Improving Access to Noninstitutional Long‐Term Care for American Indian Veterans

Home‐based primary care (HBPC) is an effective model of noninstitutional long‐term care developed in the Department of Veterans Affairs (VA) to provide ongoing care to homebound persons. Significant rural populations of American Indians have limited access to services designed for frail older adults. Fourteen Veterans Affairs Medical Centers (VAMCs) initiated efforts to expand access to HBPC in concert with local tribes and Indian Health Service (IHS) facilities. This study characterizes the resulting emerging models of HBPC and co‐management. Using an observational design, key respondent telephone interviews (n = 37) were conducted with stakeholders representing the 14 VAMCs to describe these HBPC programs, and HBPC models were evaluated in relation to VAMC organizational culture as revealed on the annual VA All Employee Survey. Twelve VAMCs independently developed HBPC expansion programs for American Indian veterans, and six different program models were implemented. Two models were unique to collaborations between VAMCs and tribes; in these collaborations, the tribes retained primary care responsibilities. VAMC used the other four models for delivery of care in remote rural areas to all veteran populations, American Indians and non‐Indians alike. Strategies to improve access by reducing geographic barriers occur in all models. Comparing mean VAMC organizational culture ratings, as defined in the Competing Values Framework, revealed significant group differences for one of these six models. Findings from this study illustrate the flexibility of the HBPC program and opportunities for co‐management and expansion of healthcare access for American Indians and non‐Indians, particularly in rural areas.     

Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis

Transient receptor potential canonical (TRPC) Ca²⁺-permeant channels, especially TRPC3, are increasingly implicated in cardiorenal diseases. We studied the possible role of fibroblast TRPC3 in the development of renal fibrosis. In vitro, a macromolecular complex formed by TRPC1/TRPC3/TRPC6 existed in isolated cultured rat renal fibroblasts. However, specific blockade of TRPC3 with the pharmacologic inhibitor pyr3 was sufficient to inhibit both angiotensin II- and 1-oleoyl-2-acetyl-sn-glycerol–induced Ca²⁺ entry in these cells, which was detected by fura-2 Ca²⁺ imaging. TRPC3 blockade or Ca²⁺ removal inhibited fibroblast proliferation and myofibroblast differentiation by suppressing the phosphorylation of extracellular signal-regulated kinase (ERK1/2). In addition, pyr3 inhibited fibrosis and inflammation-associated markers in a noncytotoxic manner. Furthermore, TRPC3 knockdown by siRNA confirmed these pharmacologic findings. In adult male Wistar rats or wild-type mice subjected to unilateral ureteral obstruction, TRPC3 expression increased in the fibroblasts of obstructed kidneys and was associated with increased Ca²⁺ entry, ERK1/2 phosphorylation, and fibroblast proliferation. Both TRPC3 blockade in rats and TRPC3 knockout in mice inhibited ERK1/2 phosphorylation and fibroblast activation as well as myofibroblast differentiation and extracellular matrix remodeling in obstructed kidneys, thus ameliorating tubulointerstitial damage and renal fibrosis. In conclusion, TRPC3 channels are present in renal fibroblasts and control fibroblast proliferation, differentiation, and activation through Ca²⁺-mediated ERK signaling. TRPC3 channels might constitute important therapeutic targets for improving renal remodeling in kidney disease.     

Junior versus senior physicians for informing families of intensive care unit patients

To compare the effectiveness of information delivered to family members of critically ill patients by junior and senior physicians, we performed a prospective randomized multicenter trial in 11 French intensive care units. Patients (n = 220) were allocated at random to having their family members receive information by only junior or only senior physicians throughout the intensive care unit stay; there were 92 and 93 evaluable cases in the junior and senior groups, respectively, with no significant differences in baseline characteristics. Between Days 3 and 5, one family representative per patient was evaluated for comprehension of the diagnosis, prognosis, and treatment in the patient; satisfaction with information and care; and presence of symptoms of anxiety and depression. No significant differences were found between the two groups for any of these three criteria. Family members informed by a junior physician were more likely to feel they had not been given enough information time (additional time wanted: 3 [0-6.5] vs. 0 [0-5] minutes, p = 0.01) and to have sought additional explanations from their usual doctor (48.9 vs. 34.4%, p = 0.004). Specialty residents, if given opportunities for acquiring experience, can become proficient in communicating with families and share this task with senior physicians.     

