Time requirements for perioperative glucose management using fully closed-loop versus standard insulin therapy: A proof-of-concept time-motion study.

AIMS: To compare the time required for perioperative glucose management using fully automated closed-loop versus standard insulin therapy. METHODS: We performed a time-motion study to quantify the time requirements for perioperative glucose management with fully closed-loop (FCL) and standard insulin therapy applied to theoretical scenarios. Following an analysis of workflows in different periods of perioperative care in elective surgery patients receiving FCL or standard insulin therapy upon hospital admission (pre- and intra-operatively, at the intermediate care unit and general wards), the time of process-specific tasks was measured by shadowing hospital staff. Each task was measured 20 times and its average duration in combination with its frequency according to guidelines was used to calculate the cumulative staff time required for blood glucose management. Cumulative time was calculated for theoretical scenarios consisting of elective minor and major abdominal surgeries (pancreatic surgery and sleeve gastrectomy, respectively) to account for the different care settings and lengths of stay. RESULTS: The FCL insulin therapy reduced the time required for perioperative glucose management compared to standard insulin therapy, across all assessed care periods and for both perioperative pathways (range 2.1-4.5). For a major abdominal surgery, total time required was 248.5 min using FCL versus 753.9 min using standard insulin therapy. For a minor abdominal surgery, total time required was 68.6 min and 133.2 min for FCL and standard insulin therapy, respectively. CONCLUSIONS: The use of fully automated closed-loop insulin delivery for inpatient glucose management has the potential to alleviate the workload of diabetes management in an environment with adequately trained staff.

Total costs of inpatient treatment for COVID-19 in a tertiary hospital in Serbia.

BACKGROUND: Our study aimed to identify the total costs of inpatient treatment for coronavirus disease 2019 (COVID-19) in a tertiary institution in Serbia, an upper-middle-income country in Southeast Europe. METHODS: An observational, retrospective, cost-of-illness study was performed from the perspective of the National Health Insurance Fund and included a cohort of 78 females and 118 males admitted to the COVID-19 ward units of a tertiary center during the first wave of the pandemic. RESULTS: The median of the total costs in the non-survivors subgroup (n =43) was 3,279.16 Euros [interquartile range (IQR): 4,023.34; range: 355.20-9,909.61) which is higher than in the survivors (n =153) subgroup 747.10 Euros (IQR: 1,088.21; 46.71-3,265.91). The cut-off value of 156.46 Euros regarding the total costs per day was estimated to have 95.3 % sensitivity and 91.5 % specificity for predicting patients' dismal prognosis, with the area under the curve (AUC) of 0.968 (95 % confidence interval: 0.940-0.996, p <0.001). CONCLUSIONS: Direct medical inpatient treatment costs for COVID-19 represent a significant economic burden. The link between increased costs and an ultimate unfavorable outcome should be further explored.HIPPOKRATIA 2022, 26 (2):62-69.

Management of the COVID-19 pandemic in Rhineland-Palatinate hospitals of all levels of care : Results of the COVID-19 Registry RLP.

The COVID-19 pandemic placed a significant burden on the German healthcare system. Based on the experience of severe disease progression of the SARS-CoV­2 infection from neighboring European countries in the early 2020s, with ICU overload and high mortality rates, efforts were made in Germany to increase the capacity of available ICU beds. Subsequently, all documentation and reporting focused on the ICU capacities for COVID-19 patients. It was hypothesized that mainly a few large hospitals provided care for the majority of COVID-19 patients. The COVID-19 Registry RLP of Rhineland-Palatinate documented SARS-CoV­2 inpatients from daily mandatory queries of all hospitals throughout the pandemic from April 2020 to March 2023, distinguishing between patients in ICUs and normal wards. In its 18th Corona Ordinance, the state government required all hospitals to participate in the care of SARS-CoV­2 inpatients. We investigated the participation of hospitals at different levels of care in Rhineland-Palatinate in the management of the COVID-19 pandemic. Nine pandemic waves were documented during the pandemic and exemplary data on the respective pandemic peaks were evaluated. A distinction was made between the burden on hospitals at different levels of care: primary care hospitals, standard care hospitals, specialty hospitals, and maximal care hospitals. Analysis of the data showed that all hospital types participated equally in the care of SARS-CoV-2 patients. The requirement of the Ministry of Health of Rhineland-Palatinate to provide at least 20% of the available capacity was met by all levels of care and there were no disparities between hospitals of different levels of care in the management of the pandemic.Hospitals at all levels of care participated equally in the care of SARS-CoV­2 inpatients and thus contributed significantly to the management of the pandemic in Rhineland-Palatinate.

