Search

Background Longitudinal integrated clerkships (LICs) are a model of clinical education growing rapidly in Western contexts. LICs use educational continuity to benefits students’ clinical learning and professional identity formation. Patient-centered care is a core component of medical professionalism in the West. To support patient-centered care, education leaders in Taiwan restructured clinical education and implemented the first longitudinal integrated clerkship in East Asia. We aimed to investigate patients’ perceptions of longitudinal relationships with the LIC students within Taiwan’s Confucian cultural and social context. Methods We invited patients or their family members who were cared for longitudinally by a LIC student to participate in the study. Participating patients or their family members undertook semi-structured interviews. We analyzed data qualitatively using a general inductive approach to identify themes in the patients’ descriptions of their experiences interacting with the LIC students. Results Twenty-five patients and family members participated in interviews: 16 patients and 9 family members. Qualitative analysis of interview transcripts identified three themes from patients’ experience receiving care from their LIC students: care facilitation, companionship, and empathy. To provide care facilitation, LIC students served as a bridge between the physicians and patients. Students served patients by reminding, consulting, tracking disease progression, and researching solutions for problems. To provide companionship, students accompanied patients interpersonally like a friend or confidant who listens and provides a presence for patients. To provide empathy, patients reported that students showed sincere concern for patients’ experience, feelings, and mood. Conclusion In our study, Taiwanese patients’ perspectives of LIC students suggested the value of care facilitation, companionship, and empathy. We discuss these themes within the context of Confucian culture and the Taiwanese context of care.

Pharmaceutical multicomponent crystals (MCCs) including salts and co-crystals of active pharmaceutical ingredients (APIs), are an active focus of research to improve various physicochemical properties of drugs. In this work, we demonstrate that the pharmaceutical artesunate (AS), a derivative of artemisinin (ART), forms a 1 : 1 salt with two cinchona alkaloids: quinine (QN) and cinchonidine (CND), representing the first report of MCCs combining two major types of antimalarial drugs.

The majority of patients and medical students experience some form of psychological trauma or adversity across their life course. All forms of trauma can be associated with adverse health consequences and can negatively affect learning and professional development. Trauma-informed care (TIC) offers a framework to address and mitigate these consequences and promote safety and health. The Substance Abuse and Mental Health Services Administration describes 6 domains of TIC: safety; trust and transparency; peer support; collaboration and mutuality; empowerment, voice, and choice; and cultural, historic, and gender issues. At present, TIC is not taught routinely in undergraduate medical education (UME)-a crucial educational gap given that UME grounds the development of key perspectives and practices that students use throughout their careers. Further, given the prevalence of preexisting trauma among learners and the likelihood of new traumatic exposures during training, medical schools' processes, practices, and learning environments may risk exacerbating or even causing trauma. To address this educational need and support students and their future patients, the authors propose a trauma-informed medical education (TIME) framework. TIME informs medical schools' curricular content and educational context. In UME, curricular content should address trauma epidemiology, physiology, and effects; trauma-informed clinical skills including sensitive communication and physical exam techniques; and trauma-informed self-care techniques including education on organizational resources, how to elicit supports, and personal self-care practices. A trauma-informed educational context encompasses curricular development, including student-faculty coproduction of educational content; curricular delivery, including faculty development on TIC principles; and learning environment, including trauma-informed educational practices, medical student advising, institutional policies, and recruitment. TIME offers practical strategies to support teaching, learning, educational administration, and professional development and aims to inspire new strategies for effective learner and faculty engagement. TIME aims to foster students' development of competency in TIC and promote student engagement, learning, health, and well-being.

