age, race, pre-chemotherapy stage, tumor type, grade, hormone receptor status, Her2 status, focality, lymphovascular invasion, radiological response to chemotherapy, type of surgery, pathological response to chemotherapy, and receipt of adjuvant radiotherapy were not significantly different between the three groups. Only receipt of adjuvant chemotherapy was statistically significant (p = 0.0230). DFS and OS between the three groups were not found to be significantly different (p = 0.520 and p = 0.369, respectively). CONCLUSION: Time to surgery after completion of neoadjuvant chemotherapy did not appear to affect recurrence or survival outcomes. Findings from this study may allow more flexibility and reduce the burden of scheduling patients for surgery within the usual four-to-eight-week window in centers with resource and scheduling constraints.

Optimal Delivery Management for the Prevention of Early Neonatal SARS-CoV-2 Infection: Systematic Review and Meta-analysis.

OBJECTIVE: Delivery management interventions (DMIs) were recommended to prevent delivery-associated transmission of maternal SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) to infants without evidence of effect on early neonatal SARS-CoV-2 infection (ENI) and neonatal death <28 days of life (ND). This systematic review describes different DMI combinations and the frequency of ENI and ND. STUDY DESIGN: Individual patient data were collected from articles published from January 1, 2020 to December 31, 2021 from Cochrane review databases, Medline, and Google Scholar. Article inclusion criteria were: documented maternal SARS-CoV-2 polymerase chain reaction (PCR)-positive status 10 days before delivery or symptomatic at delivery with a positive test within 48 hours, known delivery method, and known infant SARS-CoV-2 PCR result. Primary outcomes were ENI (positive PCR at 12 hours to 10 days) and ND. All characteristics were pooled using the DerSimonian-Laird inverse variance method. Primary outcome analyses were performed using logit transformation and random effect. Pooled results were expressed as percentages (95% confidence intervals). Continuity correction was applied for all pooled results if any included study has 0 event. RESULTS: A total of 11,075 publications were screened. 117 publications representing 244 infants and 230 mothers were included. All publications were case reports. ENI and ND were reported in 23.4% (18.2-29.18) and 2.1% (0.67-4.72) of cases, respectively. Among cases with available information, DMIs were reported for physical environment (85-100%), delivery-specific interventions (47-100%), and infant care practices (80-100%). No significant comparisons could be performed between different DMI combinations due to small sample size. CONCLUSION: The evidence supporting any DMI in SARS-CoV-2-infected mothers to prevent ENI or ND is extremely limited. Limitations of this meta-analysis include high risk of bias, small sample size, and large confidence intervals. This identifies the need for multinational database generation and specific studies designed to provide evidence of DMI guidelines best suited to prevent transmission from mother to neonate. KEY POINTS: · In this review we analyzed 2 years of maternal SARS-CoV-2 published cases.. · We assessed association of delivery management interventions with infant SARS-CoV-2 infection.. · We found no evidence supporting any DMI for that purpose..

Pregnancy-associated breast cancer: a multicenter study comparing clinicopathological factors, diagnosis and treatment outcomes with non-pregnant patients.

PURPOSE: Pregnancy-associated breast cancer (PABC), defined as breast carcinoma diagnosed during pregnancy or in the first post-partum year, is one of the most common gestation-related malignancies with reported differences in tumor characteristics and outcomes. This multicenter study aims to review cases of PABC in Singapore, including their clinicopathological features, treatment, and clinical outcomes compared to non-PABC patients. METHODS: Demographic, histopathologic and clinical outcomes of 93 PABC patients obtained from our database were compared to 1424 non-PABC patients. RESULTS: PABC patients presented at a younger age. They had higher tumor and nodal stages, higher tumor grade, were more likely to be hormone receptor negative and had a higher incidence of multicentric and multifocal tumors. Histological examination after definitive surgery showed no significant difference in tumor size and number of positive lymph nodes suggesting similar neoadjuvant treatment effects. Despite this, PABC patients had worse outcomes with poorer overall survival and disease-free survival, OS (P < 0.0001) and DFS (P < 0.0001). Termination of pregnancy did not improve survival. CONCLUSION: Patients with PABC present at a higher stage with more aggressive disease and have poorer outcomes compared to non-PABC patients. Reducing delay in diagnosis and treatment may help improve survival.

Treatment and mortality of hemophagocytic lymphohistiocytosis in critically ill children: A systematic review and meta-analysis.

OBJECTIVE: Risk factors of mortality in critically ill children with hemophagocytic lymphohistiocytosis (HLH) are not well described. This systematic review aims to determine overall mortality of critically ill children with HLH, and describes etiologies, treatment, and pediatric intensive care unit (PICU) support employed. DATA SOURCES: PubMed, Embase, Web of Science, CINAHL, and Cochrane Library from inception until February 28, 2022. STUDY SELECTION: Observational studies and randomized controlled trials reporting children aged 18 years or below, diagnosed with HLH and admitted to the PICU. DATA EXTRACTION: Etiologies, treatment modalities, PICU therapies, and mortality outcomes were summarized. Random-effects meta-analysis was performed. DATA SYNTHESIS: Total 36 studies (total patients = 493, mean age: 49.5 months [95% confidence interval (CI): 30.9-79.5]) were included. Pooled mortality rate was 32.6% (95% CI: 23.4-42.4). The most frequent etiologies for HLH were infections (53.3%) and primary HLH (12.8%), while the remaining cases were due to other causes of secondary HLH, including autoimmune diseases, malignancy, and drug-induced and idiopathic HLH. Pooled mortality rate was higher in primary than secondary HLH (72.2%, 95% CI: 57.8-84.5 vs. 23.9%, 95% CI: 14.4-35.02; p < .01). Univariate analysis found that treatment with etoposide was associated with higher mortality, while intravenous immunoglobulins (IVIGs) were associated with lower mortality. Conversely, multivariable analysis adjusted for etiology demonstrated no association between etoposide and IVIG use, and mortality. Twenty-one studies (total patients = 278) had detailed information on PICU therapies. Mechanical ventilation (MV), continuous renal replacement therapy, and inotropes were used in 107 (38.5%), 66 (23.7%), and 51 patients (18.3%), respectively. Need for MV was associated with increased risk of mortality (mean difference = 28%, 95% CI: 9-47). CONCLUSION: Critically ill children with HLH have high mortality rates and require substantial PICU support. Collaborative work between multiple centers with standardized data collection can potentially provide more robust data.

