Search

Background: Collection of real-world evidence (RWE) is important in achondroplasia. Development of a prospective, shared, international resource that follows the principles of findability, accessibility, interoperability, and reuse of digital assets, and that captures long-term, high-quality data, would improve understanding of the natural history of achondroplasia, quality of life, and related outcomes. Methods: The Europe, Middle East, and Africa (EMEA) Achondroplasia Steering Committee comprises a multidisciplinary team of 17 clinical experts and 3 advocacy organization representatives. The committee undertook an exercise to identify essential data elements for a standardized prospective registry to study the natural history of achondroplasia and related outcomes. Results: A range of RWE on achondroplasia is being collected at EMEA centres. Whereas commonalities exist, the data elements, methods used to collect and store them, and frequency of collection vary. The topics considered most important for collection were auxological measures, sleep studies, quality of life, and neurological manifestations. Data considered essential for a prospective registry were grouped into six categories: demographics; diagnosis and patient measurements; medical issues; investigations and surgical events; medications; and outcomes possibly associated with achondroplasia treatments. Conclusions: Long-term, high-quality data are needed for this rare, multifaceted condition. Establishing registries that collect predefined data elements across age spans will provide contemporaneous prospective and longitudinal information and will be useful to improve clinical decision-making and management. It should be feasible to collect a minimum dataset with the flexibility to include country-specific criteria and pool data across countries to examine clinical outcomes associated with achondroplasia and different therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background Studies of symptomatic gastroparetics consistently find poor correlation with gastric emptying. We hypothesized that concomitant small bowel dysmotility may play a role in symptom causation in gastroparesis and sought to test this hypothesis by using wireless motility capsule ( WMC) testing to simultaneously measure antral and duodenal area under pressure curve ( AUC) in patients with delayed gastric emptying. Methods Using a cohort from a multicenter clinical trial and a separate tertiary clinical database, we identified gastroparetics that underwent concurrent WMC testing and completed the Gastroparesis Cardinal Symptom Index, a validated questionnaire. Our study included 35 gastroparetics defined by a gastric emptying time ( GET) ≥5 h. Antral and duodenal AUC were assessed at 1-h windows pre- GET and post- GET, respectively. Key Results We found moderate correlations between duodenal AUC and symptom severity in the combined cohort ( n = 35; R = −0.42; p = 0.01; 95% CI −0.7, −0.1). Removing patients with colonic delay resulted in a stronger correlation of duodenal AUC to symptom severity ( n = 21; R = −0.63; p < 0.01; 95% CI −0.81, −0.31). The multicenter trial ( n = 20) and clinical practice cohorts ( n = 15) had significantly different symptom severity and exclusion criteria. When analyzed separately, significant correlations between duodenal AUC and symptom severity were observed ( R = −0.71; p < 0.01; 95% CI −0.9, −0.4 and R = −0.72; p < 0.01; 95% CI −0.9, −0.3, respectively). Symptom severity and antral motility showed no correlation. Conclusions & Inferences We found significant correlations between duodenal AUC and symptom severity in two cohorts of gastroparetics. Small bowel motility may contribute to symptom generation in gastroparetic patients and this may inform therapeutic considerations. [ABSTRACT FROM AUTHOR]

Describes the indicated uses of midplane visible plasma TV images for tokamak control corrections not evident from other diagnostics. Use of four tangential midplane vacuum viewports; Alignment of the three vacuum viewports along the inside vessel wall.

Abstract: Background: Small bowel fed response is an increased contractile activity pattern following the ingestion of a meal. Postprandial motility is traditionally evaluated using small bowel manometry. Wireless motility capsule (WMC) is an ingestible wireless capsule that measures pH, temperature, and intraluminal pressure. The primary aim of the study was to assess small bowel fed response captured with the non‐invasive WMC. The secondary aim was to compare the fed response patterns between healthy subjects and patients with motility disorders of gastroparesis and constipation. Methods: All subjects had 250 cc Ensure® meal 6 hours after WMC ingestion. Frequency of contractions (Ct), area under the curve (AUC), and motility index (MI) were analyzed during 30 minutes of pre‐prandial baseline and 60 minutes postprandially in 20‐minute windows. Key Results: One hundred and eighty‐eight subjects (107 healthy, 23 gastroparetics, 58 constipated) were analyzed. Healthy: Ct, AUC, and MI all increased significantly immediately after meal ingestion (P < .01). Motility parameters peak at 20‐40 minutes postmeal. The motor activity decreased at the end of postprandial hour, but was still significantly higher than the fasting baseline (P < .01). Gastroparetics: All motility parameters failed to increase significantly compared to the baseline throughout the entire postprandial hour. Constipated: The fed response was similar to healthy subjects. Conclusions and Inferences: The small bowel fed response was readily observed in healthy and chronic constipation subjects with WMC but is blunted in gastroparetics. A blunted small bowel fed response suggests neuropathic changes outside the stomach and may contribute to postprandial symptoms. [ABSTRACT FROM AUTHOR]

