Long-term effectiveness and persistence rate of ustekinumab dose intensification in a South East Asian inflammatory bowel disease center.

BACKGROUND AND AIMS: Ustekinumab (UST) is an effective biologic for treatment of inflammatory bowel disease (IBD). However, some patients treated with UST have suboptimal clinical response with standard dosing. The aims of this study were to determine the effectiveness of UST dose intensification (DI), identify factors associated with DI, cumulative incidence of DI and persistence of UST among treated patients. METHODS: Clinical data of patients with Crohn's disease (CD) and ulcerative colitis (UC) who received UST from September 2017 to October 2022 in Singapore General Hospital were collected. Primary outcome was defined as achieving corticosteroid-free clinical remission, biochemical remission, endoscopic healing and/or transmural healing (CD). Statistical analysis was performed to identify factors, which are predictive of UST DI and effectiveness of UST DI. RESULTS: Forty-two patients (34 CD and 8 UC) underwent UST DI to either 6-weekly (n = 19, 45.2%) or 4-weekly (n = 23, 35.9%) and the median time to intensification was 31.1 weeks (17.8-65.7). Presence of perianal disease in CD (HR 4.9; 1.47-16.4) was associated with DI. After DI, 16 (38%) patients achieved primary outcome by week 52. The overall drug persistence rates at 1 year and 2 years were 75.7% (95% CI 62.9-84.6) and 63.5% (95% CI 49.9-74.3), respectively. CONCLUSION: Two third of IBD patients underwent DI while on UST treatment and the median time to DI was about 6 months after induction. CD patients with perianal disease is more likely to undergo DI. More than one third of dose-intensified patients achieved remission by week 52.

Prognostic Value of Tumor Budding in Urothelial Carcinoma: A Meta-Analysis and Systematic Review.

Recently, tumor budding (TB) has been suggested as a strong prognostic marker in urinary tract urothelial carcinoma (UC). The aim of this systematic review is to test the prognostic value of TB in UC by a meta-analysis of previously published studies. We systematically reviewed the literature related to TB by using the databases of Scopus, PubMed, and Web of Science. The search was limited to publications in the English language up to July 2022. There were 790 patients from 7 retrospective studies in which TB has been evaluated in UC. Two authors independently extracted the results from eligible studies. The meta-analysis of eligible studies revealed that TB is a significant prognosticator for progression-free survival in UC, with a hazard ratio (HR) of 3.51 (95% CI, 1.86-6.62; P < .001) in univariate analysis and a HR of 2.78 (95% CI, 1.57-4.93; P < .001) in multivariate analysis; a significant prognosticator for overall survival and cancer-specific survival in UC, with a HR of 3.07 (95% CI, 2.04-4.64; P < .001) and a HR of 2.18 (95% CI, 1.11-4.29; P = .02) respectively in univariate analysis. Our findings confirm that UC with a high TB count is at a high risk of progress. TB could be considered as an element in pathology reports and future oncologic staging systems.

Assessment of joint inflammation at the wrist of patients with rheumatoid arthritis: thermography findings closely mirror those from ultrasonography.

OBJECTIVES: To determine if thermography (in comparison with ultrasonography) may be helpful in detecting joint inflammation at the RA wrist categorised according to its clinical manifestations. METHODS: Four wrist groups were derived from the right wrist of RA subjects as follows: (1) swollen; tender (S1T1); (2) swollen; non-tender (S1T0); (3) non-swollen; tender (S0T1); (4) non-swollen; non-tender (S0T0). Thermographic parameters included the maximum (Tmax), average (Tavg) and minimum (Tmin) temperatures. Ultrasound parameters included the Total PD (TPD) and Total GS (TGS) scores. One-way ANOVA and Kruskal-Wallis test (for normally and non-normally distributed imaging parameters, respectively) and subsequent post-hoc tests were carried out for the comparative analysis of the wrist groups. RESULTS: A total of 70 wrist joints of 70 RA subjects were included in this cross-sectional study. For all imaging parameters (Tmax, Tavg, Tmin, TPD and TGS), statistically significant differences (all p<0.05) were detected (a) between the 4 wrist groups using either the one-way ANOVA or Kruskal-Wallis test and (b) for subsequent pairwise comparison of wrist group 1 (S1T1) vs. group 4 (S0T0) and group 2 (S1T0) vs. group 4 (S0T0). No significant differences (all p>0.05) were found for pairwise comparison of wrist group 3 (S0T1) vs. group 4 (S0T0) for all imaging parameters. CONCLUSIONS: Thermography at the wrist appears promising in RA with its findings closely mirroring those from ultrasonography. Swollen joints (regardless of tenderness status) have higher joint surface temperatures and greater ultrasound-detected joint inflammation, findings which were not observed for tender only (non-swollen) joints.

