Healthcare resource utilization and costs among patients with alpha-1 antitrypsin deficiency with liver and/or lung disease: a longitudinal retrospective study in the USA.

Aim: To evaluate all-cause and liver-associated healthcare resource utilization (HCRU) and costs among patients with alpha-1 antitrypsin deficiency (AATD) with liver disease (LD) and/or lung disease (LgD). Materials & methods: This was a retrospective analysis of linked administrative claims data from the IQVIA PharMetrics® Plus and the IQVIA Ambulatory Electronic Medical Records (AEMR) databases from 1 July 2021 to 31 January 2022. Patients with AATD in the IQVIA PharMetrics Plus database were included with ≥1 inpatient or ≥2 outpatient medical claims ≥90 days apart with a diagnosis of AATD, or with records indicating a protease inhibitor (Pi)*ZZ/Pi*MZ genotype in the IQVIA AEMR database with linkage to IQVIA PharMetrics Plus. For a patient's identified continuous enrollment period, patient time was assigned to health states based on the initial encounter with an LD/LgD diagnosis. A unique index date was defined for each health state, and HCRU and costs were calculated per person-year (PPY). Results: Overall, 5136 adult and pediatric patients from the IQVIA PharMetrics Plus and IQVIA AEMR databases were analyzed. All-cause and liver-associated HCRU and costs were substantially higher following onset of LD/LgD. All-cause cost PPY ranged from US $11,877 in the absence of either LD/LgD to US $74,015 in the presence of both LD and LgD. Among liver transplant recipients in the AATD with LD health state, liver-associated total costs PPY were US $87,329 1-year pre-transplantation and US $461,752 1-year post-transplantation. In the AATD with LgD and AATD with LD and LgD health states, patients who received augmentation therapy were associated with higher all-cause total costs PPY and lower liver-associated total costs PPY than their counterparts who did not receive augmentation therapy. Conclusion: Patients with AATD had increased HCRU and healthcare costs in the presence of LD and/or LgD. HCRU and healthcare costs were highest in the AATD with LD and LgD health state.

Machine learning using longitudinal prescription and medical claims for the detection of non-alcoholic steatohepatitis (NASH).

OBJECTIVES: To develop and evaluate machine learning models to detect patients with suspected undiagnosed non-alcoholic steatohepatitis (NASH) for diagnostic screening and clinical management. METHODS: In this retrospective observational non-interventional study using administrative medical claims data from 1 463 089 patients, gradient-boosted decision trees were trained to detect patients with likely NASH from an at-risk patient population with a history of obesity, type 2 diabetes mellitus, metabolic disorder or non-alcoholic fatty liver (NAFL). Models were trained to detect likely NASH in all at-risk patients or in the subset without a prior NAFL diagnosis (at-risk non-NAFL patients). Models were trained and validated using retrospective medical claims data and assessed using area under precision recall curves and receiver operating characteristic curves (AUPRCs and AUROCs). RESULTS: The 6-month incidences of NASH in claims data were 1 per 1437 at-risk patients and 1 per 2127 at-risk non-NAFL patients . The model trained to detect NASH in all at-risk patients had an AUPRC of 0.0107 (95% CI 0.0104 to 0.0110) and an AUROC of 0.84. At 10% recall, model precision was 4.3%, which is 60× above NASH incidence. The model trained to detect NASH in the non-NAFL cohort had an AUPRC of 0.0030 (95% CI 0.0029 to 0.0031) and an AUROC of 0.78. At 10% recall, model precision was 1%, which is 20× above NASH incidence. CONCLUSION: The low incidence of NASH in medical claims data corroborates the pattern of NASH underdiagnosis in clinical practice. Claims-based machine learning could facilitate the detection of patients with probable NASH for diagnostic testing and disease management.

Non-alcoholic Steatohepatitis: From Pathophysiology to Clinical Practice.

Non-alcoholic steatohepatitis (NASH) is becoming a global disease with significant associated comorbidities. To date, there are no commercialized drugs to treat NASH, outside of India; however, there is an abundance of new molecular entities which are in clinical development, some in phase III trials. Many of these trials have created an especially heavy demand for USA-based subjects. Hepatologists currently play a major role in the diagnosis, treatment and clinical-trial enrolment of patients with NASH. However, NASH has a strong metabolic component, with patients often carrying comorbid diseases, such as type 2 diabetes mellitus, obesity, hyperlipidaemia, hypothyroidism and sex steroid disorders. The primary care physician, internist and endocrinologist stand at a pivotal position in the NASH healthcare delivery system, as many of the diseases they commonly encounter are associated with a higher risk of developing NASH. Specialty society practice guidelines are evolving regarding the identification and care of patients with NASH. This review of the literature, and assessment of IQVIA's proprietary patient claims database of diagnosis codes, patient encounters and treatments, substantiates the importance of the primary care provider and endocrinologist in the clinical care and clinical research of patients with NASH.

