Exploring Models of Exposure to Primary Care Careers in Training: a Narrative Review.

Multiple models of clinical exposure to primary care exist within undergraduate medical education (UME) and graduate medical education (GME). In this narrative review, we explore the evidence behind these different models of exposure, their alignment with positive promoters of primary care careers, and the pros and cons of each. Without positive exposure to primary care during training, sustaining the future primary care work force becomes increasingly challenging. Here, we explore multiple models of clinical exposure in UME, including longitudinal integrated clerkships, primary care tracks, and primary care clerkships. Within GME, we will review the impact of primary care tracks, Area Health Education Centers, block scheduling models, and continuity clinic scheduling models. The goal of this narrative review is to allow educators to think broadly and intentionally about the array of models to develop positive primary care experiences and perceptions in training, ultimately sustaining the primary care workforce.

The Burden of Pediatric Visual Impairment and Ocular Diagnoses in Barbados.

Visual impairment (VI) negatively affects a child's quality of life. The prevalence of VI in the Caribbean is nearly three times higher than in the United States, but the causes remain uncertain. This study leverages Barbados' unique eye care system to survey the eye diseases and VI prevalence in Barbadian children. Medical records of all patients aged <19 years who received ophthalmic care in Barbados' two public eye care centers between January and December 2019 were reviewed, capturing the entirety of public pediatric eye care within the study period. Age at the first visit to the clinic and at the final visit in 2019, sex, best-corrected visual acuity (BCVA), past medical history, and clinical diagnoses were extracted and analyzed. VI was defined as a BCVA of 6/12 or worse in the better-seeing eye. There were 3278 patient records with a mean age at the first visit of 7.8 ± 3.9 years. There were 80 (2.4%) children with VI, 62.5% of which were attributed to amblyopia. A total of 94% of VI was preventable or treatable. The most common diagnoses were refractive error (87.5%), strabismus (27.5%), and allergic eye disease (20.0%). Amblyopia is the major cause of pediatric VI in Barbados and is largely avoidable.

Management and control of yellow fever virus: Brazilian outbreak January-April, 2018.

Yellow fever virus (YFV) has a long history of causing human disease. Today, YFV is persevered in jungle environments with occasional sporadic human outbreaks in South America and periodic intermediate human transmissions with occasional urban outbreaks in sub-Saharan Africa. The ever-present risk of outbreak is primarily controlled for via vaccination coverage to vulnerable human populations. Global vaccine supplies have been strained in the setting of recent outbreaks in Africa and Brazil. The increasingly global community of today has placed an ever-growing tension on the management and control of YFV. A historic outbreak of YFV in Brazil is tracked from January to April 2018 using the International Society for Infectious Diseases' (ISID) Program for Monitoring Emerging Diseases (ProMed). A narrative summary is generated from the review of 29 ProMed reports pertaining to the key words yellow fever and Brazil. Significant topics addressed include urban proximity, vaccination dose sparing with 1/5th standard dose, international travellers, epizootic trends, vaccine hesitancy, and mass immunisation campaigns. These topics are reviewed in detail for the current outbreak in comparison to previous outbreaks. Through close attention to these topics the degree and extent of the current outbreak was attenuated.

Factors contributing to and strategies to combat emerging arboviruses.

Less than half a century ago infectious diseases appeared to be destined to be extinguished via as a culmination of medical triumphs. As focus turned towards combating non-communicable diseases, emerging and re-emerging diseases (EIDs) have bloomed from those ashes. Five epidemic mosquito-borne arboviruses (Yellow Fever virus (YFV), Dengue virus, West Nile virus, Chikungunya virus, and Zika virus) have emerged in the recent past. Arboviruses are of the utmost importance with respect to EIDs due to intensive growth of globalisation, arthropod urban fitness/adaption, and environmental changes. We focus on recent outbreaks of the arthropod borne viruses (arboviruses) Zika virus and YFV. Factors contributing to the blossoming of EIDs (environmental, globalisation, and urbanisation) and combating strategies (surveillance, containment, and prevention) will be discussed. Specifically, Zika virus and YFV will be used in the context of these factors and strategies. YFV is discussed in detail as it pertains to these factors and strategies in the United States (US), 2017 Brazil Outbreak, 2016 Africa Outbreak, and global risk. Vigilance is needed to focus on, prevent, and control the current and next arbovirus EIDs.

