Traditional, complementary and integrative medicine for fatigue post COVID-19 infection: A systematic review of randomized controlled trials.

Background: Chronic fatigue is a predominant symptom of post COVID-19 condition, or long COVID. We aimed to evaluate the efficacy and safety of Traditional, Complementary and Integrative Medicine (TCIM) for fatigue post COVID-19 infection. Methods: Ten English and Chinese language databases and grey literature were searched up to 12 April 2023 for randomized controlled trials (RCTs). Cochrane "Risk of bias" (RoB) tool was applied. Evidence certainty was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Effect estimates were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Results: Thirteen RCTs with 1632 participants were included. One RCT showed that Bufei Huoxue herbal capsules reduced fatigue (n=129, MD -14.90, 95%CI -24.53 to -5.27), one RCT reported that Ludangshen herbal liquid lowered fatigue (n=184, MD -1.90, 95%CI -2.38 to -1.42), and the other one RCT shown that fatigue disappearance rate was higher with Ludangshen herbal liquid (n=184, RR 4.19, 95%CI 2.06 to 8.53). Compared to traditional Chinese medicine rehabilitation (TCM-rahab) alone, one RCT showed that fatigue symptoms were lower following Qingjin Yiqi granules plus TCM-rehab (n=388, MD -0.48, 95%CI -0.50 to -0.46). Due to concerns with RoB and/or imprecision, the certainty in this evidence was low to very low. No serious adverse events was reported. Conclusions: Limited evidence suggests that various TCIM interventions might reduce post COVID-19 fatigue. Larger, high quality RCTs of longer duration are required to confirm these preliminary findings. Study Registration: The protocol of this review has been registered at PROSPERO: CRD42022384136.

A population health approach to workplace mental health: rationale, implementation and engagement.

Objectives: To describe a population health-based program to support employee and dependent mental health and learn from engagement trends. Methods: Retrospective analysis of a program utilizing an assessment of mental health risk. For scoring "at risk," a Care Concierge is offered to connect users with resources. Results: Participation was offered to 56,442 employees and dependents. Eight thousand seven hundred thirty-one completed the assessment (15%). Of those, 4,644 (53%) scored moderate or higher. A total of 418 (9%) engaged the Care Concierge. Factors that negatively influenced the decision to engage care included bodily pain, financial concerns. Positive influences were younger age, high stress, anxiety, PTSD and low social support. Conclusion: Proactive assessment plus access to a Care Concierge facilitates mental healthcare utilization. Several factors influence likelihood to engage in care. A better understanding of these factors may allow for more targeted outreach and improved engagement.

Fluorescence Lifetime Imaging of Human Retinal Pigment Epithelium in Pentosan Polysulfate Toxicity Using Adaptive Optics Scanning Light Ophthalmoscopy.

Purpose: Fluorescence lifetime ophthalmoscopy (FLIO) is an emerging clinical modality that could provide biomarkers of retinal health beyond fluorescence intensity. Adaptive optics (AO) ophthalmoscopy provides the confocality to measure fluorescence lifetime (FL) primarily from the retinal pigment epithelium (RPE) whereas clinical FLIO has greater influence from fluorophores in the inner retina and lens. Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) measures of FL in vivo could provide insight into RPE health at different stages of disease. In this study, we assess changes in pentosan polysulfate sodium (PPS) toxicity, a recently described toxicity that has clinical findings similar to advanced age-related macular degeneration. Methods: AOFLIO was performed on three subjects with PPS toxicity (57-67 years old) and six age-matched controls (50-64 years old). FL was analyzed with a double exponential decay curve fit and with phasor analysis. Regions of interest (ROIs) were subcategorized based on retinal features on optical coherence tomography (OCT) and compared to age-matched controls. Results: Twelve ROIs from PPS toxicity subjects met the threshold for analysis by curve fitting and 15 ROIs met the threshold for phasor analysis. Subjects with PPS toxicity had prolonged FL compared to age-matched controls. ROIs of RPE degeneration had the longest FLs, with individual pixels extending longer than 900 ps. Conclusions: Our study shows evidence that AOFLIO can provide meaningful information in outer retinal disease beyond what is obtainable from fluorescence intensity alone. More studies are needed to determine the prognostic value of AOFLIO.

