One-Week Kava Dietary Supplementation Increases Both Urinary N- and O-Glucuronides of NNAL, a Lung Carcinogen Major Metabolite, among Smokers.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (commonly known as NNK) is one of the most prevalent and potent pulmonary carcinogens in tobacco products that increases the human lung cancer risk. Kava has the potential to reduce NNK and tobacco smoke-induced lung cancer risk by enhancing urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the major metabolite of NNK) and thus reducing NNK-induced DNA damage. In this study, we quantified N-glucuronidated NNAL (NNAL-N-gluc), O-glucuronidated NNAL (NNAL-O-gluc), and free NNAL in the urine samples collected before and after 1-week kava dietary supplementation. The results showed that kava increased both NNAL-N-glucuronidation and O-glucuronidation. Since NNAL-N-glucuronidation is dominantly catalyzed by UGT2B10, its representative single-nucleotide polymorphisms (SNPs) were analyzed among the clinical trial participants. Individuals with any of the four analyzed SNPs appear to have a reduced basal capacity in NNAL-N-glucuronidation. Among these individuals, kava also resulted in a smaller extent of increases in NNAL-N-glucuronidation, suggesting that participants with those UGT2B10 SNPs may not benefit as much from kava with respect to enhancing NNAL-N-glucuronidation. In summary, our results provide further evidence that kava enhances NNAL urinary detoxification via an increase in both N-glucuronidation and O-glucuronidation. UGT2B10 genetic status has not only the potential to predict the basal capacity of the participants in NNAL-N-glucuronidation but also potentially the extent of kava benefits.

Otology: Vertigo.

Vertigo, an unexpected feeling of self-motion, is no longer characterized simply by symptom quality but by using triggers and timing. Evaluating vertigo by triggers and timing not only distinguishes serious central causes from benign peripheral causes, but also narrows the differential diagnosis by further classifying vertigo as spontaneous episodic vestibular syndrome, triggered episodic vestibular syndrome, or acute vestibular syndrome. A targeted physical examination can then be used to further delineate the cause within each of these three vestibular categories. Neuroimaging and vestibular testing are not routinely recommended. In the management of vertigo, vestibular hypofunction can be treated with vestibular rehabilitation, which can be self-administered or directed by a physical therapist. Pharmacotherapy sometimes is indicated for vertigo based on triggers, timing, and the specific condition, but it is not always beneficial and is used more often for symptom reduction than as a cure. Transtympanic corticosteroid or gentamicin injections are recommended for patients who do not benefit from nonablative therapy. Surgical ablative therapy is reserved for patients who have not benefited from less definitive therapy and have nonusable hearing.

Otology: Cerumen Impaction and Aural Foreign Bodies.

Cerumen lubricates and protects the external auditory canal, but excess accumulation can lead to ear fullness, itching, otalgia, discharge, hearing loss, and tinnitus. Cerumen should be treated whenever symptoms are present or if it limits diagnosis by preventing a needed otoscopic examination. Clinicians should evaluate for cerumen impaction in those using hearing aids and patients with intellectual disability. Cerumen impaction can be treated with cerumenolytics, ear irrigation, and manual removal with instrumentation. Aural foreign bodies can cause ear fullness, otalgia, discharge, and hearing loss. They are more common in children than adults. The most common type of aural foreign bodies in children is jewelry, followed by paper products, parts of pens or pencils, desk supplies (eg, erasers), BBs or pellets, and earplugs or earphones. In adults, the most common aural foreign bodies are cotton swabs or cotton, followed by hearing aid parts and jewelry or ear accessories. Patients should avoid using cotton tip applicators in the external auditory canal. Alligator forceps, small right angle hooks, and ear irrigation commonly are used to remove aural foreign bodies in an outpatient clinic setting, but the choice depends on the type of foreign body. Soft and irregularly shaped objects can be removed without referral to an otolaryngologist. Patients with hard, spherical, or cylindrical objects should be referred to an otolaryngologist if previous removal attempts have failed or if there is ear trauma to avoid worsening its position in the ear canal.

Otology: Hearing Loss.

Hearing loss is the cause of significant morbidity throughout the United States and the world. Because of numerous factors, such as ongoing noise exposure, poorly controlled chronic disease, and an aging population, the burden of hearing loss is expected to continue to increase. Hearing loss commonly is categorized as conductive, sensorineural, or mixed. The type of hearing loss can be determined through a combination of patient history and physical examination, and then confirmed with audiometry and tympanometry. Advanced imaging is not typically necessary, but it may be helpful in specific instances. The presentation of sudden sensorineural hearing loss should prompt urgent referral to an otolaryngologist and audiologist. Management of this condition is selective but may initially include oral corticosteroids. Management for chronic hearing loss involves the use of hearing aids, which can offer a large benefit to users but historically have been expensive and not covered by many insurance plans. Recent US legislation has made hearing aids more accessible and affordable by allowing direct-to-consumer marketing and offering over-the-counter hearing aids without a clinical evaluation.

