Consensus Recommendations for Management and Counseling of Adverse Events Associated With Lorlatinib: A Guide for Healthcare Practitioners.

Resistance to first- and second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) and development and progression of central nervous system metastases remain significant issues in the treatment of ALK-positive non-small-cell lung cancer. Lorlatinib is a novel third-generation ALK TKI that is able to penetrate the blood-brain barrier and has broad-spectrum potency against most known resistance mutations that can develop during treatment with crizotinib and second-generation ALK TKIs. The safety profile of lorlatinib is distinct from those of other ALK TKIs. Adverse events are typically mild to moderate in severity, seldom result in permanent discontinuations, and are generally manageable through lorlatinib dose modifications and/or standard medical therapy. This article provides guidance to advanced practice providers (e.g., nurses, nurse practitioners, physician assistants) and oncology pharmacists for the clinical management of key lorlatinib-emergent adverse reactions (i.e., hyperlipidemias, central nervous system effects, bodyweight increase, edema, and peripheral neuropathy). As lorlatinib is both a substrate and inducer of the CYP3A enzyme system and is contraindicated with strong CYP3A inducers, relevant drug-drug interactions are also highlighted.

Predicting Swallowing Outcomes from Objective Videofluoroscopic Timing and Displacement Measures in Head and Neck Cancer Patients.

Radiation therapy with or without chemotherapy compromises swallowing efficiency and safety in patients with head and neck cancer (HNC). The resulting dysphagia leads to overall morbidity, with altered diets, reduced nutritional intake, reduced quality of life, and potential interruption of curative cancer treatment. Despite well-documented radiation-related changes in swallowing physiology, scarce research exists on the potential clinical value for measurements of swallowing timing and displacement in this population. This study investigated the discriminatory value of quantitative timing and displacement parameters for the Functional Oral Intake Scale and Penetration Aspiration Scale scores using pre- and post-radiation videofluoroscopy data. Swallowtail Software Version 1 (Belldev Medical, Arlington Heights, IL) was used to obtain objective timing and displacement measurements from the pre- and post-radiation videofluoroscopy data for 31 patients who underwent radiation therapy, with or without chemotherapy, for head and neck cancer. The total pharyngeal transit time (BP2) (p < 0.000, r = 0.43) in pudding bolus trials and the maximal upper esophageal sphincter opening (PESMax/cm) (p = 0.001, r = 0.31) in thin bolus trials were discriminatory for Functional Oral Intake Scale (FOIS). Findings suggest that measurement of post-radiation changes using objective and quantitative parameters may offer some discriminatory value regarding future dysphagia risk and prognosis based on total pharyngeal transit time and degree of UES opening. In addition, the results suggest that different bolus types may offer different discriminatory values in HNC population, and that some timing and displacement variables may have discriminatory value for patients' diet levels independent from any aspiration risk.

Voice Outcomes Following Multiple Surgeries for Recurrent Respiratory Papillomatosis.

OBJECTIVES: Recurrent Respiratory Papillomatosis (RRP) is a rare disease caused by the human papilloma virus that presents as warty, exophytic growths in the upper airway. RRP in the larynx can lead to severe airway obstruction and voice changes. It is clinically known that patients with RRP frequently experience dysphonia. The purpose of this study was to assess the impact of multiple surgical treatments on RRP patients' voice outcomes, and to determine whether a higher number of repeated surgeries lead to decreased voice quality. METHODS: A retrospective cohort study was conducted of adult RRP patients (n = 23) who underwent multiple surgeries. Group 1 included patients (n = 11) who had <5 surgeries (range 2-4 surgeries) and Group 2 included patients (n = 12) who had ≥5 surgeries (range 5-50+ surgeries). Voice recordings were selected from the following clinic visits: initial office visit (initial presurgery), first postsurgery, and the last clinic encounter(s) with no immediate planned surgery. Blinded auditory-perceptual ratings along with cepstral and spectral acoustic measures assessed voice severity. RESULTS: There was significant improvement from the initial presurgery visit compared to each postoperative visit over time for all voice outcome measures for both Group 1 and Group 2. The results of the study indicated that the number of surgeries did not significantly affect mean postoperative voice outcomes, and there were no significant differences between patient groups for voice quality over time. CONCLUSIONS: The results of this study suggest that RRP patients' voice quality may not suffer cumulative negative effects when using modern tissue-sparing surgical techniques.

Reliability of High-speed Videoendoscopic Ratings of Essential Voice Tremor and Adductor Spasmodic Dysphonia.