Safe discharge for patients admitted for lower gastrointestinal bleeding (LGITB): derivation and validation of a novel scoring system.

AIM: Bleeding from the lower gastrointestinal tract (LGITB) is a common clinical presentation. Recent guidelines have recommended for incorporation of clinical risk assessment tools in the management for LGITB. We derived and validated a novel clinical scoring system to predict safe discharge after LGITB admission, and compared it to other published scoring systems in current literature. METHODS: A retrospective cohort of 798 patients with LGITB from August 2018 to March 2021 was included in the derivation cohort. Multivariate binary logistic regression was performed to identify significant clinical variables predictive of safe discharge. A clinical scoring system was developed based on the results, and validated on a prospective cohort of 312 consecutive patients with LGITB from April 2021 to March 2022. The performance of the novel scoring system was compared to other LGITB clinical risk assessment scores via area under the receiver operating characteristics curve (AUROC) analysis. RESULTS: Variables predictive of safe discharge included the following; absence of previous LGITB admission, absence of ischemic heart disease, absence of blood on digital rectal examination, absence of dizziness or syncope at presentation and the systolic blood pressure and haemoglobin levels at presentation. The novel score had an AUROC of 0.907. A cut-off point of 4 provided a sensitivity of 41.9%, specificity of 97.5%, positive predictive value of 96.4% and negative predictive value of 51.5% for prediction of safe discharge. The score performs comparably to the Oakland score. CONCLUSION: The novel LGITB clinical risk score has good predictive performance for safe discharge in patients admitted for LGITB.

Tranexamic acid, as an adjunct to oxytocin prophylaxis, in the prevention of postpartum haemorrhage in women undergoing elective caesarean section: A single-centre double-blind randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of tranexamic acid (TXA) in reducing blood loss during elective caesarean sections in women with and without risk factors for postpartum haemorrhage (PPH). DESIGN: A double-blind, randomised placebo-controlled trial. SETTING: An academic tertiary referral centre in Singapore. POPULATION: Multiethnic women aged 21 years or older undergoing elective caesarean section. METHODS: Randomisation to intravenous TXA or normal saline (placebo) 10 minutes before skin incision. MAIN OUTCOME MEASURES: Calculated estimated blood loss (cEBL), derived from blood volume and haematocrit levels. RESULTS: Between June 2020 and October 2021, 200 women were randomised to the placebo or TXA groups. Women who received prophylactic TXA had a significantly lower mean cEBL compared with those receiving placebo (adjusted mean difference -126.4 mL, 95% CI -243.7 to -9.1, p = 0.035). The effect was greatest in those at high risk for PPH, with a reduction in cEBL (mean difference -279.6 mL, 95% CI -454.8 to -104.3, p = 0.002) and a lower risk of cEBL ≥500 mL (risk ratio [RR] 0.54, 95% CI 0.36-0.83, p = 0.007) and cEBL ≥1000 mL (RR 0.44, 95% CI 0.20-0.98, p = 0.016). Subgroup analysis showed benefit for women with preoperative haemoglobin <10.5 g/dL (mean difference -281.9 mL, 95% CI -515.0 to -48.8, p = 0.019). There was no significant difference in need for additional medical or surgical interventions. There were no maternal or neonatal adverse outcomes. CONCLUSION: Prophylactic TXA should be considered in women with risk factors for PPH, and those most likely to benefit are those with preoperative haemoglobin <10.5 g/dL.

Survival Benefits of Therapeutic Plasma Exchange in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

OBJECTIVES: To summarize the role of therapeutic plasma exchange (TPE) in critically ill adults and children with severe sepsis. DATA COLLECTION: A systematic search was performed using the following databases: Medline, EMBASE, CINAHL, and Cochrane from January 1990 till December 2022. Comparative studies of TPE in severe sepsis were selected. Adult and pediatric data were analyzed separately. DATA SYNTHESIS: Eight randomized control trials and 6 observational studies (n = 50,142 patients) were included. Centrifugal TPE was the most common modality (209/280, 74.6% adults and 952/1026, 92.7% children). Every TPE study utilized different volume exchanges. Most TPE sessions (1173/1306, 89.8%) employed fresh frozen plasma (FFP) as replacement fluid and heparin as anticoagulant. Adults with severe sepsis supported with TPE using FFP had lower mortality (risk ratio, RR: 0.64 [95% confidence interval, CI: 0.49, 0.84]) compared to those who did not. In contrast, TPE was associated with increased mortality in septic children without thrombocytopenia-associated multiorgan failure (RR: 2.23, 95% CI: 1.93, 2.57). There was no difference in outcomes in patients supported with centrifugal and membrane TPE. In both populations, patients supported on TPE as a continuous regime had poorer outcome. CONCLUSION: Current evidence indicates that TPE is a potential adjunct therapy in adults with severe sepsis but not in children.

