Tag: nevin manimala

Ann Am Thorac Soc. 2022 May 2. doi: 10.1513/AnnalsATS.202103-343OC. Online ahead of print.

ABSTRACT

Background: To inform an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guideline, this systematic review evaluated existing interstitial lung disease (ILD) literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic nintedanib. Methods: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using nintedanib to treat patients with PPF. Mortality, disease progression, and adverse event data were extracted, and meta-analyses performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Results: Two relevant studies were selected. The annual decline in FVC was less in the nintedanib arm in the overall study population [mean difference (MD) 107 milliliters (mL)/year (yr) (95% CI 65.4-148.5 mL/yr)] and in the subgroups with usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis [MD 128.2 mL/yr (95% CI 70.8-185.6 mL/yr)], non-UIP patterns of pulmonary fibrosis [MD 75.3 mL/yr (95% CI 15.5-135.0 mL/yr)], fibrotic connective tissue disease-related ILD [MD 106.2 mL/yr (95% CI 10.6-201.9 mL/yr)], fibrotic idiopathic non-specific interstitial pneumonia [MD 141.7 mL/yr (95% CI 46.0-237.4 mL/yr)], and fibrotic occupational ILD [MD 252.8 mL/yr (95% CI 79.2-426.5 mL/yr)], but not fibrotic hypersensitivity pneumonitis [MD 72.9 mL/yr (95% CI -8.9-154.7 mL/yr)], fibrotic sarcoidosis [MD -20.5 mL/yr (95% CI -337.1-296.1 mL/yr)], or unclassified fibrotic ILD [MD 68.5 mL/yr (95% CI -31.3-168.4 mL/yr)] when compared to placebo. Gastrointestinal (GI) side effects were common. Quality of evidence for the outcomes ranged from very low to moderate GRADE. Conclusions: Nintedanib use in patients with PPF is associated with a statistically significant decrease in disease progression but increase in GI side effects regardless of the radiographic pattern of pulmonary fibrosis. However, limitations in the available evidence lead to low certainty in these effect estimates and make definitive conclusions about the differential effects by subtype of ILD difficult to determine.

PMID:35499854 | DOI:10.1513/AnnalsATS.202103-343OC

Ann Am Thorac Soc. 2022 May 2. doi: 10.1513/AnnalsATS.202103-342OC. Online ahead of print.

ABSTRACT

Background: To inform an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guideline, this systematic review evaluated existing interstitial lung disease literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic pirfenidone. Methods: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using pirfenidone to treat patients with PPF. Mortality, disease progression, lung function, and adverse event data were extracted, and meta-analyses performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Results: Two studies met inclusion criteria. Meta-analyses revealed changes in FVC % predicted [mean difference (MD) 2.3% (95% CI 0.5-4.1)], FVC in mL [MD 100.0 mL (95% CI 98.1-101.9)], and 6MWD in meters [MD 25.2 m (95% CI 8.3-42.1)] all favored pirfenidone to placebo. Change in DLCO in mmol/kPa/min [MD 0.40 mmol/kPa/min (95% CI 0.10-0.70)] and risk of DLCO declining more than 15% [relative risk (RR) 0.27 (95% CI 0.08-0.95)] also favored pirfenidone. The risks of gastrointestinal discomfort [RR 1.83 (95% CI 1.29-2.60)] and photosensitivity [RR 4.88 (95% CI 1.09-21.83)] were higher with pirfenidone. The quality of evidence was low or very low GRADE, depending on the outcome. Conclusions: Pirfenidone use in patients with PPF is associated with statistically significant decrease in disease progression and protection in lung function. However, there is very low certainty in the estimated effects due to limitations in the available evidence.

PMID:35499847 | DOI:10.1513/AnnalsATS.202103-342OC

JAMA Intern Med. 2022 May 2. doi: 10.1001/jamainternmed.2022.1449. Online ahead of print.

ABSTRACT

IMPORTANCE: Observational evidence suggests that higher physical activity is associated with slower kidney function decline; however, to our knowledge, no large trial has evaluated whether activity and exercise can ameliorate kidney function decline in older adults.

OBJECTIVE: To evaluate whether a moderate-intensity exercise intervention can affect the rate of estimated glomerular filtration rate per cystatin C (eGFRCysC) change in older adults.