Summary: Background: The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. Aims: To describe normative values for motility/contractility parameters across age, gender and testing centres. Methods: Healthy participants underwent a standardised wireless motility capsule assessment following an overnight fast and consumption of a meal of known nutritional content. Traces were divided into regions of interest and analysed using 2 software packages (MotiliGI and GIMS Data Viewer). Inter‐observer agreement was independently assessed by 2 investigators. Results: Normative data for motility/contractility parameters (maximum amplitude, mean peak amplitude, contraction frequency and motility index) are presented for 107 individuals (62 male, median age 40 years, range 18‐78). MotiliGI‐Gastric, small bowel and colonic maximal contraction amplitude correlated with age (r = .24, P = .01; r = .22, P = .02; and r = .2, P = .04 respectively). Small bowel motility index was higher in females than males (150.4 ± 12 vs 122 ± 7.6, P = .04). Inter‐observer agreement was excellent for transit times, pH and contractility/motility parameters. GIMS Data viewer‐Gastric, small bowel and colonic loge motility index correlated with the respective area under the contraction curve, total contractions, sum of amplitudes and contraction frequency (all r>.35, P < .0003) but not with transit times. Conclusions: Our analysis provides normative data for motility/contractility parameters. Log motility index summarises a number of measures. In future, the measurement of contractile activity with the wireless motility capsule may potentially aid in the diagnosis of disease states such as visceral myopathic disorders. [ABSTRACT FROM AUTHOR]

Background The wireless motility capsule ( WMC) offers the ability to investigate luminal gastrointestinal ( GI) physiology in a minimally invasive manner. Aim To investigate the effect of testing protocol, gender, age and study country on regional GI transit times and associated pH values using the WMC. Methods Regional GI transit times and pH values were determined in 215 healthy volunteers from USA and Sweden studied using the WMC over a 6.5-year period. The effects of test protocol, gender, age and study country were examined. Results For GI transit times, testing protocol was associated with differences in gastric emptying time (GET; shorter with protocol 2 (motility capsule ingested immediately after meal) vs. protocol 1 (motility capsule immediately before): median difference: 52 min, P = 0.0063) and colonic transit time (CTT; longer with protocol 2: median 140 min, P = 0.0189), but had no overall effect on whole gut transit time. Females had longer GET (by median 17 min, P = 0.0307), and also longer CTT by (104 min, P = 0.0285) and whole gut transit time by (263 min, P = 0.0077). Increasing age was associated with shorter small bowel transit time ( P = 0.002), and study country also influenced small bowel and CTTs. Whole gut and CTTs showed clustering of data at values separated by 24 h, suggesting that describing these measures as continuous variables is invalid. Testing protocol, gender and study country also significantly influenced pH values. Conclusions Regional GI transit times and pH values, delineated using the wireless motility capsule (WMC), vary based on testing protocol, gender, age and country. Standardisation of testing is crucial for cross-referencing in clinical practice and future research. [ABSTRACT FROM AUTHOR]

Summary: Indolent systemic mastocytosis (ISM) can trigger bone loss. However, the clinical relevance of different mast cell infiltration patterns for bone remains to be clarified. Here, we report increased bone turnover in individuals with ISM, and its extent is rather related to the type of mast cell distribution within the bone marrow than to the presence or absence of cutaneous manifestations. Introduction: It is well established that ISM can trigger osteopenia or osteoporosis. However, neither the clinical relevance of the infiltration pattern of mast cells within the bone marrow nor the impact of the presence or absence of cutaneous mast cell infiltration has been elucidated. Methods: We retrospectively analysed 300 cases with histologically proven ISM of the bone marrow and performed quantitative histomorphometry for a subgroup of 159 patients that did not receive any treatment before the biopsies were taken. Most importantly, since 66 % of the patients displayed ISM without the characteristic skin lesions, we were able to compare ISM with or without cutaneous manifestation. Results: We found that both forms of ISM were not only characterized by a decreased trabecular bone mass but also by an increased number of osteoclasts and osteoblasts. Interestingly, when we analysed these data in relation to mast cell distribution, we found that the bone cell numbers in cases with mast cell granulomas were significantly increased compared to cases with diffuse mast cell distribution. Moreover, evidence of increased bone turnover was also found in 16 patients displaying osteosclerosis. Conclusion: Based on the largest cohort of bone biopsies from patients with ISM analysed so far, we could demonstrate high bone turnover, more specifically increased osteoblast and osteoclast numbers and surface indices, as a cause of the skeletal changes. Moreover, the severity of the bone disease is presumably rather dependent on the amount of mast cells and their distribution within the bone marrow irrespective of the presence or absence of cutaneous involvement. [ABSTRACT FROM AUTHOR]