Reporting quality of randomised controlled trial abstracts among high-impact general medical journals: a review and analysis.

OBJECTIVE: The aim of this study was to assess adherence to the Consolidated Standards of Reporting Trials (CONSORT) for Abstracts by five high-impact general medical journals and to assess whether the quality of reporting was homogeneous across these journals. DESIGN: This is a descriptive, cross-sectional study. SETTING: Randomised controlled trial (RCT) abstracts in five high-impact general medical journals. PARTICIPANTS: We used up to 100 RCT abstracts published between 2011 and 2014 from each of the following journals: The New England Journal of Medicine (NEJM), the Annals of Internal Medicine (Annals IM), The Lancet, the British Medical Journal (The BMJ) and the Journal of the American Medical Association (JAMA). MAIN OUTCOME: The primary outcome was per cent overall adherence to the 19-item CONSORT for Abstracts checklist. Secondary outcomes included per cent adherence in checklist subcategories and assessing homogeneity of reporting quality across the individual journals. RESULTS: Search results yielded 466 abstracts, 3 of which were later excluded as they were not RCTs. Analysis was performed on 463 abstracts (97 from NEJM, 66 from Annals IM, 100 from The Lancet, 100 from The BMJ, 100 from JAMA). Analysis of all scored items showed an overall adherence of 67% (95% CI 66% to 68%) to the CONSORT for Abstracts checklist. The Lancet had the highest overall adherence rate (78%; 95% CI 76% to 80%), whereas NEJM had the lowest (55%; 95% CI 53% to 57%). Adherence rates to 8 of the checklist items differed by >25% between journals. CONCLUSIONS: Among the five highest impact general medical journals, there is variable and incomplete adherence to the CONSORT for Abstracts reporting checklist of randomised trials, with substantial differences between individual journals. Lack of adherence to the CONSORT for Abstracts reporting checklist by high-impact medical journals impedes critical appraisal of important studies. We recommend diligent assessment of adherence to reporting guidelines by authors, reviewers and editors to promote transparency and unbiased reporting of abstracts.

Vaccine hesitancy: More than a movement.

Vaccines are some of if not the most successful public health endeavors ever put into practice. Countless lives have been saved and the occurrences of vaccine preventable diseases are at a fraction of the rate experienced before vaccines. Vaccines and the realization of their compulsory scheduling are highly studied, safe, and purposeful. Despite these realities, there are an alarming number of parents who do not permit the vaccination of their children as scheduled. This is known in the health community as vaccine hesitancy and commonly portrayed in popular media as anti-vaccination sediment. This analysis opens with the topic as it was addressed during a September 2015 debate for the Republic Party's 2016 presidential nomination. Some key historical aspects of vaccine hesitancy are presented. This history leads to a description of the 2014-2015 measles outbreak in California. The factors that aide in the recruitment of under vaccination are then explored. Finally, select strategies to control, combat, and potentially attenuate vaccine hesitancy are presented.

Severe malaria in Battambang Referral Hospital, an area of multidrug resistance in Western-Cambodia: a retrospective analysis of cases from 2006-2009.