Rituximab in Subepidermal Blistering Diseases.

BACKGROUND: Although rituximab is known to be effective in the treatment of pemphigus, its role in subepidermal autoimmune blistering diseases is unclear and currently limited to off-label use. SUMMARY: This is a meta-analysis of case reports, case series, and retrospective studies on the effectiveness and safety of rituximab in bullous pemphigoid, mucous membrane pemphigoid, ocular pemphigoid, and epidermolysis bullosa acquisita. We compared remission and relapse rates in patients who received rituximab with those who only received conventional medical therapy. Comparisons were also made among disease subgroups. KEY MESSAGE: The present analysis suggests that patients with subepidermal autoimmune blistering diseases treated with rituximab achieve a higher rate of complete remission and encounter their first relapse after a longer time interval. However, time to remission and total relapse rates were similar between groups. Adverse events and mortality rates were no more common in patients who received rituximab. This analysis was limited by the absence of randomized controlled trials and the observation that rituximab was used as a late rescue therapy in most reports. In conclusion, rituximab may be effective in subepidermal blistering disease, but randomized controlled studies are required for the validation of current observational data.

Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Epidural analgesia is often used for pain relief during labour and childbirth, and involves administration of local anaesthetics (LA) into the epidural space resulting in sensory blockade of the abdomen, pelvis, and perineum. Epidural opioids are often co-administered to improve analgesia. Administration of epidural medications can be accomplished by basal infusion (BI) or automated mandatory bolus (AMB). With BI, medications are administered continuously, while AMB involves injecting medications at set time intervals. Patient-controlled epidural analgesia (PCEA) on top of AMB or BI enables patients to initiate additional boluses of epidural medications.  The superior method of delivering epidural medications would result in lower incidence of pain requiring anaesthesiologist intervention (breakthrough pain). Also, it should be associated with lower incidence of epidural-related adverse effects including caesarean delivery, instrumental delivery (use of forceps or vacuum devices), prolonged duration of labour analgesia, and LA consumption. However, clear evidence of the superiority of one technique over the other is lacking. Also, differences in the initiation of epidural analgesia such as combined spinal-epidural (CSE) (medications given into the intrathecal space in addition to the epidural space) compared to epidural only, and medications used (types and doses of LA or opioids) may not have been accounted for in previous reviews.  Our prior systematic review suggested that AMB reduces the incidence of breakthrough pain compared to BI with no significant difference in the incidence of caesarean delivery or instrumental delivery, duration of labour analgesia, and LA consumption. However, several studies comparing AMB and BI have been performed since then, and inclusion of their data may improve the precision of our effect estimates. OBJECTIVES: To assess the benefits and harms of AMB versus BI for maintaining labour epidural analgesia in women at term. SEARCH METHODS: We searched CENTRAL, Wiley Cochrane Library), MEDLINE, (National Library of Medicine), Embase(Elseiver), Web of Science (Clarivate), the WHO-ICTRP (World Health Organization) and ClinicalTrials.gov (National Library of Medicine) on 31 December 2022. Additionally, we screened the reference lists of relevant trials and reviews for eligible citations, and we contacted authors of included studies to identify unpublished research and ongoing trials. SELECTION CRITERIA: We included all randomised controlled studies that compared bolus dosing AMB with continuous BI during epidural analgesia. We excluded studies of women in preterm labour, with multiple pregnancies, with fetal malposition, intrathecal catheters, those that did not use automated delivery of medications, and those where AMB and BI were combined. DATA COLLECTION AND ANALYSIS: We used standard methodology for systematic review and meta-analysis described by Cochrane. Primary outcomes included: incidence of breakthrough pain requiring anaesthesiologist intervention; incidence of caesarean delivery; and incidence of instrumental delivery. Secondly, we assessed the duration of labour; hourly LA consumption in bupivacaine equivalents, maternal satisfaction after fetal delivery, and neonatal Apgar scores.  The following subgroup analyses were chosen a priori: epidural alone versus CSE technique; regimens that used PCEA versus those that did not; and nulliparous versus combination of nulli- and multi-parous women. We used the GRADE system to assess the certainty of evidence associated with our outcome measures. MAIN RESULTS: We included 18 studies of 4590 women, of which 13 enrolled healthy nulliparous women and five included healthy nulli- and multiparous women. All studies excluded women with preterm or complicated pregnancies. Techniques used to initiate epidural analgesia differed between the studies: seven used combined spinal epidural, 10 used epidural, and one used dural puncture epidural (DPE). There was also variation in analgesics used. Eight studies utilised ropivacaine with fentanyl, three used ropivacaine with sufentanil, two utilised levobupivacaine with sufentanil, one used levobupivacaine with fentanyl, and four utilised bupivacaine with fentanyl. Most of the studies were assessed to have low risk of randomisation, blinding, attrition, and reporting biases, except for allocation concealment where eight studies were assessed to have uncertain risk and three with high risk. Our results showed that AMB was associated with lower incidence of breakthrough pain compared to BI (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.55 to 0.91; I2 = 57%) (16 studies, 1528 participants), and lower hourly LA consumption in bupivacaine equivalents (mean difference (MD) -0.84 mg/h; 95% CI -1.29 to -0.38, I2 = 87%) (16 studies, 1642 participants), both with moderate certainty. AMB was associated with an estimated reduction in breakthrough pain incidence of 29.1% (incidence 202 per 1000, 95% CI 157 to 259), and was therefore considered clinically significant. The incidence of caesarean delivery (RR 0.85; 95% CI 0.69 to 1.06; I2 = 0%) (16 studies, 1735 participants) and instrumental delivery (RR 0.85; 95% CI 0.71 to 1.01; I2 = 0%) (17 studies, 4550 participants) were not significantly, both with moderate certainty. There was no significant difference in duration of labour analgesia (MD -8.81 min; 95% CI -19.38 to 1.77; I2 = 50%) (17 studies, 4544 participants) with moderate certainty. Due to differences in the methods and timing of outcome measurements, we did not pool data for maternal satisfaction and Apgar scores. Results reported narratively suggest AMB may be associated with increased maternal satisfaction (eight studies reported increased satisfaction and six reported no difference), and all studies showed no difference in Apgar scores. WIth the exception of epidural alone versus CSE which found significant subgroup differences in LA consumption between AMB and BI, no significant differences were detected in the remaining subgroup analyses. AUTHORS' CONCLUSIONS: Overall, AMB is associated with lower incidence of breakthrough pain, reduced LA consumption, and may improve maternal satisfaction. There were no significant differences between AMB and BI in the incidence of caesarean delivery, instrumental delivery, duration of labour analgesia, and Apgar scores. Larger studies assessing the incidence of caesarean and instrumental delivery are required.

