High-altitude is associated with better short-term survival in critically ill COVID-19 patients admitted to the ICU.

BACKGROUND: Multiple studies have attempted to elucidate the relationship between chronic hypoxia and SARS-CoV-2 infection. It seems that high-altitude is associated with lower COVID-19 related mortality and incidence rates; nevertheless, all the data came from observational studies, being this the first one looking into prospectively collected clinical data from severely ill patients residing at two significantly different altitudes. METHODS: A prospective cohort, a two-center study among COVID-19 confirmed adult patients admitted to a low (sea level) and high-altitude (2,850 m) ICU unit in Ecuador was conducted. Two hundred and thirty confirmed patients were enrolled from March 15th to July 15th, 2020. RESULTS: From 230 patients, 149 were men (64.8%) and 81 women (35.2%). The median age of all the patients was 60 years, and at least 105 (45.7%) of patients had at least one underlying comorbidity, including hypertension (33.5%), diabetes (16.5%), and chronic kidney failure (5.7%). The APACHE II scale (Score that estimates ICU mortality) at 72 hours was especially higher in the low altitude group with a median of 18 points (IQR: 9.5-24.0), compared to 9 points (IQR: 5.0-22.0) obtained in the high-altitude group. There is evidence of a difference in survival in favor of the high-altitude group (p = 0.006), the median survival being 39 days, compared to 21 days in the low altitude group. CONCLUSION: There has been a substantial improvement in survival amongst people admitted to the high-altitude ICU. Residing at high-altitudes was associated with improved survival, especially among patients with no comorbidities. COVID-19 patients admitted to the high-altitude ICU unit have improved severity-of-disease classification system scores at 72 hours.

Clinical and histopathological characterization of a large animal (ovine) model of collagen-induced arthritis.

Collagen induced arthritis (CIA) is the most studied and used rheumatoid arthritis (RA) model in animals, as it shares many pathological and immunological features of the human disease. The aim of this study was to characterize clinical and immunological aspects of the ovine CIA model, and develop lameness and histopathological scoring systems, in order to validate this model for use in therapeutic trials. Sheep were sensitized to bovine type II collagen (BCII), arthritis was induced by injection of bovine collagen type II into the hock joint and the response was followed for two weeks. Clinical signs of lameness and swelling were evident in all sheep and gross thickening of the synovium surrounding the tibiotarsal joint and erosion on the cartilage surface in the arthritic joints. Leucocyte cell counts were increased in synovial fluid and there was synovial hyperplasia, thickening of the intimal layer, inflammation and marked angiogenesis in the synovial tissue. There was a large influx of monocytes and lymphocytes into the synovial tissue, and increased expression of TNF-α and IL-1ß in arthritic intima, angiogenesis and upregulation of VCAM-1. CIA in sheep appears to be an excellent large animal model of RA and has the potential for testing biological therapeutics for the treatment of rheumatoid arthritis.

Reduced emergency department utilization associated with school-based clinic enrollment.

PURPOSE: To evaluate the change in emergency department utilization before and after enrollment in a school-based clinic (SBC). METHODS: This study was a retrospective cohort study comparing emergency department visit rate before and after SBC enrollment based on chart review. An initial cohort of 10- to 15-year-olds who used a local emergency department was divided into two samples: those who had been enrolled in the SBC and those who had not. Emergency department charts were reviewed for visits that occurred during the initial year and two subsequent school years. The change in visit rate for each sample group was measured for each school year evaluated. RESULTS: The initial cohort consisted of 2852 youth, 344 of whom who lived in the high school attendance zone. Of these, the number of students enrolled in both the high school and the SBC was 43; the number enrolled in the high school but not in the clinic was 48. The emergency department visit rate decreased for both groups for each school year evaluated; however, this decrease was significant only for the SBC sample with a 41% to 57% decrease in emergency department utilization, 18% greater than the decrease in students who did not use the SBC. CONCLUSIONS: Accessible, prevention-oriented health care provided in a SBC can decrease the utilization of episodic health care in an emergency department.

