An international, open-label, randomised trial comparing a two-step approach versus the standard three-step approach of the WHO analgesic ladder in patients with cancer.

BACKGROUND: Worldwide, cancer pain management follows the World Health Organization (WHO) three-step analgesic ladder. Using weak opioids (e.g. codeine) at step 2 is debatable with low-dose strong opioids being potentially better, particularly in low- and middle-income countries where weak opioids are expensive. We wanted to assess the efficiency, safety and cost of omitting step 2 of the WHO ladder. PATIENTS AND METHODS: We carried out an international, open-label, randomised (1 : 1) parallel group trial. Eligible patients had cancer, pain ≥4/10 on a 0-10 numerical rating scale, required at least step 1 (paracetamol) of the WHO ladder and were randomised to the control arm (weak opioid, step 2 of the WHO ladder) or the experimental arm (strong opioid, step 3). Primary outcome was time to stable pain control (3 consecutive days with pain ≤3). Secondary outcomes included distress, opioid-related side-effects and costs. The primary outcome analysis was by intention to treat and the follow-up was for 20 days. RESULTS: One hundred and fifty-three patients were randomised (76 control, 77 experimental). There was no statistically significant difference in time to stable pain control between the arms, P = 0.667 (log-rank test). The adjusted hazard ratio for the control arm was 1.03 (95% confidence interval 0.72-1.49). In the control arm, 38 patients (53%) needed to change to a strong opioid due to ineffective analgesia. The median time to change was day 6 (interquartile range 4-11). Compared to the control arm, patients in the experimental arm had less nausea (P = 0.009) and costs were less. CONCLUSION: This trial provides some evidence that the two-step approach is an alternative option for cancer pain management.

Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.

Perioperative considerations for the patient taking herbal medicines.

There has been a significant increase in the proliferation and use of dietary supplements known as neutraceuticals. Since 1994, herbal products have been regulated by the Dietary Supplement Health and Education Act (DSHEA), which does not require burden of proof to demonstrate premarketing safety and efficacy studies. Scientific literature and government policies have not adequately addressed this fast-emerging group of more than 20,000 health supplements. Lack of purity and standardization of these agents, combined with minimal education in traditional homeopathic medical education, has led to serious health-related problems including arrhythmias, cardiovascular compromise, strokes, and deaths. Even though 30% of our traditional medicines are derived from botanicals, most physicians are either unfamiliar or unwilling to develop any level of expertise with neutraceuticals. A review emphasizing perioperative considerations is provided of the history of herbal medicines, governmental policies, and specific herbal agent-drug interactions.

Perioperative considerations for the patient on herbal medicines.

Herbal medicines have enormous presence in the United States health care system. There is an increasing trend towards reimbursement of herbal medicines by insurance companies, which further encourage their utilization. Herbs are listed under the "supplement" category by the Food and Drug Administration. The Dietary Supplement and Health Education Act signed into law in October 1994, requires no proof of efficacy, no demonstration of safety, and sets no standards for quality control for the products labeled as "supplements" thereby increasing the risk of adverse effects of these herbs. The United States has experienced an epidemic of over-the-counter "natural" products over the last two decades; but there is little motivation for the manufactures to conduct randomized, placebo-controlled, double-blinded clinical trials to unequivocally prove the safety and efficacy of these drugs. Physicians, irrespective of their specialty, should not underestimate the potential risks associated with the use of herbs as reports indicate that within the last two decades, more than 100 herbogenic deaths have occurred, many serious complications have been reported, patients have required renal dialysis, renal transplantation and hepatic transplantation after taking botanicals. Internists must inquire about the patient's use of herbal products. In addition, the education of each patient regarding the serious, potential drug-herb interactions should be a routine component of preoperative assessment. The American Society of Anesthesiologists (ASA) recommends that all herbal medications should be discontinued 2-3 weeks prior to an elective surgical procedure. If the patient is not sure of the content of the herbal medicine, he/she should be urged to bring the container so that an attempt can be made to review the contents of the preparation. While such an action holds some promise in the elective setting, emergency care should be based on a thorough drug-intake history from the patient or a relative, if possible. Medical research and medical literature in general has not addressed this new group of health supplements, despite the fact that many of these herbs have the potential to cause serious health problems and drug interations. There is a need to conduct scientific clinical trials to study the anesthetic drug responses to commonly used neutraceutical agents.

Herbal medicines: current trends in anesthesiology practice--a hospital survey.

STUDY OBJECTIVES: To develop a simple survey to determine the patient population actively utilizing dietary supplements and/or herbs, during the preoperative period. DESIGN: Prospective study, with survey instrument. SETTING: University medical center. PATIENTS: 1,017 patients presenting for preanesthetic evaluation prior to outpatient surgery. INTERVENTIONS: After undergoing preanesthetic evaluation, patients were asked to complete a survey listing which of the nine most popular nutraceuticals currently available on the market they were using. MEASUREMENTS AND MAIN RESULTS: A total of 1017 surveys were submitted over a period of five months, with 32% being poorly completed and thus discarded. Of the remaining 755 valid surveys, 482 patients used at least one nutraceutical agent. 90% of these patients were using vitamins, 43% garlic extracts, 32% Gingko Biloba, 30% St. John's Wort, 18% Ma Huang, 12% Ecchinaceae, 10% Aloe, 8% Cascare, 3% licorice. CONCLUSION: A significant population of patients scheduled for an elective surgical procedure are self-administering nutraceutical agents. Some of these agents have the potential to cause serious drug interactions and hemodynamic instability during surgery. Hence, it may be important to identify patients self-administering these medications, during the preoperative period.

A portable slit lamp attachment for examination of donor cornea.

A new portable device is available for direct examination of donor cornea at the slit lamp. This attachment provides a clear view of the donor cornea and can be helpful to any corneal transplant surgeon, especially at medical centers that do not have an established eye bank.