Tobacco industry strategies to influence the regulation of new and emerging tobacco and nicotine products in Latin America and the Caribbean.

Objective: To document tobacco industry strategies to influence regulation of new and emerging tobacco and nicotine products (NETNPs) in Latin America and the Caribbean. Methods: We analyzed industry websites, advocacy reports, news media and government documents related to NETNPs, focusing on electronic cigarettes and heated tobacco products. We also conducted a survey of leading health advocates. We applied the policy dystopia model to analyze industry action and argument-based strategies on NETNP regulations. Results: Industry actors engaged in four instrumental strategies to influence NETNP regulation - coalition management, information management, direct involvement in and access to the policy process, and litigation. Their actions included: lobbying key policy-makers, academics and vaping associations; providing grants to media groups to disseminate favorable NETNP information; participating in public consultations; presenting at public hearings; inserting industry-inspired language into draft NETNP legislation; and filing lawsuits to challenge NETNP bans. The industry disseminated its so-called harm reduction argument through large/influential countries (e.g., Argentina, Brazil, and Mexico). Industry discursive strategies claimed NETNPs were less harmful, provided safer alternatives, and should be regulated as so-called harm reduction products or have fewer restrictions on their sale and use than those currently in place. Conclusion: Our analysis provides a better understanding of industry strategies to undermine tobacco and nicotine control. To help counter industry efforts, health advocates should proactively strengthen government capacities and alert policy-makers to industry attempts to create new regulatory categories (so-called reduced-risk products), provide misleading information of government authorizations of NETNPs, and co-opt so-called harm-reduction messages that serve the industry's agenda.

Immune biomarkers associated with COVID-19 disease severity in an urban, hospitalized population.

Objectives: We sought to identify immune biomarkers associated with severe Coronavirus disease 2019 (COVID-19) in patients admitted to a large urban hospital during the early phase of the SARS-CoV-2 pandemic. Design: The study population consisted of SARS-CoV-2 positive subjects admitted for COVID-19 (n = 58) or controls (n = 14) at the Los Angeles County University of Southern California Medical Center between April 2020 through December 2020. Immunologic markers including chemokine/cytokines (IL-6, IL-8, IL-10, IP-10, MCP-1, TNF-α) and serologic markers against SARS-CoV-2 antigens (including spike subunits S1 and S2, receptor binding domain, and nucleocapsid) were assessed in serum collected on the day of admission using bead-based multiplex immunoassay panels. Results: We observed that body mass index (BMI) and SARS-CoV-2 antibodies were significantly elevated in patients with the highest COVID-19 disease severity. IP-10 was significantly elevated in COVID-19 patients and was associated with increased SARS-CoV-2 antibodies. Interactions among all available variables on COVID-19 disease severity were explored using a linear support vector machine model which supported the importance of BMI and SARS-CoV-2 antibodies. Conclusions: Our results confirm the known adverse association of BMI on COVID-19 severity and suggest that IP-10 and SARS-CoV-2 antibodies could be useful to identify patients most likely to experience the most severe forms of the disease.

PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis.

Targeted therapies such as venetoclax (VEN) (Bcl-2 inhibitor) have revolutionized the treatment of chronic lymphocytic leukemia (CLL). We previously reported that persister CLL cells in treated patients overexpress multiple antiapoptotic proteins and display resistance to proapoptotic agents. Here, we demonstrated that multidrug-resistant CLL cells in vivo exhibited apoptosis restriction at a pre-mitochondrial level due to insufficient activation of the Bax and Bak (Bax/Bak) proteins. Co-immunoprecipitation analyses with selective BH domain antagonists revealed that the pleiotropic proapoptotic protein (Bim) was prevented from activating Bax/Bak by "switching" interactions to other upregulated antiapoptotic proteins (Mcl-1, Bcl-xL, Bcl-2). Hence, treatments that bypass Bax/Bak restriction are required to deplete these resistant cells in patients. Protein phosphatase 2A (PP2A) contributes to oncogenesis and treatment resistance. We observed that small-molecule activator of PP2A (SMAP) induced cytotoxicity in multiple cancer cell lines and CLL samples, including multidrug-resistant leukemia and lymphoma cells. The SMAP (DT-061) activated apoptosis in multidrug-resistant CLL cells through induction of mitochondrial permeability transition pores, independent of Bax/Bak. DT-061 inhibited the growth of wild-type and Bax/Bak double-knockout, multidrug-resistant CLL cells in a xenograft mouse model. Collectively, we discovered multidrug-resistant CLL cells in patients and validated a pharmacologically tractable pathway to deplete this reservoir.