DESIGN, SETTING, AND PARTICIPANTS: This ancillary analysis of the Lifestyle Interventions and Independence For Elders randomized clinical trial enrolled 1199 community-dwelling, sedentary adults aged 70 to 89 years with mobility limitations and available blood specimens. The original trial was conducted across 8 academic centers in the US from February 2010 through December 2013. Data for this study were analyzed from March 29, 2021, to February 28, 2022.

INTERVENTIONS: Structured, 2-year, partially supervised, moderate-intensity physical activity and exercise (strength, flexibility) intervention compared with a health education control intervention with 2-year follow-up. Physical activity was measured by step count and minutes of moderate-intensity activity using accelerometers.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in eGFRCysC. Rapid eGFRCysC decline was defined by the high tertile threshold of 6.7%/y.

RESULTS: Among the 1199 participants in the analysis, the mean (SD) age was 78.9 (5.2) years, and 800 (66.7%) were women. At baseline, the 2 groups were well balanced by age, comorbidity, and baseline eGFRCysC. The physical activity and exercise intervention resulted in statistically significantly lower decline in eGFRCysC over 2 years compared with the health education arm (mean difference, 0.96 mL/min/1.73 m2; 95% CI, 0.02-1.91 mL/min/1.73 m2) and lower odds of rapid eGFRCysC decline (odds ratio, 0.79; 95% CI, 0.65-0.97).

CONCLUSIONS AND RELEVANCE: Results of this ancillary analysis of a randomized clinical trial showed that when compared with health education, a physical activity and exercise intervention slowed the rate of decline in eGFRCysC among community-dwelling sedentary older adults. Clinicians should consider targeted recommendation of physical activity and moderate-intensity exercise for older adults as a treatment to slow decline in eGFRCysC.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01072500.

PMID:35499834 | DOI:10.1001/jamainternmed.2022.1449

Invest Ophthalmol Vis Sci. 2022 May 2;63(5):1. doi: 10.1167/iovs.63.5.1.

ABSTRACT

PURPOSE: To investigate the phenotypic changes of mature corneal epithelial cells (MCECs) that cocultured with limbal niche cells (LNCs) in three-dimensional Matrigel (3D Matrigel) in vitro.

METHODS: MCECs were isolated from central corneas, and limbal epithelial progenitor cells (LEPCs) were isolated from limbal segments with Dispase II. LNCs were isolated and cultured from limbal niche using the collagenase A digestion method and identified with PCK/VIM/CD90/CD105/SCF/PDGFRβ. MCECs were cultured on 3D Matrigel (50%, v/v) with or without LNCs for 10 days. Expression of CK12 and p63α and clone formation test were used to compare the progenitor phenotypic changes for MCECs before and after induction using LEPCs as control.

RESULTS: Homogeneous LNCs were isolated and identified as spindle shape and adherent to a plastic surface coated with 5% Matrigel. Double immunostaining of the fourth-passage LNCs was uniformly PCK-/VIM+/CD90+/CD105+/SCF+/PDGFRβ+. Reverse transcription and quantitative real-time polymerase chain reaction (RT-qPCR) revealed the decrease of PCK expression from the second passage and elevation of Vim, CD90, CD105, SCF, and PDGFRβ transcripts from the third passage, and the transcription level of Vim, CD90, CD105, SCF, and PDGFRβ was elevated statistically in the fourth passage compared to the first passage (P < 0.01). Both immunofluorescence (IF) staining for cross section and cytospin cells demonstrated that MCECs expressed higher CK12 while lower p63α than LEPCs (P < 0.01). Sphere growth formation was noticed as early as 24 hours in the MCEC + LNC group, 48 hours in the LEPC group, and 72 hours in the MCEC group. The diameters of the spheres were the biggest in the MCEC + LNC group (182.24 ± 57.91 µm), smaller in the LEPC group (125.71 ± 41.20 µm), and smallest in the MCEC group (109.39 ± 34.85 µm) by the end of the 10-day culture (P < 0.01). Double immunostaining with CK12/p63α showed that cells in the sphere formed from MCECs expressed CK12 but not p63α; in contrast, some cells in the MCEC + LNC group expressed CK12, but most of them expressed p63α. RT-qPCR revealed a significant reduction of CK12 transcript but elevation of p63α, Oct4, Nanog, Sox2, and SSEA4 (P < 0.05). Holoclone composed of cubic epithelial cells could be generated in the MCEC + LNC group but not in the other two groups.