OBJECTIVES: The main objectives of this study were to (1) examine intrarater and inter-rater reliabilities in perceptual ratings of vocal fold vibratory patterns and supraglottic characteristics for essential vocal tremor and adductor spasmodic dysphonia (AdSD) using high-speed videoendoscopy (HSV), and (2) to investigate the specificity of the parameters in differentiating these two voice disorders. METHODS: HSV recordings of 34 cases diagnosed with essential vocal tremor, AdSD, or AdSD with vocal tremor were evaluated blindly by two voice speech pathologists. The two raters examined all HSV video segments twice across nine supraglottic and vocal fold vibratory characteristics for inter-rater and intrarater reliabilities. A separate consensus rating was then developed, with the results analyzed to explore differentiation. RESULTS: Raters demonstrated moderate intrarater reliability with mean Spearman's rho correlation coefficients of 0.68 (rater 1) and 0.73 (rater 2). Moderate inter-rater reliability for the two raters was seen across all parameters with a mean Cohen's kappa coefficient of 0.51. Raters showed higher intrarater and inter-rater reliabilities for supraglottic parameters. Only the presence of tremor differentiated between the two voice disorders in cases with a consistent diagnosis. CONCLUSIONS: The high level of concomitance between vocal tremor and AdSD may affect subjective perceptual analysis of supraglottic and vocal fold vibratory patterns. Results indicate similar global involvement of supraglottic laryngeal structures for both vocal tremor and AdSD.

Thrombolysis for Massive Pulmonary Embolism in Pregnancy.

Pregnant women are at high risk for venous thromboembolism, including pulmonary embolism (PE), given expected changes in coagulation, fibrinolysis, and venous blood flow. In fact, PE is the leading cause of maternal death in the United States. Nonpregnant patients who develop PE with hypotension or show signs of deterioration after anticoagulation receive thrombolytics as a standard of care. Pregnant women, however, have been excluded from clinical trials with thrombolytics, and all data available in this population are published as case reports or case series. We reviewed all reports of thrombolytics, systemic or catheter directed, used in pregnant patients with massive PE. This article summarizes the risks for thromboembolism in pregnancy, compares and contrasts thrombolytic agents in this setting, and provides a recommendation for management of massive PE in this special population. Overall, reports suggest that the use of these agents is associated with beneficial outcomes and a relatively low risk of complications. The quality of this evidence is low, and clinical judgment is required to assess individual patients for risks versus benefits of thrombolysis.

Intra-arterial verapamil post-thrombectomy is feasible, safe, and neuroprotective in stroke.

Large vessel ischemic stroke represents the most disabling subtype. While t-PA and endovascular thrombectomy can recanalize the occluded vessel, good clinical outcomes are not uniformly achieved. We propose that supplementing endovascular thrombectomy with superselective intra-arterial (IA) verapamil immediately following recanalization could be safe and effective. Verapamil, a calcium channel blocker, has been shown to be an effective IA adjunct in a pre-clinical mouse focal ischemia model. To demonstrate translational efficacy, mechanism, feasibility, and safety, we conducted a group of translational experiments. We performed in vivo IA dose-response evaluation in our animal stroke model with C57/Bl6 mice. We evaluated neuroprotective mechanism through in vitro primary cortical neuron (PCN) cultures. Finally, we performed a Phase I trial, SAVER-I, to evaluate feasibility and safety of administration in the human condition. IA verapamil has a likely plateau or inverted-U dose-response with a defined toxicity level in mice (LD50 16-17.5 mg/kg). Verapamil significantly prevented PCN death and deleterious ischemic effects. Finally, the SAVER-I clinical trial showed no evidence that IA verapamil increased the risk of intracranial hemorrhage or other adverse effect/procedural complication in human subjects. We conclude that superselective IA verapamil administration immediately following thrombectomy is safe and feasible, and has direct, dose-response-related benefits in ischemia.

External carotid stenting for symptomatic stenosis in a patient with patent EDAS for Moyamoya disease.

BACKGROUND: Moyamoya disease is characterized by progressive narrowing of the internal carotid artery (ICA). Symptomatic patients typically undergo cerebrovascular intervention via extracranial-intracranial (EC-IC) bypass, most often with the use of the superficial temporal artery. This case of Moyamoya disease is of particular interest as the patient presented with a unilateral atherosclerotic external carotid artery (ECA) stenosis after EC-IC bypass that eliminated the benefit of his original surgery, resulting in a symptomatic presentation. CLINICAL PRESENTATION: A 53-year-old man presenting with Moyamoya disease and known left ICA occlusion had received a bilateral encephaloduroarteriosynangiosis (EDAS) bypass 10 years previously. He re-presented complaining of right-sided tingling, weakness, and numbness radiating up the arm. CT angiography indicated significant stenosis of the left ECA. ECA angioplasty and stenting with a distal protection device resulted in resolution of his symptoms. CONCLUSIONS: This case illustrates that a patient presenting with Moyamoya disease and concurrent symptomatic ECA stenosis post-EDAS can be effectively and safely treated with ECA stenting.