Investigating the association factors of acute postpartum pain: a cohort study.

BACKGROUND: Labor pain intensity is known to predict persistent postpartum pain, whereas acute postpartum pain may interfere with maternal postpartum physical, mental, and emotional well-being. Nevertheless, there is little research studying the association between labor pain intensity and acute postpartum pain. This study investigated the associations between labor pain intensity and psychological factors with acute postpartum pain. METHODS: We included women with American Society of Anesthesiologists (ASA) physical status II, having ≥ 36 gestational weeks and a singleton pregnancy. We investigated the association between labor pain intensity (primary exposure) and high acute postpartum pain at 0 to 24 h after delivery (Numeric Rating Scale (NRS) ≥ 3 of 10; primary outcome). Pre-delivery questionnaires including Angle Labor Pain Questionnaire (A-LPQ), Pain Catastrophizing Scale (PCS), Fear Avoidance Components Scale (FACS) and State Trait Anxiety Inventory (STAI) were administered. Demographic, pain, obstetric and neonatal characteristics were also collected accordingly. RESULTS: Of the 880 women studied, 121 (13.8%) had high acute postpartum pain at 0 to 24 h after delivery. A-LPQ total, PCS, FACS and STAI scores were not significantly associated with acute postpartum pain. Greater A-LPQ subscale on birthing pain (adjusted odds ratio (aOR) 1.03, 95% CI 1.01-1.05, p = 0.0008), increased blood loss during delivery (for every 10ml change; aOR 1.01, 95% CI 1.00-1.03, p = 0.0148), presence of shoulder dystocia (aOR 10.06, 95% CI 2.28-44.36, p = 0.0023), and use of pethidine for labor analgesia (aOR 1.74, 95% CI 1.07-2.84, p = 0.0271) were independently associated with high acute postpartum pain. "Sometimes" having nausea during menstruation before current pregnancy (aOR 0.34, 95% CI 0.16-0.72, p = 0.0045) was found to be independently associated with reduced risk of high acute postpartum pain. CONCLUSIONS: Pre-delivery pain factor together with obstetric complications (shoulder dystocia, blood loss during delivery) were independently associated with high acute postpartum pain. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov registry (NCT03167905) on 30/05/2017.

Effect of music listening on perioperative anxiety, acute pain and pain catastrophizing in women undergoing elective cesarean delivery: a randomized controlled trial.

BACKGROUND: Anxiety may adversely impact mother and her newborn. Music listening is a safe and efficacious treatment that may to reduce perioperative anxiety. The effect on acute pain and pain catastrophizing scores remains unclear. We aimed to determine whether perioperative music listening reduces anxiety, acute pain, and pain catastrophizing scale (PCS) scores following elective cesarean delivery under spinal anesthesia. METHODS: After randomization into music listening and control groups, baseline patient characteristics, visual analog scale-anxiety (VAS-A) scores, pain scores, PCS total and sub-scores, and music preferences were collected preoperatively. Before surgery, parturients in the experimental group listened to music of their own choice for 30 min. Music listening was continued during administration of spinal anesthesia and cesarean delivery, and for 30 min following surgery. Postoperative VAS-A score, acute pain score, PCS scores, music preferences, satisfaction score, and feedback were recorded. RESULTS: We analyzed 108 parturients (music: n = 53; control: n = 55). Music listening was associated with reduced postoperative VAS-A (mean difference (MD) -1.43, 95%CI -0.63 to -2.22), PCS total score (MD -6.39, 95%CI -2.11 to -10.66), PCS sub-scores on rumination (MD -1.68, 95%CI -0.12 to -3.25), magnification (MD -1.53, 95%CI -0.45 to -2.62), and helplessness (MD -3.17, 95%CI -1.29 to -5.06) sub-scores. There was no significant difference in postoperative acute pain scores. The majority (> 95%) of parturients reported "excellent" and "good" satisfaction with music listening, and most provided positive feedback. CONCLUSION: Perioperative music listening was associated with reduced postoperative anxiety and lower pain catastrophizing. Based on the good patient satisfaction and positive feedback received, the use of music listening in the obstetric setting is recommended. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov NCT03415620 on 30/01/2018.

Evaluating an advanced double intravenous vasopressor automated system to treat hypotension during spinal anesthesia for cesarean delivery: a randomized controlled trial.