As the U.S. health care system changes and technology alters how doctors work and learn, medical schools and their faculty are compelled to modify their curricula and teaching methods. In this article, educational leaders and key faculty describe how the Pathways curriculum was conceived, designed, and implemented at Harvard Medical School. Faculty were committed to the principle that educators should focus on how students learn and their ability to apply what they learn in the evaluation and care of patients. Using the best evidence from the cognitive sciences about adult learning, they made major changes in the pedagogical approach employed in the classroom and clinic. The curriculum was built upon 4 foundational principles: to enhance critical thinking and provide developmentally appropriate content; to ensure both horizontal integration between courses and vertical integration between phases of the curriculum; to engage learners, foster curiosity, and reinforce the importance of student ownership and responsibility for their learning; and to support students' transformation to a professional dedicated to the care of their patients and to their obligations for lifelong, self-directed learning.The practice of medicine is rapidly evolving and will undoubtedly change in multiple ways over the career of a physician. By emphasizing personal responsibility, professionalism, and thinking skills over content transfer, the authors believe this curriculum will prepare students not only for the first day of practice but also for an uncertain future in the biological sciences, health and disease, and the nation's health care system, which they will encounter in the decades to come.

This paper is a partial response to the intuitive claim that hostility to “Zionists” is not hostility to Jews and so is not antisemitic. It examines ways in which the terms “Zionist” and “Zionism” themselves feature in antisemitic text and discourse. It argues that antisem­itism should be understood as a complex phenomenon that is observable in the social world only with some difficulty, and that understanding should begin in a consideration of that observation data. This paper is critical of the opposite method, which sees the observ­able world only through pre-existing a priori concepts; an example of this is the construction of the concept of Zionism as essentially racist. This method treats observable phenomena, like racism, as inevitable manifestations of the predetermined concept, Zionism. Zionism, and its relationship to racism, should be understood after observing their actuality in the world, not as a priori definitions, which then structure what is observed. Much under­standing of Zionism therefore adds a methodological double standard to the double stan­dards of judgment, which have already been well described. The paper draws on a number of case studies, that is, actualizations of Zionism and antisemitism in the existing world: the opposition to David Unterhalter’s nomination to the Constitution Court in South Africa; the antizionist construction of Zionism as racism without the consent or the col­laboration of people who self-identify as Zionists; statements circulating in academia that define the communities of scholarship and of morality in ways that exclude most Jews; the designation of Israel as apartheid. The paper concludes with a word on how antizionist nostalgia resists facing the material changes to Jewish life, which were enforced during the twentieth century.

Introduction Trauma is ubiquitous and associated with negative effects on physical and mental health. Trauma-informed care (TIC) is a framework for mitigating these health effects and improving patients’ engagement with medical care. Despite these clinical benefits, TIC is not routinely taught in undergraduate medical education. Methods We designed a session for first-year medical and dental students to introduce TIC principles and their application in patient care. The session focused on screening for and inquiring about trauma and responding to disclosures of trauma. Using live patient interviews, small-group discussions, and case-based role-plays, the session offered expert instruction and hands-on practice. Students completed pre- and postsession surveys and a 5-month follow-up survey. Students reported their comfort with screening for trauma and responding to disclosures of trauma before and after the session and at 5 months following the session. Results Of the 164 student participants, 76% completed surveys during the session, and 50% completed the follow-up survey. More than one-third (34%) of respondents reported having received at least one disclosure of trauma from a patient within the first 5 months of medical school. Students’ comfort with screening for trauma increased from 30% to 56%, and their comfort with responding to disclosure of trauma increased from 35% to 55%. These improvements persisted on reevaluation at 5 months. Discussion We present a model for teaching trauma-informed communication skills to first-year medical and dental students. The intervention significantly increased students’ comfort level and self-reported clinical skills, and benefits persisted at 5 months.