"Mm-hm," "Uh-uh": are non-lexical conversational sounds deal breakers for the ambient clinical documentation technology?

OBJECTIVES: Ambient clinical documentation technology uses automatic speech recognition (ASR) and natural language processing (NLP) to turn patient-clinician conversations into clinical documentation. It is a promising approach to reducing clinician burden and improving documentation quality. However, the performance of current-generation ASR remains inadequately validated. In this study, we investigated the impact of non-lexical conversational sounds (NLCS) on ASR performance. NLCS, such as Mm-hm and Uh-uh, are commonly used to convey important information in clinical conversations, for example, Mm-hm as a "yes" response from the patient to the clinician question "are you allergic to antibiotics?" MATERIALS AND METHODS: In this study, we evaluated 2 contemporary ASR engines, Google Speech-to-Text Clinical Conversation ("Google ASR"), and Amazon Transcribe Medical ("Amazon ASR"), both of which have their language models specifically tailored to clinical conversations. The empirical data used were from 36 primary care encounters. We conducted a series of quantitative and qualitative analyses to examine the word error rate (WER) and the potential impact of misrecognized NLCS on the quality of clinical documentation. RESULTS: Out of a total of 135 647 spoken words contained in the evaluation data, 3284 (2.4%) were NLCS. Among these NLCS, 76 (0.06% of total words, 2.3% of all NLCS) were used to convey clinically relevant information. The overall WER, of all spoken words, was 11.8% for Google ASR and 12.8% for Amazon ASR. However, both ASR engines demonstrated poor performance in recognizing NLCS: the WERs across frequently used NLCS were 40.8% (Google) and 57.2% (Amazon), respectively; and among the NLCS that conveyed clinically relevant information, 94.7% and 98.7%, respectively. DISCUSSION AND CONCLUSION: Current ASR solutions are not capable of properly recognizing NLCS, particularly those that convey clinically relevant information. Although the volume of NLCS in our evaluation data was very small (2.4% of the total corpus; and for NLCS that conveyed clinically relevant information: 0.06%), incorrect recognition of them could result in inaccuracies in clinical documentation and introduce new patient safety risks.

New tobacco and nicotine products in Latin America and the Caribbean: assessing the market and regulatory environment.

OBJECTIVE: To document the regulatory environment of new tobacco and nicotine products (NTNPs), including electronic nicotine delivery systems (ENDS) and heated tobacco products (HTPs), in Latin America and the Caribbean (LAC). METHODS: Review of market research reports and databases, regulatory websites, Campaign for Tobacco-Free Kids, relevant published literature and the 2021 WHO Report on the Global Tobacco Epidemic. RESULTS: ENDS entered the LAC market in the 2010s and are now available in most LAC countries. A majority of LAC countries (n=18) have either banned the commercialisation of ENDS (n=7) or regulated ENDS as tobacco products (n=7), medicinal products (n=1) or consumer products (n=3). The remaining LAC countries (n=15) do not regulate ENDS. HTPs were first introduced in 2017 and have been officially launched in five countries (Colombia, Guatemala, Dominican Republic, Mexico and Costa Rica). Few countries have banned HTP commercialisation (n=3) or regulated commercialisation and use (n=7), while the majority of countries have existing legislation that applies to HTPs (n=19). A few countries (n=4) have no tobacco control legislation and therefore do not regulate HTPs. CONCLUSION: NTNPs are emerging products in the LAC region. Governments should follow WHO guidance and the decisions of the Conference of Parties to the WHO Framework Convention on Tobacco Control and ban or regulate NTNPs as tobacco products; otherwise NTNPs could create a new generation of tobacco and nicotine users.