The Effect of Vitamin D Level on the Clinical Situation in COVID-19 Patients

Objective: Vitamin D plays an important role in maintaining the integrity of mucosal barriers and in natural and acquired immunity. In the COVID-19 pandemic, the strength of personal immunity is very important in the course of the disease, despite the presence of variants of the virus or vaccination status. Method: In this study, we investigated the relationship between the clinical course and vitamin D levels of outpatient and inpatient follow-up patients admitted to our hospital due to COVID-19. A total of 94 patients, 47 outpatients and 47 inpatients, were included in the study. Results: The mean age and gender distributions of both groups were similar. Vitamin D levels were found to be normal in only 7 of 94 patients who were followed up in our hospital due to COVID-19. Patients with vitamin D levels >= 30 were significantly lower than those with "<10" and "10-29.9" (p<0.01 for each). Hospitalized patients (71%) with vitamin D levels <10 were significantly higher than those (0%) with vitamin D levels >= 30. Additionally, the outpatients (29%) with vitamin D levels <10 were significantly lower than those (100%) with vitamin D levels >= 30. Conclusion: The data showed that vitamin D deficiency may be associated with the severe clinical course of COVID-19, even in patients without comorbidities, and may also be one of the predisposing factors resulting in death in COVID-19. As a result, vitamin D levels in COVID-19 patients may be important for the course of the disease.

The Rowan Hillson Inpatient Safety Award 2022 The best interventions: redesigning, rebuilding and maintaining safe inpatient diabetes care during COVID

Introduction: The annual National Diabetes Inpatient Audit (NaDIA and NaDIA-Harms) in the UK continues to show significant problems with patient care. During the COVID pandemic patient care has been even more difficult. New initiatives are urgently required to improve inpatient safety for people with diabetes. Method: The Joint British Diabetes Societies for Inpatient Care (JBDS-IP) organised the seventh national Rowan Hillson In-patient Safety Award on the theme of "the best interventions: redesigning, rebuilding and maintaining safe inpatient diabetes care during COVID". Result: The winner was the DEKODE team, led by Dr Punith Kempegowda from University Hospitals Birmingham NHS Foundation Trust, for their innovative quality improvement project across hospitals during COVID to improve diabetes-related ketoacidosis (DKA) management and study DKA in people with COVID. Adherence to national guidance improved in some hospitals, with falls in hypoglycaemia, and overall there was a significant improvement in awareness about DKA amongst junior doctors. The King's College NHS Foundation Trust team, led by Adrian Li and colleagues, received the highly commended award for their innovative project of remote blood glucose (BG) monitoring across healthcare boundaries. This improved diabetes control and tackled health inequalities. Summary and conclusion: These and similar schemes need to be developed, promoted and shared to improve safety for people with diabetes admitted in hospital during COVID times.

Characteristics of suicidal emergency room patients before and during the COVID-19 pandemic in Japan.

AIM: Owing to the stress caused by the behavioral restrictions and lifestyle changes during the COVID-19 pandemic, suicide rates have increased in Japan, especially among young people. This study aimed to identify the differences in the characteristics of patients hospitalized for suicide attempts in the emergency room, requiring inpatient care before and during the pandemic over 2 years. METHODS: This study was a retrospective analysis. Data were collected from the electronic medical records. A descriptive survey was conducted to examine changes in the pattern of suicide attempts during the COVID-19 outbreak. Two-sample independent t-tests, Chi-square tests, and Fisher's exact test were used for data analysis. RESULTS: Two hundred one patients were included. No significant differences were found in the number of patients hospitalized for suicide attempts, average age, or sex ratio before and during the pandemic periods. Acute drug intoxication and overmedication in patients increased significantly during the pandemic. The self-inflicted means of injury with high fatality rates were similar during the two periods. The rate of physical complications significantly increased during the pandemic, while the proportion of unemployed individuals significantly decreased. CONCLUSIONS: Despite studies predicting an increase in suicides based on past statistics of young people and of women, no significant changes were observed in this survey of the Hanshin-Awaji region, including Kobe. This may have been owing to the effect of suicide prevention measures and mental health measures implemented by the Japanese government after an increase in suicides and after past natural disasters.