Exonic DNA sequence variants in the Tbk1 gene associate with both sporadic and familial amyotrophic lateral sclerosis (ALS). Here, we examine functional defects in 25 missense TBK1 mutations, focusing on kinase activity and protein-protein interactions. We identified kinase domain (KD) mutations that abolish kinase activity or display substrate-specific defects in specific pathways, such as innate immunity and autophagy. By contrast, mutations in the scaffold dimerization domain (SDD) of TBK1 can cause the loss of kinase activity due to structural disruption, despite an intact KD. Familial ALS mutations in ubiquitin-like domain (ULD) or SDD display defects in dimerization; however, a subset retains kinase activity. These observations indicate that TBK1 dimerization is not required for kinase activation. Rather, dimerization seems to increase protein stability and enables efficient kinase-substrate interactions. Our study revealed many aspects of TBK1 activities affected by ALS mutations, highlighting the complexity of disease pathogenicity and providing insights into TBK1 activation mechanism.

Variable-hydrate active pharmaceutical ingredients (APIs) are known to form thermodynamically and kinetically stabilized solid phases over a continuous range of nonstoichiometric hydration levels. Some of these forms can be problematic in the production of solid dosage forms (e.g., tablets and capsules), where manufacturing processes can induce changes in the hydration level of the API, resulting in transformations to undesirable solid phases that may affect product quality. In order to improve the development of variable-hydrate APIs for commercial use, reliable methods must be developed to not only measure the hydration levels, but also to probe the influences of water molecules on the molecular-level structures of APIs within dosage formulations. In this study, we examine a Genentech development compound, GNE-A, which is a hydrochloride (HCl) salt of an API that exhibits variable-hydrate behavior. Using a combination of 35Cl solid-state NMR (SSNMR), variable-relative humidity (RH) powder X-ray diffract...

Current safety data affirms enzalutamide does not cause clinically significant liver dysfunction that warrant therapy cessation. Therefore, clinicians should not withhold potentially successful therapy merely for suspected hepatotoxicity or PnC., We report a case of paraneoplastic cholestasis (PnC) coinciding with enzalutamide initiation and masquerading as an enzalutamide‐related adverse event. Current safety data affirms that enzalutamide does not cause clinically significant liver dysfunction. Therefore, clinicians should not withhold potentially successful therapy merely for suspected hepatotoxicity or PnC.

This paper reports on the development and testing of the AzAs (Antizionist Antisemitism) scale: a six-item questionnaire instrument for measuring antisemitic attitudes as articulated in the language of hostility to Israel and its supporters. It is important to be able to recognize and measure this kind of antisemitism because it is often embedded within ostensibly democratic discourse. The identification of this antisemitism is frequently contested even by those who are in broad agreement on the recognition of older forms of antisemitism. The scale contains a balance of protrait and contrait items, and achieved a satisfactory level of internal consistency when piloted on a sample of US-based respondents recruited through the Mechanical Turk crowdsourcing market (N = 122). There appears to be no relationship between scores on the scale and the subjective political position of respondents (as measured on a left-right self-report scale). We suggest that the AzAs scale will be of general use in measuring antizionist antisemitism because (a) it collects several familiar and demonstrably antisemitic ideas expressed in relation to Israel and its supporters and (b) it exhibits good psychometric properties.

Active pharmaceutical ingredients (APIs) can be prepared in many different solid forms and phases that affect their physicochemical properties and suitability for oral dosage forms. The development and commercialization of dosage forms require analytical techniques that can determine and quantify the API phase in the final drug product. 13C solid-state NMR (SSNMR) spectroscopy is widely employed to characterize pure and formulated solid APIs; however, 13C SSNMR experiments on dosage forms with low API loading are often challenging due to low sensitivity and interference from excipients. Here, fast magic angle spinning 1H SSNMR experiments are shown to be applicable for the rapid characterization of low drug load formulations. Diagnostic 1H SSNMR spectra of APIs within tablets are obtained by using combinations of frequency-selective saturation and excitation pulses, two-dimensional experiments, and 1H spin diffusion periods. Selective saturation pulses efficiently suppress the broad 1H SSNMR signals from the most commonly encountered excipients such as lactose and cellulose, allowing observation of high-frequency API 1H NMR signals. 1H SSNMR provides a 1-3 orders of magnitude reduction in experiment time compared to standard 13C SSNMR experiments, enabling diagnostic SSNMR spectra of dilute APIs within tablets to be obtained within minutes. The 1H SSNMR spectra can be used for quantification, provided calibrations are performed on a standard sample with known API loading.