Otology: Ear Infections.

Acute otitis media (AOM) is a common diagnosis in children who present with symptoms of otalgia, fever, or irritability and is confirmed by a bulging tympanic membrane or otorrhea on physical examination. It often is preceded by a viral infection, but the bacterial pathogens isolated most commonly are Streptococcus pneumonia, Haemophilus influenzae, and Moraxella catarrhalis. Watchful waiting may be appropriate in children 6 months or older with uncomplicated unilateral AOM. When antibiotics are indicated, amoxicillin is the first-line treatment in those without recent treatment with or allergy to this drug. Otitis media with effusion (OME) is fluid in the middle ear without symptoms of AOM and typically resolves within 3 months. Tympanostomy tube placement is the most common ambulatory surgery for children in the United States. It is used to ventilate the middle ear space and may be performed to treat recurrent AOM, persistent AOM, or chronic OME. Acute otitis externa is inflammation of the external ear canal, often due to infection. On examination, the ear canal is red and inflamed, with patients typically experiencing discomfort with manipulation of the affected ear. It is treated with a topical antibiotic with or without topical corticosteroid.

Incidental seromucinous hamartoma of the anterior nasal cavity presenting after episode of vestibular neuritis.

A woman in her 70s presented to primary care clinic complaining of acute onset dizziness for 1 day that was initially diagnosed as vestibular neuritis and treated with steroids. The next day, she presented to the emergency department with worsening symptoms. Imaging revealed no intracranial process; however, non-contrast CT imaging revealed a soft-tissue mass in the posterior ethmoid sinus. The vertigo completely resolved before an otolaryngologist surgically removed the nasal mass, which actually originated from the right cribriform plate and extended to the anterior middle turbinate head. The final pathology was consistent with seromucinous hamartoma.

Gastric and colonic metastases of malignant melanoma diagnosed during endoscopic evaluation of symptomatic anemia presenting as angina: a case report.

A 72-year-old man visited cardiology for exertional chest pain, lightheadedness, and fatigue. Six years prior, he was surgically treated for cutaneous malignant melanoma of the lower back. After a negative cardiac work-up, primary care diagnosed severe iron deficiency anemia. Emergent upper and lower gastrointestinal (GI) endoscopy revealed simultaneous melanoma metastases to the stomach and colon with discrete macroscopic features. Metastatic disease, including brain, lung, and bone, was discovered on imaging. Treatment included immunotherapy with nivolumab and stereotactic radiosurgery of the brain metastases, and our patient has remained in continued remission even after 2 years. Melanoma with GI tract (GIT) metastasis has a poor prognosis and rarely presents symptomatically or with synchronous gastric and colonic lesions. This case illustrates the importance of early primary care involvement to expedite work-up for multifocal GI metastases in patients with a remote melanoma history presenting with symptoms related to iron deficiency anemia (IDA).

Deprescribing Strategies for Opioids and Benzodiazepines with Emphasis on Concurrent Use: A Scoping Review.

While the Food and Drug Administration's black-box warnings caution against concurrent opioid and benzodiazepine (OPI-BZD) use, there is little guidance on how to deprescribe these medications. This scoping review analyzes the available opioid and/or benzodiazepine deprescribing strategies from the PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases (01/1995-08/2020) and the gray literature. We identified 39 original research studies (opioids: n = 5, benzodiazepines: n = 31, concurrent use: n = 3) and 26 guidelines (opioids: n = 16, benzodiazepines: n = 11, concurrent use: n = 0). Among the three studies deprescribing concurrent use (success rates of 21-100%), two evaluated a 3-week rehabilitation program, and one assessed a 24-week primary care intervention for veterans. Initial opioid dose deprescribing rates ranged from (1) 10-20%/weekday followed by 2.5-10%/weekday over three weeks to (2) 10-25%/1-4 weeks. Initial benzodiazepine dose deprescribing rates ranged from (1) patient-specific reductions over three weeks to (2) 50% dose reduction for 2-4 weeks, followed by 2-8 weeks of dose maintenance and then a 25% reduction biweekly. Among the 26 guidelines identified, 22 highlighted the risks of co-prescribing OPI-BZD, and 4 provided conflicting recommendations on the OPI-BZD deprescribing sequence. Thirty-five states' websites provided resources for opioid deprescription and three states' websites had benzodiazepine deprescribing recommendations. Further studies are needed to better guide OPI-BZD deprescription.