Recruitment and Retention of Patients for Nonalcoholic Steatohepatitis Clinical Trials.

The volume of clinical studies globally in nonalcoholic fatty liver disease has created tremendous competition among sponsors and investigators to identify patients. Patients with nonalcoholic steatohepatitis are often asymptomatic and personally unaware and uneducated about the disease. In addition, many physicians caring for undiagnosed patients are also poorly informed of the disease. This has created a perfect storm of high demand for clinical research participants among a pool of difficult to identify patients with nonalcoholic steatohepatitis. Based on the current data, the current volume of nonalcoholic fatty liver disease studies requires 13,049 patients to fulfill their patient enrollment requirements.

Enteral Access and Associated Complications.

Enteral access is the foundation for feeding in patients unable to meet their nutrition needs orally and have a functional gastrointestinal tract. Enteral feeding requires placement of a feeding tube. Tubes can be placed through an orifice or percutaneously into the stomach or proximal small intestine at the bedside or in specialized areas of the hospital. Bedside tubes can be placed by the nurse or the physician, such as in the intensive care unit. Percutaneous feeding tubes are placed by the gastroenterologist, surgeon, or radiologist. This article reviews the types of enteral access and the associated complications.

A nutrition strategy for obese ICU patients with special consideration for the reference of protein.

Hypocaloric, high protein feeding regimens have been proposed for feeding obese critically ill patients. However, the exact amount of energy and protein that should be provided to the obese patients with these regimens is still under discussion. Furthermore, the body compartment to be used as a reference for appropriate protein dosing has not yet been determined. While both actual and ideal body weight have been proposed, neither is an accurate reflection of total body protein content in obese individuals. Alternatively, dosing protein based on lean body mass (LBM), which is highly correlated with total body protein, might be the most appropriate method of calculating protein requirements as defined by actual body composition. LBM can be measured or estimated by various methods. We herein discuss a rationale to determine both the energy and protein needs to use in hypocaloric feeding regimens for obese patients based on the use of Standard Body Weight (SBW) and LBM, using previously published body composition data from 1420 healthy volunteers. When applied to the obese population, and compared to current practices, this method results in highly significant differences for both total and gender-specific protein dosing.

Proteins and amino acids are fundamental to optimal nutrition support in critically ill patients.

Proteins and amino acids are widely considered to be subcomponents in nutritional support. However, proteins and amino acids are fundamental to recovery and survival, not only for their ability to preserve active tissue (protein) mass but also for a variety of other functions. Understanding the optimal amount of protein intake during nutritional support is therefore fundamental to appropriate clinical care. Although the body adapts in some ways to starvation, metabolic stress in patients causes increased protein turnover and loss of lean body mass. In this review, we present the growing scientific evidence showing the importance of protein and amino acid provision in nutritional support and their impact on preservation of muscle mass and patient outcomes. Studies identifying optimal dosing for proteins and amino acids are not currently available. We discuss the challenges physicians face in administering the optimal amount of protein and amino acids. We present protein-related nutrition concepts, including adaptation to starvation and stress, anabolic resistance, and potential adverse effects of amino acid provision. We describe the methods for assessment of protein status, and outcomes related to protein nutritional support for critically ill patients. The identification of a protein target for individual critically ill patients is crucial for outcomes, particularly for specific subpopulations, such as obese and older patients. Additional research is urgently needed to address these issues.

State of nutrition support teams.

The incidence of malnutrition in hospitalized patients is relatively high (up to 55%) despite breakthroughs in nutrition support therapies. These patients have increased morbidity and mortality, extended hospital stays, and care that is associated with higher costs. These patients are often poorly managed due to inadequate nutrition assessment and poor medical knowledge and practice in the field of nutrition. Nutrition support teams (NSTs) are interdisciplinary support teams with specialty training in nutrition that are often comprised of physicians, dietitians, nurses, and pharmacists. Their role includes nutrition assessment, determination of nutrition needs, recommendations for appropriate nutrition therapy, and management of nutrition support therapy. Studies have demonstrated significant improvements in patient nutrition status and improved clinical outcomes as well as reductions in costs when patients were appropriately managed by a multispecialty NST vs individual caregivers. Despite this, there has been steady decline in the number of formal NST in recent years (65% of hospitals in 1995 to 42% in 2008) as hospitals and other healthcare organizations look for ways to cut costs. Given the importance of nutrition status on clinical outcomes and overall healthcare costs, a number of institutions have introduced and sustained strong nutrition training and support programs and teams, demonstrating both clinical and economic benefit. The benefits of NST, training and implementation strategies, and tips for justifying these clinically and economically beneficial groups to healthcare organizations and governing bodies are discussed in this review.

