High-dose pulse methylprednisolone vs. dexamethasone standard therapy for severe and critical COVID-19 pneumonia: Efficacy assessment in a retrospective single-centre experience from Malaysia.

INTRODUCTION: The use of dexamethasone (DXM) has been associated with decreased mortality in the patients with hypoxemia during the coronavirus disease-2019 (COVID-19) pandemic, while the outcomes with methylprednisolone (MTP) have been mixed. This real-life study aimed to evaluate the outcomes of patients with severe respiratory failure due to COVID-19 who were treated with high doses of MTP. MATERIALS AND METHODS: This retrospective cohort study enrolled hospitalised patients between May 2021 and August 2021, aged 18 years and above, with severe respiratory failure defined by a ratio of oxygen saturation to fraction of inspired oxygen (SF ratio) of less than 235. The treatment protocol involved administering high-dose MTP for 3 days, followed by DXM, and the outcomes were compared with those of patients who received DXM alone (total treatment duration of 10 days for both groups). RESULTS: A total of 99 patients were enrolled, with 79 (79.8%) receiving pulse MTP therapy and 20 (20.2%) being treated with DXM only. The SF ratio significantly improved from a mean of 144.49 (±45.16) at baseline to 208 (±85.19) at 72 hours (p < 0.05), with a mean difference of 63.51 (p < 0.001) in patients who received ≤750 mg of MTP. Additionally, in patients who received >750 mg of MTP, the SF ratio improved from a baseline mean of 130.39 (±34.53) to 208.44 (±86.61) at 72 hours (p < 0.05), with a mean difference of 78.05 (p = 0.001). In contrast, patients who received DXM only demonstrated an SF ratio of 132.85 (±44.1) at baseline, which changed minimally to 133.35 (±44.4) at 72 hours (p = 0.33), with a mean difference of 0.50 (p = 0.972). The incidence of nosocomial infection was higher in the MTP group compared with the DXM group (40.5% vs. 35%, p = 0.653), with a relative risk of 1.16 (95% CI: 0.60-2.23). CONCLUSION: MTP did not demonstrate a significant reduction in intubation or intensive care unit admissions. Although a high dose of MTP improved gas exchange in patients with severe and critical COVID-19, it did not provide an overall mortality benefit compared to standard treatment.

Racial representation in clinical trials for dermatological new molecular entities.

Under-representation of ethnic minorities in clinical research has major implications for equality of access to current treatments in the field of dermatology. To determine whether there has been equitable representation of black individuals in the clinical trials for dermatological new molecular entities (NMEs) approved by the US Food and Drug Administration (FDA) since 2015, we analysed data from the FDA Drug Trials Snapshots programme from January 2015 to the present. During this period, there was significant under-representation of black participants in clinical trials for NMEs treating acne vulgaris, plaque psoriasis, actinic keratosis and squamous cell carcinoma. These findings highlight the need to prioritize representation of ethnic minorities in clinical trials to enhance clinical practice in the field of dermatology and to improve the care and health of minorities.

Bariatric surgery is expensive but improves co-morbidity: 5-year assessment of patients with obesity and type 2 diabetes.