BACKGROUND: The optimal treatment of hypotension during spinal anaesthesia is uncertain. A novel double intravenous vasopressor automated (DIVA) system reduces hypotension compared to standard care, and was subsequently modified to an advanced-DIVA (ADIVA) system. The primary objective was to compare ADIVA versus DIVA on incidence of hypotension (systolic BP (SBP) < 80% baseline). METHODS: We conducted a randomized-controlled trial in women undergoing elective cesarean delivery under spinal anesthesia. SBP and heart rate were measured continuously using a Nexfin monitor. ADIVA delivered 25 µg phenylephrine (heart rate > 60 beats.min-1) or 2 mg ephedrine (heart rate < 60 beats.min-1) at SBP 90 to 110% of baseline, 50 µg phenylephrine or 4 mg ephedrine at SBP 80 to 90%, and 75 µg phenylephrine or 6 mg ephedrine at SBP < 80%. ADIVA calculated the trend of SBP; vasopressors were administered rapidly if SBP trended downward, or 30 s if SBP trended upward. In contrast, DIVA delivered 25 µg phenylephrine or 2 mg ephedrine at SBP 90 to 100% of baseline, and 50 µg phenylephrine or 4 mg ephedrine at SBP < 90%. Boluses were followed by a 10-s lockout. Other outcomes included hypertension (SBP > 120% baseline), vasopressor consumption, clinical outcomes, and performance measures from spinal anesthesia to fetal delivery. RESULTS: We analyzed 94 parturients (ADIVA: n = 46, DIVA: n = 48), with no difference in the incidence of hypotension between ADIVA (78.3%) and DIVA (83.3%, p = 0.677). ADIVA had significantly higher proportion of hypotensive SBP readings, lower phenylephrine consumption and higher umbilical arterial pH. There was no difference in hypertension, bradycardia, ephedrine consumption, intravenous fluid volume, nausea/vomiting, Apgar scores, and umbilical venous pH or lactate. ADIVA maintained SBP higher above baseline with greater fluctuation than DIVA. CONCLUSION: ADIVA was associated with a greater proportion of hypotensive SBP readings, reduced phenylephrine consumption, and increased umbilical arterial pH than DIVA. Further research is needed to determine the optimal method of vasopressor delivery in parturients undergoing cesarean delivery. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov registry (NCT03620942) on 08/08/2018.

Comparison of the neurobehavioural profile of early-preterm infants against term and late-preterm infants using the Hammersmith neonatal neurological examination.

AIM: To compare the neurobehavioural profile of early-preterm infants (<32 weeks gestation) at term-corrected age (39+0 -41+6 weeks) versus late-preterm and full-term infants at similar term gestational ages. METHODS: Early-preterm infants were assessed neurologically at term-corrected age using the Hammersmith neonatal neurological examination. The raw scores of the 34 Hammersmith neonatal neurological examination items were converted to optimality scores. Pairwise comparison of neurobehavioural patterns between early-preterm infants at term-corrected age versus late-preterm and full-term infants at similar gestational ages were made using independent sample t tests. Differences in optimality scores between the three groups were evaluated using one-way analysis of variance. RESULTS: Sixty-eight early-preterm infants assessed at term-corrected age were compared against 75 late-preterm infants and 133 full-term infants. Mean total optimality scores (±standard deviation) of early-preterm, late-preterm and full-term infants at term-corrected age were 27.68 (±3.97), 29.09 (±2.45) and 31.58 (±1.39), respectively (P < 0.001). The mean optimality score of early-preterm infants was significantly lower when compared pairwise with late-preterm infants and full-term infants with mean difference of -1.42 (P = 0.013) and -3.91 (P < 0.001), respectively. CONCLUSION: The neurobehavioural profile of early-preterm infants lags significantly behind those of late-preterm and full-term infants at term-corrected age. This study also provides reference raw and optimality scores for all items in the Hammersmith neonatal neurological examination for early-preterm infants in a predominantly Asian population.

Mortality Trends of Oncology and Hematopoietic Stem Cell Transplant Patients Supported on Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

BACKGROUND: There is an increasing frequency of oncology and hematopoietic stem cell transplant (HSCT) patients seen in the intensive care unit and requiring extracorporeal membrane oxygenation (ECMO), however, prognosis of this population over time is unclear. METHODS: MEDLINE, EMBASE, Cochrane and Web of Science were searched from earliest publication until April 10, 2020 for studies to determine the mortality trend over time in oncology and HSCT patients requiring ECMO. Primary outcome was hospital mortality. Random-effects meta-analysis model was used to obtain pooled estimates of mortality and 95% confidence intervals. A priori subgroup metanalysis compared adult versus pediatric, oncology versus HSCT, hematological malignancy versus solid tumor, allogeneic versus autologous HSCT, and veno-arterial versus veno-venous ECMO populations. Multivariable meta-regression was also performed for hospital mortality to account for year of study and HSCT population. RESULTS: 17 eligible observational studies (n = 1109 patients) were included. Overall pooled hospital mortality was 72% (95% CI: 65, 78). In the subgroup analysis, only HSCT was associated with a higher hospital mortality compared to oncology subgroup [84% (95% CI: 70, 93) vs. 66% (95% CI: 56, 74); P = 0.021]. Meta-regression showed that HSCT was associated with increased mortality [adjusted odds ratio (aOR) 3.84 (95% CI 1.77, 8.31)], however, mortality improved with time [aOR 0.92 (95% CI: 0.85, 0.99) with each advancing year]. CONCLUSION: This study reports a high overall hospital mortality in oncology and HSCT patients on ECMO which improved over time. The presence of HSCT portends almost a 4-fold increased risk of mortality and this finding may need to be taken into consideration during patient selection for ECMO.