Development and validation of the pharmaceutical care satisfaction questionnaire.

The development and validation of a survey instrument to assess consumer satisfaction with pharmacy services is discussed. The Pharmaceutical Care Satisfaction Questionnaire (PCSQ) is a 30-item instrument administered by someone other than the pharmacist that uses a Likert scale to score respondents' answers. The PCSQ is written approximately at a seventh grade reading level. Following initial development, the PCSQ was administered to 360 consumers in ambulatory pharmacies and to 311 patients in a multicenter hyperlipidemia outcomes study. The Cronbach coefficient alpha was .94 for the consumer data, with a 64.8% variance accounted for by the 4-factor solution. A coefficient alpha of .84 was found on all 30 items in the hyperlipidemia study, with a variance of 63.78% in control patients and 60.16% in treatment patients. The PCSQ is easy to administer and score, with minimal cost. Unlike other satisfaction surveys, the PCSQ contains patient evaluations regarding outcomes of care. A primary limitation of the PCSQ is that it is a newly developed instrument that needs to be used in more studies to strengthen its validity.

Instillation of 3% hydrogen peroxide or distilled vinegar in urethral catheter drainage bag to decrease catheter-associated bacteriuria.

Patients with indwelling catheters acquire urinary tractinfections ata rate of 5% perday. After 30 days of catheterization, there is a 78% to 95% incidence of bacteriuria, despite the use of meticulous catheter care. Research studies on reducing the development of bacteriuria have focused on the propagation of bacteria within the catheter drainage bag. This research proposal sought to determine the effects of instillation of 3% hydrogen peroxide versus distilled vinegar in urethral catheter drainage bags to decrease bacteriuria in 20 long-term catheterized patients. Baseline urine cultures for control and test mediums showed no significant difference in rates of bacteriuria. However, urine cultures obtained at the 48-hour interval showed significant reduction in bacteriuria in urinary bags irrigated with vinegar The implications this study has for nursing practice include a needforfurther research using a larger number of subjects and a need for improvements in the design of the catheter drainage system.

Regulation of T cell homeostasis during fetal and early postnatal life.

Before parturition the fetal lamb develops a large pool of long-lived recirculating T cells which provides a large population of naive T cells with a diverse TcR repertoire. After birth and concomitant with exposure to environment antigens, fetal T cells are rapidly replaced by short-lived cells formed postnatally. The majority of thymic emigrants homing to spleen in postnatal lambs are short-lived, in contrast to emigrants targeting lymph nodes where a population appears to be long-lived. The lifespan of thymic emigrants in the fetus is unknown as in the relative importance of antigen-driven processes versus developmental programming in regulating T cell homeostasis in early postnatal life.

L-selectin expression on thymic emigrants defines two distinct tissue-migration pathways.

We have studied the appearance and phenotype of recent thymic emigrants in blood, spleen and lymph nodes (LN) of neonatal lambs. Using in situ labelling of thymocytes with fluoroscein isothiocyanate (FITC), we examined the expression of the LN homing receptor L-selectin on alphabeta and gammadelta subsets of recent thymic emigrants 24 hr after labelling. There were marked differences in the proportions of CD4+, CD8+ and gammadelta T-cell receptor (TCR+) cells exported from the thymus to spleen compared to lymph nodes. Spleen was enriched in CD8+ and gammadelta TCR+ emigrants while LN were enriched in CD4+ emigrants. There were also marked differences in the expression of L-selectin by emigrants homing to spleen compared with those homing to lymph nodes. While the majority of thymic emigrants in LN expressed L-selectin, considerably fewer emigrants in spleen were L-selectin+. The presence of large numbers of CD8+ L-selectin- and gammadelta TCR+ L-selectin- thymic emigrants homing to spleen raises the possibility that unique homing receptor specificities underpin the migration of T cells to spleen as distinct from lymph nodes.

The ontogeny of T cell recirculation during foetal life.

