Safety and efficacy of desmopressin for the treatment of nocturia in elderly patients: a cohort study

Purpose

Desmopressin is used widely to treat nocturnal polyuria (NP), but there is concern of hyponatremia especially in elderly patients. This study aimed to evaluate the safety and efficacy of long-term desmopressin treatment in elderly patients with NP.

Methods

Patients who were ≥65 years old with NP were analyzed. All patients were started on 0.1 mg desmopressin, and the dose was escalated to 0.2 mg depending on patient symptoms. All patients were educated the mechanism of desmopressin. The voiding diary and serum sodium levels were evaluated at baseline, 3–7 days after starting treatment and every 3–6 months. Safety was evaluated by hyponatremia, hyponatremic symptoms and other adverse drug events. The mean changes in number of nocturia and nocturnal urine volume (NUV) were evaluated for efficacy.

Results

A total of 68 patients were included. The mean age was 72.6 (66–85) years. The mean night-time frequency was 3.0 ± 1.8 day, and the mean serum sodium level was 141.2 ± 2.1 mEq/L at baseline. The mean follow-up period was 27.9 months. The mean decrease in serum sodium level was 1.3 ± 3.4 mEq/L at the last follow-up (p = 0.003). Hyponatremia incidence was 4.4 %, and all patients recovered by stopping medication. Severe adverse events were not observed. The mean night-time frequency had decreased by 2.1, and the NUV had decreased by 374.2 ± 261.3 mL at the last follow-up (p < 0.001).

Conclusions

Desmopressin at doses below 0.2 mg is safe and effective in elderly patients with NP if patients are well informed and are closely followed up.     

Long-term durability,functional outcomes,and factors associated with surgical failure of tension-free vaginal tape procedure

Purpose

The cure rate of tension-free vaginal tape (TVT) appeared to decrease overtime, with an associated increased in the stress urinary incontinence (SUI) recurrence rate. We evaluated the long-term durability and functional outcomes of TVT and identified the risk factors that may affect recurrence.

Methods

Eighty-eight patients, who were cured of SUI 6 months after undergoing TVT, were followed-up for at least 12 years. At post-operative, the patients were evaluated with a Severity Index for Urinary Incontinence questions regarding cure, patient’s satisfaction, goal achievement, 3-day voiding diary with urinary urgency scale, uroflowmetry, and complications.

Results

Cure rates decreased from 96.6 % at 1-year post-surgery to 83.0 % at 5 years and that the cure rates between 5 and 12 year were similar (83.0 vs. 79.6 %). Valsalva leak point pressure (VLPP) < 60 H₂O was the only independent factor that predicted recurrence (p = 0.011; hazard radio 5.31). At last follow-up, 39.2 and 70.0 % of patients were free of urgency and urgency incontinence, respectively; and de novo urgency and urgency incontinence developed in 40.5 and 17.2 % of these patients, respectively. Age was the only factor that predicted freedom from overactive bladder (OAB) symptom. There was a significant reduction in the maximal flow rate from 23.3 ± 9.0 ml/s pre-operation to 18.8 ± 6.7 ml/s at 12 years post-operation.

Conclusions

TVT is an effective long-term treatment for SUI, although the cure rate may decrease with time. A low VLPP was predictive of SUI recurrence, and patients showing no OAB symptoms tended to be younger.     

The Clinical Utility of the Modified Checklist for Autism in Toddlers with High Risk 18–48 Month Old Children in Singapore

The modified checklist for autism in toddlers (M-CHAT) is a tool developed for 16–30 month old children to screen for autism spectrum disorders (ASD). It is a well-researched tool, but little is known about its utility with Singaporean toddlers and with older children referred for developmental concerns. This study investigated the M-CHAT’s performance with 18–30 month old (N = 173) and >30–48 month old (N = 407) developmentally at-risk Singaporean children, when used with three recommended scoring methods i.e., the total, critical and Best7 scoring methods. The results indicate that the critical and Best7 scoring methods detected most true cases of ASD without inflating the false positive rates in toddlers, and that only the total scoring method performed acceptably for the older children.     