Uterine exteriorization versus in situ repair in Cesarean delivery: a systematic review and meta-analysis.

PURPOSE: We conducted an updated systematic review and meta-analysis on maternal outcomes associated with uterine exteriorization compared with in situ repair in women undergoing Cesarean delivery. METHODS: We searched for randomized controlled trials comparing uterine exteriorization with in situ repair during Cesarean delivery. Primary outcomes were intraoperative nausea and vomiting (IONV) and perioperative decrease in hemoglobin concentration. Secondary outcomes were postoperative nausea and vomiting (PONV), estimated blood loss, fever, endometritis, wound infection, intraoperative and postoperative pain, postoperative analgesic use, duration of surgery and hospital stay, and time to return of bowel function. RESULTS: Twenty studies with 20,909 parturients were included. Exteriorization was associated with higher risk of IONV (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.66 to 2.63; I2 = 0%), with no difference in perioperative hemoglobin concentration decrease (mean difference, - 0.06 g·dL-1; 95% CI, - 0.20 to 0.08; I2 = 97%) compared with in situ repair. There were no significant differences in estimated blood loss, transfusion requirement, PONV, duration of surgery, duration of hospital stay, time to return of bowel function, fever, endometritis, or wound infection. Postoperative pain (incidence of pain graded > 5/10) at six hours (OR, 1.64; 95% CI, 1.31 to 2.03; I2 = 0%) was higher with exteriorization, but there was no difference in need for rescue analgesia (OR, 2.48; 95% CI, 0.89 to 6.90; I2 = 94%) or pain scores at 24 hr compared with in situ repair. CONCLUSIONS: In this updated systematic review and meta-analysis, uterine exteriorization was associated with an increased risk of IONV but no significant change in perioperative hemoglobin decrease compared with in situ repair. STUDY REGISTRATION: PROSPERO (CRD42020190074); registered 5 July 2020.

RéSUMé: OBJECTIF: Nous avons réalisé une mise à jour d'une revue systématique et une méta-analyse portant sur les issues maternelles associées à l'extériorisation de l'utérus par rapport à une réparation in situ chez les femmes accouchant par césarienne. MéTHODE: Nous avons recherché des études randomisées contrôlées comparant l'extériorisation de l'utérus à la réparation in situ pendant un accouchement par césarienne. Les critères d'évaluation principaux étaient les nausées et vomissements peropératoires (NVPerO) et la réduction périopératoire de l'hémoglobine. Les critères d'évaluation secondaires étaient les nausées et vomissements postopératoires (NVPO), la perte de sang estimée, la fièvre, l'endométrite, l'infection de la plaie, la douleur per- et postopératoire, l'utilisation d'analgésiques postopératoires, la durée de la chirurgie et du séjour à l'hôpital, et le délai jusqu'au retour du transit. RéSULTATS: Vingt études portant sur 20 909 parturientes ont été incluses. L'extériorisation était associée à un risque plus élevé de NVPerO (rapport de cotes [RC], 2,09; intervalle de confiance à 95 % [IC], 1,66 à 2,63; I2 = 0 %), sans différence dans la réduction de l'hémoglobine périopératoire (différence moyenne, − 0,06 g·dL-1; IC 95 %, − 0,20 à 0,08; I2 = 97 %) par rapport à une réparation in situ. Il n'y avait pas de différences significatives dans la perte de sang estimée, les besoins transfusionnels, les NVPO, la durée de la chirurgie, la durée du séjour à l'hôpital, le délai jusqu'au retour du transit, la fièvre, l'endométrite ou l'infection de la plaie. La douleur postopératoire (incidence de la douleur graduée > 5/10) à six heures (RC, 1,64; IC 95 %, 1,31 à 2,03; I2 = 0 %) était plus élevée avec une extériorisation, mais il n'y avait aucune différence dans les besoins d'analgésie de secours (RC, 2,48; IC 95 %, 0,89 à 6,90; I2 = 94 %) ou les scores de douleur à 24 heures par rapport à une réparation in situ. CONCLUSION: Dans cette revue systématique et méta-analyse mises à jour, l'extériorisation utérine était associée à un risque accru de NVPerO, mais à aucun changement significatif dans la réduction de l'hémoglobine périopératoire par rapport à la réparation in situ. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42020190074); enregistrée le 5 juillet 2020.

Development of local guidelines to prevent perioperative hypothermia in children: a prospective observational cohort study.

PURPOSE: Perioperative hypothermia (PH) is defined as core body temperature < 36°C during the perioperative period. The incidence of PH is not well established in children because of variations in perioperative temperature monitoring and control measures. We sought to 1) establish the incidence of pediatric PH, 2) assess its adverse outcomes, and 3) identify risk factors in our pediatric population to develop local guidelines for prevention of PH. METHODS: We conducted a prospective observational cohort study at a single tertiary hospital (KK Women's and Children's Hospital, Singapore) from June 2017 to December 2017 based on existing institutional practice. We recruited patients aged ≤ 16 yr undergoing surgery and determined the incidence and adverse outcomes of hypothermia. We identified risk factors for PH using univariate and multiple logistic regression analysis and used these to develop local guidelines. RESULTS: Of 1,766 patients analyzed, 213 (12.1%; 95% confidence interval, 10.6 to 13.7) developed PH. Among these cases of PH, only 4.5% would have been detected by a single measurement in the postanesthesia care unit (PACU). Adverse outcomes included a longer stay in the PACU (47 vs 39 min; P < 0.01), a higher incidence of shivering (7.1 vs 2.6%; P = 0.01), and more discomfort (3.8 vs 1.4%; P = 0.02) compared with normothermic patients. Risk factors for PH included preoperative temperature < 36°C, surgery duration > 60 min, ambient operating room temperature < 23.0°C, and several "high-risk" surgeries. Guidelines were developed based on these risk factors and customized according to clinical and workflow considerations. CONCLUSIONS: Perioperative hypothermia was a common problem in our pediatric population and was associated with significant adverse outcomes. Guidelines developed based on risk factors identified in the local context can facilitate workflow and implementation within the institution.

