Assessment of salivary alpha-amylase and cortisol as a pain related stress biomarker in dogs pre-and post-operation

Background The use of salivary biomarkers has garnered attention because the composition of saliva reflects the body’s physiological state. Saliva contains a wide range of components, including peptides, nucleic acids, electrolytes, enzymes, and hormones. It has been reported that salivary alpha-amylase and cortisol are biomarkers of stress related biomarker in diseased dogs; however, evaluation of salivary alpha-amylase and cortisol pre- and post- operation has not been studied yet. The aim of this study was to evaluate salivary alpha-amylase and cortisol levels in dogs before and after they underwent surgery and investigate the association between the salivary alpha-amylase and cortisol activity and pain intensity. For this purpose, a total of 35 dogs with disease-related pain undergoing orthopedic and soft tissue surgeries were recruited. Alpha-amylase and cortisol levels in the dogs’ saliva and serum were measured for each using a commercially available canine-specific enzyme-linked immunosorbent assay kit, and physical examinations (measurement of heart rate and blood pressure) were performed. In addition, the dogs’ pre- and post-operative pain scores determined using the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF) were evaluated. Results After surgery, there was a significant decrease in the dogs’ pain scores (0.4-fold for the CMPS-SF, p < 0.001) and serum cortisol levels (0.73-fold, p < 0.01). Based on their pre-operative CMPS-SF scores, the dogs were included in either a high-pain-score group or a low-pain-score group. After the dogs in the high-pain-score group underwent surgical intervention, there was a significant decrease in their CMPS-SF scores and levels of salivary alpha-amylase, serum alpha-amylase, and serum cortisol. Additionally, there was a positive correlation between salivary alpha-amylase levels and CMPS-SF scores in both the high- and low-pain-score groups. Conclusions The measurement of salivary alpha amylase can be considered an important non-invasive tool for the evaluation of pain-related stress in dogs.

Effectiveness of Intravenous Ibuprofen On Emergence Agitation in Children Undergoing Tonsillectomy With Propofol Anesthesia: A Double-Blind, Placebo-Controlled, Randomized Study

Background: Emergence agitation (EA) has a negative effect on recovery from general anesthesia in children. Objectives: This study aimed to evaluate the effectiveness of intravenous ibuprofen in reducing the incidence of EA in children.Methods: This randomized, double-blind, placebo-controlled study analyzed data from patients aged 3–9 years undergoing tonsillectomy with propofol general anesthesia. These patients were randomly assigned to receive either the ibuprofen or the placebo intraoperatively. The primary endpoint was between-group difference in the incidence of EA after surgery. EA was defined as Pediatric Anesthesia Emergence Delirium score ≥ 10. The secondary endpoint included the associated factors of EA.Results: Eighty-nine patients were included in the study. Ibuprofen decreased the incidence of EA (8.9% in the treatment group vs. 34.1% in the control group; odds ratio [OR], 0.261; 95% confidence interval [CI], 0.094–0.724; P = 0.004). After the logistic regression analysis, anxiety behavior pre-anesthesia and high pain score after surgery were the risk factors related to EA (OR, 8.07; 95% CI, 1.12–58.07, P = 0.038 and OR, 2.78; 95% CI, 1.60–4.82, P < 0.001, respectively). Ibuprofen administration was the protective factor related to EA (OR, 0.05; 95% CI, 0.01–0.67, P = 0.023).Conclusions: In our studied cohort, intraoperatively infusing ibuprofen and relieving preoperative anxiety and postoperative pain can significantly reduce the incidence and severity of EA after propofol general anesthesia.Trial registration: ChiCTR2100045128 (07/04/2021)

Why do women choose to undergo oocyte aspiration without sedation or analgesia?

