Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Role of resistin in the central nervous system regulation of glucose and energy homeostasis

Resistin is an adipocyte hormone in rodents that is released into circulation in proportion to fat stores. Resistin induces insulin resistance, although the target tissues mediating this effect remain to be determined. The central nervous system (CNS) is a critical mediator of the actions of peripheral humoral signals on the regulation of glucose and energy balance, including leptin and adiponectin. Resistin is present in the cerebrospinal fluid of rodents and humans, however, its role in regulating neural circuits involved in the regulation of peripheral insulin sensitivity and body weight is unknown. The goal of the present work was to further characterize the role of resistin on glucose and energy homeostasis as well as define the neural mediators functionally linked to its actions. The genetic absence of resistin improves insulin sensitivity in diet-induced and leptin deficient models of obesity, in spite of an exacerbation of obesity in retn-/- -Lep ob/ob mice. It was found that resistin deficiency is associated with altered regulation of hypothalamic neuropeptides. Intracerebroventricular (i.c.v.) resistin increased endogenous glucose production during hyperinsulinemic clamp, consistent with induction of hepatic insulin resistance. Resistin administered i.c.v. was associated with neuronal activation and enhanced expression of neuropeptide Y (NPY) in the arcuate nucleus and dorsomedial nucleus of the hypothalamus. The effects of i.c.v. resistin on hepatic insulin resistance were abrogated in mice lacking NPY as well as in mice treated with NPY Y1-receptor antagonists. Furthermore, in Lepob/ob, i.c.v. resistin enhanced thermogenesis and suppressed food intake. The thermogenic actions of resistin were prevented by pharmacological blockade of melanocortin signaling. Taken together, these data provide support for the role of resistin in regulating hepatic insulin sensitivity and energy expenditure by targeting the hypothalamus

Sarcoid polyneuropathy masquerading as chronic inflammatory demyelinating polyneuropathy.

IntroductionSarcoid polyneuropathy is a rare and clinically heterogeneous disorder that may be the initial presentation of sarcoidosis.MethodsWe report the clinical, electrophysiological, and pathological findings of a patient who carried a diagnosis of sensory-predominant chronic inflammatory demyelinating polyneuropathy (CIDP) for over a decade but was ultimately found to have sarcoid polyneuropathy.ResultsA 36-year-old man presented with a several-week history of gait difficulty and muscle cramps. He had a diagnosis of CIDP but had not received lasting benefit from steroid-sparing immunosuppressive drugs. Electrodiagnostic studies were consistent with a chronic demyelinating polyradiculoneuropathy with conduction blocks. After he developed systemic symptoms, tissue biopsies revealed granulomatous disease. Symptoms improved with steroid therapy.ConclusionsSarcoid polyneuropathy presents a diagnostic challenge, but, in patients with atypical neuropathy, characteristic systemic symptoms, or a poor response to standard treatment, nerve and muscle biopsies can help diagnose this treatable disorder

Sarcoid polyneuropathy masquerading as chronic inflammatory demyelinating polyneuropathy.

IntroductionSarcoid polyneuropathy is a rare and clinically heterogeneous disorder that may be the initial presentation of sarcoidosis.MethodsWe report the clinical, electrophysiological, and pathological findings of a patient who carried a diagnosis of sensory-predominant chronic inflammatory demyelinating polyneuropathy (CIDP) for over a decade but was ultimately found to have sarcoid polyneuropathy.ResultsA 36-year-old man presented with a several-week history of gait difficulty and muscle cramps. He had a diagnosis of CIDP but had not received lasting benefit from steroid-sparing immunosuppressive drugs. Electrodiagnostic studies were consistent with a chronic demyelinating polyradiculoneuropathy with conduction blocks. After he developed systemic symptoms, tissue biopsies revealed granulomatous disease. Symptoms improved with steroid therapy.ConclusionsSarcoid polyneuropathy presents a diagnostic challenge, but, in patients with atypical neuropathy, characteristic systemic symptoms, or a poor response to standard treatment, nerve and muscle biopsies can help diagnose this treatable disorder

Resilience to Injury: A New Approach to Neuroprotection?

Despite thousands of neuroprotectants demonstrating promise in preclinical trials, a neuroprotective therapeutic has yet to be approved for the treatment of acute brain injuries such as stroke or traumatic brain injury. Developing a more detailed understanding of models and populations demonstrating "neurological resilience" in spite of brain injury can give us important insights into new translational therapies. Resilience is the process of active adaptation to a stressor. In the context of neuroprotection, models of preconditioning and unique animal models of extreme physiology (such as hibernating species) reliably demonstrate resilience in the laboratory setting. In the clinical setting, resilience is observed in young patients and can be found in those with specific genetic polymorphisms. These important examples of resilience can help transform and extend the current neuroprotective framework from simply countering the injurious cascade into one that anticipates, monitors, and optimizes patients' physiological responses from the time of injury throughout the process of recovery. This review summarizes the underpinnings of key adaptations common to models of resilience and how this understanding can be applied to new neuroprotective approaches

Loss of resistin ameliorates hyperlipidemia and hepatic steatosis in leptin-deficient mice

Resistin has been linked to components of the metabolic syndrome, including obesity, insulin resistance, and hyperlipidemia. We hypothesized that resistin deficiency would reverse hyperlipidemia in genetic obesity. C57Bl/6J mice lacking resistin [resistin knockout (RKO)] had similar body weight and fat as wild-type mice when fed standard rodent chow or a high-fat diet. Nonetheless, hepatic steatosis, serum cholesterol, and very low-density lipoprotein (VLDL) secretion were decreased in diet-induced obese RKO mice. Resistin deficiency exacerbated obesity in ob/ob mice, but hepatic steatosis was drastically attenuated. Moreover, the levels of triglycerides, cholesterol, insulin, and glucose were reduced in ob/ob-RKO mice. The antisteatotic effect of resistin deficiency was related to reductions in the expression of genes involved in hepatic lipogenesis and VLDL export. Together, these results demonstrate a crucial role of resistin in promoting hepatic steatosis and hyperlipidemia in obese mice