Acute iliofemoral thrombosis secondary to Merkel cell carcinoma compressing the inferior vena cava

Merkel cell carcinoma (MCC) is an aggressive small cell neoplasm of the skin characterized by neuroendocrine differentiation. It most commonly involves the head and neck of elderly Caucasians. We present a patient with MCC of the buttock, who 32 months after primary surgery and 18 months after combined chemoradiotherapy developed retroperitoneal metastases causing inferior vena cava (IVC) compression and lower extremity thrombosis. He received anticoagulants, but died 2 months later. This is the first report of MCC causing IVC compression and iliofemoral venous thrombosis. This case illustrates the precarious natural history of this tumor and the controversies that surround its treatment.Presented at The 16th Annual Congress, The Phlebology Society of America, New York, New York, March 1996     

A Pantetheinase-Resistant Pantothenamide with Potent,On-Target,and Selective Antiplasmodial Activity

Pantothenamides inhibit blood-stage Plasmodium falciparum with potencies (50% inhibitory concentration [IC₅₀], ∼20 nM) similar to that of chloroquine. They target processes dependent on pantothenate, a precursor of the essential metabolic cofactor coenzyme A. However, their antiplasmodial activity is reduced due to degradation by serum pantetheinase. Minor modification of the pantothenamide structure led to the identification of α-methyl-N-phenethyl-pantothenamide, a pantothenamide resistant to degradation, with excellent antiplasmodial activity (IC₅₀, 52 ± 6 nM), target specificity, and low toxicity.     

Should Athletes Return to Activity After Cryotherapy?

Reference/Citation

Bleakley CM, Costello JT, Glasgow PD. Should athletes return to sport after applying ice? A systematic review of the effect of local cooling on functional performance. Sports Med. 2012; 42(1):69–87.

Clinical Question

Does local tissue cooling affect immediate functional performance outcomes in a sport situation?

Data Sources

Studies were identified by searching MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE, each from the earliest available record through April 2011. Combinations of 18 medical subheadings or key words were used to complete the search.

Study Selection

This systematic review included only randomized controlled trials and crossover studies published in English that examined human participants who were treated with a local cooling intervention. At least 1 functional performance outcome that was measured before and after a cooling intervention had to be reported. Excluded were studies using whole-body cryotherapy or cold-water immersion above the waist and studies that measured strength or force production during evoked muscle contraction.

Data Extraction

Data were extracted by 2 authors using a customized form to evaluate relevant data on study design, eligibility criteria, detailed characteristics of cooling protocols, comparisons, and outcome measures. Disagreement was resolved by consensus or third-party adjudication. To perform an intent-to-treat analysis when possible, data were extracted according to the original allocation groups, and losses to follow-up were noted. The review authors were not blinded to the study author, institution, or journal. For each study, mean differences or standardized mean differences and 95% confidence intervals were calculated for continuous outcomes using RevMan (version 5.1; The Nordic Cochrane Centre, Copenhagen, Denmark). Treatment effects were based on between-groups comparisons (cryotherapy versus control) using postintervention outcomes or within-group comparisons (precryotherapy versus postcryotherapy). If continuous data were missing standard deviations, other statistics including confidence intervals, standard error, t values, P values, or F values were used to calculate the standard deviation. The Cochrane risk-of-bias tool was used to assess the methodologic quality of included studies. Each study was evaluated for sequence generation, allocation concealment, assessor blinding, and incomplete outcome data. Studies were graded as low or high based on the criteria met, but the risk of bias across the studies was consistently high, so meaningful subgroup classifications were not possible. Differences in study quality and intervention details, including duration of cryotherapy interventions and time periods after intervention before follow-up, were potential sources of bias and considered for a subgroup analysis.