BACKGROUND: Despite recent malaria containment and control efforts leading to reduced incidence, Cambodia remains endemic for both Plasmodium vivax and multidrug-resistant Plasmodium falciparum malaria. Little has been reported in the peer-reviewed literature regarding the burden of severe malaria (SM) in Cambodia. METHODS: Medical records for all patients admitted to the Battambang Referral Hospital (BRH) with an admitting or discharge diagnosis of SM from 2006 to 2009 (suspected SM cases) were reviewed. Those meeting the case definition of SM according to retrospective chart review and investigator assessment of probable cases, based on published national guidelines available at the time, were analysed for trends in demographics, mortality and referral patterns. RESULTS: Of the 537 suspected SM cases at BRH during the study period, 393 (73%) met published WHO criteria for SM infection. Despite limited diagnostic and treatment facilities, overall mortality was 14%, with 7% mortality in children 14 and under, but 19% in adults (60% of cases). Cerebral malaria with coma was relatively rare (17%), but mortality was disproportionately high at 35%. Mean time to hospital presentation was five days (range one to 30 days) after onset of symptoms. While patients with delays in presentation had worse outcomes, there was no excess mortality based on treatment referral times, distance travelled or residence in artemisinin-resistance containment (ARC) Zone 1 compared to Zone 2. CONCLUSIONS: Despite limitations in diagnosis and treatment, and multiple confounding co-morbidities, mortality rates at BRH were similar to reports from other countries in the region. Interventions to improve access to early diagnosis and effective treatment, combined with modest improvements in intensive care, are likely to reduce mortality further. Patients referred from Zone 1 did not have excess mortality compared to Zone 2 ARC areas. A steep decrease in SM cases and deaths observed in the first half of 2009 has since continued, indicating some success from containment efforts despite the emergence of artemisinin resistance in this area.

Artesunate: investigational drug for the treatment of severe falciparum malaria in Hawai'i.

INTRODUCTION: There are hundreds of millions of cases of malaria each year worldwide resulting in a million deaths. These deaths are mostly due to Plasmodium falciparum. The only Federal Drug Administration approved treatment for severe malaria is intravenous quinidine gluconate. Intravenous quinidine is increasingly unavailable in the United States. In 2007, the Center for Disease Control and Prevention implemented an investigational new drug protocol to allow the use of intravenous artesunate for cases of severe malaria in the United States. The authors present such a case treated under this protocol at Tripler Army Medical Center, Hawai'i. CASE REPORT: A 49-year-old man presented to Tripler Army Medical Center, Hawai'i in February 2009 with a one-month history of fever, chills, and weight loss. He recently travelled to multiple malaria endemic areas. Physical examination was significant for fever and prostration. Laboratory studies revealed anemia, thrombocytopenia, and a high parasite load of Plasmodium falciparum. A strategic network was activated to obtain and administer intravenous artesunate. His condition rapidly improved as his parasitemia cleared. He was discharged after six days with no adverse medication effects and full recovery upon six-month follow-up. DISCUSSION: Our patient met the criteria for severe Plasmodium falciparum malaria. He was immediately treated with intravenous artesunate and manifested a quick and durable response to therapy. At present, intravenous artesunate is awaiting Federal Drug Administration approval but available via a strategic network controlled by the Centers for Disease Control and Prevention. This case highlights a common delay in diagnosis, importance of optimal prophylaxis, and attention to travel history as they relate to the development of severe malaria.

Treatment of akinetic mutism with intramuscular olanzapine: a case series.

Akinetic mutism is a wakeful state of severe apathy and paucity of volitional movement. Evidence indicates a possible dopaminergic hypofunction within the anterior cingulate cortex. The authors present three cases of acute onset akinetic mutism successfully treated with intramuscular olanzapine.

The highly cooperative folding of small naturally occurring proteins is likely the result of natural selection.

To illuminate the evolutionary pressure acting on the folding free energy landscapes of naturally occurring proteins, we have systematically characterized the folding free energy landscape of Top7, a computationally designed protein lacking an evolutionary history. Stopped-flow kinetics, circular dichroism, and NMR experiments reveal that there are at least three distinct phases in the folding of Top7, that a nonnative conformation is stable at equilibrium, and that multiple fragments of Top7 are stable in isolation. These results indicate that the folding of Top7 is significantly less cooperative than the folding of similarly sized naturally occurring proteins, suggesting that the cooperative folding and smooth free energy landscapes observed for small naturally occurring proteins are not general properties of polypeptide chains that fold to unique stable structures but are instead a product of natural selection.

Creating a learning culture for quality and leadership. Panel discussion.