Background Assessment of phase III MMC is often not performed due to the invasive nature of antroduodenal manometry used to detect it. The aim of the study was to evaluate the ability of wireless motility capsule (WMC) to detect phase III MMC and correlate it with the simultaneous measurements by antroduodenal manometry (ADM). Methods Eighteen patients underwent simultaneous ADM and WMC. MMCs were identified first on ADM and then correlated with WMC events occurring simultaneously. Frequency of contractions per min, AUC, MI, and criteria for amplitude thresholds of contractions representing MCCs on WMC tracings were defined. Key Results In 18 patients, a total of 29 MMCs were recorded by ADM. WMC detected 86% of MMC events measured by ADM. Hundred percent (10/10) of MMCs in stomach were detected by WMC, whereas 79% (15/19) of MMCs were detected in SB. The sensitivity and specificity of WMC high amplitude contractions to represent phase III MMC were 90% and 71.8% in the stomach; 73.7% and 84.7% in SB, respectively, and negative predictive value was 99.9% in both regions. Conclusions & Inferences Wireless motility capsule was able to detect the phase III MMCs as the high amplitude contractions with good fidelity. WMC does not detect the propagation of MMC. Using the pressure thresholds, WMC can detect high amplitude contraction representing phase III MMC with favorable sensitivity/specificity profile and 99.9% negative predictive value. This observation may have clinical significance, as the absence of high amplitude contractions recorded by WMC during fasting state suggests absence of MMCs. [ABSTRACT FROM AUTHOR]

number of osteoporotic patients under bisphosphonate treatment present persistent fragility fractures and bone loss despite good compliance. The objective of this 18-month prospective study was to investigate the effect of teriparatide [rhPTH(1-34)] in 25 female osteoporotics who were inadequate responders to oral bisphosphonates and to correlate microarchitectural changes in three consecutive iliac crest biopsies measured by micro-computed tomography (μCT) with bone mineral density (BMD) and bone serum markers. Scanned biopsies at baseline (M0), 6 months (M6), and 18 months (M18) demonstrated early significant ( P < 0.01) increases in bone volume per tissue volume (+34%) and trabecular number (+14%) at M6 with only moderate changes in most μCT structural parameters between M6 and M18. μCT-measured bone tissue density was significantly decreased at M18, expressing an overall lower degree of tissue mineralization characteristic for new bone formation despite unchanged trabecular thickness due to increased intratrabecular tunneling at M18. μCT results were consistent with serum bone turnover markers, reaching maximal levels of bone alkaline phosphatase and serum β-crosslaps at M6, with subsequent decline until M18. BMD assessed by DXA demonstrated persistent increases at the lumbar spine until M12, whereas no significant change was observed at the hip. Type (alendronate/risedronate) and duration (3.5 ± 4 years) of prior bisphosphonate treatment did not influence outcome on μCT, BMD, or bone marker results. The overall results indicate a positive ceiling effect of teriparatide on bone microarchitecture and bone markers after 6 and 12 months for lumbar spine BMD, with no additional gain until M18 in bisphosphonate nonresponders. [ABSTRACT FROM AUTHOR]

