Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial.

BACKGROUND: The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. CONCLUSION: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.

Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: the REPLENISH randomized clinical trial protocol.

BACKGROUND: Protein intake is recommended in critically ill patients to mitigate the negative effects of critical illness-induced catabolism and muscle wasting. However, the optimal dose of enteral protein remains unknown. We hypothesize that supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition formula to achieve high amount of enteral protein (range 2-2.4 g/kg/day) given from ICU day 5 until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve moderate amount enteral protein (0.8-1.2 g/kg/day) would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: The REPLENISH (Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial is an open-label, multicenter randomized clinical trial. Patients will be randomized to the supplemental protein group or the control group. Patients in both groups will receive the primary enteral formula as per the treating team, which includes a maximum protein 1.2 g/kg/day. The supplemental protein group will receive, in addition, supplemental protein at 1.2 g/kg/day starting the fifth ICU day. The control group will receive the primary formula without supplemental protein. The primary outcome is 90-day all-cause mortality. Other outcomes include functional and quality of life assessments at 90 days. The trial will enroll 2502 patients. DISCUSSION: The study has been initiated in September 2021. Interim analysis is planned at one third and two thirds of the target sample size. The study is expected to be completed by the end of 2025. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04475666 . Registered on July 17, 2020.

Electronic early notification of sepsis in hospitalized ward patients: a study protocol for a stepped-wedge cluster randomized controlled trial.

BACKGROUND: To evaluate the effect of screening for sepsis using an electronic sepsis alert vs. no alert in hospitalized ward patients on 90-day in-hospital mortality. METHODS: The SCREEN trial is designed as a stepped-wedge cluster randomized controlled trial. Hospital wards (total of 45 wards, constituting clusters in this design) are randomized to have active alert vs. masked alert, 5 wards at a time, with each 5 wards constituting a sequence. The study consists of ten 2-month periods with a phased introduction of the intervention. In the first period, all wards have a masked alert for 2 months. Afterwards the intervention (alert system) is implemented in a new sequence every 2-month period until the intervention is implemented in all sequences. The intervention includes the implementation of an electronic alert system developed in the hospital electronic medical records based on the quick sequential organ failure assessment (qSOFA). The alert system sends notifications of "possible sepsis alert" to the bedside nurse, charge nurse, and primary medical team and requires an acknowledgment in the health information system from the bedside nurse and physician. The calculated sample size is 65,250. The primary endpoint is in-hospital mortality by 90 days. DISCUSSION: The trial started on October 1, 2019, and is expected to complete patient follow-up by the end of October 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT04078594 . Registered on September 6, 2019.

Unusual Neurological Manifestation of Proton Pump Inhibitor: A Case Report of Acute Disseminated Encephalomyelitis and Severe Hyponatremia After Brief Use of Proton Pump Inhibitor.

Hyponatremia is commonly reported after the use of proton pump inhibitors (PPI). While omeprazole is most likely to cause hyponatremia, almost all the PPIs have been reported to cause hyponatremia. The underlying mechanism of PPI-induced hyponatremia is a syndrome of inappropriate antidiuretic hormone (SIADH) secretion which leads to hyponatremia. The hyponatremia can develop with only a few days of exposure to PPI. We present a case of a 56-year-old previously healthy female who was prescribed omeprazole for trivial acid reflux symptoms when she presented to the emergency room for evaluation of generalized weakness. She was discharged home from the emergency room after clinical evaluation as she had essentially normal lab work including a negative COVID PCR test. She subsequently developed progressive weakness of extremities and slurred speech over the next three days. She returned back to the emergency room and was found to have profound hyponatremia with MRI evidence of acute disseminated encephalomyelitis (ADEM). She was treated with hypertonic saline to correct hyponatremia and omeprazole was discontinued. The patient also received pulse dose steroids with improvement in her symptoms.

Massive Gastrointestinal Haemorrhage Unusual Presentation of Gastrointestinal Stromal Tumors of the Jejunum: Case Report and Literature Review.

