Taking a Systems Neuroscience Approach to Persistent Postsurgical Pain: Mechanisms, Prediction Tools and Preventive Strategies

Background: Persistent postsurgical pain (PPP) is an increasingly recognised complication of surgery. Various putative risk factors have been identified over the last ten years. However the prevention of this phenomenon has proven difficult. I studied PPP following cardiac surgery to identify both means of prediction and prevention. Methods: With ethics committee approval, I followed up 312 patients undergoing cardiac surgery over a six-month period in our hospitals. This established pilot data and allowed power calculation for the following prospective studies: 1. Randomised controlled trial (RCT) of pregabalin alone (P) or pregabalin combined with ketamine (PK), as compared to usual care (UC) for the prevention of PPP. 2. Quantitative Sensory testing before and after surgery, to identify central nervous system changes predictive of PPP, as well as any protective effect of P and PK in the active arms. Patients were risk stratified into vulnerable and resilient phenotypes, with the use of dynamic pain assessments of Conditioned Pain Modulation (CPM), Temporal Summation (TS) and Zone of Hyperalgesia (ZoH.) Results: In the observational pilot cohort, 39.7% of patients described PPP following elective first-time cardiac surgery. The age of the patient, duration of surgery and acute pain during the recovery period all seemed to act as strong predictors for the development of PPP in this cohort study. In the prospective RCT, pregabalin was protective for future PPP. The study demonstrated a significant improvement in PPP; OR= 0.11 and 0.046, for groups P and PK respectively at three months, as compared to the UC group. The addition of ketamine to pregabalin, as part of a multimodal regimen, had no significant effect on PPP outcomes in this trial. Tolerability of both drugs on the first day of treatment was an issue. As an example, NNH (Number Needed to Harm) for diplopia was equal to 6.3 and 4.5, in P and PK respectively. This failed to impact on recovery, however, with improvements in median length of stay of 1 and 1.5 days respectively (p=0.023 and 0.002.) The powerful and protective effects of pregabalin in the perioperative period are demonstrated by: 1. Increases in pressure pain threshold (PPT) at a site remote to the incision 2. Prevention of the development of new TS 3. Reduction in the zone of peri-incisional hyperalgesia The likelihood of developing PPP in any cardiac surgical patient may be predicted by a combination of the following perioperative risk factors: 1. Perioperative QST markers of new TS and increased ZoH, at the site of surgical incision, as well as decreased PPT remote to the incision. 2. Inefficiency of CPM 3. Poor preoperative quality of life, measured with EQ-5D 4. Increased levels of state anxiety and catastrophising 5. Young age 6. Surgical risk factors of increased duration of surgery and poorly managed acute pain - but not surgical technique and extent of dissection. Conclusion: This study suggests a potential to risk-stratify cardiac surgery patients and allow targeted preventive intervention for PPP

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Reply to Sanfilippo et al. Caution Is Warranted When Assessing Diastolic Function Using Transesophageal Echocardiography. Comment on “Kyle et al. Consensus Defined Diastolic Dysfunction and Cardiac Postoperative Morbidity Score: A Prospective Observational Study. J. Clin. Med. 2021, 10, 5198”

We thank Sanfilippo and colleagues for their insightful comments about the assessment of diastolic function with transesophageal echocardiography (TEE) [...

Epidemiology of Brucellosis in Small Ruminants of Rural and Peri-Urban Areas of Multan, Pakistan

Brucellosis is a widespread zoonotic disease of veterinary and public health importance with considerably higher prevalence in developing/underdeveloped countries. This study reports the prevalence and risk determinants of brucellosis in small ruminants of peri-urban and rural areas of district Multan, Southern Punjab, Pakistan. For this purpose, sera samples (n = 392) of small ruminants were collected and subjected to preliminary screening using commercially available RBPT reagents followed by serodetection of brucellosis using multispecies i-ELISA kit (ID.vet, France). All the ELISA positive samples were confirmed by PCR using genus-specific primers, and frequencies of Brucella species in positive samples were enumerated using species-specific primers. Results indicated seropositivity rates of 9.69, 9.95, and 10.20% in study population using RBPT reagents of IDEXX-USA, ID.Vet-France, and VRI-Pakistan, respectively, with a statistically nonsignificant difference p>0.05. Results of ELISA showed an overall seroprevalence rate of 7.14% in target population with a slightly higher rate in sheep (7.65%) as compared to goat (6.63%) population (p=0.695; OR = 1.16, 95% CI = 0.53, 2.57). Results revealed that out of total positive samples, B. abortus was detected in 60.71% of seropositive samples and B. melitensis was detected in 14.28% of positive samples. It was revealed that risk factors including body condition scores, hygienic conditions of the housing facility, farming system, reproductive disorders, educational status of farmers, and awareness of farmers about brucellosis had significant association with brucellosis in small ruminants of study area p0.05 with brucellosis. In conclusion, brucellosis is prevalent in small ruminants of Multan, Pakistan. It is recommended to devise and implement effective control strategies with a major focus on raising awareness about brucellosis in farmers for the containment of infection in the region

A study on the epidemiology of brucellosis in bovine population of peri-urban and rural areas of district Multan, southern Punjab, Pakistan