RéSUMé: OBJECTIF: L'hypothermie périopératoire (HP) est définie par une température corporelle centrale < 36 °C pendant la période périopératoire. L'incidence de l'HP chez les enfants n'est pas connue avec précision en raison des variations dans le suivi de la température périopératoire et des mesures de contrôle. Nous avons cherché à (1) déterminer l'incidence de l'HP pédiatrique, (2) évaluer ses effets préjudiciables et (3) identifier les facteurs de risque dans notre population pédiatrique afin d'élaborer des lignes directrices locales pour la prévention de l'HP. MéTHODES: Nous avons mené une étude de cohorte observationnelle prospective dans un seul hôpital de niveau tertiaire (KK Women's and Children's Hospital, Singapour) de juin 2017 à décembre 2017 sur la base des pratiques existantes dans l'établissement. Nous avons recruté des patients âgés de 16 ans ou moins subissant une intervention chirurgicale et nous avons déterminé l'incidence et les effets secondaires de l'hypothermie. Nous avons identifié les facteurs de risque de l'HP en utilisant des analyses de régression logistique monofactorielle et multifactorielle qui nous ont servi à élaborer ces lignes directrices locales. RéSULTATS: Parmi les 1 766 cas de patients analysés, 213 (12,1 %; intervalle de confiance à 95 % : 10,6 à 13,7) ont développé une HP. Parmi ceux-ci, seulement 4,5 % auraient été détectés par une mesure unique dans l'unité de soins post anesthésie (salle de réveil). Les événements indésirables ont inclus un séjour plus long en salle de réveil (47 contre 39 minutes; P < 0,01), une plus grande incidence de tremblements (7,1 % contre 2,6 %; P = 0,01) et plus d'inconfort (3,8 % contre 1,4 %; P = 0,02), comparativement aux patients normothermiques. Les facteurs de risque d'HP étaient, notamment, une température préopératoire < 36 °C, la durée de la chirurgie > 60 min, la température de la salle d'opération < 23,0°C et plusieurs chirurgies à « risque élevé ¼. Des lignes directrices ont été élaborées à partir de ces facteurs de risque et adaptées en tenant compte de considérations cliniques et des flux de travail. CONCLUSIONS: L'hypothermie périopératoire était un problème fréquent dans notre population pédiatrique et a été associée à des effets secondaires significatifs. Des lignes directrices élaborées en fonction de facteurs de risque dans un contexte local peuvent faciliter le flux de travail et leur mise en œuvre au sein d'un établissement.

Heart rate variability and haemodynamic factors associated with hypotension during spinal anaesthesia for caesarean delivery: A case-control study.

BACKGROUND: Hypotension frequently occurs during spinal anaesthesia for caesarean delivery, with potential adverse effects. OBJECTIVE: To investigate heart rate variability and haemodynamic factors associated with spinal anaesthesia-induced hypotension. DESIGN: Secondary case-control analysis of a randomised study. SETTING: Single obstetric centre. PATIENTS: Data were obtained from 230 healthy term singleton parturients who underwent elective caesarean delivery under spinal anaesthesia. INTERVENTION: With parturients at rest, continuous haemodynamic measurements were recorded using a Nexfin cardiac monitor. Baseline pre-operative values were defined as the average of five minutes of continuous measurements. After initiation of standardised spinal anaesthesia, vasopressors were administered to maintain SBP within 10% of pre-operative values. Hypotension was defined as any 10 seconds average SBP less than 80% of pre-operative values from initiation of spinal anaesthesia to foetal delivery. Parturients were classified into cases (hypotensive) or controls (normotensive), and both univariate and multivariable logistic regression models were used to identify independent factors associated with hypotension. MAIN OUTCOME MEASURES: Pre-operative standard deviation of the interbeat interval (SDNN), root mean square of successive interbeat difference, low-frequency to high-frequency ratio, SD1, SD2, approximate entropy, sample entropy, mean arterial pressure, SBP, stroke volume variation and systemic vascular resistance index were recorded, as were sensory block height, intravenous fluid volume and vasopressor use between spinal anaesthesia and foetal delivery. RESULTS: Of 230 parturients, 113 (49.1%) experienced hypotension. Pre-operative lower SDNN [odds ratio (OR) 0.87, 95% confidence interval (CI) 0.78 to 0.97], higher SD2 (OR 25.06, 95% CI 2.41 to 261.06), and lower SBP (OR 0.98, 95% CI 0.97 to 1.00) were independently associated with hypotension. Between spinal anaesthesia to foetal delivery, lower sensory block height (OR 0.76, 95% CI 0.65 to 0.90) and higher intravenous fluid volume (OR 0.98, 95% CI 0.96 to 0.99 per 15 ml change) were associated with a lower incidence of hypotension. Area under the receiver operating characteristic curve was 0.701. CONCLUSION: Pre-operative higher SD2, lower SDNN and lower SBP were associated with hypotension during spinal anaesthesia for caesarean delivery. TRIAL REGISTRATION: NCT02277730.

