Enteral nutrition tolerance in patients receiving neuromuscular blockade.

BACKGROUND: Nutrition support is an essential part of critical care medicine. It is commonly accepted that for the critically ill patient, enteral nutrition (EN) is favored. For the patient who receives neuromuscular blockades, EN may be held, or initiation delayed, because of concerns for EN intolerance. We hypothesized there would be no difference in EN tolerance between groups receiving cisatracurium while receiving EN compared with those not receiving cisatracurium. METHODS: This was a retrospective study that included 459 patients from a combined medical and surgical intensive care unit. There were 44 patients who received cisatracurium with EN and 415 who received EN alone. Data collected included gastric residual volume (GRV) and emesis occurrences, new-onset abdominal pain, new or worsening abdominal distention, and bowel ischemia. RESULTS: There were more patients with new or worsening abdominal distention in the group receiving cisatracurium (31.82% vs 14.94%; P < 0.01) as well as occurrences of GRV > 300 ml (P < 0.01). There was no statistically significant difference between the groups regarding emesis, new-onset abdominal pain, or bowel ischemia. CONCLUSION: Our findings suggest that it is acceptable to provide patients with EN who are receiving cisatracurium.

Morbidity and Functional Outcomes Following Rocky Mountain Spotted Fever Hospitalization-Arizona, 2002-2017.

Background: Rocky Mountain spotted fever (RMSF) is a deadly tickborne disease disproportionately affecting Arizona tribal communities. While the acute clinical effects of RMSF are well-documented, more complete understanding of the long-term health consequences is needed to provide guidance for providers and patients in highly impacted areas. Methods: We performed a retrospective review of hospitalized RMSF cases from 2 tribal communities in Arizona during 2002-2017. Medical records from acute illness were abstracted for information on clinical presentation, treatment, and status at discharge. Surviving patients were interviewed about disease recovery, and patients reporting incomplete recovery were eligible for a neurologic examination. Results: Eighty hospitalized cases of RMSF met our inclusion criteria and were reviewed. Of these, 17 (21%) resulted in a fatal outcome. Among surviving cases who were interviewed, most (62%) reported full recovery, 15 (38%) reported ongoing symptoms or reduced function following RMSF illness, and 9 (23%) had evidence of neurologic sequelae at the time of examination. Sequelae included impaired cognition, weakness, decreased deep tendon reflexes, seizures, and cranial nerve dysfunction. Longer hospitalization (25.5 days vs 6.2 days, P < .001), a higher degree of disability at discharge (median modified Rankin score 1 vs 0, P = .03), and delayed doxycycline administration (6.2 days vs 4.1 days, P = .12) were associated with long-term sequelae by logistic regression. Conclusions: Although the etiology of sequelae is not able to be determined using this study design, life-altering sequelae were common among patients surviving severe RMSF illness. Delayed administration of the antibiotic doxycycline after day 5 was the strongest predictor of morbidity.

Dual Anticoagulation With Warfarin and Apixaban: A Case Report.

We report the case of a female with recurrent venous thromboembolisms (VTEs) despite being appropriately anticoagulated. Different anticoagulants were trialed and all led to treatment failure. As a result, the patient was started on dual anticoagulation with warfarin and apixaban. There were no recurrences of clots while the patient was adherent to dual anticoagulation. This case report adds to current literature demonstrating the efficacy of dual anticoagulation in patients with recurrent VTE who fail single-agent therapy. It also demonstrates the need for additional studies that evaluate the utility of dual anticoagulants as a treatment modality for patients failing monotherapy.

Global Policy Barriers and Enablers to Exercise and Physical Activity in Kidney Care.

OBJECTIVE: Impairment in physical function and physical performance leads to decreased independence and health-related quality of life in people living with chronic kidney disease and end-stage kidney disease. Physical activity and exercise in kidney care are not priorities in policy development. We aimed to identify global policy-related enablers, barriers, and strategies to increase exercise participation and physical activity behavior for people living with kidney disease. DESIGN AND METHODS: Guided by the Behavior Change Wheel theoretical framework, 50 global renal exercise experts developed policy barriers and enablers to exercise program implementation and physical activity promotion in kidney care. The consensus process consisted of developing themes from renal experts from North America, South America, Continental Europe, United Kingdom, Asia, and Oceania. Strategies to address enablers and barriers were identified by the group, and consensus was achieved. RESULTS: We found that policies addressing funding, service provision, legislation, regulations, guidelines, the environment, communication, and marketing are required to support people with kidney disease to be physically active, participate in exercise, and improve health-related quality of life. We provide a global perspective and highlight Japanese, Canadian, and other regional examples where policies have been developed to increase renal physical activity and rehabilitation. We present recommendations targeting multiple stakeholders including nephrologists, nurses, allied health clinicians, organizations providing renal care and education, and renal program funders. CONCLUSIONS: We strongly recommend the nephrology community and people living with kidney disease take action to change policy now, rather than idly waiting for indisputable clinical trial evidence that increasing physical activity, strength, fitness, and function improves the lives of people living with kidney disease.