Spectral Dependence of Light Exposure on Retinal Pigment Epithelium Disruption in Living Primate Retina.

Purpose: RPE disruption with light exposures below or close to the American National Standards Institute (ANSI) photochemical maximum permissible exposure (MPE) have been observed, but these findings were limited to two wavelengths. We have extended the measurements across the visible spectrum. Methods: Retinal imaging with fluorescence adaptive optics scanning light ophthalmoscopy (FAOSLO) was used to provide an in vivo measure of RPE disruption at a cellular level. The threshold retinal radiant exposures (RREs) for RPE disruption (localized detectable change in the fluorescence image) were determined at 460, 476, 488, 530, 543, 561, 594, 632, and 671 nm (uniform 0.5° square exposure) using multiples locations in 4 macaques. Results: FAOSLO is sensitive in detecting RPE disruption. The visible light action spectrum dependence for RPE disruption with continuous wave (CW) extended field exposures was determined. It has a shallower slope than the current ANSI blue-light hazard MPE. At all wavelengths beyond 530 nm, the disruption threshold is below the ANSI blue-light hazard MPE. There is reciprocity of exposure irradiance and duration for exposures at 460 and 594 nm. Conclusions: We measured with FAOSLO the action spectrum dependence for photochemical RPE disruption across the visible light spectrum. Using this in vivo measure of phototoxicity provided by FAOSLO, we find that thresholds are lower than previously measured. The wavelength dependence in our data is considerably shallower than the spectral dependence of the traditional ANSI blue-light hazard, emphasizing the need for more caution with increasing wavelength than expected.

Is adamgammadex the brother of sugammadex or the next generation of reversal agent?

Sugammadex is now in widespread use to reverse the neuromuscular blocking effects of rocuronium. Adverse effects from sugammadex are rare, but anaphylactic and cardiovascular reactions to the drug have been reported. In an attempt to reduce such side-effects, a modified gamma-cyclodextrin, adamgammadex, has been developed. Phase 3 clinical trials suggest that it is slightly less potent than sugammadex and has a non-inferior speed of onset. In a multicentre trial of 310 patients, there was a suggestion of a lower incidence of allergic responses and recurarisation after adamgammadex compared with sugammadex. The clinical implications of this study are discussed in this editorial.

Efficacy and safety of aniseed powder for treating gastrointestinal symptoms of COVID-19: a randomized, placebo-controlled trial.

Background: Gastrointestinal symptoms are prevalent amongst patients with a confirmed diagnosis of COVID-19 and may be associated with an increased risk of disease severity. This trial aimed to evaluate the efficacy and safety of aniseed (Pimpinella anisum L.) powder as an add-on therapy to standard care for treating gastrointestinal symptoms experienced by adults with an acute SARS-CoV-2 infection. Methods: The study was a randomized parallel-group double-blinded placebo-controlled add-on therapy trial. Adults with an acute SARS-CoV-2 infection who did not require hospitalization and reported at least one gastrointestinal symptom in the preceding 48 h were assigned to either the aniseed or placebo group in a 1:4 ratio. All 225 participants (45 in the aniseed group and 180 in the placebo group) were instructed to use 25 g of powdered aniseed or placebo twice daily for 2 weeks. The primary outcomes were the proportion of patients who experienced an improvement of at least one point in the symptom score after adjusting for age group, gender, and time. Backwards stepwise logistic regression was applied to calculate the risk ratios. The clinical symptoms and adverse events were assessed at the beginning, 1 week later, and at the end of the trial (week two). Results: Participants in the aniseed group were significantly more likely to report symptom improvement for abdominal pain [adjusted risk ratio (RR):0.55; 95% confidence interval (CI): 0.46-0.72], anorexia (RR:0.62; 95% CI: 0.47-0.82), and diarrhea (RR:0.19; 95% CI: 0.12-0.30), but not nausea/vomiting (RR:0.87; 95% CI: 0.71-1.08) or bloating (RR:0.87; 95% CI: 0.72-1.05). Two participants in the aniseed group and three participants in the placebo group reported mild to moderate adverse events. Conclusion: This study showed that 2 weeks of aniseed powder containing trans-anethole (87%-94%) may help improve abdominal pain, anorexia, and diarrhea in COVID-19 patients. The findings align with the known biological, multitargeted activity of P. anisum and trans-anethole, which includes inhibiting SARS-CoV-2 along with other anti-infective, anti-inflammatory, antioxidant, hepatoprotective, and anti-dysbiosis properties. Multicenter trials with larger sample sizes and longer follow-up are warranted to confirm these findings. Clinical Trial Registration: Iranian Registry of Clinical Trials (IRCT20120506009651N3).

