Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19
European Journal of Allergy and Clinical Immunology
Connecting tobacco users in the primary care setting to comprehensive tobacco treatment: a quality improvement initiative
JOURNAL OF PUBLIC HEALTH-HEIDELBERG
Qualitative Assessment of Rapid System Transformation to Primary Care Video Visits at an Academic Medical Center.
Annals of internal medicine
Reinvigorating the clinical examination for the 21st century.
Polish archives of internal medicine
2019; 129 (12): 907–12
The coronavirus disease 2019 pandemic spurred health systems across the world to quickly shift from in-person visits to safer video visits.To seek stakeholder perspectives on video visits' acceptability and effect 3 weeks after near-total transition to video visits.Semistructured qualitative interviews.6 Stanford general primary care and express care clinics at 6 northern California sites, with 81 providers, 123 staff, and 97 614 patient visits in 2019.Fifty-three program participants (overlapping roles as medical providers [n = 20], medical assistants [n = 16], nurses [n = 4], technologists [n = 4], and administrators [n = 13]) were interviewed about video visit transition and challenges.In 3 weeks, express care and primary care video visits increased from less than 10% to greater than 80% and from less than 10% to greater than 75%, respectively. New video visit providers received video visit training and care quality feedback. New system workflows were created to accommodate the new visit method.Nine faculty, trained in qualitative research methods, conducted 53 stakeholder interviews in 4 days using purposeful (administrators and technologists) and convenience (medical assistant, nurses, and providers) sampling. A rapid qualitative analytic approach for thematic analysis was used.The analysis revealed 12 themes, including Pandemic as Catalyst; Joy in Medicine; Safety in Medicine; Slipping Through the Cracks; My Role, Redefined; and The New Normal. Themes were analyzed using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework to identify critical issues for continued program utilization.Evaluation was done immediately after deployment. Although viewpoints may have evolved later, immediate evaluation allowed for prompt program changes and identified broader issues to address for program sustainability.After pandemic-related systems transformation at Stanford, critical issues to sustain video visit long-term viability were identified. Specifically, technology ease of use must improve and support multiparty videoconferencing. Providers should be able to care for their patients, regardless of geography. Providers need decision-making support with virtual examination training and home-based patient diagnostics. Finally, ongoing video visit reimbursement should be commensurate with value to the patients' health and well-being.Stanford Department of Medicine and Stanford Health Care.
View details for DOI 10.7326/M20-1814
View details for PubMedID 32628536
The Outpatient Physical Examination
MEDICAL CLINICS OF NORTH AMERICA
2018; 102 (3): 465-+
At its most fundamental level, the clinical encounter between a patient and their doctor seeks to solve a mystery. Clinicians uncover clues through the history, physical examination, and ancillary tests to arrive at a diagnosis and develop a management plan. Despite advances in technology, the majority of clinical diagnoses are still reached through the history and physical examination without the use of laboratory and imaging tests. However, in the modern American hospital, clinicians spend as little as 12% of their time in direct contact with patients and their families. This has led to a decline in clinical examination skills and contributes to diagnostic error. There is a growing movement to return clinicians and trainees back to the bedside. In 2017, we formed the Society of Bedside Medicine to encourage innovation, education, and research on the role of the clinical encounter in 21st century medicine. Over the last 3 years, we have embraced the following 6 strategies to reinvigorate the practice of the clinical examination: 1) be present with the patient; 2) practice an evidence‑based approach to the physical exam; 3) create opportunities for intentional practice of the physical exam; 4) recognize the power of the physical examination beyond diagnosis; 5) use point‑of‑care technology to aid in diagnosis and reinforce skills; and 6) seek and provide specific feedback on physical examination skills. By employing these strategies in both teaching and practice, clinicians can maximize the value of time spent with patients and renew the importance of the clinical examination in 21st century practice.
View details for DOI 10.20452/pamw.15073
View details for PubMedID 31777402
The Five-Minute Moment.
American journal of medicine
2016; 129 (8): 792-795
The physical examination in the outpatient setting is a valuable tool. Even in settings where there is lack of evidence, such as the annual physical examination of an asymptomatic adult, the physical examination is beneficial for the physician-patient relationship. When a patient has specific symptoms, the physical examination-in addition to a thorough history-can help narrow down, or in many cases establish, a diagnosis. In a time where imaging and laboratory tests are easily available, but are expensive and can be invasive, a skilled physical examination remains an important component of patient evaluation.
