Review article: The epidemiology and management of Clostridioides difficile infection-A clinical update.

BACKGROUND: Clostridioides difficile is the most common cause of healthcare-associated infection, and severe cases can result in significant complications. While anti-microbial therapy is central to infection management, adjunctive therapies may be utilised as preventative strategies. AIM: This article aims to review updates in the epidemiology, diagnosis, and management, including treatment and prevention, of C. difficile infections. METHODS: A narrative review was performed to evaluate the current literature between 1986 and 2023. RESULTS: The incidence of C. difficile infection remains significantly high in both hospital and community settings, though with an overall decline in recent years and similar surveillance estimates globally. Vancomycin and fidaxomicin remain the first line antibiotics for treatment of non-severe C. difficile infection, though due to lower recurrence rates, infectious disease society guidelines now favour use of fidaxomicin. Faecal microbiota transplantation should still be considered to prevent recurrent C. difficile infection. However, in the past year the field has had a significant advancement with the approval of the first two live biotherapeutic products-faecal microbiota spores-live brpk, an oral capsule preparation, and faecal microbiota live-jslm-both indicated for the prevention of recurrent C. difficile infection, with additional therapies on the horizon. CONCLUSION: Although the prevalence of C. difficile infection remains high, there have been significant advances in the development of novel therapeutics and preventative measures following changes in recent practice guidelines, and will continue to evolve in the future.

The Effects of Age and Height on Gait Smoothness in Adolescent Athletes.

(1) Background: Despite evidence of increased rates of sports injury during the years surrounding peak growth in adolescents, little is known regarding the relationship between adolescent growth and gait stability. The aim of this study was to gain a better understanding of how chronological age and height relate to gait stability in both male and female adolescents. (2) Methods: Participants (N = 67; females: n = 34, ages 8.7-15.9 years; males: n = 33, ages 10.0-16.7 years) completed two trials of treadmill walking at varying speeds: the preferred walking speed and 30% above and below. Trials were separated by a bout of fatiguing exercises. HarmonicRatios of the trunk, calculated from acceleration signals taken during walking, were used to quantify gait stability. Data were separated by sex and relationships between height and chronological age, and HarmonicRatios were assessed using multiple linear regression. (3) Results: Females' HarmonicRatios improved with chronological age both before and after fatigue. Males' HarmonicRatios increased with chronological age before fatigue; however, this effect was eliminated post-fatigue. Females' height was negatively associated with HarmonicRatios post-fatigue. Males' height was positively associated with HarmonicRatios pre-fatigue. (4) Conclusions: The study findings suggest sex differences in the effects of fatigue on gait stability during adolescence. In both sexes, HarmonicRatios increased with chronological age. These improvements were eliminated for males and altered for females with fatigue. The results of this study indicate the need for the reevaluation of sports progression based on chronological age in adolescents.

Sarcopenia: no consensus, no diagnostic criteria, and no approved indication-How did we get here?

In addition to the role of skeletal muscle in movement and locomotion, muscle plays a critical role in a broad array of metabolic processes that can contribute to improved health or risk of disease. The age-associated loss of muscle has been termed sarcopenia. The muscle is the primary site of insulin-stimulated glucose disposal and the largest component of basal metabolic rate, directly and indirectly affects bone density, produces myokines with pleiotropic effect on muscle and other tissues including the brain, and stores essential amino acids essential for the maintenance of protein synthesis during periods of reduced food intake and stress. As such, not surprisingly deterioration of skeletal muscle health, typically operationalized as decline of muscle mass and muscle strength is both a powerful risk factor and main consequence of chronic diseases, disability, and loss of independence, and it is one of the strongest risk factors for mortality. However, skeletal muscle remains one of the most plastic of all tissues, with rapid changes in rates of protein synthesis and degradation in response to physical activity and inactivity, inflammation, and nutritional and hormonal status. This has made the development of pharmacological therapies to increase muscle mass (or prevent loss), an important goal for decades. However, while remarkable advances in the understanding of molecular and cellular regulation of muscle protein metabolism have occurred recently, there are no approved drugs for the treatment of sarcopenia, the loss of skeletal muscle affecting millions of older people. The goal of this paper is to describe the possible reasons for the lack of new and effective pharmacotherapies to treat one of the most important risk factors for age-associated disease and loss of independence.

Designing a Child-, Family-, and Healthcare Provider-Centered Procedure Room in a Tertiary Care Children's Hospital.