Today's fast-changing health care environment requires adept and knowledgeable leadership. Leaders must develop consistent standards across the organization to ensure quality and operational excellence. This will require the adoption of new skill sets and behaviors by clinicians and other employees. Leaders, too, will need to develop new skills and behaviors to effectively implement positive change. Health Forum convened a group of health care executives and industry experts July 13 in San Francisco to examine how hospital leaders can build and disseminate a consistent quality culture throughout the organization. Health Forum would like to thank all of the participants for their open and candid discussion, as well as GE Healthcare for sponsoring this event.

Craniofacial resections in the elderly: an outcome study.

OBJECT: The elderly population is increasing in number and is healthier now than in the past. The purpose of this study was to examine complications and outcomes following craniofacial resection (CFR) in elderly patients and to compare findings with those of a matched younger cohort. METHODS: All patients 70 years of age or older undergoing CFR at the M.D. Anderson Cancer Center (elderly group) between December 1992 and July 2003 were identified by examining the Department of Neurosurgery database. A random cohort of 28 patients younger than 70 years of age (control group) was selected from the overall population of patients who underwent CFR. There were 28 patients ranging in age from 70 to 84 years (median 74 years). Major local complications occurred in seven elderly patients (25%) and in six control patients (21%) (p = 0.75), and major systemic complications occurred in nine elderly patients (32%) and in three control patients (11%) (p = 0.05). There was one perioperative death in both groups of patients. The median duration of disease-specific survival for the elderly patients was not reached (mean 6.8 years); however, it was 8.3 years for control patients (p = 0.24). Predictors of poorer overall survival from a multivariate analysis of the elderly group included presence of cardiac disease (p = 0.005), a major systemic perioperative complication (p = 0.03), and a preoperative Karnofsky Performance Scale score less than 100 (p = 0.04). CONCLUSIONS: In this study of elderly patients who underwent CFR, there was no difference in disease-specific survival when compared with a matched cohort of younger patients. There was, however, an increased incidence of perioperative major systemic complications in the elderly group.

Sebaceous carcinoma ex-pleomorphic adenoma: a rare phenotypic occurrence.

Primary sebaceous carcinoma of salivary glands is a rare entity with approximately 22 de novo documented cases. Similar tumor arising in a benign mixed tumor has only been reported once. We report a second case of sebaceous carcinoma in a pleomorphic adenoma and discuss the clinicopathologic features, histogenesis, and the differential diagnosis of this unusual tumor.

Contributions of amino acid side chains to the kinetics and thermodynamics of the bivalent binding of protein L to Ig kappa light chain.

Protein L is a bacterial surface protein with 4-5 immunoglobulin (Ig)-binding domains (B1-B5), each of which appears to have two binding sites for Ig, corresponding to the two edges of its beta-sheet. To verify these sites biochemically and to probe their relative contributions to the protein L-Ig kappa light chain (kappa) interaction, we compared the binding of PLW (the Y47W mutant of the B1 domain) to that of mutants designed to disrupt binding to sites 1 and 2, using gel filtration, BIAcore surface plasmon resonance, fluorescence titration, and solid-phase radioimmunoassays. Gel filtration experiments show that PLW binds kappa both in 1:1 complexes and multivalently, consistent with two binding sites. Covalent dimers of the A20C and V51C mutants of PLW were prepared to eliminate site 1 and site 2 binding, respectively; both the A20C and V51C dimers bind kappa in 1:1 complexes and multivalently, indicating that neither site 1 nor site 2 is solely responsible for kappa binding. The A20R mutant was designed computationally to eliminate site 1 binding while preserving site 2 binding; consistent with this design, the A20R mutant binds kappa in 1:1 complexes but not multivalently. To probe the contributions of amino acid side chains to binding, we prepared 75 point mutants spanning nearly every residue of PLW; BIAcore studies of these mutants revealed two binding-energy "hot spots" consistent with sites 1 and 2. These data indicate that PLW binds kappa at both sites with similar affinities (high nanomolar), with the strongest contributions to the binding energy from Tyr34 (site 2) and Tyr36 (site 1). Compared to other protein-protein complexes, the binding is insensitive to amino acid substitutions at these sites, consistent with the large number of main chain interactions relative to side chain interactions. The strong binding of protein L to Ig kappa light chains of various species may result from the ambidextrous binding of the B1-B5 domains and the unimportance of specific side chain interactions.