The prevalence of Autism Spectrum Disorder (ASD) is growing rapidly, affecting 1 in 59 children in the United States in 2018. Individuals with ASD currently receive fragmented care that threatens their health and well-being. Challenges of autism care include disconnections between the medical system and school supports, poor care coordination between primary care and specialists, and saturation of neuropsychiatry-based centers' capacity to care for the ASD population. ASD treatment also lacks of a coordinated system of care for patients' multi-system comorbidities. Families are calling for an ASD care delivery system to meet their needs and the needs of their children. To serve people with ASD and their medical and other providers, we propose a coordinated approach to care grounded in primary care. We call the model the "Systematic Network of Autism Primary Care Services (SYNAPSE)." We develop the model by applying the frameworks of "coproduction" of care and chronic disease management. In this Commentary we discuss the model's rationale, underpinnings, and the implications for clinical practice. We advance these ideas to align with policy makers' recognition of the importance of primary care for ASD, as reflected by the most recent Interagency Autism Coordinating Committee (IACC) meeting at the National Institute of Mental Health.

Introduction Burnout is prevalent in health care. As professionals advocate to increase resilience training as a strategy to reduce burnout, few examples exist of practical resilience programs that equip faculty to help students build and sustain well-being over time. Method We developed two straightforward, skills-based resilience exercises. Breaking Down Easy taught individuals to identify personal strengths. My Resilience Practice helped individuals identify strategies to cope with daily stressors. We taught these exercises to international faculty in a train-the-trainer workshop format, at two medical education conferences. Faculty applied the exercises, performed pair-share reflections, and discussed opportunities to introduce the exercises in their own institutions. Postsession surveys evaluated the workshop quality and the exercises' ease of use and applicability. Results Thirty-five faculty and five students participated across two international conferences. Of participants, 83% (33 of 40) completed postsession surveys. On a 5-point Likert scale, participants rated the workshop on average 4.4 for usefulness, 4.6 for applicability, 4.4 for ease of instruction, 4.5 for clarity, and 4.8 for overall quality. Participants found the exercises to be straightforward to use and planned to use them at their institutions with students, residents, and faculty. Discussion Participants found our workshop to be relevant and effective and shared their intention to incorporate these materials into their teaching with medical students, residents, and faculty. Implementing effective programs to build resilience is critical to increasing well-being and reducing burnout. This, in turn, may enhance patient safety and improve health system outcomes.

Imagine this UME Curriculum Committee meeting. After a presentation about the institution's recent challenges and accomplishments, the committee chair requests new ideas for curriculum reform that build upon the institution's successes. A junior faculty member, new to the committee, raises an idea. Longtime educators, prominent scientists, and clinicians nod intently. Then a student offers an idea. Then one of the senior members. An open, reaching conversation about real innovation was just what the chair expected.

Cation-chloride cotransporters (CCCs) regulate the movement of chloride across membranes, controlling physiological processes from cell volume maintenance to neuronal signaling. Human CCCs are clinical targets for existing diuretics and potentially additional indications. Here, we report the X-ray crystal structure of the soluble C-terminal regulatory domain of a eukaryotic potassium-chloride cotransporter, Caenorhabditis elegans KCC-1. We observe a core α/β fold conserved among CCCs. Using structure-based sequence alignment, we analyze similarities and differences to the C-terminal domains of other CCC family members. We find that important regulatory motifs are in less-structured regions and residues important for dimerization are not widely conserved, suggesting that oligomerization and its effects may vary within the larger family. This snapshot of a eukaryotic KCC is a valuable starting point for the rational design of studies of cellular chloride regulation.