Adipose Tissue Insulin Resistance Predicts the Severity of Liver Fibrosis in Patients With Type 2 Diabetes and NAFLD.

CONTEXT: Although type 2 diabetes (T2D) is a risk factor for liver fibrosis in nonalcoholic fatty liver disease (NAFLD), the specific contribution of insulin resistance (IR) relative to other factors is unknown. OBJECTIVE: Assess the impact on liver fibrosis in NAFLD of adipose tissue (adipose tissue insulin resistance index [adipo-IR]) and liver (Homeostatic Model Assessment of Insulin Resistance [HOMA-IR]) IR in people with T2D and NAFLD. DESIGN: Participants were screened by elastography in the outpatient clinics for hepatic steatosis and fibrosis, including routine metabolites, cytokeratin-18 (a marker of hepatocyte apoptosis/steatohepatitis), and HOMA-IR/adipo-IR. SETTING: University ambulatory care practice. PARTICIPANTS: A total of 483 participants with T2D. INTERVENTION: Screening for steatosis and fibrosis with elastography. MAIN OUTCOME MEASURES: Liver steatosis (controlled attenuation parameter), fibrosis (liver stiffness measurement), and measurements of IR (adipo-IR, HOMA-IR) and fibrosis (cytokeratin-18). RESULTS: Clinically significant liver fibrosis (stage F ≥ 2 = liver stiffness measurement ≥8.0 kPa) was found in 11%, having more features of the metabolic syndrome, lower adiponectin, and higher aspartate aminotransferase (AST), alanine aminotransferase, liver fat, and cytokeratin-18 (P < 0.05-0.01). In multivariable analysis including just clinical variables (model 1), obesity (body mass index [BMI]) had the strongest association with fibrosis (odds ratio, 2.56; CI, 1.87-3.50; P < 0.01). When metabolic measurements and cytokeratin-18 were included (model 2), only BMI, AST, and liver fat remained significant. When fibrosis stage was adjusted for BMI, AST, and steatosis (model 3), only Adipo-IR remained strongly associated with fibrosis (OR, 1.51; CI, 1.05-2.16; P = 0.03), but not BMI, hepatic IR, or steatosis. CONCLUSIONS: These findings pinpoint to the central role of dysfunctional, insulin-resistant adipose tissue to advanced fibrosis in T2D, beyond simply BMI or steatosis. The clinical implication is that targeting adipose tissue should be the priority of treatment in NAFLD.

Inflammation and poverty as individual and combined predictors of 15-year mortality risk in middle aged and older adults in the US.

Background: Chronic systemic inflammation and poverty are both linked to an increased mortality risk. The goal of this study was to determine if there is a synergistic effect of the presence of inflammation and poverty on the 15-year risk of all-cause, heart disease and cancer mortality among US adults. Methods: We analyzed the nationally representative National Health and Nutrition Examination Survey (NHANES) 1999 to 2002 with linked records to the National Death Index through the date December 31, 2019. Among adults aged 40 and older, 15-year mortality risk associated with inflammation, C-reactive protein (CRP), and poverty was assessed in Cox regressions. All-cause, heart disease and cancer mortality were the outcomes. Results: Individuals with elevated CRP at 1.0 mg/dL and poverty were at greater risk of 15-year adjusted, all-cause mortality (HR = 2.45; 95% CI 1.64, 3.67) than individuals with low CRP and were above poverty. For individuals with just one at risk characteristic, low inflammation/poverty (HR = 1.58; 95% CI 1.30, 1.93), inflammation/above poverty (HR = 1.59; 95% CI 1.31, 1.93) the mortality risk was essentially the same and substantially lower than the risk for adults with both. Individuals with both elevated inflammation and living in poverty experience a 15-year heart disease mortality risk elevated by 127% and 15-year cancer mortality elevated by 196%. Discussion: This study extends the past research showing an increased mortality risk for poverty and systemic inflammation to indicate that there is a potential synergistic effect for increased mortality risk when an adult has both increased inflammation and is living in poverty.

The Impact of Initial COVID-19 Episode Inflammation Among Adults on Mortality Within 12 Months Post-hospital Discharge.