Promoting healthier options? Inside the branding of light cigarettes and targeting youth in Brazil.

This study aimed to understand how the internal strategies of British American Tobacco (BAT) selling 'light' cigarettes to young people in Brazil may inform current global efforts to promote new tobacco and nicotine products. We reviewed industry documents in the Truth Tobacco Industry Documents (TTID) Library. In 1976, Philip Morris and BAT introduced 'low tar' or 'light' cigarettes in Brazil to maintain and attract new young smokers. At the time it was a novel tobacco product that implied lower health risks. While an initial push for 'light' cigarettes in Brazil did not materialise in the 1970s, BAT launched a new 'light' cigarette, Free, in 1984, with a marketing campaign consisting of symbols of personal freedom and choice to attract young people. In the mid-1990s, BAT used the success in Brazil to expand the lights segment throughout Latin America. BAT drove the lights segment through brand marketing and claims of a healthier alternative. As tobacco companies introduce and market new tobacco and nicotine products, mixing health and imagery messages, governments should recognise aggressive brand marketing messaging to attract new tobacco users and ensure that marketing regulations are enforced.

Automatic speech recognition performance for digital scribes: a performance comparison between general-purpose and specialized models tuned for patient-clinician conversations.

One promising solution to address physician data entry needs is through the development of so-called "digital scribes," or tools which aim to automate clinical documentation via automatic speech recognition (ASR) of patient-clinician conversations. Evaluation of specialized ASR models in this domain, useful for understanding feasibility and development opportunities, has been difficult because most models have been under development. Following the commercial release of such models, we report an independent evaluation of four models, two general-purpose, and two for medical conversation with a corpus of 36 primary care conversations. We identify word error rates (WER) of 8.8%-10.5% and word-level diarization error rates (WDER) ranging from 1.8%-13.9%, which are generally lower than previous reports. The findings indicate that, while there is room for improvement, the performance of these specialized models, at least under ideal recording conditions, may be amenable to the development of downstream applications which rely on ASR of patient-clinician conversations.

Team feedback: A missing piece of the interprofessional education puzzle.

INTRODUCTION: The ambulatory care practice model has long embraced interprofessional collaboration, well before it was formalized by the Interprofessional Education Collaborative. Establishing a mechanism to gather insight from other members of the interprofessional team may facilitate further development of interprofessional education (IPE). COMMENTARY: There is limited evidence investigating non-pharmacy trainees and medical provider perceptions of advanced pharmacy practice experience (APPE) student involvement in IPE. Most available evidence evaluates the satisfaction of non-pharmacy trainees and other health care professionals with APPE student recommendations. IMPLICATIONS: Emphasis on IPE, such as formalizing feedback from other health care professionals during experiential rotations, may assist preceptors in adapting interactions, strengthening interprofessional collaborations, and ensuring that students are valued team members who contribute to providing quality patient care.

Frequent follow-up of suicidal youth assessed in the emergency room: Long-term trajectory and predictors of suicidality.

Suicide was the second­leading cause of US deaths in 2018 among 15-24-year-olds. Suicide attempts, a risk factor for completions, and suicide ideation have doubled among pediatric emergency room (ER) patients during the past decade. Borderline Personality Disorder (BPD), a comorbid condition, has a 10% suicide rate. We examined the 4-year outcome of a cohort of suicidal adolescents, many also suffering from BPD and having undergone some form of treatment, to identify baseline factors which could inform intervention that would minimize suicidality 4 years post-discharge. METHODS: We conducted a prospective longitudinal study of suicidality at twelve points (four assessment occasions) for 286 suicidal youth presenting to a pediatric ER, most suffering from BPD, with 36 suicide ratings from baseline to 2-, 6- and 48-month follow-up evaluations. We examined the trajectory and predictors of persisting suicidality. RESULTS: Suicidality rapidly decreased within 2 months post-ER-discharge, subsequently remaining low throughout 48 months. Baseline functioning, female sex, stressful life events and BPD impulsiveness were most predictive of persisting suicidality at 48-month follow-up. CONCLUSION: Most suicidal youth, many meeting BPD criteria, no longer feel suicidal 2 months after ER discharge. Management of participants' baseline poor functioning stressful life events and the impulsiveness component of BPD specifically in females could impact suicidality 4 years later, and guide treatment options. The absence of the BPD cognitive and affective subscales as predictors of suicidality at 4-year follow-up may reflect treatment received. Further investigation of treatment effects is warranted and under way.