BACKGROUND: Bariatric surgery can be effective in weight reduction and diabetes remission in some patients, but is expensive. The costs of bariatric surgery in patients with obesity and type 2 diabetes mellitus (T2DM) were explored here. METHODS: Population-based retrospectively gathered data on patients with obesity and T2DM from the Hong Kong Hospital Authority (2006-2017) were evaluated. Direct medical costs from baseline up to 60 months were calculated based on the frequency of healthcare service utilization and dispensing of diabetes medication. Charlson Co-morbidity Index (CCI) scores and co-morbidity rates were measured to compare changes in co-morbidities between surgically treated and control groups over 5 years. One-to-five propensity score matching was applied. RESULTS: Overall, 401 eligible surgical patients were matched with 1894 non-surgical patients. Direct medical costs were much higher for surgical than non-surgical patients in the index year (€36 752 and €5788 respectively; P < 0·001) mainly owing to the bariatric procedure. The 5-year cumulative costs incurred by surgical patients were also higher (€54 135 versus €28 603; P < 0·001). Although patients who had bariatric surgery had more visits to outpatient and allied health professionals than those who did not across the 5-year period, surgical patients had shorter length of stay in hospitals than non-surgical patients in year 2-5. Surgical patients had significantly better CCI scores than controls after the baseline measurement (mean 3·82 versus 4·38 at 5 years; P = 0·016). Costs of glucose-lowering medications were similar between two groups, except that surgical patients had significantly lower costs of glucose-lowering medications in year 2 (€973 versus €1395; P = 0.012). CONCLUSION: Bariatric surgery in obese patients with T2DM is expensive, but leads to an improved co-morbidity profile, and reduced length of hospitalization.

Fecobionics assessment of the effect of position on defecatory efficacy in normal subjects.

BACKGROUND: Defecation is a complex process and up to 25% of the population suffer from symptoms of defecatory dysfunction. For functional testing, diagnostics, and therapy of anorectal disorders, it is important to know the optimal defecation position. is The aim of this study was to evaluate defecation pressure patterns in side lying, seated and squatting defecation positions in normal subjects using a simulated stool device called Fecobionics. METHODS: The Fecobionics expulsion parameters were assessed in an interventional study design conducted from May 29 to December 9 2019. Subjects were invited to participate in the study through advertisement at The Chinese University of Hong Kong. The Fecobionics device consisted of a core containing pressure sensors at the front (caudal end) and rear (cranial end) and a polyester-urethane bag spanning most of the core length which also contained sensors. The Fecobionics bag was distended to 50 ml in the rectum of normal subjects (no present and past symptoms of defecatory disorders, no prior abdominal surgery, medication or chronic diseases). Studies were done in side lying (left lateral recumbent position), seated (hip flexed 90°) and squatting position (hip flexed 25°). Pressure endpoints including the rear-front pressure diagram and defecation indices were compared between positions. RESULTS: Twelve subjects (6 females/6 males, mean age 26.3 ± 2.6 [19.0-48.0] years) were included and underwent the planned procedures. The resting anal pressure for side lying and seated positions were 33.1 ± 4.1 cmH2O and 37.1 ± 4.0 cmH2O (p > 0.3). The anal squeeze pressure for side lying and seated positions were 98.4 ± 6.9 cmH2O and 142.3 ± 16.4 cmH2O (p < 0.05). The expulsion duration for the side lying, seated and squatting positions were 108.9 ± 8.3 s, 15.0 ± 2.1 s and 16.1 ± 2.9 s, respectively (p < 0.01 between lying and the two other positions). The maximum evacuation pressure for seated and squatting were 130.1 ± 12.4 cmH2O and 134.0 ± 11.1 cmH2O (p > 0.5). Rear-front pressure diagrams and distensibility indices demonstrated distinct differences in pressure patterns between the side lying position group and the other positions. CONCLUSIONS: The delay in expelling the Fecobionics device in the lying position was associated with dyssynergic pressure patterns on the device. Quantitative differences were not found between the seated and squatting position. Trial Registration http://www.clinicaltrials.gov Identifier: NCT03317938.

Medication-related problems in older people: how to optimise medication management.

Older patients are at risk of medication-related problems because of age-related physiological changes and multiple medications taken for multiple co-morbidities. The resultant polypharmacy is frequently associated with inappropriate medication use, which in turn contributes to a range of adverse consequences, including geriatric syndromes (eg, falls, cognitive decline, urinary incontinence) and hospitalisation. In addition, medication non-adherence or discrepancies between the medications prescribed and those actually taken by patients, either intentional or unintentional, are prevalent and can lead to treatment failure. A large proportion of adverse drug events are preventable, and medication errors occur most commonly at the stages of prescribing and subsequent monitoring. There are a number of strategies to address these issues with the aim of ensuring safe prescribing. Furthermore, deprescribing with withdrawal of medications that are inappropriate or of minimal value for patients is increasingly emphasised for optimising medication management. In general, optimisation of medication management should be patient-centred, considering individual circumstances and preferences to determine the treatment goals or priorities for individual patients, and a multidisciplinary approach is recommended.