Characteristics and clinical effectiveness of COVID-19 vaccination in hospitalized patients in Omicron-dominated epidemic wave - a nationwide study in Japan.

OBJECTIVES: COVID-19 was severe in the Delta variant-dominated epidemic wave (fifth wave) in Japan. The clinical characteristics and effectiveness of COVID-19 vaccination are not fully understood in the Omicron variant-dominated wave (sixth and seventh waves), especially in hospitalized patients. We investigated the relationship between vaccination and disease severity in the Omicron-dominated wave and compared these variant-dominated waves. METHODS: The nationwide COVID-19 database (Japan COVID-19 Task Force) was used to compare clinical characteristics and critical outcomes in patients hospitalized with Delta (fifth, N = 735) vs Omicron-dominated waves (sixth, N = 495; seventh, N = 128). RESULTS: Patients in the sixth and seventh waves had a lower incidence of critical outcomes and respiratory outcomes, and a higher incidence of bacterial infection, although the mortality rate did not differ significantly between waves. In the sixth and seventh waves, 138 (27.9%) and 29 (22.7%) patients with COVID-19 were unvaccinated, respectively. Multivariable analysis adjusted with previously reported factors revealed that the proportion of (1) critical outcomes and (2) respiratory outcomes decreased in a frequency-dependent manner. Thus, (1) (the number of vaccinations): 1-2 times: adjusted odds ratio (aOR) 0.37 (95% confidence interval [CI]; 0.20-0.69); 3-4 times: aOR 0.25 (95% CI; 0.11-0.58); and (2) 1-2 times: aOR 0.43 (95% CI; 0.27-0.66); 3-4 times: aOR 0.36 (95% CI; 0.21-0.60). CONCLUSIONS: Patients hospitalized with COVID-19 with Omicron infections showed a lower incidence of critical outcomes than those with Delta infections, and COVID-19 vaccination may contribute to preventing respiratory failure.

Prevalence of Psychological Distress and Posttraumatic Stress Symptoms and Associated Factors in Hospitalized Iranian COVID-19 Patients.

Objectives: To investigate the prevalence of psychiatric symptoms/distress and posttraumatic stress (PTS) and associated factors among inpatients with COVID-19 before discharge from the hospital. Methods: This cross-sectional study was conducted in two teaching referral hospitals in Babol, Iran from July to November 2020. The subjects were inpatients diagnosed with COVID-19 who were clinically stable. Before their discharge from the hospital, the patients completed three questionnaires: demographic data, Brief Symptom Inventory, and Primary Care Post Traumatic Stress Disorder Screen for Diagnostic and Statistical Manual-5. Results: The subjects were 477 inpatients diagnosed with COVID-19 including 40 (8.4%) admitted to intensive care units. Their average age was 60.5±17.9 years; 53.9% were female. Most had symptoms of significant psychological distress (96.0%) and PTS (8.1%) prior to discharge. A higher level of education (-0.18; standard error (SE) = 0.05; p < 0.001) was a negative predictor of psychiatric distress. The admission to intensive care units (0.86; SE = 0.08; p< 0.001) was a positive predictor of psychiatric distress. Conclusions: Most COVID-19 inpatients suffered significant psychiatric distress and PTS symptoms before discharge. Appropriate mental health crisis interventions are recommended for COVID-19 patients during hospitalization.

Development and evaluation of a nurse practitioner-directed rapid COVID-19 testing in an inpatient substance use disorder treatment facility

The COVID-19 global pandemic hit the United States in early 2020. The pandemic had forced many businesses to shut their doors temporarily and permanently. The mental health and substance use population was hit harder than ever before. Due to uncontrollable factors such as homelessness, and unknown or undertreated preexisting conditions, the COVID-19 virus took an intractable hold on the treatment facilities where this population of patients turned to when they were ready for change. This Doctor of Nursing Practice (DNP) project implemented rapid COVID-19 testing for all newly admitted patients into an inpatient substance use disorder (SUD) treatment facility. Testing was implemented for six weeks utilizing the rapid antigen tests. The proposal for initiating rapid COVID-19 testing, identified the problem early in treatment, allowing for the initiation of early intervention and better patient outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