Appropriateness of lumbar spine radiography and factors influencing imaging ordering patterns: paving the path toward value-driven health care.

The demand for diagnostic imaging continues to rise. Against the backdrop of rising health care costs and finite resources, this has prompted a paradigm shift toward value-driven patient care. Inappropriate imaging is a barrier toward achieving this goal, which runs counter to prevailing evidence-based guidelines and contributes to rising healthcare costs. Our objective was to evaluate the appropriateness of lumbar spine X-rays in a tertiary referral Emergency Department (ED) and assess whether physicians' specialization and years of experience influence appropriateness. A total of 1030 lumbar spine radiographs performed in the ED of an academic medical center over a consecutive 3-month period were reviewed retrospectively. Referral indications were reviewed for adherence to 2021 American College of Radiology appropriateness guidelines for lower back pain, and referral patterns were evaluated among physician groups based on specialists' training and years in practice. 63.8% of lumbar spine radiographs were appropriate, with trauma being the most common indication. 36.2% of orders were inappropriate, with lower back pain of <6 weeks duration being the most common indication. Significant differences in inappropriate orders were found (P < .001) across physician groups: qualified Emergency Medicine specialists (20.9% inappropriate orders), specialists in training (27.8%), and non-specialists with ≥3 (60.0%) and <3 (36.9%) years in practice, respectively. Approximately one-third of lumbar spine radiographs performed in the ED were inappropriately ordered by American College of Radiology guidelines; specialists training and years in practice affected referral patterns. Integrating evidence-based appropriateness guidelines into the physician order workflow and targeting older non-specialists may promote more judicious imaging and reduce health care costs.

Montreal cognitive assessment as a screening instrument for cognitive impairment in systemic lupus erythematosus patients without overt neuropsychiatric manifestations.

OBJECTIVES: The Montreal Cognitive Assessment (MoCA) is an increasingly used screening tool for cognitive impairment. The aim of this study was to examine how MoCA performed in identifying cognitive impairment (CI) domains in SLE patients compared with formal standardized neuropsychological testing (NPT). Factors related to SLE disease, immunologic and psychological state associated with CI were also explored. METHODS: This cross-sectional study recruited 50 SLE patients without overt neuropsychiatric manifestations from April 2017 to May 2018. The patients were evaluated with MoCA, formal NPT and the Depression, Anxiety, and Stress Scales (DASS) 42-item self-report questionnaire. Values of sensitivity and specificity were computed for different cut-offs of MoCA within each cognitive domain of NPT and descriptive analysis was used to identify the factors affecting cognitive function. RESULTS: The median score for MoCA was 27.5 (range 22-30). Using a MoCA cutoff of <26, 18 (36%) were identified to have CI using NPT compared to 8 (16%) using MoCA. The most frequently affected cognitive domain was executive functioning with 15 affected patients. Sensitivities and specificities of the MoCA range from 50% to 100% and 5.7% to 16.7%, respectively, across cognitive domains. A lower MoCA cutoff of <25 improve sensitivity of identifying impairment in executive functioning from 60% to 80%. In univariate analysis, DASS scores, disease activity, presence of antiphospholipid antibodies, presence of concurrent autoimmune disease, current, and cumulative corticosteroid therapy did not predict cognitive performance. CONCLUSION: MoCA may be a useful screening tool to identify the most frequently affected cognitive domain which is executive functioning using a lower cutoff of <25 in SLE patients without overt neuropsychiatric manifestations.

