Using Exogenous Social Media Exposure Measures to Assess the Effects of Smokeless Tobacco-Related Social Media Content on Smokeless Tobacco Sales in the United States.

INTRODUCTION: Prior research on the effects of social media promotion of tobacco products has predominantly relied on survey-based self-report measures of marketing exposure, which potentially introduce endogeneity, recall, and selection biases. New approaches can enhance measurement and help better understand the effects of exposure to tobacco-related messages in a dynamic social media marketing environment. We used geolocation-specific tweet rate as an exogenous indicator of exposure to smokeless tobacco (ST)-related content and employed this measure to examine the influence of social media marketing on ST sales. AIMS AND METHODS: Autoregressive error models were used to analyze the association between the ST-relevant tweet rate (aggregated by 4-week period from February 12, 2017 to June 26, 2021 and scaled by population density) and logarithmic ST unit sales across time by product type (newer, snus, conventional) in the United States, accounting for autocorrelated errors. Interrupted time series approach was used to control for policy change effects. RESULTS: ST product category-related tweet rates were associated with ST unit sales of newer and conventional products, controlling for price, relevant policy events, and the coronavirus disease 2019 (COVID-19) pandemic. On average, 100-unit increase in the number of newer ST-related tweets was associated with 14% increase in unit sales (RR = 1.14; p = .01); 100-unit increase in conventional ST tweets was associated with ~1% increase in unit sales (p = .04). Average price was negatively associated with the unit sales. CONCLUSIONS: Study findings reveal that ST social media tweet rate was related to increased ST consumption and illustrate the utility of exogenous measures in conceptualizing and assessing effects in the complex media environment. IMPLICATIONS: Tobacco control initiatives should include efforts to monitor the role of social media in promoting tobacco use. Surveillance of social media platforms is critical to monitor emerging tobacco product-related marketing strategies and promotional content reach. Exogenous measures of potential exposure to social media messages can supplement survey data to study media effects on tobacco consumption.

Clinical presentation of patients with lower limb spasticity undergoing routine treatment with botulinum toxin: baseline findings from an international observational study.

OBJECTIVE: Describe how people with lower limb spasticity present for treatment in routine clinical practice. METHODS: Prospective, observational study (Clinicaltrials.gov: NCT04050527) of ambulatory adult patients (≥ 18 years) with unilateral lower limb spasticity (able to take ≥ 5 steps with or without assistance) presenting for routine spasticity management, including treatment with abobotulinumtoxinA. RESULTS: The study population included 430 adults with lower limb spasticity. Despite their relatively young age (mean ± standard deviation 53.7 ± 13.9 years), only 20% of patients were employed. Most patients had an acquired brain injury due to cerebrovascular disease; 84.1% reported having concomitant upper limb spasticity. Using the Leg Activity Measure, most patients reported no or only mild difficulties in performing hygiene/positioning tasks, while 80.7% had at least mild difficulty with indoor ambulation and 90.5% had at least mild difficulty with walking outdoors. Sensory, communication and/or cognitive impairments were also common. At the first treatment cycle, 50.7% of patients set active function primary goals, including locomotion transferring or standing. CONCLUSION: These observations highlight the complexity of presentation that must be considered when setting treatment goals for lower limb spasticity and emphasize the types of impairment and activity (functional) limitations that treating teams may expect to encounter in their patients and should cover in their initial and follow-up assessments.