Studies on the ontogeny of the immune system in the sheep foetus, which remains immunologically naive until after birth, indicate that a large scale recirculation of T cells is just as much a feature of the foetal immune system as it is in animals after birth. An extensive recirculation of T cells and dendritic cells through peripheral tissues-including the gastrointestinal tract and skin-develops early in foetal life, although a population of gut-homing memory T cells does not develop until postnatal life. Current evidence suggests that two populations of thymic emigrants with distinct tissue-homing specificities to spleen and lymph node contribute to the development of the foetal peripheral T cell pool. CD8(+) thymic emigrants mostly target spleen while CD4(+) thymic emigrants home predominantly to lymph nodes. The lifespan of thymic emigrants is uncertain, although cells entering lymph are long-lived and form the basis of a diverse pre-immune repertoire of recirculating T cells. The life history and growth rates of non-recirculating T cells in spleen and lymph nodes during foetal life are at present unknown.

Implementing problem-based learning in a family medicine clerkship.

BACKGROUND AND OBJECTIVES: Problem-based learning (PBL) has been implemented in the curriculum of many medical schools, but limited information is available about the outcome of this learning technique. The educational intervention presented in this paper implemented a PBL learning component in our third-year family medicine clerkship and measured the outcomes of this curricular change. METHODS: One third of the curricular time devoted to didactic teaching in our family medicine clerkship was replaced with PBL activities. Simulated cases were developed and presented to students who, with the aid of faculty facilitators, studied the cases, gathered information about the cases, and developed diagnostic and management plans for the cases. The outcome of the intervention was measured by a) comparing students' scores on the National Board of Medical Examiners (NBME) family medicine clerkship examination to scores achieved by students in the year before PBL was introduced and b) students' evaluations of the relevance and success of PBL in the clerkship curriculum. RESULTS: Students' NBME clerkship examination scores increased from a mean of 66 the year before PBL began to 73 after PBL was implemented. More than 80% of students reported that PBL was a good way to learn family medicine, and 85% reported that the PBL technique provided sufficient information to formulate learning issues. CONCLUSIONS: PBL can be introduced into a third-year family medicine clerkship curriculum with general acceptance by students. Students rated the technique highly, and their examination scores improved.

Verifying the curriculum of a family medicine clerkship.

The learning experience during a medical school clinical rotation is largely shaped by students' patient encounters. This paper reports on how a log system for recording these encounters can be used for course planning and evaluation. Over the past 5 years, 960 third-year students completed log forms based on their clinical encounters during a required 4-week family medicine clerkship at UT Southwestern. These forms were then optically scanned and the information entered into a computerized database. Log form data revealed that the most common medical problems encountered by students in their ambulatory settings were similar to those reported in the general family practice literature. There was a great deal of consistency in the types of encounters from year to year. The data also showed some differences among clerkship sites in terms of patient demographics and the most frequently reported diagnoses. Information generated from student log forms has been used by the clerkship faculty to determine required readings, prioritize didactic topics and other teaching, adjust curriculum content, prepare support materials and develop examinations. Given the utility of the information obtained and the ease of use of optical mark encounter sheets, we recommend this system for other clerkships.

An immune system switch in T cell lifespan at birth results in extensive loss of naive fetal T cells during the first week of postnatal life.

Lymphocyte recirculation is critical to maximize the efficiency of immunological surveillance and is an absolute requirement for the development of systemic memory. The consensus view of the lifespan of peripheral T cells holds that naive T cells are long-lived cells and most memory T cells are short-lived cells, although the question of the lifespan of peripheral T cells is not yet fully resolved. We have studied the lifespan of T cells circulating in efferent lymph draining lymph nodes (LN) in the immunologically naive sheep fetus and in postnatal lambs immediately following birth by examining the in vivo incorporation of [3H]thymidine by newly formed T cells during continuous administration of [3H]thymidine. We report that authentically naive fetal T cells are long-lived cells which continue to recirculate between blood and lymph during fetal life. At birth, however, a process is triggered whereby fetal T cells circulating through LN are rapidly lost from the peripheral T cell pool and are replaced by freshly arriving T cells which have been formed since birth. Our results indicate that by the end of the first week of postnatal life, around three-quarters of the T cells circulating through peripheral LN have been formed since birth.

