Cimetidine repurposed as a potential immunomodulatory agent against colorectal carcinoma: A systematic review.

OBJECTIVE: To determine the survival benefit and immunomodulatory effects of cimetidine pre-, peri- or post-operatively in patients with colorectal cancer (CRC). METHODS: A systematic review was conducted using PubMed and Cochrane Library to retrieve randomized control trials (RCTs) that investigated the effects of cimetidine on survival and immunomodulation via improvement in tumor infiltrating lymphocytes (TILs) and peripheral blood lymphocytes. The review was carried out in accordance with the extended Preferred Reporting Items for Systematic Reviews and Meta-analyses. RESULTS: Four studies with the total of 267 patients were included in this systematic review. Treatment duration varied from 5 days to 1 year. Two studies reported a significant TIL response in the resected specimens after administering cimetidine, while one RCT showed an escalation of CD3, CD4 and CD57 lymphocytes in peripheral blood compared to the baseline following cimetidine treatment (p < 0.01). Of the three trials that examined the effects of cimetidine on survival, only two studies revealed significant survival benefit while the remaining study only showed a trend towards survival benefit. CONCLUSION: Repurposing of existing drugs like cimetidine has a potential to offer a survival benefit by acting as an immunomodulatory agent in patients undergoing curative resection for CRC. However, the heterogeneity seen in current studies and the evolvement of adjunctive therapies for CRC warrant large-scale, well-designed prospective RCTs to establish the efficacy of cimetidine in CRC.

Caregiver strain among patients of palliative care in Sri Lanka: validation of modified caregiver strain index - Sinhala version.

BACKGROUND: Care givers of Palliated patients are at risk of adverse physical, psychosocial and emotional sequelae in varied nature. Efficient and valid assessment tools facilitate early detection to take corrective measures. The Modified Caregiver Strain Index (MCSI), composed of domains associated with caregiver strain is a simple and brief tool that can be used in both clinical and field settings. This study aimed to adapt and validate this in order to cater effective palliative care services in Sri Lanka. METHODS: After cross-cultural adaptation, 200 primary caregivers in 3 teaching hospitals were recruited. The internal consistency, item-total correlations, of the 13-item S-MCSI were performed. The criterion validity was assessed by Pearson correlation between the total scores of S-MCSI, the Karnofky Performance Scale and the Barthel index. Construct validity was determined by the principal component analysis keeping the Varimax with Keiser normalization as the rotation method. The Kaiser-Meyer-Olkin test (KMO) and Bartlett's test of sphericity statistics were also performed to determine the adequacy of the sample and correlations between items, respectively. The number of factors was determined by the Scree plot, percentage of variance explained by each component and number of Eigen values over 01 (Kaiser-Guttman rule). RESULTS: The total MCSI score ranged 0 to 26. The overall Cronbach's alpha of the 13-item questionnaire was 0.80 while item-total corrections ranged 0.34 to 0.62, exception of one item (0.11). Inverse correlations were demonstrated in total scores of MCSI and Karnofky Performance Scale (r =- 0.32, p < 0.001) and Barthel index (r =-0.34, P < 0.001). A Kaiser-Meyer-Olkin value of 0.79 (p < 0.001) for Bartlett's test indicated adequate sampling and nonlinearity of factors. The Scree plot showed a three-factor structure explaining 57% of the variation. Items regarding personal wellbeing of caregiver loaded together while the effects on the family loaded separately. Adjustment of personal concerns and family issues along with time alteration grouped as the third factor. CONCLUSIONS: The study showed that the Sinhala version of MCSI has adequate psychometric properties and reliability to be used as a validated tool to estimate the caregiver burden within a short time period for any health care workers.

Development of the Asia Pacific Consortium on Osteoporosis (APCO) Framework: clinical standards of care for the screening, diagnosis, and management of osteoporosis in the Asia-Pacific region.

Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.

IQ driving QI: the Asia Pacific Consortium on Osteoporosis (APCO): an innovative and collaborative initiative to improve osteoporosis care in the Asia Pacific.