An advanced double intravenous vasopressor automated system to treat hypotension during spinal anaesthesia for caesarean section: A pilot study.

BACKGROUND: During spinal anaesthesia for caesarean section, haemodynamic instability may lead to maternal and foetal complications. We developed a novel advanced double intravenous vasopressor automated system (ADIVA) by using a continuous blood pressure and heart rate monitor. Treatment of hypotension was based on three criteria: the drug (phenylephrine or ephedrine) according to the heart rate; the dose of vasopressor determined by the degree of hypotension; a fast or slow bolus of vasopressor administered depending on whether there was a negative or positive gradient of SBP changes, respectively. OBJECTIVE: The aim of this pilot study was to investigate the feasibility of the ADIVA algorithm. DESIGN: A prospective pilot study. SETTING: Single obstetrics and gynaecology centre in Singapore. PATIENTS: Women undergoing elective caesarean delivery under spinal anaesthesia. INTERVENTION: Automated administration of ephedrine or phenylephrine based on changes in blood pressure and heart rate (via the ADIVA algorithm) detected on continuous noninvasive haemodynamic monitoring using noninvasive continuous haemodynamic monitor (Nexfin). MAIN OUTCOME MEASURES: The primary outcome was the incidence of hypotension, defined as SBP less than 80% of baseline. The secondary outcome measures were reactive hypertension, total vasopressor requirement, maternal and neonatal outcomes and system performance. RESULTS: Forty-five women were recruited. Thirty-one women (69.9%) had at least one reading of hypotension. SBP was within ±20% of the baseline in a mean ±â€ŠSD of 79.7 ±â€Š17.6% of measurements. Forty-four (97.8%) women required phenylephrine before delivery, while 15 (33.3%) required ephedrine. No rescue medications were required. Three women (6.7%) had nausea and two (4.4%) vomiting. All neonates had APGAR scores of 9 at 5 min. CONCLUSION: The ADIVA system, with noninvasive continuous haemodynamic monitoring, was able to maintain maternal SBP within ±20% of baseline for the vast majority of the measurements. This system had good maternal and foetal outcomes with minimal intervention from the attending anaesthetist. TRIAL REGISTRATION: NCT03620942.

Stress and emotional distress: their associations with somatic and temporomandibular disorder-related symptoms.

Although Asians are posited to be predisposed to somatization, studies on the inter-relationships between emotional and physical symptoms in Asian youths are still limited. This study determined the associations between emotional, somatic, and Temporomandibular Disorder (TMD)-related symptoms in Asian youths. Youths were recruited from a local polytechnic and the prevalence/severity of emotional distress was ascertained with the Depression, Anxiety, and Stress Scale-21. Somatic and TMD-related symptoms were appraised with the Patient Health Questionnaire-15 and Fonseca Anamnestic Index. Data were analysed using non-parametric statistical and logistic regression analysis (p < 0.05). The study sample (n = 400; 209 females) had a mean age of 18.7 ± 1.7 years. Moderate-to-severe depression, anxiety, and stress were present in 31.0%, 36.8%, and 16.5% of the subjects respectively. Subjects with moderate-to-severe emotional distress had significantly higher somatic and TMD symptom scores (p < 0.001). Correlations between emotional and somatic/TMD symptom scores were moderately strong (rs = 0.46-0.61). Stepwise logistic regression indicated that moderate-to-severe somatization was associated with the female gender, anxiety, and stress, and moderate-to-severe TMDs were related to somatization and stress. Asian youths with elevated emotional distress experienced significantly higher levels of somatic and TMD-related symptoms. The stress construct appears to pose a greater risk for somatization and TMDs than depression and anxiety.

Reassessing the Use of Proton Pump Inhibitors and Histamine-2 Antagonists in Critically Ill Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the associations of stress ulcer prophylaxis with gastrointestinal (GI) bleeding, nosocomial pneumonia (NP), mortality, and length of stay in the pediatric intensive care unit (PICU). STUDY DESIGN: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies in the English language assessing the effects of proton pump inhibitors and histamine-2 receptor antagonists on patients in the PICU published before October 2018 from the PubMed, Embase, CINAHL, and Cochrane Central Register of Controlled Trials databases. A random-effects Mantel-Haenszel risk difference (MHRD) model was used to pool all the selected studies for meta-analysis. Primary outcomes were the incidences of GI bleeding and NP. Secondary outcomes included mortality and length of PICU stay. RESULTS: Seventeen studies (4 RCTs and 13 observational studies) with a total of 340 763 patients were included. The overall incidence of GI bleeding was 15.2%. There was no difference in the risk of GI bleeding based on stress ulcer prophylaxis status (MHRD, 5.0%; 95% CI, -1.0% to 11.0%; I2 = 62%). There was an increased risk of NP in patients who received stress ulcer prophylaxis compared with those who did not (MHRD, 5.3%; 95% CI, 3.5%-7.0%; I2 = 0%). An increased risk of mortality was seen in patients receiving stress ulcer prophylaxis (MHRD, 2.1%; 95% CI, 2.0%-2.2%; I2 = 0%), although this association was no longer found when 1 large study was removed in a sensitivity analysis. There was no statistically significant difference in length of PICU stay between the groups (standardized mean difference, 0.42 days; 95% CI, -0.16 to 1.01 days; I2 = 89.8%). CONCLUSIONS: Stress ulcer prophylaxis does not show a clear benefit in reducing GI bleeding or length of PICU stay. Observational studies suggest an increased risk of NP and mortality with stress ulcer prophylaxis, which remains to be validated in clinical trials.