Hypercoagulability, endotheliopathy, and inflammation approximating 1 year after recovery: Assessing the long-term outcomes in COVID-19 patients.

Sustained hypercoagulability and endotheliopathy are present in convalescent COVID-19 patients for up to 4 months from recovery. The hemostatic, endothelial, and inflammatory profiles of 39 recovered COVID-19 patients were evaluated up to 16 months after recovery from COVID-19. These values were compared with a control group of healthy volunteers (n = 124). 39 patients (71.8% males, median age 43 years) were reviewed at a mean of 12.7 ± 3.6 months following recovery. One patient without cardiovascular risk factors had post COVID-19 acute ischaemic limb. Elevated D-dimer and Factor VIII levels above normal ranges were noted in 17.9% (7/39) and 48.7% (19/39) of patients respectively, with a higher median D-dimer 0.34 FEU µg/mL (IQR 0.28, 0.46) (p < .001) and Factor VIII 150% (IQR 171, 203) (p = .004), versus controls. Thrombin generation (Thromboscreen) showed a higher median endogenous thrombin potential (ETP) of 1352 nM*min (IQR 1152, 1490) (p = .002) and a higher median peak height of 221.4 nM (IQR 170.2, 280.4) (p = 0.01) and delayed lag time 2.4 min (1.42-2.97) (p = 0.0002) versus controls. Raised vWF:Ag and ICAM-1 levels were observed in 17.9% (7/39) and 7.7% (3/39) of patients respectively, with a higher median VWF:Ag 117% (IQR 86, 154) (p = 0.02) and ICAM-1 54.1 ng/mL (IQR 43.8, 64.1) (p = .004) than controls. IL-6 was noted to be raised in 35.9% (14/39) of patients, with a higher median IL-6 of 1.5 pg/mL (IQR 0.6, 3.0) (p = 0.004) versus controls. Subgroup analysis stratifying patients by COVID-19 severity and COVID-19 vaccination preceding SARS-CoV-2 infection did not show statistically significant differences. Hypercoagulability, endothelial dysfunction, and inflammation are still detectable in some patients approximately 1 year after recovery from COVID-19.

Global haemostatic tests demonstrate the absence of parameters of hypercoagulability in non-hypoxic mild COVID-19 patients: a prospective matched study.

Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 µg/mL (IQR 0.6, 1.4) (p = 0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) (p = 0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) (p = 0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) (p = 0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p = 0.004), PT min1 7.1%/s (IQR 6.3, 9.0) (p = 0.02), PT clot acceleration (min 2) 3.6%/s2 (IQR 3.2, 4.5) (p = 0.02) and PT clot deceleration (max2) 2.9%/s2 (IQR 2.5, 3.5) (p = 0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) (p = 0.003), CRT Angle 78.9° (IQR 78.3, 80.0) (p = 0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) (p = 0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) (p = 0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels.

COVID-19 associated coagulopathy in critically ill patients: A hypercoagulable state demonstrated by parameters of haemostasis and clot waveform analysis.

Patients with COVID-19 are known to be at risk of developing both venous, arterial and microvascular thrombosis, due to an excessive immuno-thrombogenic response to the SARS-CoV-2 infection. Overlapping syndromes of COVID-19 associated coagulopathy with consumptive coagulopathy and microangiopathy can be seen in critically ill patients as well. Blood was collected from 12 Intensive Care Unit (ICU) patients with severe COVID-19 who were on either mechanical ventilation or on high flow oxygen with a PaO2/FiO2 ratio of <300 mmHg. Laboratory tests were performed for parameters of haemostasis, clot waveform analysis and anti-phospholipid antibodies. CWA parameters were raised with elevated aPTT median Min1 (clot velocity) 9.3%/s (IQR 7.1-9.9%/s), elevated PT median Min1 10.3%/s (IQR 7.1-11.1%/s), elevated aPTT median Min2 (clot acceleration) 1.5%/s2 (IQR 1.0-1.6%/s2), elevated PT median Min2 5.2%/s2 (3.6-5.7%/s2), elevated aPTT median Max2 (clot deceleration) 1.3%/s2 (IQR 0.8-1.4%/s2) elevated PT median Max2 3.8%/s2 (IQR 2.6-4.2%/s2), increased aPTT median Delta change (decreased light transmission due to increased clot formation) 87.8% (IQR 70.2-91.8%) and PT median Delta change 33.0%. This together with raised median Factor VIII levels of 262.5%, hyperfibrinogenemia (median fibrinogen levels 7.5 g/L), increased median von Willebrand factor antigen levels 320% and elevated median D-dimer levels 1.7 µg/dl support the diagnosis of COVID-19 associated coagulopathy. A lupus anticoagulant was present in 50% of patients. Our laboratory findings further support the view that severe SARS-CoV-2 infection is associated with a state of hypercoagulability.

Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries.

BACKGROUND: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. METHODS: CONCORD-3 includes individual records for 37·5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89·5% in Australia and 90·2% in the USA, but international differences remain very wide, with levels as low as 66·1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68·9%), colon (71·8%), and rectum (71·1%); in Japan for oesophageal cancer (36·0%); and in Taiwan for liver cancer (27·9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59·9% in South Korea, 52·1% in Taiwan, and 49·6% in China), and for both lymphoid malignancies (52·5%, 50·5%, and 38·3%) and myeloid malignancies (45·9%, 33·4%, and 24·8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49·8% in Ecuador to 95·2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28·9% in Brazil to nearly 80% in Sweden and Denmark). INTERPRETATION: The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer. FUNDING: American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation.

Post-stroke patients with moderate function have the greatest risk of falls: a National Cohort Study.

BACKGROUND: Stroke patients have increased risks of falls. We examined national registry data to evaluate the association between post-stroke functional level and the risk of low falls among post-stroke patients. METHODS: This retrospective cohort study analyzed data from national registries to examine the risk factors for post-stroke falls. Data for patients who suffered ischemic strokes and survived the index hospital admission was obtained from the Singapore National Stroke Registry and matched to the National Trauma Registry, from 2011 to 2015. The primary outcome measure was a low fall (fall height ≤ 0.5 m). Competing risk analysis was performed to examine the association between functional level (by modified Rankin score [mRS] at discharge) and the risk of subsequent low falls. RESULTS: In all, 2255 patients who suffered ischemic strokes had recorded mRS. The mean age was 66.6 years and 58.5% were men. By the end of 2015, 54 (2.39%) had a low fall while 93 (4.12%) died. After adjusting for potential confounders, mRS was associated with fall risk with an inverted U-shaped relationship. Compared to patients with a score of zero, the sub-distribution hazard ratio (SHR) increased to a maximum of 3.42 (95%CI:1.21-9.65, p = 0.020) for patients with a score of 2. The SHR then declined to 2.45 (95%CI:0.85-7.12, p = 0.098), 2.86 (95%CI:0.95-8.61, p = 0.062) and 1.93 (95%CI:0.44-8.52, p = 0.38) for patients with scores of 3, 4 and 5 respectively. CONCLUSIONS: An inverted U-shaped relationship between functional status and fall risk was observed. This is consistent with the complex interplay between decreasing mobility (hence decreased opportunity to fall) and increasing susceptibility to falls. Fall prevention intervention could be targeted accordingly. (263 words).

Buckling up in Singapore: residency and other risk factors for seatbelt non-compliance - a cross-sectional study based on trauma registry data.