When Is My Care Team Rounding? A Simple Signage Intervention to Increase Awareness of Rounding Times.

Patient and caregiver awareness of multidisciplinary rounds (MDR) times, and their subsequent involvement in MDR, aids in decreasing adverse health outcomes, reducing average length of stay, and increasing satisfaction. The objective of this study was to increase patient and caregiver awareness of MDR times using signage interventions and to assess the state of rounding processes with patient and caregiver satisfaction pre- and post-intervention. We administered survey questions to assess MDR interaction and awareness regarding MDR times. Patient and caregiver awareness of rounding times increased significantly by 25.87% (P = .0043) post-intervention. Although patients' confidence in the physician remained largely unchanged after the intervention due to high initial confidence levels, MDR satisfaction metrics increased slightly post-intervention. Thus, our signage intervention increased rounding time awareness in the MDR process.

An interview study with medical scribes on how their work may alleviate clinician burnout through delegated health IT tasks.

OBJECTIVES: To understand how medical scribes' work may contribute to alleviating clinician burnout attributable directly or indirectly to the use of health IT. MATERIALS AND METHODS: Qualitative analysis of semistructured interviews with 32 participants who had scribing experience in a variety of clinical settings. RESULTS: We identified 7 categories of clinical tasks that clinicians commonly choose to offload to medical scribes, many of which involve delegated use of health IT. These range from notes-taking and computerized data entry to foraging, assembling, and tracking information scattered across multiple clinical information systems. Some common characteristics shared among these tasks include: (1) time-consuming to perform; (2) difficult to remember or keep track of; (3) disruptive to clinical workflow, clinicians' cognitive processes, or patient-provider interactions; (4) perceived to be low-skill "clerical" work; and (5) deemed as adding no value to direct patient care. DISCUSSION: The fact that clinicians opt to "outsource" certain clinical tasks to medical scribes is a strong indication that performing these tasks is not perceived to be the best use of their time. Given that a vast majority of healthcare practices in the US do not have the luxury of affording medical scribes, the burden would inevitably fall onto clinicians' shoulders, which could be a major source for clinician burnout. CONCLUSIONS: Medical scribes help to offload a substantial amount of burden from clinicians-particularly with tasks that involve onerous interactions with health IT. Developing a better understanding of medical scribes' work provides useful insights into the sources of clinician burnout and potential solutions to it.

Using Intern-Led Quality Improvement to Reduce Readmissions for Specialty Service Patients Within an Academic Medical Center.

Introduction: Postdischarge patient calls are an effective intervention to decrease unplanned readmissions. Despite its efficacy, calls are time consuming and compete with other clinical obligations. The purpose of this study was to evaluate the viability of intern-led quality improvement (QI) on conducting initial postdischarge calls to filter patients who require clinical or nurse follow-up. Methods: QI interns from an academic medical center's QI program completed postdischarge patient calls within 72 hours of patient discharge from a neurosurgery service between June 2018 and July 2019. QI interns filtered patients who required follow-up calls from a clinical service or nurse department. The departments called patients within 48 hours of requests. Unplanned readmission rate was compared between the cohort of patients who requested and received a follow-up call versus a cohort of patients who requested and did not receive a follow-up call (control). Results: QI interns completed 83.8% postdischarge patient calls within 72 hours of discharge. Reasons for unsuccessful calls included patient unresponsiveness (74.6%), wrong phone number on file (13.9%), and request to be called at a different time (11.5%). Nurses completed 57.2% follow-up requests within the targeted 48 hours and completed remaining requests within 7 days. QI intern postdischarge follow-up calls, in conjunction with nurse follow-up intervention, showed a significant (risk ratio = -3.31, p = 0.012) preventive effect on unplanned readmission rate. Conclusions: QI interns are a viable alternative to nurses to conduct the first contact of postdischarge patient follow-up calls. This system of QI interns filtering calls to the correct clinical service or nurse department increased postdischarge patient follow-up calls success rate and decreased readmission rates.