No description supplied

Background: Patient-centered care is a core component of medical professionalism. East Asian cultures hold different conceptualizations of medical professionalism than Western cultures. To support patient-centered care, education leaders in Taiwan restructured clinical education and implemented the first longitudinal integrated clerkship (LIC) in East Asia. We aimed to investigate patients’ perceptions of longitudinal relationships with the LIC students within Taiwan’s Confucian cultural and social context.Methods: We invited patients or their family members who were cared for longitudinally by a LIC student to participate in the study. Participating patients or their family members undertook semi-structured interviews. We analyzed data qualitatively using a general inductive approach to identify themes in the patients’ descriptions of their experiences interacting with the LIC students.Results: Twenty-five patients and family members participated in interviews: 16 patients and 9 family members. Qualitative analysis of interview transcripts identified three themes from patients’ experience receiving care from their LIC students: care facilitation, companionship, and empathy. To provide care facilitation, LIC students served as a bridge between the physicians and patients. Students served patients by reminding, consulting, tracking disease progression, and researching solutions for problems. To provide companionship, students accompanied patients interpersonally like a friend or confidant who listens and provides a presence for patients. To provide empathy, patients reported that students showed sincere concern for patients’ experience, feelings, and mood.Conclusion: In our study, Taiwanese patients’ perspectives of LIC students suggested the value of care facilitation, companionship, and empathy. We discuss these themes within the context of Confucian culture and the Taiwanese context of care.

Introduction: This study evaluated noninferiority of darbepoetin alfa versus placebo for overall survival (OS) and progression-free survival (PFS) in anemic patients with NSCLC treated to a 12.0-g/dL hemoglobin (Hb) ceiling. Methods: Adults with stage IV NSCLC expected to receive two or more cycles of myelosuppressive chemotherapy and Hb less than or equal to 11.0 g/dL were randomized 2:1 to blinded 500 mg darbepoetin alfa or placebo every 3 weeks. The primary endpoint was OS; a stratified Cox proportional hazards model was used to evaluate noninferiority (upper confidence limit for hazard ratio [HR] < 1.15). Secondary endpoints were PFS and incidence of transfusions or Hb less than or equal to 8.0 g/dL from week 5 to end of the efficacy treatment period. Results: The primary analysis set included 2516 patients: 1680 were randomized to darbepoetin alfa; 836 to placebo. The study was stopped early per independent Data Monitoring Committee recommendation after the primary endpoint was met with no new safety concerns. Darbepoetin alfa was noninferior to placebo for OS (stratified HR = 0.92; 95% confidence interval [CI]: 0.83.1.01) and PFS (stratified HR = 0.95; 95% CI: 0.87.1.04). Darbepoetin alfa was superior to placebo for transfusion or Hb less than or equal to 8.0 g/dL from week 5 to end of the efficacy treatment period (stratified odds ratio = 0.70; 95% CI: 0.57.0.86; p < 0.001). Objective tumor response was similar between the groups (darbepoetin alfa, 36.4%; placebo, 32.6%). Incidence of serious adverse events was 31.1% in both groups. No unexpected adverse events were observed. Conclusions: Darbepoetin alfa dosed to a 12.0-g/dL Hb ceiling was noninferior to placebo for OS and PFS and significantly reduced odds of transfusion or Hb less than or equal to 8.0 g/dL in anemic patients with NSCLC receiving myelosuppressive chemotherapy. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

Reliable methods for the characterization of drug substances are critical for evaluating stability and bioavailability, especially in dosage formulations under varying storage conditions and usage. Such methods must also give information on the molecular identities and structures of drug substances and any potential byproducts of the formulation process, as well as providing a means of quantifying the relative amounts of these substances. For example, active pharmaceutical ingredients (APIs) are often formulated as ionic salts to improve the pharmaceutical properties of dosage forms; however, exposure of such formulations to elevated temperature and/or humidity can trigger the conversion of an ionic salt of an API to a neutral form with different properties, through a process known as disproportionation. It is particularly challenging to identify changes of pharmaceutical components in solid dosage formulations, which are complex heterogeneous mixtures of the API and excipient components (e.g., binders, d...