Clinical Outcome of Palliative Radiotherapy for Locally Advanced Symptomatic Gastric Cancer in the Modern Era

The purpose of this study was to report the outcomes of patients with symptomatic locally advanced/recurrent gastric cancer treated with radiotherapy (RT) using modern 3-dimensional conformal techniques.We retrospectively reviewed patients who had palliative RT for index symptoms of gastric bleeding, pain, and obstruction. Study endpoints included symptom response, median survival, and treatment toxicity.Of 115 patients with median age of 77 years, 78 (67.8%) patients had metastatic disease at the time of treatment. Index symptoms were gastric bleeding, pain, and obstruction in 89.6%, 9.2%, and 14.3% of patients, respectively. Dose fractionation regimen ranged from 8-Gy single fraction to 40 Gy in 16 fractions. One hundred eleven patients (93.3%) were computed tomography (CT) planned. Median follow-up was 85 days. Response rates for bleeding, pain, and obstruction were 80.6% (83/103), 45.5% (5/11), and 52.9% (9/17), respectively, and median duration of response was 99 days, 233 days, and 97 days, respectively. Median survival was 85 days. Actuarial 12-month survival was 15.3%. There was no difference in response rates between low (≤39 Gy) and high (>39 Gy) biologically effective dose (BED) regimens (α/β ratio = 10). Median survival was significantly longer in patients who responded to RT compared with patients who did not (113.5 vs 47 days, P < 0.001). Three patients (2.6%) had grade 3 Common Toxicity Criteria equivalent toxicity (nausea/vomiting/anorexia).External beam RT delivered using 3-dimensional conformal techniques is highly effective and well tolerated in the local palliation of gastric cancer, with palliation lasting the majority of patient’s lives. Short (≤39 Gy BED) RT schedules are adequate for effective symptom palliation. A phase II study of palliative gastric RT is ongoing.     

Computer-aided diabetic retinopathy detection using trace transforms on digital fundus images

Diabetic retinopathy (DR) is a leading cause of vision loss among diabetic patients in developed countries. Early detection of occurrence of DR can greatly help in effective treatment. Unfortunately, symptoms of DR do not show up till an advanced stage. To counter this, regular screening for DR is essential in diabetic patients. Due to lack of enough skilled medical professionals, this task can become tedious as the number of images to be screened becomes high with regular screening of diabetic patients. An automated DR screening system can help in early diagnosis without the need for a large number of medical professionals. To improve detection, several pattern recognition techniques are being developed. In our study, we used trace transforms to model a human visual system which would replicate the way a human observer views an image. To classify features extracted using this technique, we used support vector machine (SVM) with quadratic, polynomial, radial basis function kernels and probabilistic neural network (PNN). Genetic algorithm (GA) was used to fine tune classification parameters. We obtained an accuracy of 99.41 and 99.12 % with PNN–GA and SVM quadratic kernels, respectively.     

No difference in omalizumab efficacy in patients with asthma by number of asthma-related and allergic comorbidities

BackgroundComorbidities are common in asthma and may complicate treatment response.ObjectiveTo examine response to omalizumab in patients with moderate-to-severe allergic asthma by asthma-related and allergic comorbidities.MethodsPatients aged 12 years or more from placebo-controlled 008/009 (n = 1071), EXTRA (n = 848), and INNOVATE (n = 419), and single-armed PROSPERO (n = 801) omalizumab studies were included. Poisson regression/analysis of covariance models were used to estimate adjusted exacerbation rates and forced expiratory volume in 1 second (FEV1) change from baseline after omalizumab initiation for subgroups by number of comorbidities (0, 1 [008/009]; 0, 1, ≥2 [EXTRA and INNOVATE]; 0, 1, 2, ≥3 [PROSPERO]). Self-reported comorbidities included allergic rhinoconjunctivitis, chronic rhinosinusitis, recurrent acute sinusitis, nasal polyps, atopic and contact dermatitis, urticaria, food allergy, anaphylaxis, other allergies, gastroesophageal reflux disease, eosinophilic esophagitis, and eosinophilic granulomatosis with polyangiitis.ResultsIn the EXTRA and INNOVATE studies, no consistent pattern was observed for placebo-corrected relative rate reduction in normalized asthma exacerbations among omalizumab-treated comorbidity subgroups. In PROSPERO, on-study exacerbation rates in the comorbidity subgroups were similar (0, 0.68; 1, 0.70; 2, 0.77; ≥3, 0.80). FEV1 improvements were observed throughout the study for omalizumab vs placebo for all comorbidity subgroups. There were no consistent differences in FEV1 improvements among comorbidity subgroups in 008/009, EXTRA, or INNOVATE. Similarly, no among-group differences were observed for FEV1 change from baseline at month 12 in PROSPERO (0, 0.05 L; 1, 0.08 L; 2, 0.00 L; ≥3, 0.04 L). The 95% confidence intervals overlapped substantially in all instances.ConclusionIn these analyses of placebo-controlled/single-armed studies, on-study exacerbation rates and FEV1 improvements with omalizumab treatment were similar irrespective of comorbidity burden.Trial RegistrationClinicalTrials.gov identifiers are as follows: EXTRA, NCT00314574 (https://clinicaltrials.gov/ct2/show/NCT00314574); INNOVATE, NCT00046748 (https://clinicaltrials.gov/ct2/show/NCT00046748); and PROSPERO, NCT01922037 (https://clinicaltrials.gov/ct2/show/NCT01922037).     