Physical activity and exercise in peritoneal dialysis: International Society for Peritoneal Dialysis and the Global Renal Exercise Network practice recommendations.

Life participation requiring physical activity and physical function is a key patient-reported outcome for people receiving peritoneal dialysis (PD). Clinician guidance is required from multidisciplinary sources regarding exercise and activity advice to address the specific needs of this group. From August 2020 through to June 2021, the Global Renal Exercise Network and the International Society for Peritoneal Dialysis reviewed the published literature and international clinical experience to develop a set of clinical practice points. A set of questions relevant to physical activity and exercise were developed from the perspective of a person receiving PD and were the basis for the practice point development. The GRADE framework was used to evaluate the quality of evidence and to guide clinical practice points. The review of the literature found sparse quality evidence, and thus the clinical practice points are generally based on the expert consensus of people receiving PD, PD exercise expert clinicians and experienced PD exercise researchers. Clinical practice points address timing of exercise and activity (post-catheter insertion, peritoneal space empty or full), the uptake of specific activities (work, sex, swimming, core exercise), potential adverse outcomes related to activity and exercise (exit site care, perspiration, cardiovascular compromise, fatigue, intra-abdominal pressure), the effect of exercise and activity on conditions of interest (mental health, obesity, frailty, low fitness) and exercise nutrition.

High-Risk Outreach for COVID-19 Mortality Reduction in an Indigenous Community.

Indigenous populations have been disproportionally affected by COVID-19, particularly those in rural and remote locations. Their unique environments and risk factors demand an equally unique public health response. Our rural Native American community experienced one of the highest prevalence outbreaks in the world, and we developed an aggressive management strategy that appears to have had a considerable effect on mortality reduction. The results have implications far beyond pandemic response, and have reframed how our community addresses several complicated health challenges. (Am J Public Health. 2021;111(11):1939-1941. https://doi.org/10.2105/AJPH.2021.306472).

Reasons for Nonparticipation in a Sustained Hemodialysis Intradialytic Exercise Program.

OBJECTIVE(S): Patients with end-stage kidney disease requiring hemodialysis suffer frailty and poor physical function. Exercise can improve physical function; however, barriers exist to intradialytic exercise programs. The objective of this study was to explore patients' reasons for not exercising in an extant intradialytic exercise program. DESIGN AND METHODS: We conducted a retrospective analysis reporting the reasons for not exercising in an intradialytic exercise program in two hemodialysis centers over a 4-week period. We explored whether patient characteristics and the presence of an exercise professional were associated with missed exercise sessions. RESULTS: Seventy-five patients participating in the intradialytic exercise program completed 57% of prescribed intradialytic exercise sessions. The three most frequently reported reasons from patients not exercising were refusal (24%), followed by fatigue (19%) and symptoms (14%). Patients were more than twice as likely to exercise if a kinesiologist was present (odds ratio [OR]: 2.26, confidence interval [CI]: 1.5, 3.4 P = .03). They were less likely to exercise if they were women (OR: 0.66, CI: 0.45, 0.95 P = .002), had been on dialysis greater than 60 months (OR: 0.55, CI: 0.37, 0.80 P < .002), or had more than two comorbid conditions (OR: 0.63, CI: 0.43, 0.90, P = .01). CONCLUSION: Patient adherence to intradialytic exercise programs is strongly associated with the presence of exercise professionals.

Sustained exercise programs for hemodialysis patients: The characteristics of successful approaches in Portugal, Canada, Mexico, and Germany.

Despite having good intentions, hemodialysis (HD) clinics often fail to sustain exercise programs that they initiate. There are many reasons for this, including a lack of funding, inadequate training of the clinic staff, a lack of exercise professionals to manage the program or train the staff, and the many challenges inherent to exercising a patient population with multiple comorbid diseases. Despite these barriers, there are several outstanding examples of successful exercise programs in HD clinics throughout the world. The aim of this manuscript is to review the characteristics of four successfully sustained HD exercise programs in Portugal, Canada, Mexico, and Germany. We describe the unique approaches they have used to fund and manage their programs, the varied exercise prescriptions they incorporate, the unique challenges they face, and discuss the benefits they have seen. While the programs differ in many regards, a consistent theme is that they each have substantial and committed support from the entire clinic staff, including the nephrologists, administration, nurses, dietitians, and technicians. This suggests that exercise programs in HD clinics can be successfully implemented and sustained provided significant effort is made to foster a culture of physical activity throughout the clinic.