Using Unsupervised Machine Learning to Predict Quality of Life After Total Knee Arthroplasty.

BACKGROUND: Patient-reported outcome measures (PROMs) are an important metric to assess total knee arthroplasty (TKA) patients. The purpose of this study was to use a machine learning (ML) algorithm to identify patient features that impact PROMs after TKA. METHODS: Data from 636 TKA patients enrolled in our patient database between 2018 and 2022, were retrospectively reviewed. Their mean age was 68 years (range, 39 to 92), 56.7% women, and mean body mass index of 31.17 (range, 16 to 58). Patient demographics and the Functional Comorbidity Index were collected alongside Patient-Reported Outcome Measures Information System Global Health v1.2 (PROMIS GH-P) physical component scores preoperatively, at 3 months, and 1 year after TKA. An unsupervised ML algorithm (spectral clustering) was used to identify patient features impacting PROMIS GH-P scores at the various time points. RESULTS: The algorithm identified 5 patient clusters that varied by demographics, comorbidities, and pain scores. Each cluster was associated with predictable trends in PROMIS GH-P scores across the time points. Notably, patients who had the worst preoperative PROMIS GH-P scores (cluster 5) had the most improvement after TKA, whereas patients who had higher global health rating preoperatively had more modest improvement (clusters 1, 2, and 3). Two out of Five patient clusters (cluster 4 and 5) showed improvement in PROMIS GH-P scores that met a minimally clinically important difference at 1-year postoperative. CONCLUSIONS: The unsupervised ML algorithm identified patient clusters that had predictable changes in PROMs after TKA. It is a positive step toward providing precision medical care for each of our arthroplasty patients.

Under-dosing and over-dosing of neuromuscular blocking drugs and reversal agents: beware of the risks.

The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium were well recognised 60 years ago. But the incidence seemed to decline with the introduction of atracurium and vecuronium. However, recently there have been an increasing number of reports of residual and recurrent neuromuscular block. Some of these reports are a result of inappropriate doses of rocuronium, sugammadex or both, together with inadequate neuromuscular monitoring. We urge clinicians to review their practice to ensure the highest standards of clinical care when using neuromuscular blocking drugs and reversal agents. This includes the use of quantitative neuromuscular monitoring whenever neuromuscular blocking drugs are administered.

What is integrative medicine? Establishing the decision criteria for an operational definition of integrative medicine for general practice health services research in Australia.

Background: Operational definitions outline how a conceptual definition will be measured for consistent, reproducible data collection and analysis. This article reports the decision criteria that will be used for an operational definition of integrative medicine (IM) in a secondary analysis of an Australian national survey of general practitioner activity. Methods: A multidisciplinary team applied an iterative approach, informed by expert knowledge and literature reviews to establish decision criteria for categorizing the terms in the Australian clinical interface terminology of the International Classification of Primary Care, second edition (ICPC-2 PLUS) and the Coding Atlas for Pharmaceutical Substances, according to whether they reflected IM, conventional/mainstream medicine (MM), or both IM and MM (IM/MM). Results: The final decision criteria categorized all terms for examinations, investigations, advice/counselling, and drugs with synthetic ingredients, and terms for referrals to secondary care services and healthcare practitioners that are not a traditional or complementary medicine practitioner as MM. Terms that could apply to both styles of clinical practice (e.g., preventive health, lifestyle medicine, psychosocial and some drugs with natural ingredients) were categorised as IM/MM. The remaining terms, that mostly reflected the World Health Organization's theoretical definitions of traditional and complementary medicine, were categorized as IM. Conclusion: Differentiating between integrative and conventional/mainstream medicine in general practice is context specific and not always possible. The category IM/MM proposes integrative medicine as an extension, rather than an alternative. The rationale for the integrative medicine operational definition has relevance for researchers and health services in Australia, and internationally.