Abstract Background Brucellosis is a zoonotic disease caused by a bacterial pathogen belonging to the genus Brucella. It is one of the most frequent bacterial zoonoses globally but unfortunately, it is still considered as a neglected disease in the developing world. Keeping in view, this study was conducted to determine the prevalence and risk determinants of brucellosis in large ruminants of peri-urban and rural areas of district Multan-Pakistan. For this purpose, blood samples (n = 490) were collected from the cattle (n = 245) and buffalo (n = 245) population of the study area and subjected to preliminary screening of brucellosis using local and imported RBPT reagents. All the samples were further analyzed using commercially available multi-specie indirect ELISA kit followed by their confirmation by PCR using genus and species-specific primers. Data obtained from lab analysis and questionnaires were subjected to statistical analysis for Pearson Chi-square, Odds Ratio and Confidence intervals (95%). Results The results showed that the maximum seropositivity was recorded with local RBPT reagent (VRI, Pakistan; 12.45%; 95%CI = 9.72–15.65%) followed by RBPT-IDEXX (12.24%; 95%CI = 9.52–15.45%) and RBPT-ID.vet (11.84%; 95%CI = 9.18–14.95%) however statistical difference was non-significant (P = 0.956). The ELISA results showed an overall seroprevalence rate of 11.22% (95%CI = 8.59–14.33%) with comparatively higher rate in cattle (12.65%; 95%CI = 8.82–17.44%) as compared to buffaloes (9.80%; 95%CI = 6.49–14.15%). The PCR analysis confirmed the presence of genus Brucella in all seropositive samples whereas frequency of B. abortus and B. melitensis in seropositive samples was 80% and 20%, respectively. The co-existence of both species was also observed in 5.45% samples. The statistical analysis showed a significant association of bovine brucellosis with herd size, breed, reproductive disorders, mode of insemination, educational status and farmers’ awareness about brucellosis (P  0.05). Conclusion In conclusion, brucellosis is prevalent in large ruminants of district Multan, Pakistan. It is suggested to devise and implement stringent policies for the effective control and prevention of brucellosis in the region. Further, the current situation also warrants the need to strengthen interdisciplinary coordination among veterinarians and physicians in one health perspective to ensure and strengthen the human and animal health care systems in the region

Care of elderly patients: a prospective audit of the prevalence of hypotension and the use of BIS intraoperatively in 25 hospitals in London

Background: Anaesthesia is frequently complicated by intraoperative hypotension (IOH) in the elderly, and this is associated with adverse outcome. The definition of IOH is controversial, and although management guidelines for IOH in the elderly exist, the frequency of IOH and typical clinically applied treatment thresholds are largely unknown in the UK. Methods: We audited frequency of intraoperative blood pressure against national guidelines in elderly patients undergoing surgery. Depth of anaesthesia (DOA) monitoring was also audited due to the association between low DOA values and IOH with increased mortality (as part of "double" and "triple low" phenomena) and because it is a suggested management strategy to reduce IOH. Results: Twenty-five hospitals submitted data on 481 patients. Hypotension varied depending on the definition, but affected 400 patients (83.3 %) using the AAGBI standard. Furthermore, 2.9, 13.5, and 24.6 % had mean arterial blood pressures < 50, < 60, and < 70 mmHg for 20 min, respectively, and 136 (28.4 %) had systolic blood pressure decrease by 20 % for 20 min. DOA monitors were used for 45 (9.4 %) patients. Conclusions: IOH is common and use of DOA monitors is less than implied by guidelines. Improved management of IOH may be a simple intervention with real potential to reduce morbidity in this vulnerable group

Self-reported health and smoking status, and body mass index: a case-control comparison based on GEN SCRIP (GENetics of SChizophRenia In Pakistan) data

Introduction Individuals with schizophrenia are at a high risk of physical health comorbidities and premature mortality. Cardiovascular and metabolic causes are an important contributor. There are gaps in monitoring, documenting and managing these physical health comorbidities. Because of their condition, patients themselves may not be aware of these comorbidities and may not be able to follow a lifestyle that prevents and manages the complications. In many low-income and middle-income countries including Pakistan, the bulk of the burden of care for those struggling with schizophrenia falls on the families.Objectives To determine the rate of self-reported physical health disorders and risk factors, like body mass index (BMI) and smoking, associated with cardiovascular and metabolic disorders in cases of schizophrenia compared with a group of mentally healthy controls.Design A case-controlled, cross-sectional multicentre study of patients with schizophrenia in Pakistan.Settings Multiple data collection sites across the country for patients, that is, public and private psychiatric OPDs (out patient departments), specialised psychiatric care facilities, and psychiatric wards of teaching and district level hospitals. Healthy controls were enrolled from the community.Participants We report a total of 6838 participants’ data with (N 3411 (49.9%)) cases of schizophrenia compared with a group of healthy controls (N 3427 (50.1%)).Results BMI (OR 0.98 (CI 0.97 to 0.99), p=0.0025), and the rate of smoking is higher in patients with schizophrenia than in controls. Problems with vision (OR 0.13 (0.08 to 0.2), joint pain (OR 0.18 (0.07 to 0.44)) and high cholesterol (OR 0.13 (0.05 to 0.35)) have higher reported prevalence in controls. The cases describe more physical health disorders in the category ‘other’ (OR 4.65 (3.01 to 7.18)). This captures residual disorders not listed in the questionnaire.Conclusions Participants with schizophrenia in comparison with controls report more disorders. The access in the ‘other’ category may be a reflection of undiagnosed disorders