Main Results

Using the search criteria, the authors originally identified 1449 studies. Of these, after title and abstract review, 99 studies were deemed potentially relevant and kept for further analysis (1350 studies were excluded). Of the 99 potentially relevant studies, 35 were included in the final review (64 studies were excluded), with relevant outcomes of strength, power, vertical jump, endurance, agility, speed, performance accuracy, and dexterity reported. The 64 excluded studies were rejected due to intervention relevancy, outcome relevancy, and non-English language. In the 35 studies meeting the inclusion criteria, 665 healthy participants were assessed. Muscle strength (using an isokinetic dynamometer, cable tensiometer, strain-gauge device, or load cell) was assessed in 25 studies, whole-body exercise (vertical jump height, power, timed hop test, sprint time, and time taken to complete running-based agility tests, including carioca runs, shuttle sprints, T-shuttle, and cocontraction tests) was assessed in 6, performance accuracy (throwing or shooting) was assessed in 2, and hand dexterity was assessed in 2. Outcomes before and immediately after cryotherapy intervention were reported in all studies; additional outcome assessments at times ranging from 5 to 180 minutes postintervention were recorded in 11 studies. The review authors reported a high risk of bias: selection bias (poor randomization and concealment of group allocation), performance and detection bias (poor blinding of assessors), and attrition bias (incomplete data). Because of the diversity of studies, particularly with respect to cryotherapy protocols and the potential for rewarming before the posttest, the effects of cryotherapy on functional performance were mixed. From the included studies, the authors concluded that cryotherapy treatment reduced upper and lower extremity muscle strength immediately after cryotherapy. However, increases in force output after cryotherapy were reported in 5 studies. Regardless of the effect of cryotherapy on strength, the clinical meaningfulness of most of the data may not be important due to variability and small effects. Studies reporting outcomes of muscle endurance resulted in conflicting evidence: endurance increased immediately after cryotherapy in 6, whereas muscle endurance decreased in 3 . These conflicting results limit the ability to draw clinically relevant conclusions about the effect of cryotherapy on muscle endurance. The majority of studies evaluating whole-body exercise demonstrated decreases in performance after cryotherapy; these outcomes included vertical jump, sprint, and agility, even when cryotherapy was applied only to a body part. Additionally, cryotherapy appeared to decrease hand dexterity and throwing accuracy immediately after intervention, although an increase in shooting performance postintervention was reported in 1 study .

Conclusions

The authors suggested that the available evidence indicates that athletic performance may be adversely affected when athletes return to play immediately after cryotherapy treatments. Many of the included studies used variable cooling protocols, reflecting differences in time, temperature, and mode of cryotherapy. The majority of the included studies used cryotherapy for at least 20 minutes. However, when considering an immediate return to activity, this cooling duration may not be clinically relevant because cryotherapy applications during practice and competitions usually last less than 20 minutes. When immediate return to activity occurs after cryotherapy, short-duration cold applications or progressive warm-ups should be implemented to prevent a deleterious effect on functional performance.Key Words: cold modalities, functional performance, strength, endurance     

Association between in-hospital acute hypertensive episodes and outcomes in older trauma patients

Although chronic hypertension is associated with long-term complications, few studies directly examine the effects of in-hospital acute hypertensive episodes in trauma patients. The aim was to determine whether there is an association between in-hospital acute hypertension and morbidity. We included trauma patients between 45 and 89 years who presented to a level I trauma center between January and September 2008. Patients were classified as either experiencing or not experiencing acute hypertensive episode(s) as defined by systolic blood pressure ≥180, or diastolic blood pressure ≥110 mmHg, or at least two readings of systolic blood pressure ≥160 or diastolic blood pressure ≥100 mmHg. The primary outcome was a composite endpoint of myocardial infarction, stroke, venous thromboembolism, new-onset atrial fibrillation, or acute kidney injury. At least one acute hypertensive episode occurred in 42.6 % (69/162) of patients. A total of 10.5 % patients developed the composite endpoint, 17.4 % in the acute hypertensive episode group compared to 5.4 % in the non-hypertensive group, p = 0.012. Patients in the acute hypertensive group were more likely to require an intensive care unit admission compared to the non-hypertensive group (33.3 versus 14.0 %, p = 0.004). Of the 17 patients who developed an acute hypertensive episode and met the primary endpoint, 10 were on home antihypertensive medications. Of those, four were restarted on all medications initially, three on some, two were started on new medications, and one was not resumed on home medications. Development of acute hypertensive episode(s) in older trauma patients was associated with an increase in the composite endpoint. Prospective studies are needed.