Strategies to Diagnose Nonalcoholic Steatohepatitis: A Novel Approach to Take Advantage of Pharmacokinetic Alterations.

Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD) and is diagnosed by a liver biopsy. Because of the invasiveness of a biopsy, the majority of patients with NASH are undiagnosed. Additionally, the prevalence of NAFLD and NASH creates the need for a simple screening method to differentiate patients with NAFLD versus NASH. Noninvasive strategies for diagnosing NAFLD versus NASH have been developed, typically relying on imaging techniques and endogenous biomarker panels. However, each technique has limitations, and none can accurately predict the associated functional impairment of drug metabolism and disposition. The function of several drug-metabolizing enzymes and drug transporters has been described in NASH that impacts drug pharmacokinetics. The aim of this review is to give an overview of the existing noninvasive strategies to diagnose NASH and to propose a novel strategy based on altered pharmacokinetics using an exogenous biomarker whose disposition and elimination pathways are directly impacted by disease progression. Altered disposition of safe and relatively inert exogenous compounds may provide the sensitivity and specificity needed to differentiate patients with NAFLD and NASH to facilitate a direct indication of hepatic impairment on drug metabolism and prevent subsequent adverse drug reactions. SIGNIFICANCE STATEMENT: This review provides an overview of the main noninvasive techniques (imaging and panels of biomarkers) used to diagnose NAFLD and NASH along with a biopsy. Pharmacokinetic changes have been identified in NASH, and this review proposes a new approach to predict NASH and the related risk of adverse drug reactions based on the assessment of drug elimination disruption using exogenous biomarkers.

Changes in admission rates to an Aotearoa New Zealand hospital general medical service during COVID-19 lockdowns.

AIM: To better understand the reasons for reduced hospital admissions to a hospital general medicine service during COVID-19 lockdowns. METHODS: A statistical model for admission rates to the General Medicine Service at Wellington Hospital, Aotearoa New Zealand, since 2015 was constructed. This model was used to estimate changes in admission rates for transmissible and non-transmissible diagnoses during and following COVID-19 lockdowns for total admissions and various sub-groups. RESULTS: For the 2020 lockdown (n=734 admissions), the overall rate ratio of admissions was 0.71 compared to the pre-lockdown rate. Non-transmissible diagnoses, which constitute 87% of admissions, had an admission rate ratio of 0.77. Transmissible diagnoses, constituting 13% of admissions, had an admission rate ratio of 0.44. Reductions in admissions did not exacerbate existing ethnic disparities in access to health services. The lag in recovery of admission rates was more pronounced for transmissible than non-transmissible diagnoses. The 2021 lockdown (n=105 admissions) followed this pattern, but was of shorter duration with small numbers, and therefore measures were frequently not statistically significant. CONCLUSIONS: The biggest relative reduction in hospital admission was due to a reduction in transmissible illness admissions, likely due to COVID-related public health measures. However, the biggest reduction in absolute terms was in non-transmissible illnesses, where hospital avoidance may be associated with increased morbidity or mortality.

Rethinking resuscitation: moving the goals.

Cardiopulmonary resuscitation (CPR) techniques have developed remarkably since first described. CPR is now both a default treatment and a public expectation. However, anticipated outcomes are not matched by reality. The differences between in- and out-of-hospital cardiac arrests are often not recognised and almost never taught. 'Do Not Resuscitate' orders developed to provide the ability to opt-out of this treatment. Nevertheless, CPR is still inappropriately used in settings where reversibility and likelihood of benefit are not meaningfully considered or discussed with the patient. Further, treatment escalation is a continuum, so resuscitation orders present a false dichotomy of 'do' or 'do not' resuscitate. Asking patients about their goals, and only offering treatments aligned with those goals, allows consideration of the burden of treatment and the likelihood of success. Shared decision models improve communication and patient autonomy. Tools are available to help clinicians with the difficult conversation and document the outcomes. Now, in both our training and practice, it is time to move beyond the stark and often irrelevant choice between CPR and 'Not for Resuscitation'.

Did an acute medical assessment unit improve the initial assessment and treatment of community acquired pneumonia--a retrospective audit.