Objective Oocyte pick-up (OPU) is a painful but essential part of in-vitro fertilization (IVF) that is usually performed under sedation and analgesia (SaA). Our aim was to study that why some women decide to undergo OPU without SaA? Methods This was a prospective study using patient questionnaires and the standardized 7-item generalized anxiety disorder (GAD-7) score. The patients were asked to assess the pain experienced during OPU using a visual analog scale (VAS). The study sample was a convenience sample of 100 healthy women undergoing OPU at our unit with or without SaA. Results Women who chose to undergo OPU without SaA were significantly more likely to express the fear of anesthesia. A high pain score (VAS ≥ 6) was reported by significantly more patients who underwent OPU without SaA than with SaA. Yet, 98% of the patients who underwent OPU without SaA stated that in future IVF cycles, they would still choose to undergo OPU without SaA. More patients had high anxiety scores among those who underwent OPU with than without SaA. Conclusions Women who chose to undergo OPU without SaA reported more often fear of anesthesia. Although these women experienced significantly more pain during OPU, almost all of them suggested that they would still choose to undergo OPU without SaA. Increased anxiety, as expressed by higher GAD-7 scores, was not associated with a tendency to choose SaA during OPU. The option of OPU without SaA seems to be an acceptable option for selected women. Lay summary Egg retrieval from the ovaries is a painful part of in vitro fertilization (IVF). It is, therefore, usually performed under sedation and pain relief (analgesia). The aim of this study was to investigate: Why some women decide to undergo egg retrieval without sedation? We prospectively studied 100 women using patient questionnaires and standardized scores in order to measure patient's pain and anxiety levels. We found that women who chose to undergo egg retrieval without sedation were significantly more likely to express fear of anesthesia. As expected, women who decided to forgo sedation experienced more pain during egg retrieval, yet, 98% of them decided that in future IVF cycles, they would still choose to undergo egg retrieval without sedation. Surprisingly, women who had high anxiety scores were not more likely to ask for sedation during egg retrieval. The option to undergo egg retrieval without sedation during IVF seems to be acceptable for some women.

Estrogen Receptor 1 Gene rs22346939 and rs9340799 Variants are associated with Major Depressive Disorder and its Clinical Features

Objective: Major depressive disorder (MDD) is a major health problem worldwide. Estrogen interacts with the central nervous system and has been shown to affect anxiety and depressive behavior. Estrogen mediates its effects by connecting its receptors, estrogen receptors 1 and 2. The purpose of this case-control study was to clarify the association between MDD risk and estrogen receptor 1 (ESR1) gene variants. Methods: This study included 245 individuals (125 MDD patients and 120 healthy controls). Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) technics were used for genotyping ESR1 XbaI (rs9340799) and PvuII (rs22346939) variants. Results: There were statistically significant differences between the groups in terms of genotype frequencies of the ESR1 PvuII (-397 T > C) variant (p = 0.049) but not for the XbaI (-351 A > G) variant (p > 0.05). However, a correlation was observed between MDD and ESR1 XbaI variant after male participants were excluded (p = 0.028). Also, the high pain score of MDD patients was associated with the ESR1 PvuII variant, especially in female patients (p = 0.021). According to the results of combined genotype analysis, AA-TC combined genotype was correlated with a decreased risk in patients with MDD compared to controls (p = 0.016), while the combined genotype of GG-CC was associated with increased risk in the patients with MDD compared to controls (p = 0.042). Conclusion: he two ESR1 variants were associated with MDD risk and its features in both individual and combined forms.

Paracetamol versus Diclofenac as Intravenous Post-Operative Analgesia in Patients after Laparoscopic Surgeries

BACKGROUND Laparoscopic surgery is becoming a widely used procedure in recent days due to its minimal invasive nature and faster recovery. Pain is a stressful stimulus in postoperative period. Pain is a subjective experience. Poor pain management may hinder better postoperative outcome, leading to patient suffering and lengthened recovery period. We wanted to compare the efficacy of intravenous paracetamol and intravenous diclofenac for post-operative analgesia following laparoscopic surgeries. METHODS This randomised controlled double-blind prospective study was conducted between October 2017 and May 2019 among 48 participants posted for laparoscopic abdominal surgeries, block randomised into 24 participants each in 2 groups. All patients were given general anaesthesia and 30 minutes prior to extubation patients were given the test drug according to the groups assigned using closed envelop technique. The test drugs were continued post operatively at prescribed intervals. Visual analogue score (VAS) score, systolic and diastolic blood pressure (BP) and heart rate were monitored at 2, 4, 6, 12 and 24 hours postoperatively. Furthermore, need for rescue analgesia with inj. tramadol 50 mg intramuscular (IM) and post-operative nausea and vomiting (PONV) were noted. RESULTS The study results showed increased pain scores in diclofenac group up to 12 hours but were statistically insignificant. High pain score was seen in diclofenac group at 24 hours with statically significant P-value of 0.022 and PONV occurring in 3 patients. Paracetamol group had better haemodynamic stability. CONCLUSIONS Intravenous paracetamol and intravenous diclofenac were found to be equally effective in post-operative analgesia in patients undergoing laparoscopic surgeries; however, paracetamol has an advantage of providing better analgesia for longer duration with better haemodynamic stability. KEYWORDS Intravenous Paracetamol, Intravenous Diclofenac, Laparoscopic Surgeries, PostOperative Analgesia