Cost-effectiveness of fine-needle aspiration cytology (FNAC) and watchful observation for incidental thyroid nodules.

OBJECTIVES: A trial-based comparison of the use of resources, costs and health utility outcomes of fine-needle aspiration cytology (FNAC), and watchful observation for incidental small (< 2 cm) thyroid nodules was performed using data from the randomized controlled trial (RCT). METHODS: Using data from 314 patients, healthcare-related use of resources, costs, health utility, and quality-adjusted life years (QALYs) were estimated at 12 months after first presentation of incidental thyroid nodule(s) on an intention-to-treat basis with adjustment for covariates. Uncertainty about the incremental cost-effectiveness ratio for FNAC versus watchful management at 12 months of follow-up was incorporated using bootstrapping. Multiple imputation methods were used to deal with missing data. RESULTS: FNAC management was associated with greater use of healthcare resources and mean direct healthcare costs per patient (US$542.47 vs US$411.55). Lower mean 12-month QALYs per patient in FNAC was observed in comparison to watchful observation (0.752 versus 0.758). The probability that FNAC management was cost-effective compared with watchful management at a willingness-to-pay threshold of US50,000 per QALY gained was 26.5%. CONCLUSION: Based on 12-month data from RCT, watchful observation appeared cost-saving compared to FNAC in patients with incidental thyroid nodules that have a low-suspicion sonographic pattern and measure between 1.0 and 2.0 cm from healthcare provider perspective. CLINICALTRIALS. GOV IDENTIFIER: NCT02398721.

Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: a diagnostic validity study.

OBJECTIVES: Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva. METHODS: This was a prospective diagnostic validity study comparing the detection rate of respiratory viruses between saliva and nasopharyngeal aspirate (NPA) among adult hospitalized patients using Xpert® Xpress Flu/RSV. The cost and time associated with the collection of saliva and nasopharyngeal specimens were also estimated. RESULTS: Between July and October 2017, 214 patients were recruited. The overall agreement between saliva and NPA was 93.3% (196/210, κ 0.851, 95% CI 0.776-0.926). There was no significant difference in the detection rate of respiratory viruses between saliva and NPA (32.9% (69/210) versus 35.7% (75/210); p 0.146). The overall sensitivity and specificity were 90.8% (81.9%-96.2%) and 100% (97.3%-100%), respectively, for saliva, and were 96.1% (88.9%-99.2%) and 98.5% (94.7%-99.8%), respectively, for NPA. The time and cost associated with the collection of saliva were 2.26-fold and 2.59-fold lower, respectively, than those of NPA. CONCLUSIONS: Saliva specimens have high sensitivity and specificity in the detection of respiratory viruses by an automated multiplex Clinical Laboratory Improvement Amendments-waived point-of-care molecular assay when compared with those of NPA. The use of saliva also reduces the time and cost associated with specimen collection.

Diagnostic performance of cytology for assessment of hepatic lipid content in dairy cattle.