Efficacy and safety of purslane (Portulaca oleracea) for mild to moderate chronic hand eczema; A randomized, double-blind, placebo-controlled clinical trial.

INTRODUCTION: Chronic hand eczema (CHE) is a common skin inflammation with a complex pathophysiology. Due to its anti-inflammatory properties, Portulaca oleracea L. (purslane) is traditionally used in Persian medicine for skin ailments. This study aimed to evaluate the safety and efficacy of a standardized purslane extract (based on traditional Persian medicine) for adults with mild or moderately severe CHE. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted at Razi Hospital in Iran from January to June 2022. Participants were randomly allocated to receive an oral purslane or placebo syrup plus topical Vaseline for four weeks. Seventy participants were randomly allocated into the intervention (n = 35) and placebo (n = 35) groups. The primary outcomes were the extent and severity of CHE symptoms over the four weeks after adjusting for age, gender and baseline score. Secondary outcomes were quality of life, symptom recurrence, treatment satisfaction, and adverse events. RESULTS: After 4 weeks of treatment, compared to the placebo group (n = 31), the purslane group (n = 31) had significantly lower physician-reported fissure scores (adjusted mean difference (adjMD): -0.50, 95 %CI -3.93 to -0.34, p = 0.043), participant-reported itching (adjMD -0.51, 95 %CI -2.32 to -0.31, p = 0.041), dryness (adjMD -1.46, 95 %CI -2.89 to -0.03, p = 0.045), and total itching, dryness and thickness (adjMD -2.36, 95 %CI -6.23 to -1.51, p = 0.023) scores. Fourteen participants (purslane n = 10; placebo n = 4, p = 0.068) experienced adverse events of mild to moderate severity. CONCLUSION: Purslane has some promising effects for reducing the extent and severity of CHE symptoms, and no direct comparisons have been made with commonly used treatments. Future multicenter trials and mechanistic studies are warranted to establish the safety and effectiveness of purslane as a potential therapeutic agent for CHE. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT20200707048040N1).

Predicting Food Sources of Listeria monocytogenes Based on Genomic Profiling Using Random Forest Model.

Listeria monocytogenes can cause severe foodborne illness, including miscarriage during pregnancy or death in newborn infants. When outbreaks of L. monocytogenes illness occur, it may be possible to determine the food source of the outbreak. However, most reported L. monocytogenes illnesses do not occur as part of a recognized outbreak and most of the time the food source of sporadic L. monocytogenes illness in people cannot be determined. In the United States, L. monocytogenes isolates from patients, foods, and environments are routinely sequenced and analyzed by whole genome multilocus sequence typing (wgMLST) for outbreak detection by PulseNet, the national molecular surveillance system for foodborne illnesses. We investigated whether machine learning approaches applied to wgMLST allele call data could assist in attribution analysis of food source of L. monocytogenes isolates. We compiled isolates with a known source from five food categories (dairy, fruit, meat, seafood, and vegetable) using the metadata of L. monocytogenes isolates in PulseNet, deduplicated closely genetically related isolates, and developed random forest models to predict the food sources of isolates. Prediction accuracy of the final model varied across the food categories; it was highest for meat (65%), followed by fruit (45%), vegetable (45%), dairy (44%), and seafood (37%); overall accuracy was 49%, compared with the naive prediction accuracy of 28%. Our results show that random forest can be used to capture genetically complex features of high-resolution wgMLST for attribution of isolates to their sources.

'To see ourselves as others see us'.

Shaw and colleagues, who are medical historians, have published a detailed review of the social history of the British Journal of Anaesthesia (BJA) to celebrate its first 100 years. In this editorial, we note some additional contributions and financial details that are relevant to the development of the BJA into the international high-impact journal it is today.

Interactions between complementary medicines and drugs used in primary care and oral COVID-19 antiviral drugs.