Asia Pacific Consortium on Osteoporosis (APCO) comprises of clinical experts from across the Asia Pacific region, uniting to develop solutions to problems facing osteoporosis management and care. The vision of APCO is to reduce the burden of osteoporosis and fragility fractures in the Asia Pacific region. INTRODUCTION: The Asia Pacific (AP) region comprises 71 countries with vastly different healthcare systems. It is predicted that by 2050, more than half the world's hip fractures will occur in this region. The Asia Pacific Consortium on Osteoporosis (APCO) was set up in May 2019 with the vision of reducing the burden of osteoporosis and fragility fractures in the AP region. METHODS: APCO has so far brought together 39 clinical experts from countries and regions across the AP to develop solutions to challenges facing osteoporosis management and fracture prevention in this highly populous region of the world. APCO aims to achieve its vision by engaging with relevant stakeholders including healthcare providers, policy makers and the public. The initial APCO project is to develop and implement a Framework of pan-AP minimum clinical standards for the screening, diagnosis and management of osteoporosis. RESULTS AND CONCLUSIONS: The Framework will serve as a platform upon which new national clinical guidelines can be developed or existing guidelines be revised, in a standardised fashion. The Framework will also facilitate benchmarking for provision of quality of care. It is hoped that the principles underlying the formation and functioning of APCO can be adopted by other regions and that every health care facility and progressively every country in the world can follow our aspirational path and progress towards best practice.

Cutoff values for the determination of sarcopenia and the prevalence of the condition in middle-aged women: A study from Sri Lanka

Introduction: There is a scarcity of studies related to sarcopenia in Sri Lanka. This partly is due to lack of cutoff values to define muscle mass, strength and physical functions. Objective: This cross-sectional study determined the cutoff values of sarcopenia measures and evaluated the prevalence of sarcopenia among middle-aged Sri Lankan women. Method: A reference group of 117 young women (20-40 years) was used for cutoff value determination. The prevalence of sarcopenia was estimated among a group of 270 women (41-60 years). Appendicular Skeletal Muscle Mass (ASMM, kg) was measured by DXA and was adjusted for height (ASMM/height2) to determine Relative Skeletal Muscle mass Index (RSMI, kg/m2). Hand Grip Strength (HGS, kg) and Gait Speed (GS, m/s) were also measured. Cutoff values for measures of sarcopenia were taken as 2SD below the mean value of the young reference group. Result: Mean(SD) ages of the participants; young reference group and middle-aged group were 35.5(3.8) and 52.2(5.8) years respectively. Cutoff values for the main three measures of sarcopenia; RSMI, HGS and GS were 5.03kg/m2, 9.66kg and 0.96m/s respectively. Prevalence of pre-sarcopenia, sarcopenia and severe-sarcopenia among middle-aged women were 3.0%, 2.2%, 0.7% respectively. The corresponding values among postmenopausal women were 4.2%, 3.0%, 1.2% and among premenopausal women were 1.0%, 1.0%, 0.0%. Prevalence of sarcopenia was higher among women aged between 51-60 years and severe sarcopenia was observed only in this age group. Conclusions: This study provides cutoff values for the measures of sarcopenia for Sri Lankan women. Prevalence was higher among postmenopausal women compared to premenopausal women.

Performance of Sri Lankan FRAX algorithm without bone mineral density and with Quantitative Ultrasound data input

Introduction: Fracture risk assessment algorithm (FRAX) is the most validated method available to predict fracture risk. Its use is restricted due to limited availability of Dual Energy X-ray Absorptiometry (DXA). FRAX has the option of assessing facture risk without BMD data. Objectives: To assess the ability of Sri Lankan FRAX algorithm without BMD input in evaluating fracture risk. The possibility of replacing the BMD input with Quantitative Ultrasound (QUS) data of radius in calculating fracture risk also assessed. Method: Data of clinical risk factors associated with fractures were collected from community dwelling postmenopausal women (n=339). DXA scans were performed in all subjects and QUS scans (in radius) were performed in a randomly selected sample (n=207). Ten-year risks of major osteoporotic fracture (MOFR) and hip fracture (HFR) were calculated with BMD, without BMD (FRAX-FN0) and with US T score instead of BMD (FRAX-UST). Result and conclusions: Nearly 35.7% had high risk of fractures. FRAX-FN0 had 79.2% sensitivity, 80.1% specificity, 68.8% positive predictive value (PPV) and 87.4% negative predictive value (NPV). FRAX-UST showed 78.4% sensitivity, 70% specificity, 59.8% PPV and 85% NPV. ROC AUCs were above 0.80 in both FRAX-FN0 and FRAX-UST. The standard errors of estimate (SEE) were less in FRAX-FN0 (3.96 and 2.76 for MOFR-FN0 and HFR-FN0 respectively) compared to FRAX-UST (6.13 and 4.83 for MOFR-UST and HFR-UST, respectively). In conclusion, Sri Lankan FRAX without BMD is an acceptable alternative in areas with restricted DXA facility. Radial QUS data cannot be used as a substitute to FN-BMD in Sri Lankan FRAX.

Effect of Vitamin D therapy on urinary albumin excretion, renal functions, and plasma renin among patients with diabetic nephropathy: A randomized, double-blind clinical trial.