The objective of our study was to characterize the diagnostic performance of cytology for assessing hepatic lipid content (HLC) in dairy cows by comparing microscopic evaluation of lipid vacuolation in touch imprint slide preparations of liver biopsies with quantitative measurement of triglyceride concentration ([TG]; mg/mg of wet weight) in paired biopsy samples. Our study also sought to compare the diagnostic performance of liver cytology, plasma nonesterified fatty acid concentration ([NEFA]), and plasma ß-hydroxybutyrate concentration ([BHB]) derived from a measurement performed on whole blood, for assessing HLC. Chemical extraction of TG from liver tissue remains the gold standard for quantifying HLC, largely because available blood tests, although useful for detecting some types of pathology, such as increased lipid mobilization, ketosis, or hepatocellular injury, are nonspecific as to etiology. Veterinary practitioners can sample bovine liver for cytological evaluation in a fast, minimally invasive, and inexpensive manner. Thus, if highly predictive of HLC, cytology would be a practical diagnostic tool for dairy veterinarians. In our study, liver biopsy samples from Holstein cows (219 samples from 105 cows: 52 from cows 2 to 20 d prepartum, 105 from cows 0 to 10 d in milk, 62 from cows 18 to 25 d in milk) were used to prepare cytology slides and to quantify [TG] using the Folch extraction method followed by the Hantzch condensation reaction and spectrophotometric measurement. An ordinal scale (0-4) based on amount of hepatocellular cytoplasm occupied by discrete clear vacuoles was used by 3 blinded, independent observers to rank HLC in Wright-Giemsa-stained slides. Interobserver agreement in cytology scoring was good. Corresponding plasma [NEFA] and [BHB] measurements were available for 187 and 195 of the 219 samples, respectively. Liver [TG] correlated more strongly with cytology score than with NEFA or BHB, and receiver operating characteristic curve analysis showed that cytology had better diagnostic performance than either NEFA or BHB for correctly categorizing [TG] at thresholds of 5, 10, and 15%. Hepatic lipidosis in high-producing dairy cows is of major clinical and economic importance, and this study demonstrates that cytology is an accurate means of assessing HLC. Additional work is indicated to evaluate the diagnostic utility of liver cytology.

Annual direct medical costs associated with diabetes-related complications in the event year and in subsequent years in Hong Kong.

AIM: To develop models to estimate the direct medical costs associated with diabetes-related complications in the event year and in subsequent years. METHODS: The public direct medical costs associated with 13 diabetes-related complications were estimated among a cohort of 128 353 people with diabetes over 5 years. Private direct medical costs were estimated from a cross-sectional survey among 1825 people with diabetes. We used panel data regression with fixed effects to investigate the impact of each complication on direct medical costs in the event year and subsequent years, adjusting for age and co-existing complications. RESULTS: The expected annual public direct medical cost for the baseline case was US$1,521 (95% CI 1,518 to 1,525) or a 65-year-old person with diabetes without complications. A new lower limb ulcer was associated with the biggest increase, with a multiplier of 9.38 (95% CI 8.49 to 10.37). New end-stage renal disease and stroke increased the annual medical cost by 5.23 (95% CI 4.70 to 5.82) and 5.94 (95% CI 5.79 to 6.10) times, respectively. History of acute myocardial infarction, congestive heart failure, stroke, end-stage renal disease and lower limb ulcer increased the cost by 2-3 times. The expected annual private direct medical cost of the baseline case was US$187 (95% CI 135 to 258) for a 65-year-old man without complications. Heart disease, stroke, sight-threatening diabetic retinopathy and end-stage renal disease increased the private medical costs by 1.5 to 2.5 times. CONCLUSIONS: Wide variations in direct medical cost in event year and subsequent years across different major complications were observed. Input of these data would be essential for economic evaluations of diabetes management programmes.

Standard vs. intensified management of heart failure to reduce healthcare costs: results of a multicentre, randomized controlled trial.