MicroRNA-362 negatively and positively regulates SMAD4 expression in TGF-β/SMAD signaling to suppress cell migration and invasion

Cell migration and invasion are modulated by epithelial-to-mesenchymal transition (EMT) and the reverse MET process. Despite the detection of microRNA-362 (miR-362, both the miR-362-5p and -3p species) in cancers, none of the identified miR-362 targets is a mesenchymal or epithelial factor to link miR-362 with EMT/MET and metastasis. Focusing on the TGF-β/SMAD signaling pathway in this work, luciferase assays and western blot data showed that miR-362 targeted and negatively regulated expression of SMAD4 and E-cadherin, but not SNAI1, which is regulated by SMAD4. However, miR-362 knockdown also down-regulated SMAD4 and SNAI1, but up-regulated E-cadherin expression. Wound-healing and transwell assays further showed that miR-362 knockdown suppressed cell migration and invasion, effects which were reversed by over-expressing SMAD4 or SNAI1, or by knocking down E-cadherin in the miR-362 knockdown cells. In orthotopic mice, miR-362 knockdown inhibited metastasis, and displayed the same SMAD4 and E-cadherin expression profiles in the tumors as in the in vitro studies. A scheme is proposed to integrate miR-362 negative regulation via SMAD4, and to explain miR-362 positive regulation of SMAD4 via miR-362 targeting of known SMAD4 suppressors, BRK and DACH1, which would have resulted in SMAD4 depletion and annulment of subsequent involvement in TGF-β signaling actions. Hence, miR-362 both negatively and positively regulates SMAD4 expression in TGF-β/SMAD signaling pathway to suppress cell motility and invasiveness and metastasis, and may explain the reported clinical association of anti-miR-362 with suppressed metastasis in various cancers. MiR-362 knockdown in miR-362-positive cancer cells may be used as a therapeutic strategy to suppress metastasis.     

Computer-aided diagnosis of diabetic retinopathy: A review

Diabetes mellitus may cause alterations in the retinal microvasculature leading to diabetic retinopathy. Unchecked, advanced diabetic retinopathy may lead to blindness. It can be tedious and time consuming to decipher subtle morphological changes in optic disk, microaneurysms, hemorrhage, blood vessels, macula, and exudates through manual inspection of fundus images. A computer aided diagnosis system can significantly reduce the burden on the ophthalmologists and may alleviate the inter and intra observer variability. This review discusses the available methods of various retinal feature extractions and automated analysis.     

Prediction of Motor Function in Stroke Patients Using Machine Learning Algorithm: Development of Practical Models

BackgroundMachine learning (ML) techniques are being increasingly adopted in the medical field.ObjectiveWe developed a deep neural network (DNN) model and applied 2 well-known ML algorithms, logistic regression and random forest, in predicting motor outcome at 6 months after stroke.MethodsIn the present study, by using 14 input variables which are easily measured by clinicians, we developed ML models and investigated their applicability to predicting motor outcome in hemiplegic stroke patients. We retrospectively analyzed data of 1,056 consecutive stroke patients. Favorable outcomes of the upper and lower limbs were defined as a modified Brunnstrom classification (MBC) score of ≥5 (able to perform activities of daily living with the affected upper limb) and a functional ambulation category (FAC) score of ≥4 (able to walk without guardian's assistance), respectively. Poor outcomes of the upper and lower limbs were defined as MBC and FAC scores of <5 and <4, respectively. We developed 3 ML algorithms, namely the DNN, logistic regression, and random forest.ResultsRegarding the prediction of upper limb function, for the DNN model, the area under the curve (AUC) was 0.906. For the logistic regression and random forest models, the AUC were 0.874 and 0.882, respectively. For the prediction of lower limb function, for the DNN, logistic regression, and random forest models, the AUCs were 0.822, 0.768, and 0.802, respectively.ConclusionsWe demonstrated that the ML algorithms, particularly the DNN, can be useful for predicting motor outcomes in the upper and lower limbs at 6 months after stroke.