The Effect of the COVID-19 Pandemic on Use of Select Child Health Services in Kenyan Hospitals

Introduction. Kenya reported its first case of coronavirus disease (COVID-19) in March 2020. Pandemics may disrupt provision of essential health services. This study sought to find out if the COVID-19 outbreak had any effect on reported paediatric workload in Kenya. Methods. Aggregate workload data for 12 months before COVID-19 outbreak and 12 months of the COVID-19 outbreak were extracted from the Kenya Health Information System and negative binomial regression conducted. Results. A significant decline was observed across all indicators. Paediatric clinics attendance declined by 36%, paediatric admissions by 31.4%, outpatient attendance by 28.7%, and child wellness clinics attendance by 10.3%. In outpatient attendance, the five conditions with the highest attendance reported a decline ranging from 17.3% to 33.8%. Conclusion. COVID-19 partially disrupted essential health services among children in Kenya. Children in need of specialized treatment were more disadvantaged.

Experience of psychosis during the COVID-19 pandemic among hospitalized patients

The content of auditory hallucinations (AHs) and delusions is malleable and reflects the social environment and the local culture. COVID-19 is a significant new feature of the social environment, yet research has not yet determined how the phenomenology of psychosis has changed since the COVID-19 outbreak. Adult patients (N = 17) receiving care within an acute inpatient psychiatric care setting in Boston were recruited to participate in an hour-long Zoom interview about their psychosis phenomenology and the potential impact of COVID-19. Thematic analysis of interview data found that for many, ideas about COVID-19 were present in the content of their AHs and shaped their paranoid ideation. Some felt that the frequency and loudness of the AHs had increased. However, not all participants spoke in ways that suggested the virus had affected their experience. Results demonstrate that COVID-19 influenced the content of psychosis for many, but the effect of COVID-19 on psychosis was not uniform. The increased social isolation, financial insecurity, and socio-political climate of the period also seemed to negatively impact individuals with psychosis. Understanding how COVID-19 specifically has influenced psychosis helps to illustrate how societal and external factors may shape this experience.

Increasing the Level of Neopterin in patients infected with SARS-CoV-2 Indicates Fatal Mortality

Background: The severity of Coronavirus Disease-2019 (COVID-19) cases is associated with hyperinflammation. Patients with critical and severe COVID-19 have been observed to have high amounts of circulating cytokines. Neopterin, a crucial cytokine in the antiviral immune response that is released by macrophages upon stimulation with interferon-gamma, can be utilized to forecast the severity of illness in COVID-19 patients. Methods: The study included 185 patients with COVID-19. The patients with COVID-19 were divided into three groups according to disease severity as critical disease (n=51), severe disease (n=81), and moderate disease (n=53). All basic demographic and clinical data of the patients were recorded and blood samples were collected. Results: Neopterin levels were significantly higher in critical COVID-19 patients compared with severe and moderate COVID-19 patients (p < 0.0001). Further, neopterin showed significantly higher levels in the age group >50 years of patients with COVID-19 than in the age group <50 years. Neopterin levels were correlated with WBCs, Platelet, CRP, D-Dimer, Ferritin, Fibrinogen, IL-6, and Procalcitonin levels positively (ρ= 0.569, 0.474, 0.338, 0.696, 0.605, 0.77, 0.727, and 0.585;p < 0.01 respectively), and correlated with BMI, SpO2, and lymphocyte negatively (ρ= - 0.165;p < 0.05, p= - 0.754, - 0. 548;p < 0.01 respectively). A cutoff value of 23.62 nmol/L for neopterin predicted COVID-19 with a sensitivity of 95.7% and a specificity of 95.5% (AUC: 0.986;p < 0.0001). Conclusion: Neopterin may be a useful prognostic biomarker for assessing the severity of COVID-19.

Postscript: Responding to the COVID-19 pandemic

The risk posed to health facilities by COVID-19 is well recognised. From the first wave of infections in 2020, protective measures have been in place. In accordance with health district policy, staff and visitors were screened before entry to the Walker Unit. Along with the rest of the world, Walker staff became familiar with conducting meetings through online platforms such as Zoom. Compliance with ever changing infection control directives was a challenge, indeed a threat to the viability of the programme. There have been direct impacts on the operation of the Walker Unit, with travel and visiting severely restricted. The chapter will outline the adaptations made to the Walker programme through the pandemic. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Implementing caregiver management measures in general hospitals to prevent the COVID-19 pandemic.