Impact of intradialytic exercise intensity on urea clearance in hemodialysis patients.

Intradialytic exercise (IDE) has been shown to benefit dialysis efficacy; however, the effect of IDE intensity is unknown. Dialyzer urea clearance (K urea, mL/min) was significantly greater during both IDE protocols (55% and 70% maximal heart rate, HRmax), compared with no IDE (p < 0.05). No significant difference in K urea was found between IDE protocols (55% vs. 70% HRmax) (p > 0.05). Results show that higher intensity IDE has no additional benefit on K urea.

The physical deterioration of dialysis patients-Ignored, ill-reported, and ill-treated.

The progressive physical deterioration of dialysis patients is apparent to all who are involved in their care. Exercise can help stem this decline, yet exercise uptake in chronic and end-stage kidney disease is low. The involvement of exercise professionals has been shown to significantly increase patients' physical function and improve their quality of life. However, exercise professionals are scarce in renal programs, far less than dietetic and social work services. A review of 10 years of renal exercise publications in the physical therapy and rehabilitation literature found that only 0.4% (7 out of a total of 1763) of all published articles were focused on people with kidney disease. This compared with stroke (44%, n=883), arthritis/bone (29%, n=458), cancer (9%, n=168), respiratory (8%, n=106), cardiac (5%, n=82), and diabetes (3%, n=45). These results reflect the low emphasis placed on renal rehabilitation by the physical therapy professions and the low renal content in physical therapy tertiary education programs. This is likely to have an impact on the level of involvement of physical therapists in renal programs leading to lower physical function and poorer quality of life for renal patients.

Intradialytic Exercise is Medicine for Hemodialysis Patients.

When a person's kidneys fail, hemodialysis (HD) is the most common treatment modality. With a growing number of patients requiring this life-sustaining treatment, and with evidence illustrating the significant physical dysfunction of this population, encouraging exercise is essential. The use of intradialytic exercise, as a novel and efficient use of time during HD, is well established in Australia and some European nations; however, it is slower to start in North America. While a large number of small studies have demonstrated numerous benefits and safe delivery of intradialytic exercise training for patients with end-stage kidney disease, intradialytic exercise is rarely delivered as standard of care. It is of utmost importance for health care staff to overcome barriers and bring theory into practice. Included in this report are current recommendations from governing bodies, expert opinion, as well as established policies and procedures from a successful intradialytic exercise program in Canada.

Quantitative, Qualitative and Geospatial Methods to Characterize HIV Risk Environments.

Increasingly, 'place', including physical and geographical characteristics as well as social meanings, is recognized as an important factor driving individual and community health risks. This is especially true among marginalized populations in low and middle income countries (LMIC), whose environments may also be more difficult to study using traditional methods. In the NIH-funded longitudinal study Mapa de Salud, we employed a novel approach to exploring the risk environment of female sex workers (FSWs) in two Mexico/U.S. border cities, Tijuana and Ciudad Juárez. In this paper we describe the development, implementation, and feasibility of a mix of quantitative and qualitative tools used to capture the HIV risk environments of FSWs in an LMIC setting. The methods were: 1) Participatory mapping; 2) Quantitative interviews; 3) Sex work venue field observation; 4) Time-location-activity diaries; 5) In-depth interviews about daily activity spaces. We found that the mixed-methodology outlined was both feasible to implement and acceptable to participants. These methods can generate geospatial data to assess the role of the environment on drug and sexual risk behaviors among high risk populations. Additionally, the adaptation of existing methods for marginalized populations in resource constrained contexts provides new opportunities for informing public health interventions.

The association between intradialytic exercise and hospital usage among hemodialysis patients.