AIMS: To determine if an intensified form of heart failure management programme (INT-HF-MP) based on individual profiling is superior to standard management (SM) in reducing health care costs during 12-month follow-up (primary endpoint). METHODS AND RESULTS: A multicentre randomized trial involving 787 patients (full analysis set) discharged from four tertiary hospitals with chronic HF who were randomized to SM (n = 391) or INT-HF-MP (n = 396). Mean age was 74 ± 12 years, 65% had HF with a reduced ejection fraction (31.4 ± 8.9%) and 14% were remote-dwelling. Study groups were well matched. According to Green, Amber, Red Delineation of rIsk And Need in HF (GARDIAN-HF) profiling, regardless of location, patients in the INT-HF-MP received a combination of face-to-face (home visits) and structured telephone support (STS); only 9% (`low risk') were designated to receive the same level of management as the SM group. The median cost in 2017 Australian dollars (A$1 equivalent to ∼EUR €0.7) of applying INT-HF-MP was significantly greater than SM ($152 vs. $121 per patient per month; P < 0.001), However, at 12 months, there was no difference in total health care costs for the INT-HF-MP vs. SM group (median $1579, IQR $644 to $3717 vs. $1450, IQR $564 to $3615 per patient per month, respectively). This reflected minimal differences in all-cause mortality (17.7% vs. 18.4%; P = 0.848) and recurrent hospital stay (18.6 ± 26.5 vs. 16.6 ± 24.8 days; P = 0.199) between the INT-HF-MP and SM groups, respectively. CONCLUSION: During 12-months follow-up, an INT-HF-MP did not reduce healthcare costs or improve health outcomes relative to SM.

Developmental origins of type 2 diabetes: a perspective from China.

There has been a marked increase in the prevalence of diabetes in Asia, including China, over the last few decades. While the increased prevalence of diabetes has often been attributed to the nutritional transition associated with recent economic development, emerging data suggest that early-life exposures also play a major role in shaping developmental trajectories, and contributes to alter an individual's susceptibility to diabetes and other non-communicable diseases (NCDs). Early-life exposures such as in utero exposure to undernutrition has been consistently linked with later risk of diabetes and obesity. Furthermore, in utero exposure to maternal hyperglycemia, maternal obesity and excess gestational weight gain are all linked with increased childhood obesity and later risk of diabetes. Emerging data have also highlighted the potential link between early-feeding practices, the role of one-carbon metabolism in metabolic programming and endocrine disrupting chemicals (EDCs) with later risk of diabetes. These different developmental exposures may all be highly relevant to the current epidemic of diabetes in China. For example, the prevalence of gestational diabetes has increased markedly over the last two decades, and may contribute to the diabetes epidemic by driving macrosomia, childhood obesity and later risk of diabetes. In order to address the current burden of diabetes, a lifecourse perspective, incorporating multisectoral efforts from public health policy down to the individuals, will be needed. Several major initiatives have been launched in China as part of its national plans for NCD prevention and treatment, and the experience from these efforts would be invaluable.

Improving medication safety and diabetes management in Hong Kong: a multidisciplinary approach.

INTRODUCTION: Patients with diabetes often require complex medication regimens. The positive impact of pharmacists on improving diabetes management or its co-morbidities has been recognised worldwide. This study aimed to characterise drug-related problems among diabetic patients in Hong Kong and their clinical significance, and to explore the role of pharmacists in the multidisciplinary diabetes management team by evaluating the outcome of their clinical interventions. METHODS: An observational study was conducted at the Diabetes Clinic of a public hospital in Hong Kong from October 2012 to March 2014. Following weekly screening, and prior to the doctor's consultation, selected high-risk patients were interviewed by a pharmacist for medication reconciliation and review. Drug-related problems were identified and documented by the pharmacist who presented clinical recommendations to doctors to optimise a patient's drug regimen and resolve or prevent potential drug-related problems. RESULTS: A total of 522 patients were analysed and 417 drug-related problems were identified. The incidence of patients with drug-related problems was 62.8% with a mean of 0.9 (standard deviation, 0.6) drug-related problems per patient. The most common categories of drug-related problems were associated with dosing (43.9%), drug choice (17.3%), and non-allergic adverse reactions (15.6%). Drugs most frequently involved targeted the endocrine or cardiovascular system. The majority (71.9%) of drug-related problems were of moderate clinical significance and 28.1% were considered minor problems. Drug-related problems were totally solved (50.1%) and partially solved (11.0%) by doctors' acceptance of pharmacist recommendations, or received acknowledgement from doctors (5.5%). CONCLUSIONS: Pharmacists, in collaboration with the multidisciplinary team, demonstrated a positive impact by identifying, resolving, and preventing drug-related problems in patients with diabetes. Further plans for sustaining pharmacy service in the Diabetes Clinic would enable further studies to explore the long-term impact of pharmacists in improving patients' clinical outcomes in diabetes management.