BACKGROUND: Patient harm resulting from drug interactions between conventional and traditional or complementary medicines (CM) are avoidable. OBJECTIVE: To provide a clinical overview of a selection of CM interactions with drugs commonly used in Australian general practice or in the management of COVID-19. DISCUSSION: Many herb constituents are substrates for cytochrome P450 enzymes, and inducers and/or inhibitors of transporters such as P-glycoprotein. Hypericum perforatum (St John's Wort), Hydrastis canadensis (golden seal), Ginkgo biloba (ginkgo) and Allium sativum (garlic) are reported to interact with many drugs. Simultaneous administration of certain anti-viral drugs with zinc compounds and several herbs should also be avoided. Preventing and identifying unwanted CM-drug interactions in primary care requires vigilance, access to CM-drug interaction checkers and excellent communication skills. Potential risks from interactions should be balanced against the potential benefits of continuing the drug and/or CM and involve shared decision making.

Educating anaesthetists on neuromuscular monitoring: the challenges continue.

The need to introduce guidelines on neuromuscular monitoring emphasising the use of quantitative techniques that record the train-of-four ratio is now recognised by an increasing number of national anaesthetic societies in the Western world. But the challenge of convincing individual anaesthetists to adopt and use this practice routinely remains. For >10 yr, it has been recognised that all staff in anaesthetic departments need to have regular training in modern neuromuscular monitoring techniques. We discuss a publication in this journal that describes the challenges of setting up multicentre training in Spain to expand the use of quantitative neuromuscular monitoring and their short-term results.

Erratum: Adaptive optics fluorescence lifetime imaging ophthalmoscopy of in vivo human retinal pigment epithelium: erratum.

[This corrects the article on p. 1737 in vol. 13, PMID: 35414970.].

Outbreaks of SARS-CoV-2 Infections in Nursing Homes during Periods of Delta and Omicron Predominance, United States, July 2021-March 2022.

SARS-CoV-2 infections among vaccinated nursing home residents increased after the Omicron variant emerged. Data on booster dose effectiveness in this population are limited. During July 2021-March 2022, nursing home outbreaks in 11 US jurisdictions involving >3 infections within 14 days among residents who had received at least the primary COVID-19 vaccine(s) were monitored. Among 2,188 nursing homes, 1,247 outbreaks were reported in the periods of Delta (n = 356, 29%), mixed Delta/Omicron (n = 354, 28%), and Omicron (n = 536, 43%) predominance. During the Omicron-predominant period, the risk for infection within 14 days of an outbreak start was lower among boosted residents than among residents who had received the primary vaccine series alone (risk ratio [RR] 0.25, 95% CI 0.19-0.33). Once infected, boosted residents were at lower risk for all-cause hospitalization (RR 0.48, 95% CI 0.40-0.49) and death (RR 0.45, 95% CI 0.34-0.59) than primary vaccine-only residents.

Separate lifetime signatures of macaque S cones, M/L cones, and rods observed with adaptive optics fluorescence lifetime ophthalmoscopy.

In the retina, several molecules involved in metabolism, the visual cycle, and other roles exhibit intrinsic fluorescence. The overall properties of retinal fluorescence depend on changes to the composition of these molecules and their environmental interactions due to transient functional shifts, especially in disease. This behooves the understanding of the origins and deviations of these properties within the multilayered retina at high lateral and axial resolution. Of particular interest is the fluorescence lifetime, a potential biomarker of function and disease independent of fluorescence intensity that can be measured in the retina with adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO). This work demonstrates the utility of the phasor method of analysis, an alternate approach to traditional multiexponential fitting, to evaluate photoreceptor two-photon excited AOFLIO data and separate them based on functional differences. Phasor analysis on fluorescence lifetime decay data allowed the repeatable segregation of S from M/L cones, likely from differences in functional or metabolic demands. Furthermore, it is possible to track the lifetime changes in S cones after photodamage. Phasor analysis increases the sensitivity of AOFLIO to functional differences between cells and has the potential to improve our understanding of pathways involved in normal and diseased conditions at the cellular scale throughout the retina.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) outbreaks in nursing homes involving residents who had completed a primary coronavirus disease 2019 (COVID-19) vaccine series-13 US jurisdictions, July-November 2021.

Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.