Although gastrointestinal stromal tumors (GISTs) are rare tumors, they are the most common tumors of mesenchymal origin of the gastrointestinal tract. GISTs present with nonspecific clinical manifestation and they are discovered incidentally during endoscopic or radiological investigations. Massive life-threatening bleeding that requires urgent surgery is rare. We present a case of small bowel GIST that presented with massive lower gastrointestinal bleeding that required urgent surgical intervention.

Neglected Foreign Body Aspiration Mimicking Lung Cancer: A Case Report.

Tracheobronchial aspiration is relatively rare in adults as compared to children although incidence rates tend to increase with advancing age. The diagnosis of tracheobronchial foreign body aspiration can be challenging and warrants a high index of suspicion as the symptoms are often vague and patients may fail to recall the history of choking. The failure to diagnose the condition promptly may result in serious complications such as recurrent pneumonia, hemoptysis, or atelectasis. We present the case of a 72-year-old female with multiple comorbidities who presented with acute respiratory failure, which required urgent intubation and mechanical ventilation. Eventually, she was found to have aspirated green peas and pomegranate seeds, which were successfully removed by flexible bronchoscopy, leading to a dramatic improvement in both clinical condition and radiological imaging findings.

Delayed Post-Laparoscopic Sleeve Gastrectomy Leak Successfully Treated With Endoscopic Clips and Tissue Adhesive: Case Report and Literature Review.

Since it was first introduced, laparoscopic sleeve gastrectomy (LSG) has gained wide popularity and it is one of the most performed bariatric surgical procedures for weight reduction throughout the world. LSG is a simple and effective procedure for the reduction of excess body weight, but it is not without serious complications. We present a case of a 46-year-old obese male with multiple co-morbidities who presented with a delayed post-LSG leak that was successfully managed with endoscopic clips and tissue adhesive.

Neurological Manifestations of COVID-19 in Absence of Respiratory Symptoms or Fever.

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in the Hubei region of China and was declared a pandemic by the World Health Organization (WHO) in March 2020. The clinical presentation of COVID-19 ranges from asymptomatic/mild symptoms to severe illness with associated mortality. The most commonly reported symptoms of COVID-19 are cough, myalgia, and headache. Other well-described features include shortness of breath, fever, sore throat, diarrhea, and smell or taste abnormalities. Although COVID-19 infection is primarily a disease of the respiratory system affecting lung parenchyma, it can affect multiple organ systems and cause variable extra-pulmonary symptoms. A broad spectrum of neurologic manifestations has been reported in association with SARS-CoV-2 infection, most probably due to different pathogenic pathways. We report a case of a rare presentation of a COVID-19-positive female who presented with slurred speech, dizziness, and left-sided weakness without the other common symptoms of the disease.

Use of bladder pressure to correct for the effect of expiratory muscle activity on central venous pressure.

OBJECTIVE: To assess whether subtracting the expiratory change in intra-abdominal (bladder) pressure (Delta IAP) from central venous pressure (CVP) provides a reliable estimate of transmural CVP in spontaneously breathing patients with expiratory muscle activity. DESIGN AND SETTING: Prospective observational study in a medical ICU. PATIENTS: Twenty-four spontaneously breathing patients with central venous and bladder catheters: 18 with no clinical evidence of active expiration (group 1) and 6 with active expiration (group 2). INTERVENTIONS: Patients in group 1 were coached to change their breathing pattern to one of active expiration for several breaths; those in group 2 were asked to sip water through a straw to briefly interrupt active expiration. MEASUREMENTS AND RESULTS: During active expiration end-expiratory CVP (uncorrected CVP) and Delta IAP were measured; Delta IAP was subtracted from uncorrected CVP to obtain corrected CVP. End-expiratory CVP during relaxed breathing (best CVP) was assumed to represent the best estimate of transmural CVP. The absolute difference between corrected CVP and best CVP was much less than the difference between uncorrected CVP and best CVP (2.3+/-2.0 vs. 12.5+/-4.7 mmHg). CONCLUSIONS: In patients with active expiration, subtracting Delta IAP from end-expiratory CVP yields a more reliable (and lower) estimate of transmural CVP than does the uncorrected CVP value.