Freeman-Sheldon (whistling face) syndrome. Anaesthetic and airway management.

We describe the anaesthetic management of Freeman-Sheldon syndrome in a two-and-a-half year old undergoing club foot correction. Following an inhalational induction using halothane, tracheal intubation by direct laryngoscopy proved impossible. A laryngeal mask airway was inserted and intubation with a 4.5 tracheal tube was successfully achieved using a fibreoptic bronchoscope passed through the LMA. The child had an uneventful anaesthetic course. A caudal epidural was used for postoperative analgesia and the child was discharged home on day two. The anaesthetic and airway management options of this syndrome are outlined.

An immune system switch at birth triggers a change in the lifespan of peripheral T cells.

Lymphocyte recirculation is an essential element in the integration of immune responses and is an absolute requirement for the development of systemic memory in postnatal animals. During foetal life a large pool of recirculating T cells develops and migration pathways of naive T cells to skin and peripheral tissues as well as LN are established. At birth a process is triggered whereby naive fetal T cells are rapidly lost from the circulating pool and are replaced by newly arriving T cells which have been formed since birth. At present our data suggest that the thymic export in the fetus creates a pool of long-lived naive T cells of wide diversity. The situation in neonatal lambs is more complex since the thymus is exporting large numbers of short-lived thymic emigrants which enter a peripheral T-cell population where many T cells are dividing.

Origin and development of the gamma delta T-cell system in sheep: a critical role for the thymus in the generation of TcR diversity and tissue tropism.

Ruminant gamma delta T cells are concentrated at epithelial surfaces and share many features in common with species such as mice and humans which contain relatively fewer gamma delta T cells than ruminants. To date no gamma delta T cells with invariant TcR have been found in sheep and the generation of gamma delta TcR diversity which is thymic dependent follows a developmentally regulated sequence. Analysis of thymic export of gamma delta T cells shows that emigration of gamma delta T-cell subsets increases markedly during fetal life and after birth suggesting intrathymic processes leading to mature gamma delta T cells may change during development. Skin homing gamma delta T cells acquire their tissue tropism inside the thymus and pathways of recirculation of gamma delta T cells to skin are laid down during fetal development independent of antigen and remain stable through into adult life.

Risk factors for invasive cervical cancer in Latino women.

Most invasive cervical cancer research in the United States has been conducted on non-Latino-White (NLW) and African-American women. Incidence, mortality, stage at diagnosis and survival indicators for invasive cervical cancer in Latino women in California are compared to NLW and African-American women. A model is presented which depicts structural, behavioral, genetic and biological risk factors for invasive cervical cancer. A literature review of risk factors and their association with invasive cervical cancer was conducted using MEDLINE and PsychINFO databases to determine if ethnic differences in risk factors explain observed differences in morbidity and mortality. Latino women experience a significantly higher incidence and mortality associated with invasive cervical cancer than NLW women. The review of risk factors found that rate differences of cervical cancer screening, early detection and human papilloma virus (HPV) type-specific infection explain much of the disparity in disease burden. Further research must clarify if ethnic differences exist in risk factors associated with ethnic variation in HPV-type prevalence in both cases and their sexual partners, in host immune responses, and multiparity.

Preventing and managing pelvic inflammatory disease: key questions, practices, and evidence.

Clinicians play a pivotal role in protecting women from pelvic inflammatory disease (PID), one of the most prevalent and serious diseases affecting women of reproductive age. This article examines PID prevention and management by critically addressing five questions: (1) What are the key risk factors for PID? (2) What are the principal microorganisms involved in PID? (3) What are the appropriate diagnostic criteria for PID? (4) What are the best treatment regimens for PID? and (5) What are the effective strategies for preventing PID? In addressing each of these questions, the quality of available evidence and recommended practice is discussed and gaps in the evidence are highlighted.