Fluoxetine hydrochloride, the active pharmaceutical ingredient (API) in the antidepressant Prozac®, can form cocrystals with numerous organic acid coformers. The solvothermal syntheses of cocrystals with (i) fumaric acid, (ii) benzoic acid, and (iii) succinic acid coformers were first reported by Childs et al. in 2004. Herein, we report the novel mechanochemical syntheses of these cocrystals, and their structural characterization using a combination of powder X-ray diffraction (PXRD) and solid-state NMR (SSNMR) spectroscopy. It is demonstrated that high-purity samples of fluoxetine HCl cocrystals can be synthesized using neat grinding or liquid assisted grinding in a fraction of the time required for analogous solvothermal syntheses. 35Cl SSNMR spectroscopy is used as a primary characterization technique of the materials, providing a spectral fingerprint and unique set of 35Cl electric field gradient (EFG) tensor parameters for each system, due to the extreme sensitivity of the 35Cl EFG tensor to unique hydrogen bonding arrangements about the Cl− anions. It is also demonstrated that first-principles quantum chemical calculations conducted using the DFT-D2* method, which introduces two-body semiempirical dispersion corrections, can be applied to obtain better models of the true molecular-level structures of the API salts than is possible through XRD alone, because of the ability to accurately position hydrogen atoms. The combined use of 35Cl SSNMR spectroscopy, PXRD, and DFT-D2* calculations, may find extensive future use in NMR crystallographic refinements of numerous organic HCl salts, including HCl APIs in bulk forms, cocrystals, and dosage formulations.

We were taken by surprise when we heard about the sudden death of Esti Webman on June 16. Esti was a friend and a scholar of antisemitism. She had been a core colleague in the European Sociological Association Research Network 31 on Ethnic Relations, Racism, and Antisemitism, and had given papers at a number of its meetings and conferences over the years....

The authors argue that Nel Noddings' philosophy, "an ethic of caring," may illuminate how students learn to be caring physicians from their experience of being in a caring, reciprocal relationship with teaching faculty. In her philosophy, Noddings acknowledges two important contextual continuities: duration and space, which the authors speculate exist within longitudinal integrated clerkships. In this Perspective, the authors highlight core features of Noddings' philosophy and explore its applicability to medical education. They apply Noddings' philosophy to a subset of data from a previously published longitudinal case study to explore its "goodness of fit" with the experience of eight students in the 2012 cohort of the Columbia-Bassett longitudinal integrated clerkship. In line with Noddings' philosophy, the authors' supplementary analysis suggests that students (1) recognized caring when they talked about "being known" by teaching faculty who "cared for" and "trusted" them; (2) responded to caring by demonstrating enthusiasm, action, and responsibility toward patients; and (3) acknowledged that duration and space facilitated caring relations with teaching faculty. The authors discuss how Noddings' philosophy provides a useful conceptual framework to apply to medical education design and to future research on caring-oriented clinical training, such as longitudinal integrated clerkships.

SummaryBackground The Harvard Medical School Cambridge Integrated Clerkship longitudinal cancer curriculum directly facilitates students’ engagement with cancer patients to develop a comprehensive understanding of the disease and the patient's experience of illness. Third-year medical students follow newly diagnosed cancer patients over the course of a year, across all disciplines, and make formal presentations to a multidisciplinary forum at the end of the year. The aim of the study was to discover which aspects of longitudinal care were most meaningful to the students themselves. Method Researchers performed a qualitative thematic analysis of students’ presentations. Basing the analysis on principles of grounded theory, researchers took an inductive approach using the constant comparative method to discover core themes and to cluster themes into encompassing domains. Result Researchers identified 33 individual themes among 60 presentations, reflecting five major domains: clinical issues; patient characteristics; systems problems; psychosocial response to cancer; and existential decision making. Conclusions In this qualitative study of students’ year-end final presentations after a year of cancer care experiences, two areas stood out: students perceived the complexities of medical decision making and students considered the impact of psychosocial factors on patients facing this disease over time. Which aspects of longitudinal care were most meaningful to the students(?)