AIM: To summarize the whole process management measures for caregivers of inpatients in a non-new coronavirus pneumonia designated hospital in China during the novel coronavirus pneumonia epidemic. The implementation of these measures is mainly to prevent the virus pandemic caused by crowd gathering. DESIGN: A quasi-experimental study. METHODS: Novel coronavirus pneumonia prevention and control measures were implemented in the 'pre-hospital link, hospitalization link and discharge link' for the whole process of the hospitalized patients' caregivers. To evaluate the effects by time point inspection, the results were fed back using information technology for quality improvement. RESULTS: The results of three time point inspections indicated that the management quality of many projects improved continuously (p < 0.05). From January to June of 2021, 20 departments implemented a facial recognition information management system. The ratio of patients/caregivers admitted was 1:0.528~1:0.965; It was found that it is effective to implement the whole process management measures. The facial recognition system plays a key role in the comprehensive management of the caregivers.

Dynamic Changes of ORF1ab and N Gene Ct Values in COVID-19 Omicron Inpatients of Different Age Groups - Beijing Municipality, China, November-December 2022.

Introduction: In November 2021, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was identified as the variant of concern and has since spread globally, replacing other cocirculating variants. To better understand the dynamic changes in viral load over time and the natural history of the virus infection, we analyzed the expression of the open reading frames 1ab (ORF1ab) and nucleocapsid (N) genes in patients infected with Omicron. Methods: We included patients initially admitted to the hospital for SARS-CoV-2 infection between November 5 and December 25, 2022. We collected daily oropharyngeal swabs for quantitative reverse transcriptase-polymerase chain reaction tests using commercial kits. We depicted the cycle threshold (Ct) values for amplification of ORF1ab and N genes from individual patients in age-specific groups in a time series. Results: A total of 480 inpatients were included in the study, with a median age of 59 years (interquartile range, 42 to 78; range, 16 to 106). In the <45-year-old age group, the Ct values for ORF1ab and N gene amplification remained below 35 for 9.0 and 11.5 days, respectively. In the ≥80-year-old age group, the Ct values for ORF1ab and N genes stayed below 35 for 11.5 and 15.0 days, respectively, which was the longest among all age groups. The Ct values for N gene amplification took longer to rise above 35 than those for ORF1ab gene amplification. Conclusion: The time to test negative varied among different age groups, with viral nucleic acid shedding taking longer in older age groups compared to younger age groups. As a result, the time to resolution of Omicron infection increased with increasing age.

Post-traumatic stress disorder among COVID-19-affected high-risk cardiac patients.

BACKGROUND: During the first coronavirus disease 2019 (COVID-19) wave there was a high prevalence of mental health impairments and post-traumatic stress disorder (PTSD), particularly in patients with comorbid cardiac diseases. METHODS: During waves 2-5, all hospitalized patients with cardiac problems and suspected COVID-19 were eligible to participate in this study. RESULTS: The prevalence of PTSD was 31.4% (n=48) in 153 participants. No age- and gender-related differences for PTSD were found. CONCLUSIONS: The prevalence is lower than during the first wave but higher than in patients reported in other studies who were isolated at home. Routine mental health assessments are strongly recommended for patients at risk.

The clinical practice of palliative sedation in patients dying from COVID-19: a retrospective chart review.