A scoping review of qualitative research in JAMIA: past contributions and opportunities for future work.

OBJECTIVE: Qualitative methods are particularly well-suited to studying the complexities and contingencies that emerge in the development, preparation, and implementation of technological interventions in real-world clinical practice, and much remains to be done to use these methods to their full advantage. We aimed to analyze how qualitative methods have been used in health informatics research, focusing on objectives, populations studied, data collection, analysis methods, and fields of analytical origin. METHODS: We conducted a scoping review of original, qualitative empirical research in JAMIA from its inception in 1994 to 2019. We queried PubMed to identify relevant articles, ultimately including and extracting data from 158 articles. RESULTS: The proportion of qualitative studies increased over time, constituting 4.2% of articles published in JAMIA overall. Studies overwhelmingly used interviews, observations, grounded theory, and thematic analysis. These articles used qualitative methods to analyze health informatics systems before, after, and separate from deployment. Providers have typically been the main focus of studies, but there has been an upward trend of articles focusing on healthcare consumers. DISCUSSION: While there has been a rich tradition of qualitative inquiry in JAMIA, its scope has been limited when compared with the range of qualitative methods used in other technology-oriented fields, such as human-computer interaction, computer-supported cooperative work, and science and technology studies. CONCLUSION: We recommend increased public funding for and adoption of a broader variety of qualitative methods by scholars, practitioners, and policy makers and an expansion of the variety of participants studied. This should lead to systems that are more responsive to practical needs, improving usability, safety, and outcomes.

The discovery and development of binimetinib for the treatment of melanoma.

INTRODUCTION: Binimetinib is an uncompetitive, small-molecule inhibitor of selective mitogen-activated protein kinase (MEK1/2) and was recently approved in 2018 in combination with encorafenib for the treatment of metastatic melanomas. Preclinical and clinical trial data on the drug demonstrate its potent efficacy in cancers, especially melanomas with BRAF and NRAS mutations. AREAS COVERED: The authors review the preclinical as well as clinical Phase 1, 2 and 3 trial data leading to its FDA approval in 2018 for metastatic melanoma. Phase 3 data in combination with encorafenib demonstrated double the PFS (14.9 months) compared to vemurafenib alone (7.3 months) in patients with BRAF-mutated metastatic melanoma. EXPERT OPINION: No longer-term data is available yet to demonstrate any durable complete responses to therapy with binimetinib or improvements in overall survival compared to other FDA-approved therapies including immunotherapy or vemurafenib. Treatment approaches to patients with BRAF-mutated metastatic melanoma should be individualized and binimetinib in combination with encorafenib is a reasonable oral strategy with a reasonably tolerated toxicity profile. The cost of treatment and durability of response should be incorporated into the discussion as part of the overall medical decision-making.

How does medical scribes' work inform development of speech-based clinical documentation technologies? A systematic review.