AIM: The study aim was to co-design new pediatric procedure room prototypes with children, caregivers, and healthcare providers (HCPs). BACKGROUND: Medical procedures can cause pain and anxiety for children and their families. If spaces are not designed for patients' needs, procedures may take longer, require sedation, and result in an inferior care experience. Involving HCPs in co-designing optimal spaces can result in more efficient and safer environments. co-designing spaces with patients and their families can inform psychologically safer and less traumatic environments. METHODS: We followed human-centered design methodology. Data were collected via semi-structured interviews, field observations, and two multidisciplinary design workshops with patients, caregivers, and HCPs. Themes from the data were extracted using a content analysis and used to make evidence-informed recommendations for design features. RESULTS: The study took place from October 2021 to February 2022. Patients, families, and HCPs reported similar needs: (1) control over the environment, including the ability to adjust lighting, temperature, and sound; (2) space that supports patient privacy; (3) the use of evidence-based pain reduction and distraction methods; (4) attention to the sensory environment, including visual (light, color), tactile (textures of furniture and equipment), auditory, and olfactory stimuli; (5) human factors organization of the space and equipment; (6) accessible and equitable spatial design; and (7) the significance of the journey leading up to and after the procedure. CONCLUSIONS: It is feasible to co-design procedure rooms that support evidence-based psychological, physical, and pharmacological interventions that are known to minimize pain for children.

Evaluating sleep in covert encephalopathy with wearable technology: results from the WATCHES study.

BACKGROUND AND AIMS: Covert HE (CHE) is a common early stage of HE associated with poor outcomes. Available neuropsychiatric diagnostic testing is underutilized and has significant clinical limitations. Sleep deterioration is consistently associated with CHE and HE; however, objective data is sparse and it has not been studied longitudinally. We longitudinally study and describe an association of sleep metrics with CHE as detected by a commercial wearable technology. METHODS: We monitored sleep for 6 months using a commercial fitness tracker in 25 participants with cirrhosis, hypothesizing that CHE as diagnosed by psychometric testing would be associated with significant reductions in sleep quality, especially restorative sleep (deep sleep + rapid eye movement). Mixed-effects modeling was performed to evaluate sleep factors associated with CHE and developed and internally validated a score based on these sleep metrics for associated CHE. RESULTS: Across 2862 nights with 66.3% study adherence, we found that those with CHE had consistently worse sleep, including an average of 1 hour less of nightly restorative sleep, driven primarily by reductions in rapid eye movement. A model including albumin, bilirubin, rapid eye movement, sleep disturbances, and sleep consistency showed good discrimination (area under the receiver operating curve=0.79) for CHE status with a sensitivity of 76% and specificity of 69%. CONCLUSIONS: Our large longitudinal study of sleep in cirrhosis suggests that sleep derangements in CHE can be detected using wearable technology. Given the known importance of sleep to overall health and CHE/HE to prognosis in cirrhosis, the ability to associate dynamic sleep metrics with CHE may in the future help with the detection and passive monitoring as factors that precipitate decompensation of cirrhosis become better understood and mobile health data validation and integration improves.

Limited physician knowledge of sarcopenia: A survey.

BACKGROUND: Sarcopenia, a reduction in skeletal muscle mass and function, is a condition that contributes to functional decline and disability in older adults. Although research on this geriatric condition has developed rapidly in recent years, little work has been done to document whether practicing physicians are incorporating sarcopenia into their clinical practice. METHODS: An online survey of 253 practicing U.S. physicians assessed knowledge of sarcopenia, use of the term in practice, motivation for screening patients, and diagnostic and treatment approaches. They were board certified in four practice areas: internal medicine (n = 69), family medicine (n = 69), geriatrics (n = 40), or physical medicine and rehabilitation (PM&R) (n = 75). RESULTS: Less than 20% of internists and family medicine physicians reported being very familiar with the term sarcopenia, with substantially higher familiarity at this level reported among geriatricians (70%) and among PM&R specialists (41%). Two additional findings pointed to deficiencies in sarcopenia knowledge and practice: participants substantially overestimated the prevalence of sarcopenia in older adults (44% of participants reported an expected prevalence of >25%) compared to findings from published studies (indicating 10% of older adults experience sarcopenia); over 75% reported not typically using specific diagnostic criteria or being unsure if their approach utilized any specific criteria. When asked what terminology they use in a medical chart for a patient presenting with significant loss of muscle mass and strength, only 8% said sarcopenia. CONCLUSIONS: Sarcopenia, a condition that can have a major impact on older adults as they age, has not been fully incorporated into the knowledge base and practices of active physicians. The survey data suggest that improving physician familiarity with sarcopenia and having universal agreement on criteria for diagnosis may increase the screening for and treatment of sarcopenia.

The Key to R-E-S-P-E-C-T Is Human-Centred Design.

Disrespect and burnout are long-standing systemic issues causing nurses to leave the profession at an alarming rate. Human-centred design offers a fresh approach to tackling this challenge and recognizes that the journey to discover what is important to nurses is just as meaningful as the destination. Leveraging "inside/outside" expertise and individuals with advanced training in creative problem solving, nurse leaders are empowered to adopt a beginner's mindset and openly explore the challenge. Leading with empathy and engaging with authenticity allows for a deeper understanding of the problem. This understanding opens a path to co-design solutions that enhance nurses' feelings of respect.