External carotid stenting for symptomatic stenosis in a patient with patent EDAS for Moyamoya disease.

BACKGROUND: Moyamoya disease is characterized by progressive narrowing of the internal carotid artery (ICA). Symptomatic patients typically undergo cerebrovascular intervention via extracranial-intracranial (EC-IC) bypass, most often with the use of the superficial temporal artery. This case of Moyamoya disease is of particular interest as the patient presented with a unilateral atherosclerotic external carotid artery (ECA) stenosis after EC-IC bypass that eliminated the benefit of his original surgery, resulting in a symptomatic presentation. CLINICAL PRESENTATION: A 53-year-old man presenting with Moyamoya disease and known left ICA occlusion had received a bilateral encephaloduroarteriosynangiosis (EDAS) bypass 10 years previously. He re-presented complaining of right-sided tingling, weakness, and numbness radiating up the arm. CT angiography indicated significant stenosis of the left ECA. ECA angioplasty and stenting with a distal protection device resulted in resolution of his symptoms. CONCLUSIONS: This case illustrates that a patient presenting with Moyamoya disease and concurrent symptomatic ECA stenosis post-EDAS can be effectively and safely treated with ECA stenting.

Self-reported and clinical measurement of three chronic disease risks among low-income women in West Virginia.

BACKGROUND: This study assessed the validity of several self-reported cardiovascular risk factors among low-income women aged 40-64 years in West Virginia. METHODS: A cross-sectional survey was conducted of 733 women participating in the Well Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) project in West Virginia to examine agreement between self-report and clinical screenings in the prevalence of risk factors related to coronary heart disease (CHD). Women participating in the study were interviewed face-to-face before administration of clinical screenings that assessed height, weight, Quetelet's index, high blood pressure (systolic > or =140 mm Hg or diastolic > or =90 mm Hg), and elevated total cholesterol concentrations (> or =200 mg/dL and > or =240 mg/dL). RESULTS: The overall results showed high sensitivity and specificity for each of the risk factors examined; for overweight/obesity, the sensitivity was 96% and specificity was 93%; for cholesterol > or =240 mg/dL, sensitivity was 85% and specificity was 67%; for hypertension, sensitivity was 77% and specificity was 86%. Using a threshold value of > or =240 mg/dL for hypercholesterolemia led to higher sensitivity but a lower specificity than for a value of > or =200 mg/dL. CONCLUSIONS: This study found that among low-income women at higher risk for cardiovascular disease (CVD), self-reported values for high body mass index (BMI), hypercholesterolemia, and hypertension were well correlated with clinical measures, as indicated by high sensitivity values. Thus, self-reported values can be used for surveillance, targeted screenings, and health promotion activities, including lifestyle changes.

Effectiveness of a nutrition intervention with rural low-income women.

OBJECTIVES: To evaluate Cookin' Up Health, a computer-based interactive nutrition intervention. METHODS: After randomization to intervention and control groups, 262 women in rural clinics in West Virginia completed both a baseline and 3-month follow-up survey. RESULTS: Compared to the control group, the intervention group had significantly improved scores on knowledge of dietary fats, food label reading, and readiness to eat 5 fruits and vegetables a day and foods lower in fat. CONCLUSIONS: This brief interactive nutrition intervention shows potential as a strategy to begin the process of change, but follow-up may be needed for actual behavior change to occur.

Cookin' Up Health: developing a nutrition intervention for a rural Appalachian population.

Cookin' Up Health is a culturally targeted and individualized tailored nutrition intervention using a computer-based interactive format. Using a cooking show theme, the program demonstrates step-by-step meal preparation emphasizing healthy selection and portion control. Focus groups were conducted with women in two rural counties in West Virginia to guide the development of the intervention. Women felt more susceptible to heart disease because the changing role of women creates more stress and less time; weight loss was a greater motivator for dietary change than was preventing heart disease; social support is a barrier and facilitator for dietary change; cultural heritage and the way women were raised were major barriers to making health changes as adults; convenience and the cost of eating healthier were major factors when trying to make changes in diet; and women did not feel confident in their ability to maintain dietary changes.

Correlates of physical activity in a community sample of older adults in Appalachia.

Although much has been learned about the global determinants of physical activity in adults, there has been a lack of specific focus on gender, age, and urban/rural differences. In this church-based community sample of Appalachian adults (N = 1,239), the primary correlates of physical activity included age, gender, obesity, and self-efficacy. Overall, 42% of all participants and 31% of adults age 65 years or older met recommended guidelines for physical activity, which suggests that most participants do not engage in adequate levels of physical activity. Of participants who met physical activity guidelines, the most common modes of moderate and vigorous activity were walking briskly or uphill, heavy housework or gardening, light strength training, and biking. These particular activities that focus on building self-efficacy might be viable targets for intervention among older adults in rural communities.