Preoperative Cognitive Impairment and the Prevalence of Postoperative Delirium in Elderly Cancer Patients—A Prospective Observational Study

Preoperative cognitive impairment (PCI) in cancer patients includes a broad spectrum of neurocognitive changes produced by complex interplay of patient, tumoural and treatment-related factors. Reduced preoperative cognitive reserve can favour the emergence of postoperative delirium (POD). The study aims to document PCI prevalence and to assess the relationship with POD in elderly cancer patients. The prospective observational study included consecutive patients scheduled for elective surgery; PCI was assessed with Mini-Cog test and defined at a score ≤ 3, POD was screened using Nursing Delirium Screening Scale (Nu-DESC) and defined at a score ≥ 2. Data on education, American Society of Anesthesiologists (ASA) score, preoperative medications, substance use, comorbidities, sensorial deficits, surgery and anaesthesia type, anaesthetic drugs, Mini-Cog score, postoperative pain, Nu-DESC were collected. In total, 131 patients were enrolled, mean age 72.1 ± 5.9 years. PCI prevalence was 51.9% (n = 68). POD prevalence was 19.8% (n = 26), with significantly higher value in PCI patients (27.9% vs. 11.1%, p = 0.016). In multivariate analysis, Mini-Cog score ≤ 3 (OR = 2.6, p = 0.027), clock draw (OR: 2.9, p = 0.013), preoperative renal dysfunction (OR = 2.6, p = 0.012), morphine (OR = 2.7, p = 0.007), metoclopramide (OR = 6.6, p = 0.006), and high pain score (OR = 1.8, p = 0.018) had a significant association with POD development. In this sample of elderly patients, PCI had a high prevalence and predicted the emergence of POD. Incorporating Mini-Cog test into the preoperative evaluation of onco-geriatric patients seems valuable and feasible.

“Holding–Cuddling” and Sucrose for Pain Relief During Venepuncture in Newborn Infants: A Randomized, Controlled Trial (CÂSA)

Objectives: Oral sucrose is commonly used to provide analgesia to neonates during painful procedures, such as venepuncture. The additional benefits of reducing pain during venepuncture when oral sucrose is combined with nonpharmacological strategies have not been extensively studied. This randomized controlled trial compared the efficacy of oral sucrose with nonnutritive sucking vs. oral sucrose with nonnutritive sucking plus “holding–cuddling” for pain management during venepuncture in term infants from birth to 3 months of life.Methods: Seventy-eight infants were equally randomized to receive 24% oral sucrose with nonnutritive sucking (control group) or 24% oral sucrose with nonnutritive sucking plus “holding–cuddling” (being held in a secure, cuddling position; experimental group) before venepuncture. Behavioral response to pain was measured by the 0–10 ranking scale “acute pain for neonates (APN)” at 30 and 60 s after venepuncture.Results: Within the study sample, APN scores were ≥ 2 for 32/68 (47%) infants. “Holding–cuddling” did not significantly reduce mean APN scores at 30 and 60 s, but the rate of infants experiencing a high pain score (APN ≥ 8) at 60 s after the venepuncture was significantly lower in the experimental group compared to controls [4/34 vs. 12/34 (p = 0.04)].Conclusions: Venepuncture is a painful procedure in newborn and young infants. The implementation of behavioral strategies in association with oral sucrose may mitigate pain during this procedure.Clinical Trial Registration: This trial was registered at http://clinicaltrials.gov/ (NCT number 02803723).