In this work, we show how to obtain efficient dynamic nuclear polarization (DNP) enhanced 35Cl solid-state NMR (SSNMR) spectra at 9.4 T and demonstrate how they can be used to characterize the molecular-level structure of hydrochloride salts of active pharmaceutical ingredients (APIs) in both bulk and low wt% API dosage forms. 35Cl SSNMR central-transition powder patterns of chloride ions are typically tens to hundreds of kHz in breadth, and most cannot be excited uniformly with high-power rectangular pulses or acquired under conditions of magic-angle spinning (MAS). Herein, we demonstrate the combination of DNP and 1H–35Cl broadband adiabatic inversion cross polarization (BRAIN-CP) experiments for the acquisition of high quality wideline spectra of APIs under static sample conditions, and obtain signals up to 50 times greater than in spectra acquired without the use of DNP at 100 K. We report a new protocol, called spinning-on spinning-off (SOSO) acquisition, where MAS is applied during part of the polarization delay to increase the DNP enhancements and then the MAS rotation is stopped so that a wideline 35Cl NMR powder pattern free from the effects of spinning sidebands can be acquired under static conditions. This method provides an additional two-fold signal enhancement compared to DNP-enhanced SSNMR spectra acquired under purely static conditions. DNP-enhanced 35Cl experiments are used to characterize APIs in bulk and dosage forms with Cl contents as low as 0.45 wt%. These results are compared to DNP-enhanced 1H–13C CP/MAS spectra of APIs in dosage forms, which are often hindered by interfering signals arising from the binders, fillers and other excipient materials.

Herein, we demonstrate the use of 35Cl solid-state NMR (SSNMR) at moderate (9.4 T) and high (21.1 T) magnetic field strengths for the structural fingerprinting of hydrochloride (HCl) salts of active pharmaceutical ingredients (APIs) and several polymorphs, in both bulk and dosage forms. These include salts of metformin, diphenhydramine, nicardipine, isoxsuprine and mexiletine (the crystal structure of a mexiletine polymorph is reported herein). Signal-enhancing pulse sequences utilizing frequency-swept pulses and broadband cross polarization were employed to significantly decrease experimental times. In most cases, powder X-ray diffraction (pXRD) patterns and 13C SSNMR spectra are not useful for characterizing the APIs in dosage forms, due to interfering signals from the excipients (e.g., fillers and binders). However, it is demonstrated that 35Cl SSNMR can be used independently to fingerprint individual APIs and to detect the nature of the solid phases in the dosage forms without interference from the excipient. 35Cl SSNMR experiments were also conducted on systems with multiple polymorphs (i.e., isoxsuprine HCl and mexiletine HCl), and the solid phases of these APIs in their dosage forms are identified. 35Cl EFG tensors obtained from plane-wave DFT calculations on model systems are also presented and discussed in the context of their relationship to the local hydrogen-bonding environments of the chloride ions. This methodology shows great promise for identification of solid phases and detection of polymorphs and impurities, which are matters of importance for quality assurance in the pharmaceutical industry.

The prevalence of atrial fibrillation (AF) increases with age, with about one-third of patients with AF older than 80 years. Rate control is the preferable strategy using beta blockers or, if left ventricular systolic function is intact, non-dihydropyridine calcium channel blockers. A more lenient heart rate target (2DS2-VASC score greater than 2; since age over 75 years is assigned 2 points, most such patients should be anticoagulated. Of concern in ascertaining the risk:benefit ratio of anticoagulation is that the study cohorts in AF anticoagulant trials are younger than community AF patients. This chapter includes a table listing the dose reductions required for the newer direct acting oral anticoagulants (dabigatran, rivaroxaban, and apixaban). In general, clinical practitioners overestimate the fall risk in their elderly patients, denying them the benefit of anticoagulation. The HAS-BLED and HEMOR2HAGES scores can aid in determining bleeding risk at elderly age.