Goal Attainment after Treatment with Abobotulinumtoxina and a Tailored Home Therapy Programme in Children with Upper Limb Spasticity: Descriptive, Exploratory Analysis of a Large Randomized, Controlled Study

OBJECTIVE: This exploratory analysis of a large, randomized, double-blind study (NCT02106351) describes the effect of treatment with abobotulinumtoxinA followed by a tailored home exercises therapy programme in enabling children with upper limb spasticity due to cerebral palsy to achieve their functional goals using goal attainment scaling (GAS). METHODS: Children with cerebral palsy and spasticity in ≥ 1 upper limb received up to 4 injection cycles of abobotulinumtoxinA (2 U/kg (cycle 1 only), 8U/kg and 16U/kg) into the elbow and wrist flexors and other upper limb muscles selected to support individual treatment goals. Children followed a home exercises therapy programme, which included stretches and exercises specifically chosen to facilitate goal achievement and engagement in activities. RESULTS: For cycle 1, most children had active function goals set as their primary goal (69.7% vs 19.2% passive function goals). GAS T- scores and goal responder rates at week 16 indicated that most types of primary goal were achieved at least as expected during cycle 1 (all groups). Primary goal GAS T-scores were generally maintained for the first 3 abobotulinumtoxinA treatment cycles. CONCLUSION: Most children with upper limb spasticity treated with repeat cycles of abobotulinumtoxinA supported by an individualized home exercises therapy programme achieved their functional goals.

Muscle Selection and Dosing in a Phase 3, Pivotal Study of AbobotulinumtoxinA Injection in Upper Limb Muscles in Children With Cerebral Palsy.

Background: Guidelines recommend botulinum toxin-A in pediatric upper limb spasticity as part of routine practice. Appropriate dosing is a prerequisite for treatment success and it is important that injectors have an understanding on how to tailor dosing within a safe and effective range. We report upper limb dosing data from a phase 3 study of abobotulinumtoxinA injections in children with cerebral palsy. Methods: This was a double-blind, repeat-treatment study (NCT02106351). In Cycle 1, children were randomized to abobotulinumtoxinA at 2 U/kg control dose or clinically relevant 8 U/kg or 16 U/kg doses. Doses were divided between the primary target muscle group (PTMG, wrist or elbow flexors) and additional muscles tailored to clinical presentation. During Cycles 2-4, children received doses of 8 U/kg or 16 U/kg and investigators could change the PTMG and other muscles to be injected. Injection of muscles in the other upper limb and lower limbs was also permitted in cycles 2-4, with the total body dose not to exceed 30 U/kg or 1,000 U (whichever was lower) in the case of upper and lower limb treatment. Results: 212 children were randomized, of which 210 received ≥1 abobotulinumtoxinA injection. Per protocol, the elbow and wrist flexors were the most commonly injected upper limb muscles. Across all 4 cycles, the brachialis was injected in 89.5% of children (dose range 0.8-6 U/kg), the brachioradialis in 83.8% (0.4-3 U/kg), the flexor carpi ulnaris in 82.4% (0.5-3 U/kg) and the flexor carpi radialis in 79.5% (0.5-4 U/kg). Other frequently injected upper limb muscles were the pronator teres(70.0%, 0.3-3 U/kg). adductor pollicis (54.3%, 0.3-1 U/kg), pronator quadratus (44.8%, 0.1-2 U/kg), flexor digitorum superficialis (39.0%, 0.5-4 U/kg), flexor digitorum profundus (28.6%, 0.5-2 U), flexor pollicis brevis/opponens pollicis (27.6%, 0.3-1 U/kg) and biceps (27.1%, 0.5-6 U/kg). AbobotulinumtoxinA was well-tolerated at these doses; muscular weakness was reported in 4.3% of children in the 8 U/kg group and 5.7% in the 16 U/kg group. Conclusions: These data provide information on the pattern of injected muscles and dose ranges used in this study, which were well-tolerated. Per protocol, most children received injections into the elbow and wrist flexors. However, there was a wide variety of other upper limb muscles injected as physicians tailored injection patterns to clinical need.

Pituitary metastases of Hürthle cell carcinoma of the thyroid.