AIM: Medical Assessment and Planning Units (MAPUs) are proposed as a means to treat medically unwell patients in a timely and clinically appropriate manner, thus improving quality, facilitating safe early discharge, and reducing congestion in emergency departments. This study assessed the impact of opening a MAPU on the initial assessment and treatment of patients with community-acquired pneumonia (CAP). METHOD: A retrospective audit of patients presenting to Wellington Hospital was conducted from January to March 2009 and January to March 2010, straddling the opening of a MAPU. Outcome measures included timeliness of assessment, indicators of clinical quality, length of stay, recommended follow-up and mortality. RESULTS: MAPU referred patients were less unwell and younger. Times to first doctor assessment and X-ray were longer than in the Emergency Department (ED) following the introduction of the MAPU; time to physician review for all admitted patients was unchanged compared to before the opening of the MAPU. Compliance with other aspects of evidence based guidelines was patchy and showed no improvement following the opening of the MAPU. Most patients whose length of stay was short were appropriately admitted to the MAPU. CONCLUSION: The MAPU has successfully streamed a cohort of less unwell patients away from the ED. Opportunity exists to improve the timeliness of treatment and compliance with guidelines. A disease-specific audit has served as a useful adjunct to other approaches to assessing a unit's impact.

Old man's friend? Resuscitation decisions in patients hospitalised with pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a common illness, for which hospitalisation leads to significant inpatient and subsequent mortality. The frequency and timing of discussion of end-of-life issues with these inpatients is therefore relevant. AIM: To determine whether end-of-life discussions occurred for patients with CAP whose prognostic indicators suggested a high risk of dying. METHODS: A retrospective review of 155 admissions with CAP was conducted. The nature and timing of resuscitation decisions were correlated with age, illness severity and mortality. RESULTS: Mortality following admission with CAP increases with age and severity. Of those over 65, 37% die within 12 months of discharge; 11% die on the index admission, and a further 26% die in the 12 months following discharge. Mortality increases dramatically with older age: those over 80 had a 47% 12-month mortality. End-of-life decisions were documented prior to death for all inpatient deaths. However, end-of-life decisions were only documented in a minority of other cases, even amongst those with highest risk of subsequent mortality. CONCLUSIONS: In a common illness with significant mortality, opportunity exists to better identify those at high risk of mortality and initiate discussions about end-of-life care. A not-for-resuscitation discussion currently appears to function as a surrogate marker for impending death rather than an opportunity to elicit a patient's wishes for their care should they be at high risk of dying in the near future.

Using a sterile disposable protective surgical drape for reduction of radiation exposure to interventionalists.

OBJECTIVE: The purpose of this paper is to show the effectiveness of a new radiation protection method designed to decrease the amount of scatter radiation received by practitioners performing procedures under fluoroscopic guidance. MATERIALS AND METHODS: A sterile, disposable, lead-free surgical drape containing radiation protection material composed primarily of bismuth was evaluated for effectiveness in reducing radiation doses to health care personnel. Measurements of phantom scatter, patient scatter, skin entrance, and the effects of collimation, together with comparative monthly thermoluminescent dosimeter recordings, were taken to determine the effectiveness of X-ray beam attenuation using the bismuth drapes. RESULTS: Scatter radiation to physicians, as measured by thermoluminescent dosimeters placed on each eye, the thyroid, and the wrist, was reduced by 12-fold for the eyes, 25-fold for the thyroid, and 29-fold for the hands when the radiation-attenuating surgical drape was used when compared with control studies performed with a standard nonattenuating surgical drape alone. Monthly thermoluminescent dosimeter measurements decreased fourfold in one physician. Using the protective drape reduced exposure to the assistant in each case to negligible levels. Skin entrance dose was not increased unless the protective drape was placed directly in the X-ray beam. An X-ray attenuation factor equivalent to 0.1 mm of lead with 8 x 8 cm collimation reduced the scatter rates from five- to ninefold despite a 30-40% increase in entrance exposure rate as the lead equivalence increased. CONCLUSION: Depending on the procedure, the height of the practitioner, and the positioning of the radiation-attenuating surgical drape, use of this drape can substantially reduce the radiation dose to personnel with minimal or no additional radiation exposure to the patient.