View details for PubMedID 29650068
Conceptual basis and clinical rationale for the development of a multidisciplinary weight management center.
International journal of obesity supplements
2012; 2: S43-S46
In today's hospital and clinic environment, the obstacles to bedside teaching both for faculty and trainees are considerable. As Electronic Health Records (EHR) systems become increasingly prevalent, trainees are spending more time performing patient care tasks from computer workstations, limiting opportunities to learn at the bedside. Physical examination skills are rarely emphasized and low confidence levels, especially in junior faculty, pose additional barriers to teaching the bedside exam.
View details for DOI 10.1016/j.amjmed.2016.02.020
View details for PubMedID 26972793
Conditional telomerase induction causes proliferation of hair follicle stem cells
2005; 436 (7053): 1048-1052
Overweight (body mass index (BMI) 25 kg m(-2)) or obesity (BMI 30>kg m(-2)) affects more than two-thirds of Americans. Overweight and obesity are commonly associated with multiple coexisting conditions, such as hypertension, diabetes, dyslipidemia, cardiovascular disease, obstructive sleep apnea and cancer. Lifestyle modification can induce a modest weight loss, which is associated with the prevention or improvement of many of these comorbidities. A combination of diet, exercise and behavioral therapy is considered the cornerstone of treatment for all overweight and obese individuals. As the etiology and therapy of obesity is complex, what is needed for these patients is a multidisciplinary clinic where specialists from different disciplines share their knowledge and participate in the treatment of the obese patient.
View details for PubMedID 25018870
Constitutive telomerase expression promotes mammary carcinomas in aging mice
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2002; 99 (12): 8191-8196
TERT, the protein component of telomerase, serves to maintain telomere function through the de novo addition of telomere repeats to chromosome ends, and is reactivated in 90% of human cancers. In normal tissues, TERT is expressed in stem cells and in progenitor cells, but its role in these compartments is not fully understood. Here we show that conditional transgenic induction of TERT in mouse skin epithelium causes a rapid transition from telogen (the resting phase of the hair follicle cycle) to anagen (the active phase), thereby facilitating robust hair growth. TERT overexpression promotes this developmental transition by causing proliferation of quiescent, multipotent stem cells in the hair follicle bulge region. This new function for TERT does not require the telomerase RNA component, which encodes the template for telomere addition, and therefore operates through a mechanism independent of its activity in synthesizing telomere repeats. These data indicate that, in addition to its established role in extending telomeres, TERT can promote proliferation of resting stem cells through a non-canonical pathway.
View details for DOI 10.1038/nature03836
View details for Web of Science ID 000231263900057
View details for PubMedID 16107853
View details for PubMedCentralID PMC1361120
Phase II study of systemic gemcitabine chemotherapy for advanced unresectable hepatobiliary carcinomas
2001; 48 (39): 783-789
Telomerase is up-regulated in the vast majority of human cancers and serves to halt the progressive telomere shortening that ultimately blocks would-be cancer cells from achieving a full malignant phenotype. In contrast to humans, the laboratory mouse possesses long telomeres and, even in early generation telomerase-deficient mice, the level of telomere reserve is sufficient to avert telomere-based checkpoint responses and to permit full malignant progression. These features in the mouse provide an opportunity to determine whether enforced high-level telomerase activity can serve functions that extend beyond its ability to sustain telomere length and function. Here, we report the generation and characterization of transgenic mice that express the catalytic subunit of telomerase (mTERT) at high levels in a broad variety of tissues. Expression of mTERT conferred increased telomerase enzymatic activity in several tissues, including mammary gland, splenocytes, and cultured mouse embryonic fibroblasts. In mouse embryonic fibroblasts, mTERT overexpression extended telomere lengths but did not prevent culture-induced replicative arrest, thus reinforcing the view that this phenomenon is not related to occult telomere shortening. Robust telomerase activity, however, was associated with the spontaneous development of mammary intraepithelial neoplasia and invasive mammary carcinomas in a significant proportion of aged females. These data indicate that enforced mTERT expression can promote the development of spontaneous cancers even in the setting of ample telomere reserve.