Background: Inflammation in the initial COVID-19 episode may be associated with post-recovery mortality. The goal of this study was to determine the relationship between systemic inflammation in COVID-19 hospitalized adults and mortality after recovery from COVID-19. Methods: An analysis of electronic health records (EHR) for patients from 1 January, 2020 through 31 December, 2021 was performed for a cohort of COVID-19 positive hospitalized adult patients. 1,207 patients were followed for 12 months post COVID-19 episode at one health system. 12-month risk of mortality associated with inflammation, C-reactive protein (CRP), was assessed in Cox regressions adjusted for age, sex, race and comorbidities. Analyses evaluated whether steroids prescribed upon discharge were associated with later mortality. Results: Elevated CRP was associated other indicators of severity of the COVID-19 hospitalization including, supplemental oxygen and intravenous dexamethasone. Elevated CRP was associated with an increased mortality risk after recovery from COVID-19. This effect was present for both unadjusted (HR = 1.60; 95% CI 1.18, 2.17) and adjusted analyses (HR = 1.61; 95% CI 1.19, 2.20) when CRP was split into high and low groups at the median. Oral steroid prescriptions at discharge were found to be associated with a lower risk of death post-discharge (adjusted HR = 0.49; 95% CI 0.33, 0.74). Discussion: Hyperinflammation present with severe COVID-19 is associated with an increased mortality risk after hospital discharge. Although suggestive, treatment with anti-inflammatory medications like steroids upon hospital discharge is associated with a decreased post-acute COVID-19 mortality risk.

Is There Limited Utility for Lifestyle Recommendations for Diabetes Prevention Among Overweight or Obese Depressed Patients?

Background: Lifestyle interventions like diet and exercise are commonly recommended for diabetes prevention, but it is unclear if depression modifies the likelihood of adherence. We evaluated the relationship between high depressive symptomatology and adherence to lifestyle interventions among patients with pre-diabetes. Methods: We conducted an analysis of the nationally representative National Health and Nutrition Examination Survey (NHANES) 2017-2018. Adults, aged ≥18 years old who were overweight or obese (BMI ≥25) and had diagnosed or undiagnosed pre-diabetes (HbA1c 5.7-6.4) were included. Depressive symptomatology was classified by the Patient Health Questionniare-9 (PHQ-9). We used self-reported adherence to physician suggested lifestyle changes of diet and exercise. Results: In this nationally representative survey of overweight or obese adults with pre-diabetes, 14.8% also have high depressive symptomatology. In unadjusted analyses, an interaction was observed with high depressive symptomatology acting as an effect modifier for adherence to exercise oriented interventions among patients with diagnosed pre-diabetes (p = 0.027). In logistic regressions, adjusting for age, sex, race, outpatient medical care in the past 12 months, and obesity, among patients with diagnosed pre-diabetes, depressed patients were less likely to attempt to exercise more (OR = 0.31; 95% CI: 0.10, 0.94) and no association between high depressive symptomatology and attempting to lose weight was observed (OR = 0.45; 95% CI: 0.14, 1.42). Conclusions: The findings of this nationally representative study of US adults, high depressive symptomatology decreases the likelihood of adherence to exercise based lifestyle recommendations among patients with diagnosed pre-diabetes.

COVID-19 Post-acute Sequelae Among Adults: 12 Month Mortality Risk.

Background: There are concerns regarding post-acute sequelae of COVID-19, but it is unclear whether COVID-19 poses a significant downstream mortality risk. The objective was to determine the relationship between COVID-19 infection and 12-month mortality after recovery from the initial episode of COVID-19 in adult patients. Methods: An analysis of electronic health records (EHR) was performed for a cohort of 13,638 patients, including COVID-19 positive and a comparison group of COVID-19 negative patients, who were followed for 12 months post COVID-19 episode at one health system. Both COVID-19 positive patients and COVID-19 negative patients were PCR validated. COVID-19 positive patients were classified as severe if they were hospitalized within the first 30 days of the date of their initial positive test. The 12-month risk of mortality was assessed in unadjusted Cox regressions and those adjusted for age, sex, race and comorbidities. Separate subgroup analyses were conducted for (a) patients aged 65 and older and (b) those <65 years. Results: Of the 13,638 patients included in this cohort, 178 had severe COVID-19, 246 had mild/moderate COVID-19, and 13,214 were COVID-19 negative. In the cohort, 2,686 died in the 12-month period. The 12-month adjusted all-cause mortality risk was significantly higher for patients with severe COVID-19 compared to both COVID-19 negative patients (HR 2.50; 95% CI 2.02, 3.09) and mild COVID-19 patients (HR 1.87; 95% CI 1.28, 2.74). The vast majority of deaths (79.5%) were for causes other than respiratory or cardiovascular conditions. Among patients aged <65 years, the pattern was similar but the mortality risk for patients with severe COVID-19 was increased compared to both COVID-19 negative patients (HR 3.33; 95% CI 2.35, 4.73) and mild COVID-19 patients (HR 2.83; 95% CI 1.59, 5.04). Patients aged 65 and older with severe COVID-19 were also at increased 12-month mortality risk compared to COVID-19 negative patients (HR 2.17; 95% CI 1.66, 2.84) but not mild COVID-19 patients (HR 1.41; 95% CI 0.84, 2.34). Discussion: Patients with a COVID-19 hospitalization were at significantly increased risk for future mortality. In a time when nearly all COVID-19 hospitalizations are preventable this study points to an important and under-investigated sequela of COVID-19 and the corresponding need for prevention.