CONCLUSIONS: The data shows that human MCEC cell phenotype could be induced to the dedifferentiation stage when cocultured with LNCs in 3D Matrigel that simulated the microenvironment of limbal stem cells in vitro.

PMID:35499835 | DOI:10.1167/iovs.63.5.1

JAMA Netw Open. 2022 May 2;5(5):e229712. doi: 10.1001/jamanetworkopen.2022.9712.

ABSTRACT

IMPORTANCE: The factors associated with the failure of nonoperative management of appendicitis and the differences in patient-reported outcomes between successful and unsuccessful nonoperative management remain unknown.

OBJECTIVES: To investigate factors associated with the failure of nonoperative management of appendicitis and compare patient-reported outcomes between patients whose treatment succeeded and those whose treatment failed.

DESIGN, SETTING, AND PARTICIPANTS: This study was a planned subgroup secondary analysis conducted in 10 children’s hospitals that included 370 children aged 7 to 17 years with uncomplicated appendicitis enrolled in a prospective, nonrandomized clinical trial between May 1, 2015, and October 31, 2018, with 1-year follow-up comparing nonoperative management with antibiotics vs surgery for uncomplicated appendicitis. Statistical analysis was performed from November 1, 2019, to February 12, 2022.

INTERVENTIONS: Nonoperative management with antibiotics vs surgery.

MAIN OUTCOMES AND MEASURES: Failure of nonoperative management and patient-reported outcomes. The relative risk (RR) of failure based on sociodemographic and clinical characteristics was calculated. Patient-reported outcomes were compared based on the success or failure of nonoperative management.

RESULTS: Of 370 patients (34.6% of 1068 total patients; 229 boys [61.9%]; median age, 12.3 years [IQR, 10.0-14.6 years]) enrolled in the nonoperative group, treatment failure occurred for 125 patients (33.8%) at 1 year, with 53 patients (14.3%) undergoing appendectomy during initial hospitalization and 72 patients (19.5%) experiencing delayed treatment failure after hospital discharge. Higher patient-reported pain at presentation was associated with increased risk of in-hospital treatment failure (RR, 2.1 [95% CI, 1.0-4.4]) but not delayed treatment failure (RR, 1.3 [95% CI, 0.7-2.3]) or overall treatment failure at 1 year (RR, 1.5 [95% CI, 1.0-2.2]). Pain duration greater than 24 hours was associated with decreased risk of delayed treatment failure (RR, 0.3 [95% CI, 0.1-1.0]) but not in-hospital treatment failure (RR, 1.2 [95% CI, 0.5-2.7]) or treatment failure at 1 year (RR, 0.7 [95% CI, 0.4-1.2]). There was no increased risk of treatment failure associated with age, white blood cell count, sex, race, ethnicity, primary language, insurance status, transfer status, symptoms at presentation, or imaging results. Health care satisfaction at 30 days and patient-reported, health-related quality of life at 30 days and 1 year were not different. Satisfaction with the decision was higher with successful nonoperative management at 30 days (28.0 vs 27.0; difference, 1.0 [95% CI, 0.01-2.0]) and 1 year (28.1 vs 27.0; difference, 1.1 [95% CI, 0.2-2.0]).

CONCLUSIONS AND RELEVANCE: This analysis suggests that a higher pain level at presentation was associated with a higher risk of initial failure of nonoperative management and that a longer duration of pain was associated with lower risk of delayed treatment failure. Although satisfaction was high in both groups, satisfaction with the treatment decision was higher among patients with successful nonoperative management at 1 year.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02271932.

PMID:35499827 | DOI:10.1001/jamanetworkopen.2022.9712

Ann Surg Oncol. 2022 May 2. doi: 10.1245/s10434-022-11758-z. Online ahead of print.

ABSTRACT

BACKGROUND: Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes.

METHODS: This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS).

RESULTS: For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND.

CONCLUSION: This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.