Abatacept in rheumatoid arthritis: survival on drug, clinical outcomes, and their predictors—data from a large national quality register

Background There are limited data regarding efficacy of abatacept treatment for rheumatoid arthritis (RA) outside clinical trials. Quality registers have been useful for observational studies on tumor necrosis factor inhibition in clinical practice. The aim of this study was to investigate clinical efficacy and tolerability of abatacept in RA, using a national register. Methods RA patients that started abatacept between 2006 and 2017 and were included in the Swedish Rheumatology Quality register (N = 2716) were investigated. Survival on drug was estimated using Kaplan-Meier analysis. The European League Against Rheumatism (EULAR) good response and Health Assessment Questionnaire (HAQ) response (improvement of ≥ 0.3) rates (LUNDEX corrected for drug survival) at 6 and at 12 months were assessed. Predictors of discontinuation were investigated by Cox regression analyses, and predictors of clinical response by logistic regression. Significance-based backward stepwise selection of variables was used for the final multivariate models. Results There was a significant difference in drug survival by previous biologic disease-modifying antirheumatic drug (bDMARD) exposure (p < 0.001), with longer survival in bionaïve patients. Men (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.74–0.98) and methotrexate users (HR 0.85, 95% CI 0.76–0.95) were less likely to discontinue abatacept, whereas a high pain score predicted discontinuation (HR 1.14 per standard deviation, 95% CI 1.07–1.20). The absence of previous bDMARD exposure, male sex, and a low HAQ score were independently associated with LUNDEX-corrected EULAR good response. The absence of previous bDMARD exposure also predicted LUNDEX-corrected HAQ response. Conclusions In this population-based study of RA, bDMARD naïve patients and male patients were more likely to remain on abatacept with a major clinical response.

Pengaruh Pemberian Magnesium Sulfat Intravena Prainduksi terhadap Kebutuhan Analgetik Pasca-Simple Mastectomy

Nyeri pascabedah masih menjadi masalah dan perhatian di dunia. Pemberian analgetik preventif merupakan salah satu cara untuk mengurangi nyeri pascabedah. Beberapa obat digunakan sebagai terapi analgetik preventif antara lain opioid dan NSAID, namun obat ini mempunyai banyak efek samping. MgSO4 dapat digunakan sebagai analgetik preventif karena bersifat antagonis reseptor NMDA nonkompetitif. Tindakan operasi yang memiliki skor nyeri yang tinggi salah satunya adalah simple mastectomy dengan skor nyeri 4 sampai 8. Penelitian ini bertujuan mengetahui pengaruh MgSO4 i.v. dengan dosis bolus 50 mg/kgBB 20 menit prainduksi terhadap kebutuhan analgetik pasca-simple mastectomy. Penelitian ini merupakan penelitian analitik komparatif dengan data tidak berpasangan secara prospektif dengan uji klinis acak terkontrol buta ganda (RCT double blind) yang dilakukan terhadap 26 subjek penelitian yang menjalani simple mastectomy di RSUP Dr. Hasan Sadikin Bandung pada bulan Agustus sampai Desember 2018. Analisis statistik pada data numerik diuji dengan uji t berpasangan, sedangkan data kategorik diuji dengan uji chi-Square. Subjek dibagi menjadi kelompok M (MgSO4 20% 50 mg/kgBB) dan kelompok C (NaCl 0,9%). Hasil penelitian ini didapatkan kebutuhan opioid pascabedah pada kelompok yang diberikan MgSO4 lebih rendah dibanding dengan kelompok yang mendapatkan NaCl dengan perbedaan bermakna (p<0,05). Simpulan penelitian ini adalah MgSO4 i.v. prainduksi menurunkan kebutuhan opioid dibanding dengan kelompok kontrol pada simple mastectomy. Effect of Intravenous Magnesium Sulfate Pre-induction on Analgesics Consumption in Post-Simple MastectomyPostoperative pain is still a global problem that raises concerns all over the world. Preventive analgesics is one method to reduce postoperative pain. Several drugs are used as preventive analgesics including opioids and NSAIDs. However, these drugs have many side effects. MgSO4 can be used as alternative preventive analgesic as it is a non-competitive NMDA receptor antagonist. One of the surgical procedure that has a high pain score is simple mastectomy with a pain score of 4 to 8. The aim of this study was to determine the effect of MgSO4 i.v. with a bolus dose of 50 mg/kgBW, 20 minutes pre-induction, on the need for post-simple mastectomy analgesics. This was a comparative double blind randomized controlled trial (RCT) analytical study on prospective unpaired data from 26 study subjects who underwent simple mastectomy at Dr. Hasan Sadikin General Hospital Bandung during the period of August to December 2018. Subjects were divided into group M (MgSO4 20% 50 mg/kgBW) and group C (NaCl 0.9%). The results of this study revealed that the need for postoperative opioids in the group given MgSO4 was significantly lower compared to the group receiving NaCl (p<0.05). Therefore, MgSO4 i.v. preinduction has the ability to reduce opioid requirements in simple mastectomy when compared to NaCl.