Factors Associated With Emergency Department Discharge, Outcomes and Follow-Up Rates of Stable Patients With Lower Gastrointestinal Bleeding.

BACKGROUND: Lower gastrointestinal bleeding (LGIB) is a common reason for hospitalization. However, recent data suggest low-risk patients may be safely evaluated as an outpatient. Here, we compare stable LGIB patients discharged from the emergency department (ED) with those admitted, determine factors associated with discharge and 30-day outcomes, and evaluate follow-up rates amongst the discharged cohort. METHODS: A retrospective study of stable LGIB patients (heart rate < 100 beats/min, systolic blood pressure > 100 mm Hg and blood on rectal exam) who presented to the ED was conducted. Factors associated with discharge and rates of outpatient follow-up were determined in the discharged cohort. Therapeutic interventions and 30-day outcomes (including re-bleeding, re-admission and mortality rates) were compared between the admitted and discharged groups. RESULTS: Ninety-seven stable LGIB patients were reviewed, of whom 38% were discharged and characteristics associated with discharge included age (P < 0.001), lack of aspirin (P < 0.002) and anticoagulant (P < 0.004) use, higher index hemoglobin (P < 0.001) and albumin (P < 0.001), lower blood urea nitrogen (P < 0.001) and creatinine (P = 0.008), lower Oakland score (P < 0.001), lower Charlson Comorbidity Index (P < 0.001) and lack of transfusion requirements (P < 0.001). There was no statistical difference in 30-day re-bleeding, re-admission or mortality rates between admitted and discharged patients. Discharged patients had a 46% outpatient follow-up rate. CONCLUSIONS: While early discharge in low-risk LGIB patients appears to be safe and associated with a decrease in length of stay, further studies are needed to guide timely and appropriate outpatient evaluation.

Safety of administration of BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccine in youths and young adults with a history of acute lymphoblastic leukemia and allergy to PEG-asparaginase.

Vaccinationis a critical tool in the prevention of COVID-19 infection for individuals and for communities. The mRNA vaccines contain polyethylene glycol (PEG) as a stabilizer. Currently, in North America, only the BNT162b2 (Pfizer-BioNTech) mRNA vaccine is approved for individuals aged 12-17. Most patients treated with contemporary regimens for acute lymphoblastic leukemia receive PEG-asparaginase (PEG-ASNase) and 10%-30% will develop allergic reactions. Optimizing access and safety for vaccine administration for these patients is critical. This report describes a process developed to support COVID vaccination in a cohort of adolescents and young adults with a history of PEG-ASNase allergy.

Cyclosporine-Induced Kaposi Sarcoma in a Patient With Ulcerative Colitis.

Kaposi sarcoma (KS) is an angioproliferative neoplasm associated with human herpesvirus-8. Gastrointestinal KS has been well documented in immunosuppressed solid organ transplant patients, with only 26 iatrogenic cases published in patients with inflammatory bowel disease. We report a 24-year-old patient with ulcerative colitis, maintained on cyclosporine for 2 years, who presented with watery, nonbloody diarrhea and weight loss. Colonoscopy revealed human herpesvirus-8-positive hemorrhagic nodules throughout the colon and terminal ileum, with diffuse lymphadenopathy on computed tomography consistent with KS. As gastrointestinal KS may present with symptoms that mimic inflammatory bowel disease, it is critical to maintain suspicion in patients on prolonged immunosuppression to reduce complications.

Priorities for Patient-Centered Research in Valvular Heart Disease: A Report From the National Heart, Lung, and Blood Institute Working Group.

Over the past decade, the field of valvular heart disease (VHD) has rapidly transformed, largely as a result of the development and improvement of less invasive transcatheter approaches to valve repair or replacement. This transformation has been supported by numerous well-designed randomized trials, but they have centered almost entirely on devices and procedures. Outside this scope of focus, however, myriad aspects of therapy and management for patients with VHD have either no guidelines or recommendations based only on expert opinion and observational studies. Further, research in VHD has often failed to engage patients to inform study design and identify research questions of greatest importance and relevance from a patient perspective. Accordingly, the National Heart, Lung, and Blood Institute convened a Working Group on Patient-Centered Research in Valvular Heart Disease, composed of clinician and research experts and patient advocacy experts to identify gaps and barriers to research in VHD and identify research priorities. While recognizing that important research remains to be done to test the safety and efficacy of devices and procedures to treat VHD, we intentionally focused less attention on these areas of research as they are more commonly pursued and supported by industry. Herein, we present the patient-centered research gaps, barriers, and priorities in VHD and organized our report according to the "patient journey," including access to care, screening and diagnosis, preprocedure therapy and management, decision making when a procedure is contemplated (clinician and patient perspectives), and postprocedure therapy and management. It is hoped that this report will foster collaboration among diverse stakeholders and highlight for funding bodies the pressing patient-centered research gaps, opportunities, and priorities in VHD in order to produce impactful patient-centered research that will inform and improve patient-centered policy and care.