PMID:35499783 | DOI:10.1245/s10434-022-11758-z

Arch Orthop Trauma Surg. 2022 May 2. doi: 10.1007/s00402-022-04450-0. Online ahead of print.

ABSTRACT

BACKGROUND: Use of multimodal analgesia (MMA) prior to orthopedic surgery has been adopted by many practitioners as a strategy to minimize use of opioid medications. The purpose of this investigation was to quantify the effect of a preemptive three-drug regimen (acetaminophen, celecoxib, and gabapentin) in terms of post-operative opioid consumption and pain control in the field of total joint arthroplasty.

METHODS: A retrospective chart review was conducted on 1691 patients who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA) and stratified by whether they received a preemptive three medication analgesic therapy (acetaminophen, celecoxib, and gabapentin) within 30 to 60 min prior to entering the operating room. Post-operative opioid consumption as well as subjectively reported patient pain scores were assessed throughout their hospital stay.

RESULTS: A total of 1416 eligible patients were identified with 485 undergoing THA and 931 undergoing TKA. Statistically significant reductions in oral morphine equivalents were shown on post-operative day zero and two within the TKA cohort, and non-significant reductions were demonstrated in other intervals for both procedure types. Statistically significant reductions in patient reported pain scores were shown in nearly every time interval in both procedure types.

CONCLUSION: The receipt of preemptive acetaminophen, celecoxib, and gabapentin 30-60 min prior to total joint arthroplasty demonstrated modest reductions in opioid requirements post-operatively. Patients receiving preemptive MMA reported lower pain scores throughout nearly every time interval during their admission after surgery. Further investigations are warranted regarding optimal preoperative medication therapies to promote adequate post-operative pain control-and ultimately diminished opioid consumption-in the setting of total joint arthroplasty.

PMID:35499774 | DOI:10.1007/s00402-022-04450-0

Arch Womens Ment Health. 2022 May 2. doi: 10.1007/s00737-022-01230-y. Online ahead of print.

ABSTRACT

Rapid screening tools are useful for identifying at-risk patients and referring them for further assessment and treatment, but none exist that consider the unique medical needs of pregnant women with eating disorders (EDs). There is a need for a rapid, sensitive, and specific screening tool that can be used to identify a potential ED in pregnancy. We started with a set of 25 questions, developed from our qualitative work along with other ED screening tools, and tested on a development (n = 190) and validation sample (n = 167). Statistical analysis included factor analysis and logistic regressions with ROC curves. Development and validation samples were combined for trimester analysis (n = 357). Refining the tool to 12 items demonstrated strong internal reliability (development alpha = 0.95, validation alpha = 0.91). With correlated errors, questions demonstrated acceptable CFA fit (development: GFI: 0.91, RMSEA: 0.10, NNFI: 0.95; validation: GFI: 0.85, RMSEA: 0.14, NNFI: 0.86). Similar fits were seen by trimester: first trimester n = 127, GFI: 0.89, RMSEA: 0.12, NNFI: 0.94; second trimester n = 150, GFI: 0.83, RMSEA: 0.14, NNFI: 0.88; third trimester n = 80, GFI: 0.99, NNFI: 0.99. Validation against current ED diagnosis demonstrated acceptable sensitivity and specificity using a cutoff of 39 (development sensitivity = 80.7%, specificity = 79.7%, OR = 16.42, 95% CI: 7.51, 35.88; validation sensitivity = 69.2%, specificity = 86.5%, OR: 17.43, 95% CI: 6.46, 47.01). Findings suggest the PEBS tool can reliably and sensitively detect EDs across pregnancy trimesters with 12 questions. A further implication of this work is to reduce health and mental health treatment disparities through this standard and rapid screening measure to ensure early identification and treatment.

PMID:35499780 | DOI:10.1007/s00737-022-01230-y

Clin Rheumatol. 2022 May 2. doi: 10.1007/s10067-022-06167-2. Online ahead of print.