BACKGROUND: Seatbelt non-compliance is a problem in middle income countries, and little is known about seatbelt compliance in populations with a high proportion of non-residents. This study analyses the profile of seatbelt non-compliance in Singapore based on trauma registry data from five of the six public hospitals. METHODS: This is a cross-sectional study of seatbelt compliance of patients aged over 18 years, attending the emergency departments of five public hospitals in Singapore after road collisions from 2011-2014. Seatbelt data was obtained from paramedic and patient history. RESULTS: There were 4,576 patients studied. Most were Singapore citizens (83.4 %) or permanent residents (2.4 %), with the largest non-resident groups from Malaysia, India, and China. Overall seatbelt compliance was 82.1 %. On univariate analysis, seatbelt compliance was higher in older patients (OR 1.02, 95 % CI 1.001-1.021, p < 0.0001); drivers, followed by front passengers (OR 0.65, 95 % CI 0.51-0.83, p < 0.0001), were more compliant than rear passengers (OR 0.08, 0.06-0.09, p < 0.0001); occupants of larger vehicle types (buses, heavy transport vehicles, minibuses and vans) were more non-compliant compared to occupants of private cars and taxis. Morning peak travel (0700 h-0900 h) and being a non-resident were other risk factors for non-compliance. On multivariable analysis, older age (OR 1.01, 95 % CI 1.001-1.014, p = 0.03) was associated with compliance, while non-residents from China (OR 0.43, 95 % CI 0.18-0.99, p = 0.05), seat position (front passenger compared to driver, OR 0.64, 95 % CI 0.48-0.85, p = 0.002; rear passenger compared to driver, OR 0.067, 95 % CI 0.05-0.09, p < 0.0001), vehicle type (bus compared to car, OR 0.04, 95 % CI 0.017-0.11, p < 0.0001, van compared to car, OR 0.55, 95 % CI 0.36-0.83, p = 0.004), and travel at morning peak periods were independent predictors of seatbelt non-compliance. When the sub-group of drivers was analysed, only vehicle type was a significant predictor of seatbelt compliance, with bus drivers least likely to be compliant to seatbelts (multivariable analysis, OR 0.057 compared to cars, 95 % CI 0.019-0.18, p < 0.0001). CONCLUSIONS: While overall seatbelt compliance in our study is high, efforts can be made to increase compliance for morning rush hour passengers, rear seat passengers, and occupants of buses, heavy transport vehicles, and vans or pickups.

Gender and ethnic differences in incidence and survival of lymphoid neoplasm subtypes in an Asian population: Secular trends of a population-based cancer registry from 1998 to 2012.

Descriptive epidemiology on incidence and survival by lymphoid neoplasm (LN) subtypes using the 2008 World Health Organisation (WHO) classification remained limited in Asia. The aim of this study was to evaluate whether gender and ethnic differences in incidence and survival of LN subtypes existed using the Singapore Cancer Registry (SCR) from 1998 to 2012. We derived age standardised incidence rates (ASIRs) by the direct standardisation method and 5-year relative survival (RSR) by the Ederer II method and period approach. Five-year observed survival (OS) was obtained for each ethnicity. Malays had the highest ASIR of total LNs among the three ethnicities for each time period. The largest increase in 5-year RSR subtypes was follicular lymphoma from 43.8% in 1998-2002 to 82.3% in 2008-2012; followed by chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL) from 48.1% in 1998-2002 to 77.9% in 2008-2012. Although males had higher incidence than females in each time period, females had greater 5-year RSR for follicular lymphoma (89.8% in 2008-2012 for females vs. 76.6% in 2008-2012 for males) and CLL/SLL (78.7% in 2008-2012 for females vs. 76.7% in 2008-2012 for males). All three ethnicities experienced an overall increase in 5-year OS for mature B-cell lymphoma, with Indians experiencing the greatest increase (37.1% in 1998-2002 to 61.1% in 2008-2012), followed by Malays (30.8% in 1998-2002 to 48.7% in 2008-2012) and then Chinese (36.4% in 1998-2002 to 51.3% in 2008-2012). Our study demonstrated that improved mature B-cell lymphoma survival was not only observed in the West, but also in Singapore.

Subclinical joint inflammation in rheumatoid arthritis: comparing thermal and ultrasound imaging at the metacarpophalangeal joint.