OBJECTIVE: Use of medical scribes reduces clinician burnout by sharing the burden of clinical documentation. However, medical scribes are cost-prohibitive for most settings, prompting a growing interest in developing ambient, speech-based technologies capable of automatically generating clinical documentation based on patient-provider conversation. Through a systematic review, we aimed to develop a thorough understanding of the work performed by medical scribes in order to inform the design of such technologies. MATERIALS AND METHODS: Relevant articles retrieved by searching in multiple literature databases. We conducted the screening process following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) in guidelines, and then analyzed the data using qualitative methods to identify recurring themes. RESULTS: The literature search returned 854 results, 65 of which met the inclusion criteria. We found that there is significant variation in scribe expectations and responsibilities across healthcare organizations; scribes also frequently adapt their work based on the provider's style and preferences. Further, scribes' job extends far beyond capturing conversation in the exam room; they also actively interact with patients and the care team and integrate data from other sources such as prior charts and lab test results. DISCUSSION: The results of this study provide several implications for designing technologies that can generate clinical documentation based on naturalistic conversations taking place in the exam room. First, a one-size-fits-all solution will be unlikely to work because of the significant variation in scribe work. Second, technology designers need to be aware of the limited role that their solution can fulfill. Third, to produce comprehensive clinical documentation, such technologies will likely have to incorporate information beyond the exam room conversation. Finally, issues of patient consent and privacy have yet to be adequately addressed, which could become paramount barriers to implementing such technologies in realistic clinical settings. CONCLUSIONS: Medical scribes perform complex and delicate work. Further research is needed to better understand their roles in a clinical setting in order to inform the development of speech-based clinical documentation technologies.

A Liver-Specific Thyromimetic, VK2809, Decreases Hepatosteatosis in Glycogen Storage Disease Type Ia.

Background: Glycogen storage disease type Ia (GSD Ia), also known as von Gierke disease, is the most common glycogen storage disorder. It is caused by the deficiency of glucose-6-phosphatase, the enzyme that catalyzes the final step of gluconeogenesis and glycogenolysis. The accumulation of glucose-6-phosphate leads to increased glycogen and triglyceride levels in the liver. Patients with GSD Ia can develop steatohepatitis, cirrhosis, and increased risk for hepatocellular adenomas and carcinomas. We previously showed that animal models of GSD Ia had defective autophagy and dysfunctional mitochondria. In this study, we examined the effect of VK2809, a liver-specific thyroid hormone receptor ß agonist, on hepatic steatosis, autophagy, and mitochondrial biogenesis in a mouse model of GSD Ia. Methods:G6pc-/--deficient (GSD Ia) mice were treated with VK2809 or vehicle control by daily intraperitoneal injection for four days. The hepatic triglyceride and glycogen were determined by biochemical assays. Autophagy and mitochondrial biogenesis were measured by Western blotting for key autophagy and mitochondrial markers. Results: VK2809 treatment decreased hepatic mass and triglyceride content in GSD Ia mice. VK2809 stimulated hepatic autophagic flux as evidenced by increased microtubule-associated protein light chain 3-II (LC3B-II), decreased p62 protein levels, activation of AMP-activated protein kinase (AMPK), inhibition of the mammalian target of rapamycin (mTOR) signaling, enhancement of protein levels of ATG5-ATG12, and increased lysosomal protein expression. VK2809 also increased the expression of carnitine palmitoyltransferase 1a (CPT1α) and fibroblast growth factor 21 (FGF21), as well as mitochondrial biogenesis to promote mitochondrial ß-oxidation. Conclusions: In summary, VK2809 treatment decreased hepatic triglyceride levels in GSD Ia mice through its simultaneous restoration of autophagy, mitochondrial biogenesis, and ß-oxidation of fatty acids. Liver-specific thyromimetics represent a potential therapy for hepatosteatosis in GSD Ia as well as nonalcoholic fatty liver disease.

Burnout and EHR use among academic primary care physicians with varied clinical workloads.

Burnout is becoming increasingly prevalent among primary care physicians. Recent studies have attributed electronic health record (EHR) related tasks as a potential source of physician burnout. In this cross-sectional study, EHR use was compared to self-reported burnout for 107 faculty physicians at 10 university-affiliated primary care clinics. Physicians who self-reported burnout spent more time managing their inbox and in the EHR after hours. Burnout was associated with lower rates of same day chart closure, longer completion time for inbox messages, and more incomplete messages. Burnout, while related to overall workload, had a complex relationship with EHR use, which was influenced by but could not wholly explained by clinical workload. Our results suggest that burnout is less prevalent with less allocated clinical time, however, more research is necessary to identify the optimal balance between clinical duties and academic pursuits. Segmenting providers based on relative workload to determine variation within similar groups may help optimize EHR use.

The complexity of minocycline serum protein binding.