Hemodialysis (HD) patients have high hospitalization rates. Benefits of intradialytic exercise have been proven in numerous studies yet exercise programs are still rarely used in the treatment of end-stage kidney disease (ESKD). Our objective was to determine if there was an association between a 6-month intradialytic bicycling program and hospitalization rates and length of stay (LOS) in ESKD patients. This was a retrospective cohort study that took place 6 months prior to and 6 months during an intradialtyic exercise program at an outpatient HD unit in Calgary, Alberta, Canada. Participants comprised 102 patients who had commenced HD <6 months (incident) or >6 months (prevalent) prior to starting exercise. The intervention comprised a 6-month intradialytic bicycling program. Main outcome measures were hospitalization rate, cause of hospitalization, and LOS. Patients were predominantly male (67.6%) aged 65.6 ± 13.5 years and median HD vintage 1 year (range: 0-12). Comorbidities included diabetes mellitus (50%) and cardiac disease (38.2%). The hospitalization incidence rate ratio (IRR) was 0.48 (0.23-0.98; P = 0.04) in incident and 0.89 (0.56-1.42; P = 0.64) in prevalent patients. The LOS decreased from 7.8 (95% confidence interval (CI): 7.3-8.4) to 3.1 (95% CI: 2.8-3.4) days and LOS IRR was 0.39 (0.35-0.45; P < 0.001). The main predictors of hospitalization were lower albumin levels (P = 0.007) and lack of intradialytic exercise program participation (P < 0.001). In conclusion, 6 months of intradialytic exercise was associated with decreased LOS in both incident and prevalent HD patients.

Atypical presentation of ovarian remnant syndrome in a dog.

A 2 yr old spayed female dog presented for evaluation of abdominal pain, decreased appetite, dysuria, and frantic licking of her vulva. A midventral, soft, fluctuant mass was detected on abdominal palpation. Diagnostic testing and exploratory celiotomy revealed remnant ovarian tissue and a cystic uterine remnant. The ovary and cystic uterine remnant were removed and submitted for histopathological evaluation. Ovarian remnant syndrome (ORS) is an infrequently encountered condition of dogs. This dog had none of the classic signs of estrus associated with ORS but instead presented for sharp, intermittent, abdominal pain that is similar to women with ORS.

Oronasal blastomycosis in a golden retriever.

Blastomycosis is one of the most common systemic fungal infections in dogs in North America Pulmonary manifestations are most common; localized disease is rare. A case of localized oronasal blastomycosis mimicking oral neoplasia is described. Long-term therapy with itraconazole resulted in clinical cure.

Blastomycose oronasale chez un golden retriever. La blastomycose est l'une des infections fongiques systémiques les plus courantes chez les chiens en Amérique du Nord. Les manifestations pulmonaires sont les plus fréquentes; une maladie localisée est rare. Un cas de blastomycose orale imitant la néoplasie orale est décrit. Un traitement à long terme avec l'itraconazole a produit une guérison clinique.(Traduit par Isabelle Vallières).

XIAP regulates caspase activity in degenerating axons.

Our knowledge of the destructive events that regulate axonal degeneration is rudimentary. Here, we examine the role of caspases and their endogenous inhibitor, the X-linked inhibitor of apoptosis protein (XIAP), in axonal degeneration of dorsal root ganglion (DRG) axons. We show that caspase-3, caspase-6, and caspase-9 are present in axons and are cleaved upon nerve growth factor (NGF) withdrawal. We observed that caspase-3 activity is high in NGF-withdrawn axons and that CASP3(-/-) axons are protected from degeneration. XIAP(-/-) DRG sensory neurons degenerate more rapidly and contain more active caspase-3 than their wild-type counterparts, indicating that axonal caspases are normally regulated by XIAP. Importantly, axonal XIAP levels drop sharply after NGF withdrawal; if XIAP levels are maintained by overexpression, axonal caspase-3 activation and axonal degeneration are suppressed. Finally, we show that XIAP(-/-) embryos have stunted dermal innervation. We propose that XIAP-mediated caspase inhibition plays an important role in regulating morphogenic events that shape the nervous system during development.

Notch signaling in osteocytes differentially regulates cancellous and cortical bone remodeling.