Risk of New Hospitalization Post-COVID-19 Infection for Non-COVID-19 Conditions.

INTRODUCTION: Reports of post-acute sequelae of COVID-19 continue to emerge, but it remains unclear how the severity of a patient's COVID-19 infection affects risk for future hospitalizations for non-COVID-19 problems. METHODS: An analysis of electronic health records (EHR) was performed for a cohort of 10,646 patients who were followed for 6 months post-COVID-19 episode at 1 health system. COVID-19-positive patients were classified as severe if they were hospitalized within the first 30 days of their initial positive test. Assessment of hospitalizations overall and conditions that could be seen as complications of COVID-19 (cardiovascular, respiratory, and clotting diagnoses) was assessed. The 6-month risk of a new hospitalization was assessed in both unadjusted and adjusted Cox regressions. RESULTS: Of the 10,646 patients included in this cohort,114 had severe COVID-19, 211 had mild/moderate COVID-19, and 10,321 were COVID-19 negative. After adjustment for potential confounding variables, there was no significantly increased risk in future hospitalization for any condition for patients who were COVID-19 positive versus those who were COVID-19 negative (HR, 1.31; 95% CI, 0.98-1.74). In adjusted analyses, individuals with severe COVID-19 had an increased risk of hospitalization for potential complications compared with both mild/moderate COVID-19 (HR, 2.20; 95% CI, 1.13-4.28) and COVID-19 negative patients (HR, 2.24; 95% CI, 1.52-3.30). DISCUSSION: Patients with a severe COVID-19 episode were at greater risk for future hospitalizations. This study reinforces the importance of preventing infection in patients at higher risk for severe COVID-19 cases.

Daily self-regulation with biofeedback to improve stress and job satisfaction in a primary care clinic.

BACKGROUND: Burnout in healthcare professions is higher than other careers. An undesirable work-life balance has resulted in declining job satisfaction among primary care physicians. Biofeedback devices teach self-regulation techniques, which reduce stress and increase resilience. OBJECTIVES: We assessed whether self-regulation with biofeedback is effective at decreasing stress and improving job satisfaction among primary care clinicians and nurses. METHODS: Two naturally occurring cohorts of clinicians and nurses were followed over 12 weeks. The treatment group (N = 9) completed 12 weeks of self-regulation with optional clinic-based biofeedback and received peer support for the first half. The control group (N = 9) started a delayed intervention after 6 weeks without peer support. Descriptive and bivariate analyses were conducted. RESULTS: The treatment group averaged one biofeedback session weekly for 6 min and the control group two sessions for 11 min. Adherence differed by age. Subjects also reported using self-regulation techniques without biofeedback. Perceived stress initially increased in both groups with intervention implementation, more so in the treatment group (P = 0.03) whose stress then decreased but was not significant. Overall and extrinsic job satisfaction similarly increased but were not significance. CONCLUSION: The initial increase in perceived stress was related to daily biofeedback adherence and clinic responsibilities. Treatment group stress then decreased with self-regulation but was difficult to quantify in a small cohort. Larger studies could increase daily self-regulation adherence by improving biofeedback accessibility for leisurely use. Using self-regulation with biofeedback may be an innovative approach to reduce stress and improve job satisfaction in primary care.

Functional medicine: Focusing on imbalances in core metabolic processes.

This medical field surveys details of assimilation, defense and repair, energy, biotransformation and elimination, transport, communication, and structural integrity, and addresses 5 lifestyle factors.

Horner syndrome with transient visual impairment.

A 57-year-old female presented with headache, miosis, and ptosis diagnosed as Horner syndrome (HS). After delaying the recommended diagnostic imaging, she experienced transient, unilateral visual impairment in bright light. The patient was subsequently determined to have a spontaneous internal carotid artery dissection (ICAD) and secondary retinal ischemia with minimal cardiovascular risk factors and no history of preceding trauma. She wore dark glasses, received gabapentin for pain control, and was anticoagulated for a total of 4 months at which time the ICAD resolved despite a residual blepharoptosis and anisocoria.