Objectives: Serum protein binding is critical for understanding the pharmacology of antimicrobial agents. Tigecycline and eravacycline were previously reported to have atypical non-linear protein binding; the percentage of free fraction decreased with increasing total concentration. In this study, we extended the investigation to other tetracyclines and examined the factors that might impact protein binding. Methods: Different minocycline concentrations (0.5-50 mg/L) and perfusion media (saline, 0.1 M HEPES buffer and 0.1 and 1 M PBS) were examined by in vitro microdialysis. After equilibration, two dialysate samples were taken from each experiment and the respective antimicrobial agent concentrations were analysed by validated LC-MS/MS methods. For comparison, the serum protein bindings of doxycycline and levofloxacin were also determined. Results: The free fraction of minocycline decreased with increasing total concentration, and the results depended on the perfusion media used. The trends of minocycline protein binding in mouse and human sera were similar. In addition, serum protein binding of doxycycline showed the same concentration-dependent trend as minocycline, while the results of levofloxacin were concentration independent. Conclusions: The serum protein bindings of minocycline and doxycycline are negatively correlated with their total concentrations. It is possible that all tetracyclines share the same pharmacological property. Moreover, the specific perfusion media used could also impact the results of microdialysis. Additional studies are warranted to understand the mechanism(s) and clinical implications of serum protein binding of tetracyclines.

Exercise and Repeated Testing Improves Accuracy of Laser Doppler Assessment of Microvascular Function Following Shortened (1-minute) Blood Flow Occlusion.

OBJECTIVES: To determine whether stability/accuracy of post-occlusive LDF following shortened, one-minute blood flow occlusion, increases in the post-exercise state or by averaging multiple measurements. METHODS: Six healthy adults (3F) underwent LDF eight times at rest and following exercise, assessing post-occlusive (one-minute occlusion) reactive hyperemia in the cutaneous microcirculation of the forefinger. Measured variables included: pre- and post-occlusion steady-state perfusion (Plat1, Plat2), maximum post-occlusive perfusion (Max), PkT, and the ratio Max/Plat1. RESULTS: Stability/accuracy of all variables improved performing measurements after exercise (p < 0.05 Plat 1, Plat 2, Max and Max/Plat1). PkT and Max/Plat 1 displayed the greatest accuracy at rest (26.6 ± 5.1% and 26.6 ± 4.4% average difference, %Diff, of single measurements from individual "true" means, respectively); for these variables, %Diff improved to 19.5 ± 5.3 and 17.6 ± 2.1, respectively, following exercise. Overall, averaging multiple measurements performed at rest also improved stability/accuracy in all variables. This improvement was comparable to that obtained with a single measurement following exercise. CONCLUSIONS: A standardized exercise stimulus prior to testing significantly improves stability/accuracy of LDF following shortened, one-minute blood flow occlusion. Our results suggest the possibilities of broader applications of exercise to optimize measurements from a variety of skin perfusion methodologies.

Exercise in pediatric type 1 diabetes.

The beneficial effects of exercise, including reduction of cardiovascular risk, are especially important in children with type 1 diabetes (T1DM), in whom incidence of lifetime cardiovascular complications remains elevated despite good glycemic control. Being able to exercise safely is therefore a paramount concern. Dysregulated metabolism in T1DM however, causes frequent occurrence of both hypo- and hyperglycemia, the former typically associated with prolonged, moderate exercise, the latter with higher intensity, if shorter, challenges. While very few absolute contraindications to exercising exist in these children, exercise should not be started with glycemia outside the 80-250 mg/dl range. Within this glycemic range, careful adjustments in insulin administration (reduction or infusion rate via insulin pumps, or overall reduction of dosage of multiple injections) should be combined with carbohydrate ingestion before/during exercise, based on prior, individual experience with specific exercise formats. Unfamiliar exercise should always be tackled with exceeding caution, based on known responses to other exercise formats. Finally, gaining a deep understanding of other complex exercise responses, such as the modulation of inflammatory status, which is a major determinant of the cardio-protective effects of exercise, can help determine which exercise formats and which individual metabolic conditions can lead to maximally beneficial health effects.