An 85-year-old man was referred to endocrinology following the discovery of an incidental pituitary mass on cranial imaging which was thought to be a non-functioning adenoma during an admission with headaches, lethargy, confusion and hyponatraemia. He had a history of Hürthle cell carcinoma of the thyroid treated with total thyroidectomy, ablative radioiodine therapy and thyroxine replacement. Subsequently, he developed metastatic spread to the neck, lungs and skeleton. About 9 months later, the patient had deterioration of vision. MRI showed a rapidly expanding pituitary mass with compression of the optic chiasm. Biochemical investigations confirmed hypocortisolism and hypogonadism. The patient underwent trans-sphenoidal resection of the pituitary mass followed by external beam radiotherapy to the pituitary bed. Histopathology confirmed a metastatic deposit of Hürthle cell carcinoma, which is a rare and aggressive variant of follicular thyroid carcinoma.

Systemic treatment of brain metastases in non-small cell lung cancer.

Brain metastases (BrMs) are associated with significant morbidity and are found in up to 50% of patients with advanced non-small cell lung cancer (NSCLC). Most of the literature focuses on symptomatic BrMs, with a lack of baseline brain imaging in asymptomatic patients. Unfortunately, much of the data on local treatments with or without systemic treatment is retrospective. Clinical trials of systemic treatments largely exclude patients with BrMs. Chemotherapy is an active treatment for BrM with response rates in the brain similar to other sites of disease. Targeted systemic treatments in patients with driver mutations (EGFR and ALK-MET to date) have impressive central nervous system (CNS) penetrance and response rates. Unfortunately, no prospective data can currently guide the timings or modality of local therapies with systemic treatments in these patients who have a high incidence of CNS disease, but retrospective data suggest that early local therapies may give better intracranial progression-free survival (ICPFS). Recent immunotherapy trials have included patients with BrMs. These patients have largely been pre-treated with local therapies and are asymptomatic. Thus, the current standard is becoming, early local therapies before or in conjunction with immunotherapy agents. The approach seems to be safe. Prospective studies are needed in NSCLC BrMs patients to make sure any benefit from local therapies on the ICPFS and quality of life is not overlooked. Here we report what we think are reasonable conclusions from the available data and make suggestions for future clinical trials in the management of NSCLC BrMs.

Bacterial meningitis as a first presentation of pituitary macroprolactinoma.

UNLABELLED: A 56-year-old man was brought to the Emergency Department after being found collapsed at his office with a reduced level of consciousness. From clinical examination and initial investigations, he was diagnosed as having bacterial meningitis and was promptly commenced on empirical i.v. antibiotics. Computed tomography of the brain revealed a parenchymal mass at the base of the skull and subsequent magnetic resonance imaging of the head 4 days later confirmed a large soft tissue mass, which extended through to the cavernous sinus. Examination of the cerebrospinal fluid (CSF) following lumbar puncture confirmed pneumococcal meningitis and antibiotics were continued for 2 weeks in total. During the admission, hormone profiling revealed a grossly elevated prolactin. When coupled with the initial results of the brain imaging, this result helped to confirm a macroprolactinoma that was invading the postnasal space. A final diagnosis of pneumococcal meningitis secondary to invading prolactinoma was made. The patient was started on cabergoline and was followed up in the outpatient clinic upon discharge. He made a full recovery from the meningitis. Over the next few months, prolactin levels returned to be normal and the prolactinoma shrank significantly in size. The patient remains on cabergoline that will most likely be continued indefinitely. LEARNING POINTS: Bacterial meningitis is a rare first presentation of pituitary macroprolactinoma.Patients with invasive macroprolactinoma do not always present with CSF leakage.Prompt treatment with antibiotics and a dopamine agonist is of great importance for a favourable outcome.Close monitoring of the patient for signs of raised intracranial pressure is essential in the management of macroprolactinoma.Note the risk of CSF leakage after initiation of dopamine agonist therapy irrespective of concomitant meningitis in macroprolactinoma.

Folates are potential ligands for ruthenium compounds in vivo.