Background Colon transit (CT) measurements are used in the management of significant constipation. The radiopaque marker (ROM) method provides limited information. Methods We proposed to validate wireless motility capsule (WMC), that measures pH, pressure and temperature, to ROM measurement of CT in patients with symptomatic constipation evaluated at multiple centers. Of 208 patients recruited, 158 eligible patients underwent simultaneous measurement of colonic transit time (CTT) using ROM (Metcalf method, cut off for delay >67 h), and WMC (cutoff for delay >59 h). The study was designed to demonstrate substantial equivalence, defined as diagnostic agreement >65% for patients who had normal or delayed ROM transit. Key Results Fifty-nine of 157 patients had delayed ROM CT. Transit results by the two methods differed: ROM median 55.0 h [IQR 31.0–85.0] and WMC (43.5 h [21.7–70.3], P < 0.001. The positive percent agreement between WMC and ROM for delayed transit was ∼80%; positive agreement in 47 by WMC/59 by ROM or 0.796 (95% CI = 0.67–0.98); agreement vs null hypothesis (65%) P = 0.01. The negative percent agreement (normal transit) was ∼91%: 89 by WMC/98 by ROM or 0.908 (95% CI = 0.83–0.96); agreement vs null hypothesis (65%), P = 0.00001. Overall device agreement was 87%. There were significant correlations ( P < 0.001) between ROM and WMC transit (CTT [ r = 0.707] and between ROM and combined small and large bowel transit [ r = 0.704]). There were no significant adverse events. Conclusions & Inferences The 87% overall agreement (positive and negative) validates WMC relative to ROM in differentiating slow vs normal CT in a multicenter clinical study of constipation. [ABSTRACT FROM AUTHOR]

Background The wireless motility capsule (WMC) measures intraluminal pH and pressure, and records transit time and contractile activity throughout the gastrointestinal tract. Our hypothesis is that WMC can differentiate antroduodenal pressure profiles between healthy people and patients with upper gut motility dysfunctions. This study aims to analyze differences in the phasic pressure profiles of the stomach and small intestine in healthy and gastroparetic subjects. Methods Data from 71 healthy and 42 gastroparetic subjects were analyzed. The number of contractions (Ct), area under the pressure curve and motility index (MI = Ln (Ct *sum amplitudes +1)) were analyzed for 60 min before gastric emptying of the capsule (GET), (gastric window) and after GET (small bowel window) and results between groups were compared with the Wilcoxon rank sum test. Key Results Significant differences were observed between healthy and gastroparetic subjects for Ct and MI ( P < 0.05). Median values of the motility parameters in gastric window were Ct = 72, MI = 11.83 for healthy and Ct = 47, MI = 11.12 for gastroparetics. In the small bowel, median values were Ct = 144.5, MI = 12.78 for healthy and Ct = 93, MI = 12.12 for gastroparetics. Diabetic subjects with gastroparesis showed significantly lower Ct and MI compared with healthy subjects in both gastric and small bowel windows while idiopathic gastroparetic subjects did not show significant differences. Conclusions & Inferences The WMC is able to differentiate between healthy and gastroparetic subjects based on gastric and small bowel motility profiles. [ABSTRACT FROM AUTHOR]

Background Wireless pH and pressure motility capsule (wireless motility capsule) technology provides a method to assess regional gastrointestinal transit times. Aims To analyse data from a multi-centre study of gastroparetic patients and healthy controls and to compare regional transit times measured by wireless motility capsule in healthy controls and gastroparetics (GP). Methods A total of 66 healthy controls and 34 patients with GP (15 diabetic and 19 idiopathic) swallowed wireless motility capsule together with standardized meal (255 kcal). Gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT) and whole gut transit time (WGTT) were calculated using the wireless motility capsule. Results Gastric emptying time, CTT and WGTT but not SBTT were significantly longer in GP than in controls. Eighteen percent of gastroparetic patients had delayed WGTT. Both diabetic and idiopathic aetiologies of gastroparetics had significantly slower WGTT ( P < 0.0001) in addition to significantly slower GET than healthy controls. Diabetic gastroparetics additionally had significantly slower CTT than healthy controls ( P = 0.0054). Conclusions In addition to assessing gastric emptying, regional transit times can be measured using wireless motility capsule. The prolongation of CTT in gastroparetic patients indicates that dysmotility beyond the stomach in GP is present, and it could be contributing to symptom presentation. Aliment Pharmacol Ther 31, 313–322 [ABSTRACT FROM AUTHOR]