Notch receptors play a role in skeletal development and homeostasis, and Notch activation in undifferentiated and mature osteoblasts causes osteopenia. In contrast, Notch activation in osteocytes increases bone mass, but the mechanisms involved and exact functions of Notch are not known. In this study, Notch1 and -2 were inactivated preferentially in osteocytes by mating Notch1/2 conditional mice, where Notch alleles are flanked by loxP sequences, with transgenics expressing Cre directed by the Dmp1 (dentin matrix protein 1) promoter. Notch1/2 conditional null male and female mice exhibited an increase in trabecular bone volume due to an increase in osteoblasts and decrease in osteoclasts. In male null mice, this was followed by an increase in osteoclast number and normalization of bone volume. To activate Notch preferentially in osteocytes, Dmp1-Cre transgenics were crossed with Rosa(Notch) mice, where a loxP-flanked STOP cassette is placed between the Rosa26 promoter and Notch1 intracellular domain sequences. Dmp1-Cre(+/-);Rosa(Notch) mice exhibited an increase in trabecular bone volume due to decreased bone resorption and an increase in cortical bone due to increased bone formation. Biomechanical and chemical properties were not affected. Osteoprotegerin mRNA was increased, sclerostin and dickkopf1 mRNA were decreased, and Wnt signaling was enhanced in Dmp1-Cre(+/-);Rosa(Notch) femurs. Botulinum toxin A-induced muscle paralysis caused pronounced osteopenia in control mice, but bone mass was preserved in mice harboring the Notch activation in osteocytes. In conclusion, Notch plays a unique role in osteocytes, up-regulates osteoprotegerin and Wnt signaling, and differentially regulates trabecular and cortical bone homeostasis.

Over-expression of X-linked inhibitor of apoptosis protein modulates multiple aspects of neuronal Ca2+ signaling.

X-linked inhibitor of apoptosis (XIAP) protects and preserves the function of neurons in both in vitro and in vivo models of excitotoxicity. Since calcium (Ca(2+)) overload is a pivotal event in excitotoxic neuronal cell death, we have determined whether XIAP over-expression influences Ca(2+)-signaling in primary cultures of mouse cortical neurons. Using cortical neuron cultures derived from wild-type (Wt) mice transiently transfected with XIAP or from transgenic mice that over-express XIAP, we show that XIAP opposes the rise in intracellular Ca(2+) concentration by a variety of triggers. Relative to control neurons, XIAP over-expression produced a slight, but significant, elevation of resting Ca(2+) concentrations. By contrast, the rise in intracellular Ca(2+) concentrations produced by N-methyl-D-aspartate receptor stimulation and voltage gated Ca(2+) channel activation were markedly attenuated by XIAP over-expression. The release of Ca(2+) from intracellular stores induced by the sarco/endoplasmic reticulum Ca(2+) ATPase inhibitor thapsigargin was also inhibited in neurons transiently transfected with XIAP. The pan-caspase inhibitor zVAD did not, however, diminish the rise in intracellular Ca(2+) concentrations elicited by L-glutamate suggesting that XIAP influences Ca(2+) signaling in a caspase-independent manner. Taken together, these findings demonstrate that the ability of XIAP to block excessive rises in intracellular Ca(2+) by a variety of triggers may contribute to the neuroprotective effects of this anti-apoptotic protein.

Osteoblast lineage-specific effects of notch activation in the skeleton.

Transgenic overexpression of the Notch1 intracellular domain inhibits osteoblast differentiation and causes osteopenia, and inactivation of Notch1 and Notch2 increases bone volume transiently and induces osteoblastic differentiation. However, the biology of Notch is cell-context-dependent, and consequences of Notch activation in cells of the osteoblastic lineage at various stages of differentiation and in osteocytes have not been defined. For this purpose, Rosa(Notch) mice, where a loxP-flanked STOP cassette placed between the Rosa26 promoter and the NICD coding sequence, were crossed with transgenics expressing the Cre recombinase under the control of the Osterix (Osx), Osteocalcin (Oc), Collagen 1a1 (Col2.3), or Dentin matrix protein1 (Dmp1) promoters. At 1 month, Osx-Cre;Rosa(Notch) and Oc-Cre;Rosa(Notch) mice exhibited osteopenia due to impaired bone formation. In contrast, Col2.3-Cre;Rosa(Notch) and Dmp1-Cre;Rosa(Notch) exhibited increased femoral trabecular bone volume due to a decrease in osteoclast number and eroded surface. In the four lines studied, cortical bone was either not present, was porous, or had the appearance of trabecular bone. Oc-Cre;Rosa(Notch) and Col2.3-Cre;Rosa(Notch) mice exhibited early lethality so that their adult phenotype was not established. At 3 months, Osx-Cre;Rosa(Notch) and Dmp1-Cre;Rosa(Notch) mice displayed increased bone volume, and increased osteoblasts although calcein-demeclocycline labels were diffuse and fragmented, indicating abnormal bone formation. In conclusion, Notch effects in the skeleton are cell-context-dependent. When expressed in immature osteoblasts, Notch arrests their differentiation, causing osteopenia, and when expressed in osteocytes, it causes an initial suppression of bone resorption and increased bone volume, a phenotype that evolves as the mice mature.