View details for DOI 10.1073/pnas.112515399
View details for Web of Science ID 000176217700071
View details for PubMedID 12034875
View details for PubMedCentralID PMC123043
Murine models of malignant melanoma
MOLECULAR MEDICINE TODAY
2000; 6 (10): 408-410
I kappa B alpha gene therapy in tumor necrosis factor-alpha- and chemotherapy-mediated apoptosis of hepatocellular carcinomas
CANCER GENE THERAPY
2000; 7 (10): 1315-1323
Patients with advanced unresectable hepatobiliary carcinomas have a dismal prognosis. The efficacy of systemic chemotherapy in these patients is negligible and often, in particular in patients with hepatocellular carcinomas, the toxicity of chemotherapy outweighs the potential palliative effect of antineoplastic agents. Gemcitabine is a new anticancer agent with a mild toxicity profile, which has demonstrated antineoplastic activity in many solid tumors. Therefore we investigated the effect of gemcitabine in patients with advanced nonresectable hepatocellular and cholangiocellular carcinomas in a phase II study.Twenty-three patients with cholangiocellular carcinoma and 20 patients with hepatocellular carcinoma were enrolled into the study. Eighteen of the 20 patients with hepatocellular carcinomas had liver cirrhosis. Gemcitabine was administered once weekly over 30 min for 3 consecutive weeks out of every 4 weeks. Patients with cholangiocellular carcinomas received gemcitabine also in the forth week of the first cycle with no rest to the following cycle. Disease status was assessed every 4 weeks.Overall the regimen was well tolerated. The median number of gemcitabine administration was 15 (range, 3-37) in the group of patients with cholangiocellular carcinomas and 7.6 (range, 3-21) in the group of patients with hepatocellular carcinomas. In the group of patients with hepatocellular carcinomas thrombocytopenia was the most frequent side effect (30% grade 3/4). Among the patients with cholangiocellular carcinomas nausea and neutropenia were the most commonly observed side effects. The overall response rate of hepatocellular carcinomas was only 5% and chemotherapy generally did not improve the tumor symptoms of the patients in this group. In contrast, in the group of cholangiocellular carcinomas, seven patients achieved a partial response (overall response rate 30%). Eleven patients with cholangiocellular carcinomas revealed tumor symptoms before the onset of gemcitabine treatment. Seven of these patients developed a treatment related clinical benefit as defined as a relief of tumor symptoms or gain of weight.Our results indicate that the treatment of cholangiocarcinomas with gemcitabine is effective and should be further evaluated in phase III studies. In contrast, palliative chemotherapy with gemcitabine cannot be recommended in patients with hepatocellular carcinoma and liver cirrhosis.
View details for Web of Science ID 000169631600042
View details for PubMedID 11462924
The transcription factor nuclear factor kappaB (NFkappaB) is an essential antagonist of apoptosis during liver regeneration and embryonal development of hepatocytes. Several reports have indicated that NFkappaB may also inhibit the programmed cell death induced by cytokines, ionizing radiation, or cytotoxic drugs in some cancer cell lines. Because hepatocellular carcinomas (HCCs) are one of the most resistant tumors to systemic chemotherapy, we investigated the activation of NFkappaB and the consequence of its inhibition by an IkappaBalpha-super repressor during tumor necrosis factor alpha (TNFalpha)- and chemotherapy-induced apoptosis in HCC cell lines. We demonstrate that both TNFalpha and adriamycin activate NFkappaB in hepatoma cells. Activation of NFkappaB could be blocked through an adenoviral vector expressing the IkappaBalpha super repressor, regardless of the activating agent. Inhibition of NFkappaB enhanced the apoptosis induced by TNFalpha, whereas IkappaBalpha had an anti-apoptotic effect on chemotherapy-induced programmed cell death. A strong inhibition of chemotherapy- and TNFalpha-induced apoptosis by dominant-negative Fas-associated death domain indicated an essential contribution of death receptor-mediated apoptosis. To elucidate the different role of NFkappaB in chemotherapy-induced apoptosis, we investigated the expression of Fas (CD95) and Fas ligand (CD95 ligand), which have been described as important mediators of chemotherapy-induced cell death and as target genes of NFkappaB. However, our investigations demonstrated that in hepatoma cells, the chemotherapy-induced up-regulation of Fas (CD95) and Fas ligand (CD95 ligand) is not transcriptionally mediated through NFkappaB. Thus, other molecular mechanisms must account for the anti-apoptotic effect of IkappaBalpha in adriamycin-induced death of hepatoma cells. In summary, our investigations indicate that the activation of NFkappaB in response to cytotoxic drugs, in contrast to TNFalpha, exerts a pro-apoptotic stimulus rather than an anti-apoptotic function, which has implications for therapy of HCCs.
View details for Web of Science ID 000090073200004
View details for PubMedID 11059688