A large scale test of computational protein design: folding and stability of nine completely redesigned globular proteins.

A previously developed computer program for protein design, RosettaDesign, was used to predict low free energy sequences for nine naturally occurring protein backbones. RosettaDesign had no knowledge of the naturally occurring sequences and on average 65% of the residues in the designed sequences differ from wild-type. Synthetic genes for ten completely redesigned proteins were generated, and the proteins were expressed, purified, and then characterized using circular dichroism, chemical and temperature denaturation and NMR experiments. Although high-resolution structures have not yet been determined, eight of these proteins appear to be folded and their circular dichroism spectra are similar to those of their wild-type counterparts. Six of the proteins have stabilities equal to or up to 7kcal/mol greater than their wild-type counterparts, and four of the proteins have NMR spectra consistent with a well-packed, rigid structure. These encouraging results indicate that the computational protein design methods can, with significant reliability, identify amino acid sequences compatible with a target protein backbone.

Characterization of laryngopharyngeal reflux in patients with premalignant or early carcinomas of the larynx.

BACKGROUND: An association between laryngopharyngeal reflux (LPR) and laryngeal carcinoma has been suggested, but remains unproven. The current pilot study was performed to determine the incidence of LPR among patients with early laryngeal carcinomas or dysplasia and to examine the associations between levels of LPR and histologic stage, smoking status, the symptom of heartburn, and body position during reflux episodes. METHODS: Behavioral and 24 hour pH monitoring data were prospectively acquired and analyzed for 40 previously untreated adults with dysplasia, T1 or T2 laryngeal carcinomas. RESULTS: Eighty-five percent of patients had LPR. No significant association was shown between the level of LPR and histologic stage or smoking status. Heartburn did not predict LPR. The incidence of LPR in the upright body position was 91%, compared with 9% in the supine position, among patients with LPR. CONCLUSIONS: When compared to available normative data, the current findings show a high incidence of LPR in patients with premalignant and early laryngeal cancer. These findings highlight the need for a matched-control study evaluating LPR as a potential predisposing factor for laryngeal carcinoma.

Molecular analysis of chromosome 16q regions in dermal analogue tumors of salivary glands: a genetic link to dermal cylindroma?

Dermal analogue tumor, an uncommon subtype of basal cell monomorphic adenoma of the parotid gland, has a remarkable clinical and histologic resemblance to dermal cylindroma. Molecular studies of familial and sporadic cylindromas have shown frequent alterations at chromosome 16q12-13 that have recently been found to house the cylindromatosis gene (CYLD). To determine the involvement of the chromosome 16q12-13 region in dermal analogue tumors, we performed loss of heterozygosity analysis using microsatellite markers flanking the cylindromatosis gene locus in 21 sporadic dermal analogue salivary tumors and 12 salivary and dermal lesions from two sisters. Loss of heterozygosity was identified in 17 (80.9%) of the 21 sporadic tumors and in nine of the 12 dermal and salivary gland dermal analogue tumors from the two sisters; a parathyroid adenoma from one sister and two lymphoepithelial lesions from the second sister showed no microsatellite alterations. Microsatellite instability was only identified in three sporadic tumors at marker D16S308. Markers D16S409 (centromeric), D16S541, and D16S308 (telomeric) to the CYLD gene showed the highest incidence of loss of heterozygosity (>65%). The minimally deleted region was flanked proximally by marker D16S389 and distally by marker D16S419 and spanned the 771.5-megabase fragment that included the CYLD locus. We conclude that dermal analogue tumor and cylindroma share similar incidence of alterations at the 16q12-13 region, supporting a common molecular origin.