BACKGROUND: Clinical experts experienced challenges in the practice of palliative sedation (PS) during the COVID-19 pandemic. Rapid deterioration in patients' situation was observed while the indications for starting PS seemed to differ compared to other terminal patients. It is unclear to which extent clinical trajectories of PS differ for these COVID patients compared to regular clinical practice of PS. OBJECTIVES: To describe the clinical practice of PS in patients with COVID versus non-COVID patients. METHODS: A retrospective analysis of data from a Dutch tertiary medical centre was performed. Charts of adult patients who died with PS during hospitalisation between March '20 and January '21 were included. RESULTS: During the study period, 73 patients received PS and of those 25 (34%) had a COVID infection. Refractory dyspnoea was reported as primary indication for starting PS in 84% of patients with COVID compared to 33% in the other group (p < 0.001). Median duration of PS was significantly shorter in the COVID group (5.8 vs. 17.1 h, p < 0.01). No differences were found for starting dosages, but median hourly dose of midazolam was higher in the COVID group (4.2 mg/hr vs. 2.4 mg/hr, p < 0.001). Time interval between start PS and first medication adjustments seemed to be shorter in COVID patients (1.5 vs. 2.9 h, p = 0.08). CONCLUSION: PS in COVID patients is characterized by rapid clinical deterioration in all phases of the trajectory. What is manifested by earlier dose adjustments and higher hourly doses of midazolam. Timely evaluation of efficacy is recommended in those patients.

Comparative Analysis of 30-Day Readmission, Reoperation, and Morbidity between Posterior Cervical Decompression and Fusion Performed in Inpatient and Outpatient Settings.

STUDY DESIGN: A retrospective cohort study. PURPOSE: To compare 30-day readmission, reoperation, and morbidity for patients undergoing posterior cervical decompression and fusion (PCDF) in inpatient vs. outpatient settings. OVERVIEW OF LITERATURE: PCDF has recently been increasingly performed in outpatient settings, often utilizing minimally invasive techniques. However, literature evaluating short-term outcomes for PCDF is scarce. Moreover, no currently large-scale database studies have compared short-term outcomes between PCDF performed in the inpatient and outpatient settings. METHODS: Patients who underwent PCDF from 2005 to 2018 were identified using the National Surgical Quality Improvement Program database. Regression analysis was utilized to compare primary outcomes between surgical settings and evaluate for predictors thereof. RESULTS: We identified 8,912 patients. Unadjusted analysis revealed that outpatients had lower readmission (4.7% vs. 8.8%, p =0.020), reoperation (1.7% vs. 3.8%, p =0.038), and morbidity (4.5% vs. 11.2%, p <0.001) rates. After adjusting for baseline differences, readmission, reoperation, and morbidity no longer statistically differed between surgical settings. Outpatients had lower operative time (126 minutes vs. 179 minutes) and levels fused (1.8 vs. 2.2) (p <0.001). Multivariate analysis revealed that age (p =0.008; odds ratio [OR], 1.012), weight loss (p =0.045; OR, 2.444), and increased creatinine (p <0.001; OR, 2.233) independently predicted readmission. The American Society of Anesthesiologists (ASA) classification of ≥3 predicted reoperation (p =0.028; OR, 1.406). Rehabilitation discharge (p <0.001; OR, 1.412), ASA-class of ≥3 (p =0.008; OR, 1.296), decreased hematocrit (p <0.001; OR, 1.700), and operative time (p <0.001; OR, 1.005) predicted morbidity. CONCLUSIONS: The 30-day outcomes were statistically similar between surgical settings, indicating that PCDF can be safely performed as an outpatient procedure. Surrogates for poor health predicted negative outcomes. These results are particularly important as we continue to shift spinal surgery to outpatient centers. This importance has been highlighted by the need to unburden inpatient sites, particularly during public health emergencies, such as the coronavirus disease 2019 pandemic.

Surfing the Waves: Differences in Hospitalised COVID-19 Patients across 4 Variant Waves in a Belgian University Hospital.

The unprecedented COVID-19 pandemic took the form of successive variant waves, spreading across the globe. We wanted to investigate any shift in hospitalised patients' profiles throughout the pandemic. For this study, we used a registry that collected data automatically from electronic patient health records. We compared clinical data and severity scores, using the National Institute of Health (NIH) severity scores, from all patients admitted for COVID-19 during four SARS-CoV-2 variant waves. Our study concluded that patients hospitalised for COVID-19 showed very different profiles across the four variant waves in Belgium. Patients were younger during the Alpha and Delta waves and frailer during the Omicron period. 'Critical' patients according to the NIH criteria formed the largest fraction among the Alpha wave patients (47.7%), while 'severe' patients formed the largest fraction among Omicron patients (61.6%). We discussed host factors, vaccination status, and other confounders to put this into perspective. High-quality real-life data remain crucial to inform stakeholders and policymakers that shifts in patients' clinical profiles have an impact on clinical practice.