BACKGROUND: While ultrasound and MRI are both superior to clinical examination in the detection of joint inflammation, there is presently a lack of data whether thermography may be similarly useful in the assessment of joint inflammation in patients with RA. Our study aims to evaluate the use of thermography in detecting subclinical joint inflammation at clinically quiescent (non-tender and non-swollen) metacarpophalangeal joints (MCPJs) in patients with rheumatoid arthritis (RA). The outcomes from thermography in our study will be compared with ultrasonography (which is a more established imaging tool used for joint inflammation assessment in RA). METHODS: The minimum (Tmin), average (Tavg) and maximum (Tmax) temperatures at the 10 MCPJs of each patient were summed to obtain the Total Tmin, Total Tavg and Total Tmax, respectively. Ultrasound grey-scale (GS) and power Doppler (PD) joint inflammation (scored semi-quantitatively, 0-3) at the 10 MCPJs were summed up to derive the respective TGS and TPD scores per patient. Pearson's correlation and simple linear regression were respectively used to assess correlation and characterize relationships between thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TGS, TPD and the number of joint(s) with PD ≥ 1 or GS ≥ 2). RESULTS: In this cross-sectional study, 420 clinically non-swollen and non-tender MCPJs from 42 RA patients were examined. All thermographic parameters (Total Tmin, Total Tavg and Total Tmax) correlated significantly (P-values ranging from 0.001 to 0.0012) with TGS score (correlation coefficient ranging from 0.421 to 0.430), TPD score (correlation coefficient ranging from 0.383 to 0.424), and the number of joint(s) with PD ≥ 1 or GS ≥ 2 (correlation coefficient ranging from 0.447 to 0.465). Similarly, simple linear regression demonstrated a statistically significant relationship (P-values ranging from 0.001 to 0.005) between all thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TPD and TGS). CONCLUSION: For the first time, thermographic temperatures were shown to correlate with ultrasound-detected joint inflammation at clinically quiescent MCPJs. The use of thermography in the detection of subclinical joint inflammation in RA appears promising and warrants further investigation.

Outcome of 6 fractions of 5.3 Gray HDR brachytherapy in combination with external beam radiotherapy for treatment of cervical cancer.

OBJECTIVE: To review the characteristics, outcomes and toxicities of cervical cancer patients treated with 6 fractions of brachytherapy after external beam radiotherapy (EBRT). METHODS: All patients diagnosed with cervical cancer from 2000 to 2009 who were referred for radical treatment and who received 6 fractions of brachytherapy were retrospectively reviewed. Overall survival (OS), disease free survival (DFS), local control (LC), distant control (DC) rate, acute and late toxicities were the primary endpoints. RESULTS: Thirty-two patients with mainly advanced stage squamous cell carcinoma were identified and reviewed. Patients received EBRT of 45 to 50.4 Gy in 1.8 Gy daily fractions followed by 6 sessions of 3 channel brachytherapy of 5.3 Gy prescribed to point H. Response rates to treatment were good, with no residual disease in 84% six weeks after the completion of treatment. With a median follow up time of 8.1 years, the five-year OS, DFS, LC and distant control rates were 75%, 68.5%, 92.8% and 76.9% respectively. None of the patients developed any G3-4 acute toxicity but one patient who had advanced disease developed G3-4 proctitis with a fistula formation. CONCLUSIONS: HDR brachytherapy utilizing 6 fractions of 5.3 Gy prescribed to point H with concurrent chemo-radiation is superior in terms of OS and LC to regimens that deliver a lower EQD2 dose to point A/H and is associated with very low rates of toxicities.

Relationship between CGM-derived nocturnal hypoglycemia and subjective sleep quality in people with type 1 diabetes.

This pilot study explores the relationship between nocturnal hypoglycemia (NH) and subjective sleep quality in people with type 1 diabetes (T1D). Twenty-seven adults with T1D wore a Freestyle Libre Pro CGM and recorded subjective sleep quality daily, as assessed by a single Likert scale question. Frequency, duration, area under the curve (AUC) of NH (00:00-06:00) defined as sensor glucose below threshold (< 3.9 mmol/L; < 3 mmol/L) for ≥ 15 min, nocturnal mean glucose, Time in Range (3.9-10 mmol/L), and coefficient of variation were calculated. Twenty-seven adults, 18 (66.7%) women, with median (IQR) age of 27 (26, 32) years and HbA1c of 7.6 (7.1, 8.1) participated. Nights with NH < 3.9 mmol/L resulted in a lower (worse) sleep score than nights without NH [Mean (SD): 3.3 (1.2) vs 3.5 (1.0), p = 0.03). A higher frequency and longer duration but not AUC [adjusted OR (95% CI) 0.52 (0.38, 0.72), 0.961 (0.932, 0.991), 0.999 (0.998, 1.001) respectively)], of NH < 3.9 mmol/L, were associated with a lower sleep score. NH < 3.0 mmol/L metrics were not associated with sleep quality. Recurrent NH < 3.9 mmol/L, rather than prolonged NH < 3.0 mmol/L, seems associated with subjective sleep quality, implying that those with the highest burden of NH are likely unaware of it.