ABSTRACT

Homelessness is a public health crisis and there is a paucity of information about patients with rheumatic disease experiencing homelessness. We sought to develop approaches to improve care for this unique patient population. We previously reported observations on 17 homeless patients with inflammatory arthritis (15 rheumatoid arthritis (RA), 2 psoriatic arthritis (PsA)). We obtained follow-up information from our original 17 patients and compared this to data summarized and published about them from 12 months previously. We also created and administered a 100-question needs assessment survey. Follow-up 12-month clinical information was available from 13/17 homeless and 13/17 non-homeless controls. Homeless patients remained less well with more disease than non-homeless patients-poorer access to clinic appointments (80% vs 91%, p < 0.05), more emergency services use (20 vs 5 ED visits), less DMARDs use (43% vs 100%, p < 0.01), and more steroid use (29% vs 0%, p < 0.01). Homeless patients also had higher inflammatory markers than non-homeless patients (ESR 32 vs 26 mm/h and CRP 17 vs 5 mg/L), although these findings were not statistically significantly different. Seventy-eight percent of homeless patients were stable, 14% improved, and 7% worse; 21% had stable controlled and 57% stable active disease vs 62% and 0% of non-homeless (p < 0.01). Among the homeless, 6 (4 RA, 2 PsA) completed the survey, 2 declined, and 9 could not be reached. All 6 had found housing although all still had housing insecurity; 4 (67%) were homeless in the past. Three out of six (50%) obtained housing from social assistance during hospitalization following disease exacerbation while homeless. The average monthly income was $873. 5/6 (83.3%), were unable to work due to health, and were in considerable pain that adversely impacted their physical and mental health and ability to perform ADLs. Their perceived “greatest need” included dental care, physical therapy, knee surgery, employment, socialization secondary to isolation, and stable housing. Our understanding of the unique challenges of patients with rheumatic disease experiencing homelessness is improved, but not complete. Strengthened collaboration between street medicine providers and rheumatologists is necessary to improve care for homeless patients, especially given poorer outcomes compared with non-homeless counterparts. Key Points • We report 12-month follow-up information from our original 17 homeless patients with inflammatory arthritis (related in this journal in 2021) and their responses to an extensive needs assessment survey designed to identify barriers to care. • Homeless patients with inflammatory arthritis continued to have worse disease outcomes, use more corticosteroids and less DMARDs, and be seen less often in rheumatology clinics and more frequently in emergency departments than their non-homeless counterparts. • Survey data indicated that social assistance during hospitalization was a key area where healthcare providers could intervene to provide housing security for homeless patients and improve outcomes. Patients perceived “greatest needs” went beyond housing and rheumatological care and critically included access to social/specialty services. • Street medicine is the direct delivery of healthcare to people experiencing homelessness wherever they reside. Our observations, obtained in collaboration with street medicine colleagues, suggest important and salutary opportunities for this partnership to improve care for these particular patients.

PMID:35499771 | DOI:10.1007/s10067-022-06167-2

Environ Sci Pollut Res Int. 2022 Apr 30. doi: 10.1007/s11356-022-19761-3. Online ahead of print.

ABSTRACT

Rapid urbanisation has had a significant negative influence on the water bodies that flow through and around urban areas. This study aims to evaluate the water quality and analyse the suitability for drinking and irrigation uses. This study envisaged assessing the water quality status of the groundwater using the pollution index of groundwater (PIG), ecological risk index (ERI) and multivariate statistical techniques, namely cluster analysis (CA) and principal component analysis (PCA), that were applied to differentiate the sources of water quality variation and determine the cause of pollution in the study area. Most groundwater is unsuitable for drinking and irrigation consumption, depending on analyses. PIG values indicated high pollution levels in the studied water body, rendering it unsuitable for any practical purpose. CA results showed the impact of surface water and treatment plant on groundwater. PCA was used to identify four important factors in the groundwater, including mineral and nutrient pollution, heavy metal pollution, organic pollution and faecal contamination. The deteriorating water quality of the groundwater was demonstrated to originate from vast sources of anthropogenic activities, especially municipal sewage discharge. Study wells had greater concentrations of Cl^– and Na⁺ in their water because seawater flows into the aquifer system and mixes with the marine aquifer matrix. Thus, the current work reveals how to employ the PIG and multivariate statistical approaches to obtain more accessible and more meaningful information about the water quality of groundwater and to identify the sources of pollution.

PMID:35499738 | DOI:10.1007/s11356-022-19761-3