Under physiologically relevant conditions, cis-bis(2,2'-bipyridine)dichlororuthenium(II), [cis-Ru(2,2'-bipy)2Cl2] was observed to bind to folic acid via replacement of the two chloride ligands. This binding was shown to be pH dependent and afforded diastereomers, the structures of which were determined by 1- and 2D NMR spectroscopic techniques. We propose that when studying the cytotoxicity of labile ruthenium complexes in cells, folate coordination should be considered.

Tuning heavy metal compounds for anti-tumor activity: is diversity the key to ruthenium's success?

This review aims to bring the reader up to date with the more recent ruthenium compounds that have been synthesized and tested for their cytotoxicity. The chemistry of these transition metal complexes will be introduced and the basic principles that govern their common behavior outlined. The recent history of established compounds within this field will be presented alongside those that now represent the cutting-edge. The inherent variety within this class of compounds will lead the reader to appreciate their diversity and pose questions as to their similarities aside from the presence of a shared metal ion. This review aims to discuss and contextualize the state-of-the-art research within the context of the speculative advancement of this developing field. There is an evident need to specify the molecular and cellular targets of these drug molecules in order to ultimately elucidate their mode or modes of action. The evidence presented herein suggests that new avenues of research require novel analytical probes and methods for tracing the fate of ruthenium complexes in cells in order to understand their very promising cytotoxic activity.

Altering the Balance between Ligand-Based Radical Anion Formation and Dechelation in Electrochemically Reduced Binuclear Copper(I) Complexes: A Resonance Raman Spectroelectrochemical Study.

The electrochemistry and spectral properties of a series of mono- and binuclear complexes with bridging ligands based on 2,3-di(2-quinolyl)quinoxaline are reported. The ligands are 2,3-di(2-quinolyl)quinoxaline (dqq), 6,7-dimethyl-2,3-di(2-quinolyl)quinoxaline (dqqMe(2)), and 6,7-dichloro-2,3-di(2-quinolyl)quinoxaline (dqqCl(2)). The complexes are [Cu(dqq)(PPh(3))(2)]BF(4), 1.[BF(4)]; [Cu(dqqMe(2))(PPh(3))(2)]BF(4), 2.[BF(4)]; [Cu(dqqCl(2))(PPh(3))(2)]BF(4), 3.[BF(4)]; [(PPh(3))(2)Cu(dqq)Cu(PPh(3))(2)](BF(4))(2), 4.[BF(4)](2); [(PPh(3))(2)Cu(dqqMe(2))Cu(PPh(3))(2)](BF(4))(2), 5.[BF(4)](2); [(PPh(3))(2)Cu(dqqCl(2))Cu(PPh(3))(2)](BF(4))(2), 6.[BF(4)](2). The mononuclear complexes reduce at the metal and dechelate, as evidenced by UV/vis spectroelectrochemistry. Reduction of the binuclear complexes results in ligand-based radical anion formation for 4 and 6 but decomposition of 5 to 2. The reduction species are identified using resonance Raman spectroscopy. The structures of [Cu(PPh(3))(2)(C(26)H(14)Cl(2)N(4))][BF(4)] (3.[BF(4)]) and [(Cu(PPh(3))(2))(2)(C(26)H(14)Cl(2)N(4))][BF(4)](2).2CH(2)Cl(2) (6.[BF(4)](2)) were determined by single-crystal X-ray diffraction. 3.[BF(4)] crystallized in the monoclinic space group P&onemacr; with cell dimensions a = 10.956(2) Å, b = 15.278(3) Å, c = 16.032(3) Å, alpha = 100.342(8) degrees, beta = 95.291(13) degrees, gamma = 93.968(12) degrees, Z = 2, rho(calcd) = 1.431 g/cm(3), and R(F(o)) = 0.0589. 6.[BF(4)](2) crystallized in the monoclinic space group C2/c with cell dimensions a = 21.295(4) Å, b = 24.322(5) Å, c = 20.034(4) Å, beta = 112.64(3) degrees, Z = 8, rho(calcd) = 1.486 g/cm(3), and R(F(o)) = 0.0422.