Effectiveness of the multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) for diabetic microvascular complications: A population-based cohort study.

AIM: To evaluate the effectiveness of the multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) in reducing the risks of microvascular complications. METHODS: This prospective cohort study was conducted with 29,670 propensity-score-matched RAMP-DM participants and diabetes patients under the usual primary care (14,835 in each group). Study endpoints were the first occurrence of any diabetic microvascular complications, non-proliferative diabetic retinopathy/preproliferative diabetic retinopathy (NPDR/prePDR), sight-threatening diabetic retinopathy (STDR) or blindness, nephropathy, end-stage renal disease (ESRD), neuropathy and lower-limb ulcers or amputation. Log-rank tests and multivariable Cox proportional-hazards regressions were employed to estimate between-group differences in incidences of study endpoints. RESULTS: After a median follow-up of 36 months with>41,000 person-years in each group, RAMP-DM participants had a lower incidence of microvascular complications (760 vs 935; adjusted hazard ratio [HR]: 0.73; 95% confidence interval [CI]: 0.66-0.81; P<0.001) and lower incidences of all specific microvascular complications except neuropathy (adjusted HR: 0.94; 95% CI: 0.61-1.45; P=0.778). Adjusted HRs for the RAMP-DM vs control group for ESRD, STDR or blindness, and lower-limb ulcers or amputation were 0.40 (95% CI: 0.24-0.69; P<0.001), 0.55 (95% CI: 0.39-0.78; P=0.001) and 0.49 (95% CI: 0.30-0.80; P=0.005), respectively. CONCLUSION: The RAMP-DM intervention was associated with lower incidences of all microvascular complications except neuropathy over a 3-year follow-up. These encouraging results constitute evidence that structured risk assessment and risk-stratified management provided by a multidisciplinary team is effective for reducing microvascular complications in diabetes patients. CLINICAL TRIAL REGISTRY: NCT02034695, www.ClinicalTrials.gov.

Optimisation of preoperative assessment in patients diagnosed with rectal cancer.

AIMS: Treatment decision making for patients with rectal cancer is complex and optimal preoperative assessment is important to ensure patients receive appropriate and high-quality care. Therefore, our objective was to develop an evidence-based, multidisciplinary guideline to assist physicians treating rectal cancer to ensure that preoperative assessment is optimal. MATERIALS AND METHODS: A multidisciplinary expert panel of physicians who treat rectal cancer was selected as members of the Cancer Care Ontario Preoperative Assessment for Rectal Cancer Guideline Development Group (GDG). This group initially met to identify important clinical questions with respect to optimisation of preoperative assessment in patients diagnosed with rectal cancer. A systematic review, specific to each of these clinical questions, was then conducted using MEDLINE, EMBASE and the Cochrane Library databases. The GDG met at regular intervals to review the evidence and to develop guidelines to address each of the clinical questions. RESULTS: The GDG identified seven important clinical questions with respect to the optimisation of preoperative assessment in patients diagnosed with rectal cancer. The clinical questions pertained to: (i) investigations required to assess distant metastasis (one question); (ii) imaging for local staging of rectal cancer (five questions); (iii) multidisciplinary cancer conference (MCC) (one question); (iv) restaging-magnetic resonance imaging (one question). The systematic reviews related to these clinical questions yielded 31 articles that were abstracted and reviewed by the GDG. Based on the systematic reviews, a guideline was developed containing seven recommendations that were either adapted from existing guidelines, based on review of the evidence or by consensus when evidence was limited. CONCLUSIONS: A set of seven recommendations have been developed in order to optimise pretreatment assessment in patients with rectal cancer by promoting evidence-based practice. These guidelines are based on the best available evidence and have been peer reviewed by two independent multidisciplinary expert panels for relevance and validity.