Nutrition support in the intensive care patient.

Nutrition intervention plays a significant role in changing patient clinical outcomes in the intensive care unit. Identifying patients at nutrition risk with a validated tool is essential. The decision to use enteral or parenteral nutrition is patient dependent and should include an assessment of the patient's gastrointestinal function. Protein is a critical component of the nutrition prescription, and prescribed levels may need to be higher than current guidelines recommend. Alternative lipids, such as olive oil and fish oil, are still being evaluated for their potential clinical impact. Avoiding nutrition therapy-associated complications, such as catheter infection and hyperglycemia, are important factors in being able to maximize the effectiveness of a nutritional intervention.

Mortality among patients who receive or defer gastrostomies.

BACKGROUND & AIMS: There are few data on outcomes and mortality of patients who have received gastrostomies. We assessed 30-day and 1-year mortalities of patients in the United Kingdom who were referred to hospitals for gastrostomies and of patients who deferred this intervention. METHODS: We collected data from 1327 patients referred to 2 hospitals in Sheffield, United Kingdom, for gastrostomies from February 2004 through May 2010. Data were analyzed to determine 30-day and 1-year mortalities. Predicted mortality by using the validated Sheffield Gastrostomy Scoring System (SGSS) was then compared with actual mortality by using area under the receiver operator curves to determine levels of agreement in patients referred for gastrostomy. RESULTS: Three hundred four patients (23%) did not undergo gastrostomy after multidisciplinary team discussion, which was based on physicians' recommendations. This group had 35.5% mortality at 30 days and 74.3% at 1 year, whereas mortality among patients who underwent gastrostomy (n = 1027) was 11.2% at 30 days and 41.1% at 1 year (P < .0001, compared with patients who deferred the procedure). The area under the receiver operator curves for the SGSS demonstrated acceptable agreement between predicted and actual mortality in patients who underwent or were deferred gastrostomy. CONCLUSIONS: On the basis of data from 1327 patients, those who undergo gastrostomy have significantly lower mortality than those who defer the procedure. Without applying the SGSS, clinicians are able to select patients most likely to benefit from gastrostomy. The SGSS could provide objective support to clinicians involved in making ethically contentious or potentially litigious decisions.

The ratio of energy expenditure to nitrogen loss in diverse patient groups--a systematic review.

BACKGROUND & AIMS: The ratio of energy expenditure to nitrogen loss respectively of energy to nitrogen provision (E/N) is considered a valuable tool in the creation of an enteral or parenteral formulation. Specific E/N ratios for parenteral nutrition (PN) have not yet been clearly defined. To determine the range of energy expenditure, nitrogen (protein) losses, and E/N ratios for various patient groups, we performed a systematic review of the literature. METHODS: Medline 1950-2011 was searched for all studies on patients or healthy controls reporting energy expenditure and nitrogen loss at the same time. RESULTS: We identified 53 studies with 91 cohorts which comprised 1107 subjects. Mean TEE ± standard deviation (SD) was 31.2 ± 7.2 kcal/kg BW/day in patients (n = 881) and 35.6 ± 4.3 kcal/kg BW/day in healthy controls (n = 266). Mean total protein loss (TPL) was 1.50 ± 0.57 g/kg BW/day in patients and 0.94 ± 0.24 g/kg BW/day in healthy controls. A non-linear significant correlation was found between TPL and the E/N ratio. CONCLUSION: The E/N ratio is not a constant value but decreases continuously with increasing protein loss. These variations should be considered in the nutritional support of patients.

Parenteral nutrition therapy over the next 5-10 years: where are we heading?

Parenteral nutrition (PN) is one of the most complex medical therapies prescribed by healthcare professionals because it is dependent on the compounding of multiple base solutions to arrive at the final formulation. The delivery of PN is associated with errors in ordering, transcribing, compounding, and delivery of the PN formulations. New compounding technologies will attempt to minimize the potential for these errors. In addition, the associated infectious complications associated with PN therapy need to be minimized. Commercially prepared, premixed, terminally sterilized PN solutions may have an impact. Broader decontamination technologies will be implemented to reduce the incidence of overall nosocomial infections. Modification of PN nutrients, particularly intravenous fat emulsions, will be provided by alternative biological sources, creating fats that may have an improved impact on the patient's immune system and ultimately affecting clinical outcomes.

The gastroenterologist and industry: changing winds.

The medical device and pharmaceutical industry is facing mounting pressure to produce cost-effectiveness and clinical-effectiveness data in order for their products to be acceptable for approval by the Federal Drug Administration and then for payer reimbursement. The implications of these increasing burdens on our field will become apparent in everyday practice. This article outlines these challenges and discusses possible ways to improve the situation.