Association of Smartphone-Based Activity Tracking and Nocturnal Hypoglycemia in People With Type 1 Diabetes.

BACKGROUND: Nocturnal hypoglycemia (NH) remains a major burden for people with type 1 diabetes (T1D). Daytime physical activity (PA) increases the risk of NH. This pilot study tested whether cumulative daytime PA measured using a smartphone-based step tracker was associated with NH. METHODS: Adults with T1D for ≥ 5 years (y) on multiple daily insulin or continuous insulin infusion, not using continuous glucose monitoring and HbA1c 6 to 10% wore blinded Freestyle Libre Pro sensors and recorded total daily carbohydrate (TDC) and total daily dose (TDD) of insulin. During this time, daily step count (DSC) was tracked using the smartphone-based Fitbit MobileTrack application. Mixed effects logistic regression was used to estimate the effect of DSC on NH (sensor glucose <70, <54 mg/dl for ≥15 minutes), while adjusting for TDC and TDD of insulin, and treating participants as a random effect. RESULTS: Twenty-six adults, with 65.4% females, median age 27 years (interquartile range: 26-32) mean body mass index 23.9 kg/m2, median HbA1c 7.6% (7.1-8.1) and mean Gold Score 2.1 (standard deviation 1.0) formed the study population. The median DSC for the whole group was 2867 (1820-4807). There was a significant effect of DSC on NH episodes <70 mg/dl. (odds ratio 1.11 [95% CI: 1.01-1.23, P = .04]. There was no significant effect on NH <54 mg/dl. CONCLUSION: Daily PA measured by a smartphone-based step tracker was associated with the risk of NH in people with type 1 diabetes.

Associations Between Mean HbA1c, HbA1c Variability, and Both Mortality and Macrovascular Complications in Patients with Diabetes Mellitus: A Registry-Based Cohort Study.

Background: We investigate the association between mean HbA1c, HbA1c variability, and all-cause mortality and diabetes-related macrovascular complications in patients with diabetes. Methods: We performed a retrospective cohort study using patients present in the Singapore Health Services diabetes registry (SDR) during 2013 to 2014. We assessed mean HbA1c using three models: a baseline mean HbA1c for 2013-14, the mean across the whole follow-up period, and a time-varying yearly updated mean. We assessed HbA1c variability at baseline using the patient's HbA1c variability score (HVS) for 2013-14. The association between mean HbA1c, HVS, and 6 outcomes were assessed using Cox proportional hazard models. Results: We included 43,837-53,934 individuals in the analysis; 99.3% had type 2 diabetes mellitus. The data showed a J-shaped distribution in adjusted hazard ratios (HRs) for all-cause mortality, ischemic heart disease, acute myocardial infarction, peripheral arterial disease, and ischemic stroke, with an increased risk of developing these outcomes at HbA1c <6% (42 mmol/mol) and ≥8% (64 mmol/mol). With the addition of HVS, the J-shaped distribution was maintained for the above outcomes, but HRs were greater at HbA1c <6.0% (42 mmol/mol) and reduced at HbA1c ≥8.0% (64 mmol/mol) when compared to models without HVS. The risk for all outcomes increased substantially with increasing glycaemic variability. Conclusion: Both low (<6.0% [42 mmol/mol]) and high (≥8.0% [64 mmol/mol]) levels of glycaemic control are associated with increased all-cause mortality and diabetes-related macrovascular complications. Glycaemic variability is independently associated with increased risk for these outcomes. Therefore, patients with stable glycaemic level of 6-8% (42-64mmol/mol) are at lowest risk of all-cause mortality and diabetes-related macrovascular complications.