Utility of Diagnostic Studies for Upper Gastrointestinal Symptoms in Children with Orthostatic Intolerance.

OBJECTIVE: To assess the utility of gastrointestinal (GI) diagnostic studies in the evaluation of patients with orthostatic intolerance. STUDY DESIGN: Medical records of 103 consecutive children/young adults with orthostatic intolerance and gastrointestinal symptoms were reviewed. All patients had undergone antroduodenal manometry in conjunction with the tilt table test, autonomic testing, and upper gastrointestinal endoscopy (EGD). A gastric emptying study (GES) was performed in 81 patients. RESULTS: The median age of the cohort was 17 years (IQR, 15-19) with a female predominance (females:males, 3:1). As expected, the tilt table test was abnormal in all patients. Antroduodenal manometry was abnormal in 83 of 103 patients (81%), showing neurogenic intestinal dysmotility in 50%, rumination in 20%, and visceral hyperalgesia in 10%. The GES results were abnormal in 23 of 81 patients (28.4%), mostly (21 of 23) with delayed GES. None of the tilt table test or autonomic results were predictive of abnormal antroduodenal manometry or GES. Analysis of EGD biopsy samples revealed nonspecific esophagitis and/or gastritis in 16 of 103 patients (15%). CONCLUSIONS: Antroduodenal manometry with the tilt table test were the most insightful investigations in adolescents and young adults with orthostatic intolerance and gastrointestinal symptoms. GES and EGD provided limited information. Gastrointestinal symptoms were related more to functional rather than mucosal or organic etiologies, suggesting a limited role of endoscopy alone in evaluating patients with orthostatic intolerance presenting with gastrointestinal symptoms.

"Cerebral Palsy" in a Patient With Arginase Deficiency.

Inborn errors of metabolism (IEMs) are thought to present in infancy with acute decompensation including feeding intolerance and vomiting, lethargy, and coma. Most practitioners assume that children will be diagnosed in their first months of life. However, certain IEMs present more insidiously, and occasionally children fail to receive newborn screening resulting in delayed diagnoses, as metabolic and genetic disorders are overlooked causes of cognitive and neurologic deficits. Although signs and symptoms may be present but subtle, careful and detailed history taking, particularly of a child's diet and neurologic medical history, in addition to certain physical examination findings may suggest a diagnosis that is later supported by laboratory and radiographic testing. We present the case of an 11-year-old girl who presented with a diagnosis of cerebral palsy, seizure disorder, and concerns of fatigue and increasing seizure frequency. During hospitalization, she was found to have hyperammonemia, and a diagnosis of arginase deficiency was made. More thorough review of her previous records may have raised suspicion for IEM earlier.

Antroduodenal Manometry Is Abnormal in Children Presenting With Orthostatic Intolerance and Gastrointestinal Symptoms.

OBJECTIVES: Gastrointestinal (GI) symptoms of nausea, vomiting, and abdominal pain are common in patients with orthostatic intolerance (OI), including neurally mediated hypotension (NMH) and postural orthostatic tachycardia syndrome (POTS). Autonomic dysregulation is considered the underlying pathophysiology behind the cardiovascular symptoms of POTS. Because the autonomic nervous system also regulates GI motility, we hypothesized that patients with POTS and GI symptoms will have evidence of autonomic dysmotility of the upper GI tract. METHODS: Thirty-five subjects with OI and GI symptoms were studied. All the subjects had a 24-hour antroduodenal manometry (ADM) study, in conjunction with pharmacologic challenge and autonomic and tilt table testing (TTT). RESULTS: The mean subject age was 16.2 ±â€Š2.8 years (range 10-23.8 years), and male to female ratio was 10:25. TTT was abnormal in all the 35 subjects, whereas Valsalva testing was abnormal (+40 mmHG) in 21 of 34 (62%) subjects, and corrected QT interval was ≥0.44 seconds in 19 of 35 (54%) subjects. During TTT, GI symptoms were reproduced in 31 of 35 (89%) studies. ADM was found to be abnormal at baseline, before the TTT in 5 of 35 (14%) subjects, whereas it became abnormal in 23 of 34 (68%) subjects during TTT. In addition, the expected response to the pharmacologic challenge was limited. Overall, ADM was abnormal in 26 of 35 (74%) patients either at baseline or during TTT in these subjects with OI. CONCLUSIONS: ADM is frequently abnormal in children with OI and GI symptoms. Upper GI motility studies should be a part of the comprehensive evaluation in this population.