Effects of early life stress and chronic mild stress exposure in adulthood on sleep and wakefulness in rats

Masteroppgave i psykologiMAPSYK360INTL-PSYKINTL-JUSINTL-HFMAPS-PSYKINTL-SVINTL-MNINTL-KMDINTL-ME

The effect of wound instillation of a novel purified capsaicin formulation on postherniotomy pain: a double-blind, randomized, placebo-controlled study

BACKGROUND: Acute postoperative pain is common after most surgical procedures. Despite the availability of many analgesic options, postoperative pain management is often unsatisfactory. Purified capsaicin (ALGRX 4975 98% pure) has demonstrated prolong inhibition of C-fiber function in in vitro, preclinical, and clinical studies, and may be an effective adjunct to postoperative pain management. METHODS: We performed a single-center, randomized, double-blind, placebo-controlled study of the analgesic efficacy of a single intraoperative wound instillation of 1000 mu g ultrapurified capsaicin (ALGRX 4975) after open mesh groin hernia repair in 41 adult male patients. The primary end-point was average daily visual analog scale (VAS) pain scores during the first week after surgery assessed as area under the curve (AUC). Pain was recorded twice daily in a pain diary for 4 wk. Physical examination and laboratory tests were done before and I wk after surgery, together with recordings of adverse events up to 28 days. Adverse events were recorded. Data were also analyzed using a mixed-effects analysis with NONMEM. RESULTS: VAS AUC was significantly lower during the first 3 days postoperatively (P < 0.05), but not for the whole I or 4 wk postoperatively. Mixed-effects analysis with NONMEM revealed that pain scores were significantly lower (P < 0.05) in the capsaicin group during the first 4 days. No clinically significant serious adverse events were observed, although a mild transient increase in liver enzymes was seen more often in the capsaicin-treated group. CONCLUSION: In the setting of a well-defined analgesic protocol standard, VAS AUC analysis and a mixed-effect analysis showed superior analgesia of capsaicin relative to placebo during the first 3-4 days after inguinal hernia repair

Update of the international HerniaSurge guidelines for groin hernia management

International guidelines; Hernia managementDirectrices internacionales; Hernia inguinalDirectrius internacionals; Hèrnia inguinalBackground Groin hernia repair is one of the most common operations performed globally, with more than 20 million procedures per year. The last guidelines on groin hernia management were published in 2018 by the HerniaSurge Group. The aim of this project was to assess new evidence and update the guidelines. The guideline is intended for general and abdominal wall surgeons treating adult patients with groin hernias. Method A working group of 30 international groin hernia experts and all involved stakeholders was formed and examined all new literature on groin hernia management, available until April 2022. Articles were screened for eligibility and assessed according to GRADE methodologies. New evidence was included, and chapters were rewritten. Statements and recommendations were updated or newly formulated as necessary. Results Ten chapters of the original HerniaSurge inguinal hernia guidelines were updated. In total, 39 new statements and 32 recommendations were formulated (16 strong recommendations). A modified Delphi method was used to reach consensus on all statements and recommendations among the groin hernia experts and at the European Hernia Society meeting in Manchester on October 21, 2022. Conclusion The HerniaSurge Collaboration has updated the international guidelines for groin hernia management. The updated guidelines provide an overview of the best available evidence on groin hernia management and include evidence-based statements and recommendations for daily practice. Future guideline development will change according to emerging guideline methodology.The present guidelines were produced with the funding from European Hernia Society (EHS). The EHS provided funds to cover the budget of the process including online meetings with members and stakeholders. The executive board of the society did not interfere with the process of guidelines development

Evaluation of Postsurgical Hyperalgesia and Sensitization After Open Inguinal Hernia Repair: A Useful Model for Neuropathic Pain?

Cutaneous mechanical hyperalgesia can be induced in healthy volunteers in early phase analgesic studies to model central sensitization, a key mechanism of persistent pain. However, such hyperalgesia is short-lived (a matter of hours), and is used only for assessing only single drug doses. In contrast, postsurgical peri-incisional hyperalgesia may be more persistent and hence be a more useful model for the assessment of the efficacy of new analgesics. We undertook quantitative sensory testing in 18 patients at peri-incisional and nonoperated sites before open inguinal hernia repair and up to the 24th postsurgical week. The spatial extent of punctate hyperalgesia and brush allodynia at the peri-incisional site were greatest at weeks 2 and 4, but had resolved by week 24. Heat allodynia, suggestive of local inflammation or peripheral sensitization, was not observed; instead, there were deficits in cold and heat sensory detection that persisted until week 24. The findings suggest that central sensitization contributes significantly to mechanical hyperalgesia at the peri-incisional site. The prolonged duration of hyperalgesia would be advantageous as a pain model, but there was considerable variability of mechanical hyperalgesia in the cohort; the challenges of recruitment may limit its use to small, early phase analgesic studies. PERSPECTIVE: Peri-incisional mechanical hyperalgesia persists for ≥4 weeks after open inguinal hernia repair and reflects central sensitization; this may have usefulness as a model of chronic pain to assess the potential of antineuropathic analgesics.Unrestricted educational grant from GlaxoSmithKline U

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defi ned criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted causespecifi c DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient defi ciencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading fi ve risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden.publishedVersio

Biologic response of inguinal hernia prosthetics: A comparative study of conventional static meshes versus 3D dynamic implants

Despite improvements in prosthetics and surgical techniques, the rate of complications following inguinal hernia repair remains high. Among these, discomfort and chronic pain have become a source of increasing concern among surgeons. Poor quality of tissue ingrowth, such as thin scar plates or shrinking scars-typical results with conventional static implants and plugs-may contribute to these adverse events. Recently, a new type of 3D dynamically responsive implant was introduced to the market. This device, designed to be placed fixation-free, seems to induce ingrowth of viable and structured tissue instead of regressive fibrotic scarring. To elucidate the differences in biologic response between the conventional static meshes and this 3D dynamically responsive implant, a histological comparison was planned. The aim of this study was to determine the quality of tissue incorporation in both types of implants excised after short, medium, and long periods post-implantation. The results showed large differences in the biologic responses between the two implant types. Histologically, the 3D dynamic implant showed development of tissue elements more similar to natural abdominal wall structures, such as the ingrowth of loose and well-hydrated connective tissue, well-formed vascular structures, elastic fibers, and mature nerves, with negligible or absent inflammatory response. All these characteristics were completely absent in the conventional static implants, where a persistent inflammatory reaction was associated with thin, hardened, and shrunken fibrotic scar formation. Consequently, as herniation is a degenerative process, the 3D dynamic implants, which induce regeneration of the typical groin components, seem to address its pathogenesis