Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.

Modified Severity of Dyspepsia Assessment pain scale: a new tool for measuring upper abdominal pain in osteoarthritis patients taking NSAIDs.

BACKGROUND: This study evaluated the electronically administered modified Severity of Dyspepsia Assessment (mSODA) pain scale, a six-item measure of upper abdominal pain intensity, for daily use in osteoarthritis patients taking nonsteroidal anti-inflammatory drugs. METHODS: Once the mSODA pain scale was isolated, cognitive debriefing interviews (n = 30) were used to examine its appropriateness in the target population. Following administration of the instrument in two Phase III pivotal trials, the data were analyzed to examine reliability, validity, responsiveness, and the minimal important difference. RESULTS: Using a subset of trial data (n = 90 patients), the mSODA pain scale proved to be a unidimensional, highly internally consistent instrument (α = 0.93) with good test-retest reliability (intraclass correlation coefficient 0.77). Construct validity was established via moderate correlations with other similar patient-reported outcomes. Additionally, known-groups validity demonstrated that the mSODA pain scale could distinguish between subjects who did and did not report gastrointestinal symptoms and antacid use (both P values ≤ 0.05). The mSODA pain scale was also responsive to change in heartburn at weeks 6 and 12 (Guyatt's statistic = 1.7 and 2.6, respectively), and the minimal important difference obtained via ½ SD was 5.7 (range 2-47). CONCLUSION: This research suggests that the mSODA pain scale is both feasible and valid for assessing dyspepsia in patients taking nonsteroidal anti-inflammatory drugs for relief of symptoms of osteoarthritis.

Minimal clinically important difference for the ocular surface disease index.

OBJECTIVE: To assess the minimal clinically important difference (MCID) for the Ocular Surface Disease Index (OSDI; Allergan Inc, Irvine, California, holds the copyright), a 12-item patient-reported outcome questionnaire designed to quantify ocular disability due to dry eye disease. METHODS: Study data were collected within the Restasis Review of Efficacy and Safety vs Tears in the Relief of Dry Eye (RESTORE), an observational registry. A clinician global impression (CGI) and a subject global assessment (SGA) served as anchors to estimate the MCID for the overall OSDI score (range, 0-100). The overall OSDI score defined the ocular surface as normal (0-12 points) or as having mild (13-22 points), moderate (23-32 points), or severe (33-100 points) disease. RESTORE patients were included if they completed the OSDI at the baseline visit and at a follow-up visit and had a global change rating (SGA or CGI). RESULTS: Three hundred ten patients were included (82.3% white and 81.6% female [mean age, 57.8 years]). The CGI and SGA correlated with the OSDI score change for all OSDI categories except the normal category. The MCID ranged from 7.0 to 9.9 for all OSDI categories. The MCID ranged from 4.5 to 7.3 for mild or moderate disease and from 7.3 to 13.4 for severe disease. CONCLUSIONS: Using observational data, we estimated the MCIDs for different baseline OSDI categories of dry eye disease. These results will assist clinicians and researchers when interpreting OSDI score changes.

Impact of chronic Immune Thrombocytopenic Purpura (ITP) on health-related quality of life: a conceptual model starting with the patient perspective.

BACKGROUND: Immune thrombocytopenic purpura (ITP), a condition characterized by autoimmune-mediated platelet destruction and suboptimal platelet production, is associated with symptoms such as bruising, epistaxis, menorrhagia, mucosal bleeding from the gastrointestinal and urinary tracts and, rarely central nervous system bleeding. The aim of this research is to develop a conceptual model to describe the impact of ITP and its treatment on patients' health-related quality of life (HRQoL). METHODS: A literature search and focus groups with adult ITP patients were conducted to identify areas of HRQoL affected by ITP. Published literature was reviewed to identify key HRQoL issues and existing questionnaires used to assess HRQoL. Focus group transcripts were reviewed, and common themes were extracted by grouping conceptual categories that described the impact on HRQoL. RESULTS: The literature synthesis and themes from the focus group data suggest that decreased platelet counts, disease symptoms, and treatment side effects influence multiple domains of HRQoL for ITP patients. Key areas affected by ITP and its treatments include emotional and functional health, work life, social and leisure activities, and reproductive health. CONCLUSION: ITP affects various areas of HRQoL. This conceptual model will help inform the evaluation of therapeutic strategies for ITP.

Fenestrations enhance tear mixing under silicone-hydrogel contact lenses.

PURPOSE: Extended wear of conventional hydrogel soft contact lenses (SCLs) is associated with adverse ocular responses. Some of these ocular events are thought to result from inadequate tear mixing in the postlens tear film (PoLTF). Therefore, strategies to increase tear mixing may improve the safety of extended-wear SCLs. Recently, it has been suggested that placing fenestrations in soft lenses increases tear mixing. In the present study, hydrodynamic modeling and tear-mixing measurements were used to explore the effects of fenestrations on tear exchange under an SCL. METHODS: Tear mixing, expressed as the time to deplete 95% of fluorescent dye from the PoTLF (T(95)), was measured in 20 subjects fitted with two pairs of silicone hydrogel SCLs. The lenses were identical except that one pair was fenestrated (F) with 40 holes each 100 microm in diameter. The effect of fenestrations on improving tear mixing is explained and enhancement of tear mixing is predicted, with the use of hydrodynamic modeling. RESULTS: T(95) estimates were significantly lower (P < 0.001) in the F (mean T(95) = 18.3 minutes) lenses compared with the standard unfenestrated (S-uF) (mean T(95) = 22.6 minutes) lenses (DeltaT(95) = 4.3 minutes, 95% CI = 2.5-6.2) and were in general agreement with the proposed mixing model. Optimization of tear mixing can be achieved by selectively placing fenestrations in the pooling regions before the thinnest regions. The model predictions were sensitive to the distribution of tear-film thickness under the lens. CONCLUSIONS: Fenestrations improve tear-mixing efficiency. Accurate prediction of the effects of lens parameters on tear mixing, however, demands quantitative measurement of the postlens distribution of tear-film thickness.

Black-line formation and the "perched" human tear film.

Introduction. McDonald and Brubaker(1) observed that after instillation of fluorescein, dark lines appear near the upper and lower lid margins of the human eye immediately following a blink. Methods. This paper numerically models the dynamic black-line formation under the lubrication approximation at low Reynolds number, including gravity and surface tension forces. Results. The hydrodynamic model predicts that menisci at the lid margins draw liquid from the tear film, resulting in local thinning close to the lids (i.e., black lines) due to capillary suction. Once the film thins locally, resistance to further thinning increases. No vertical gravity-induced drainage occurs between blinks, and the tear film is trapped in its initially deposited state or "perched" between the two black lines. Conclusions. We demonstrate quantitatively that due to rapid formation of black lines, the tear film is trapped for extended periods. Lid action is therefore required to disturb the perched tear film.