Gastric emptying of digestible solids occurs after trituration of food particles. Non-digestible solids are thought to empty with phase III of the migrating motor complex (MMC). The aim of this study was to determine if a non-digestible capsule given with a meal empties from the stomach with return of the fasting phase III MMC or during the fed pattern with the solid meal. Fifteen normal subjects underwent antroduodenal manometry and ingestion of a radiolabelled meal and SmartPill wireless pH and pressure capsule. In five subjects, emptying of the SmartPill was studied in the fasting period by ingesting the SmartPill with radiolabelled water. The SmartPill emptied from the stomach within 6 h in 14 of 15 subjects. SmartPill pressure recordings showed high amplitude phasic contractions prior to emptying. SmartPill gastric residence time (261 ± 22 min) correlated strongly with time to the first phase III MMC (239 ± 23 min; r = 0.813; P < 0.01) and correlated moderately with solid-phase gastric emptying ( r = 0.606 with T-50% and r = 0.565 with T-90%). Nine of 14 subjects emptied the capsule with a phase III MMC. In five subjects, the SmartPill emptied with isolated distal antral contractions. In five subjects ingesting only water, SmartPill gastric residence time (92 ± 44 min) correlated with the time to the first phase III MMC (87 ± 30 min; r = 0.979; P < 0.01). The non-digestible SmartPill given with a meal primarily empties from the stomach with the return of phase III MMCs occurring after emptying the solid-phase meal. However, in some subjects, the SmartPill emptied with isolated antral contractions, an unappreciated mechanism for emptying of a non-digestible solid. [ABSTRACT FROM AUTHOR]

Background Gastric emptying scintigraphy (GES) using a radio-labelled meal is used to measure gastric emptying. A nondigestible capsule, SmartPill, records luminal pH, temperature, and pressure during gastrointestinal transit providing a measure of gastric emptying time (GET). Aims To compare gastric emptying time and GES by assessing their correlation, and to compare GET and GES for discriminating healthy subjects from gastroparetics. Methods Eighty-seven healthy subjects and 61 gastroparetics enrolled with simultaneous SmartPill and GES. Fasted subjects were ingested capsule and [99mTc]-SC radio-labelled meal. Images were obtained every 30 min for 6 h. Gastric emptying time and percentage of meal remaining at 2/4 h were determined for each subject. The sensitivity/specificity and receiver operating characteristic analysis of each measure were determined for each subject. Results Correlation between GET and GES-4 h was 0.73 and GES-2 h was 0.63. The diagnostic accuracy from the receiver operating characteristic curve between gastroparetics and healthy subjects was GET = 0.83, GES-4 h = 0.82 and GES-2 h = 0.79. The 300-min cut-off time for GET gives sensitivity of 0.65 and specificity of 0.87 for diagnosis of gastroparesis. The corresponding sensitivity/specificity for 2 and 4 h standard GES measures were 0.34/0.93 and 0.44/0.93, respectively. Conclusion SmartPill GET correlates with GES and discriminates between healthy and gastroparetic subjects offering a nonradioactive, standardized, ambulatory alternative to scintigraphy. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal (GI) symptoms, such as nausea and bloating, are common in people with type 1 diabetes (T1DM). Autonomic dysfunction can lead to changes in the GI secreto‐motor function which can be associated with GI symptom development. We hypothesized that regional pH profiles in T1DM differs from health and would be associated with objective physiological/clinical markers. Methods: Forty‐seven T1DM with confirmed diabetic sensory peripheral neuropathy and 41 healthy age‐matched subjects underwent standardized wireless motility capsule testing. T1DM completed the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale. Disease duration, glycemic control, insulin usage, and 24‐hour heart rate variability testing were evaluated. Key Results: In comparison to healthy subjects, gastric, and large bowel median pH were lower in T1DM (1.8 ± 1.6 vs 2.9 ± 1.5, P = 0.001 and 6.7 ± 0.6 vs 7.0 ± 0.5, P = 0.003, respectively). Additionally, change in pH across the pylorus was lower while change in pH across the ileocecal junction was higher in T1DM (5.2 ± 1.5 vs 5.8 ± 0.5, P = 0.003 and 1.8 ± 0.4 vs 1.3 ± 0.4, P < 0.0001, respectively). No difference was found in small bowel median pH. Gastric median pH was associated with small bowel transit time (r = 0.30, P = 0.049). Change in pH across the pylorus was negatively associated with fasting glycose (r = −0.35, P = 0.027). Small bowel median pH was associated with nausea (r = 0.42, P = 0.005) and small bowel transit time (r = 0.48, P = 0.0007). Large bowel median pH was associated with nausea (r = 0.35, P = 0.018) and the total GCSI score (r = 0.34, P = 0.023). Conclusions and Inferences: The GI pH profile in T1DM with DSPN is different from healthy subjects. Changes in pH profile may have important therapeutic implications and influence pharmacotherapeutic bioavailability. Forty‐seven people with type 1 diabetes and confirmed diabetic sensory peripheral neuropathy and 41 healthy age‐matched subjects underwent standardized wireless motility capsule testing showing lower gastric and large bowel median pH in patients than in healthy. [ABSTRACT FROM AUTHOR]