BACKGROUND: Despite different management strategies, progression of proteinuria occurs in a sizable category of patients with diabetic nephropathy (DN). Increase in serum renin levels induced by the renin-angiotensin system (RAS) may contribute to this. Vitamin D therapy is found to have an inhibitory effect on the RAS. We aimed to study the effects of Vitamin D therapy on renal functions of patients with DN. METHODS: This was a double-blind, randomized, placebo-controlled study. Patients with DN (urinary albumin [UA] >30 mg/g of creatinine) whose estimated glomerular filtration rate (eGFR) was more than 30 mL/min were selected and their plasma renin, parathyroid hormone, serum Vitamin D, serum calcium, serum creatinine, fasting blood sugar were done as baseline measurements. Subjects were randomized into two groups and treatment group was given Vitamin D, 50000 IU (0.25 ml) intramuscularly (IM) monthly for 6 months; control group received distilled water IM. Investigations were repeated after 6 months of therapy. RESULTS: Of 155 patients invited, 85 were randomly assigned to two groups. After 6 months, mean reduction of UA to creatinine ratio in the treatment and control group was 51.8 mg/g (95% confidence interval [CI]; 66.1--37.5, P ≤ 0.001); 22.4 mg/g (95% CI; -45.7-0.8, P = 0.06), respectively (between group difference P = 0.001). Significant increase in the eGFR observed in the treatment group while eGFR remained unchanged in the control group (P = 0.03 for the between-group difference). Mean reduction in plasma renin in treatment group and control group was 5.85 pg/mL (95% CI; -6.7--4.6) (P < 0.001) and 0.95 pg/mL (95% CI; -1.4--0.14, P = 0.02), respectively. CONCLUSIONS: Vitamin D 50000 IU given IM monthly for 6 months reduces urine albumin, serum creatinine, and renin levels in patients with DN.

Concordance between measured and estimated appendicular muscle mass in adult females.

This study assessed the accuracy of a selected formula used to estimate the appendicular muscle mass (AMM) which is linked with many clinical outcomes. A group of community-dwelling adult women (n=80) had their AMM measured using dual energy x-ray absorptiometry (DXA). The same was estimated using a formula already published {Skeletal muscle mass = (0.244 × BW in kg) + (7.80 × Ht in meters) + (6.6 × Sex) - (0.098 × Age) + race - 3.3} (sex=0 for female and 1 for male, race =-1.2 for Asian, 1.4 for African American and 0 for White and Hispanic).The two datasets were compared for accuracy and precision. Mean AMM measured by DXA and estimated by the formula were very close (14.8 and 14.5 kg) and the difference ranged from -1.2 to 3.6 kg. Correlation between the two datasets was high (r=0.92) and the Bland-Altman plot showed an acceptable measurement agreement between the two methods. Results were independent of age and BMI. The formula used in this analysis gave an accurate estimation of the absolute AMM in women included in this study.

Evaluating compliance with the care standard of proactively assessing bone health in patients with diabetes: a pilot audit of practice across Asia by the Asia Pacific Consortium on Osteoporosis (APCO).

This pilot audit explored how bone health is assessed patients with diabetes in diverse centres across Asia. Only 343 of 1092 (31%) audited patients had a bone health assessment, 27% of whom were diagnosed with osteoporosis. Quality improvement strategies are needed to address gaps in patient care in this area. PURPOSE: The Asia Pacific Consortium on Osteoporosis (APCO) Framework outlines clinical standards for assessing and managing osteoporosis. A pilot audit evaluated adherence to clinical standard 4, which states that bone health should be assessed in patients with conditions associated with bone loss and/or increased fracture risk; this report summarises the audit findings in patients with diabetes. A secondary aim was to assess the practicality and real-world use of the APCO bone health audit tool kit. METHODS: Eight centres across Asia participated in the pilot audit, selecting diabetes as the target group. Participants reviewed their practice records for at least 20 consecutively treated patients with the target condition. Questions covered routine investigations, bone health assessment, osteoporosis diagnosis, and patient referral pathways. Data were summarised descriptively. RESULTS: The participants represented public hospitals, university medical centres, and private clinics from India, Malaysia, Pakistan, Singapore, Taiwan, and Vietnam that see an estimated total of 95,000 patients with diabetes per year. Overall, only 343 of 1092 audited patients (31%) had a bone health assessment. Osteoporosis was subsequently diagnosed in 92 of 343 (27%) patients. CONCLUSION: Bone health was not assessed in most patients with diabetes. The results provide insight into current practices across diverse Asian centres and demonstrate the practical value of the audit tool kit. Participant feedback has been used to improve the tool kit. Results of this pilot audit are being used in the respective centres to inform quality improvement projects needed to overcome the gap in patient care.