ResearchPad - clinical-articles https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Two‐year safety and efficacy outcomes for the treatment of overactive bladder using a long‐lived rechargeable sacral neuromodulation system]]> https://www.researchpad.co/article/elastic_article_7136 Sacral neuromodulation (SNM) therapy for overactive bladder (OAB) has proven long‐term safety and efficacy. Historically, the only commercially available SNM device was nonrechargeable requiring replacement surgery due to battery depletion. The Axonics System is the first rechargeable SNM device and is qualified to last a minimum of 15 years in the body. The study objective was to evaluate the safety and efficacy of this rechargeable SNM system. This study reports 2‐year outcomes.MethodsA total of 51 subjects were implanted with the Axonics System in a single nonstaged procedure. Subjects had OAB, confirmed on a 3‐day voiding diary (≥8 voids/day and/or ≥2 incontinence episodes over 72 hours). Test Responders were defined as subjects that were responders at 1 month postimplant. The efficacy analysis included therapy responder rates, change in the quality of life, and subject satisfaction reported in Test Responders (n = 30) and all implanted subjects (n = 37) that completed the follow‐up visits. Adverse events (AEs) are reported in all implanted subjects.ResultsAt 2 years, 90% of the Test Responders continued to respond to the therapy based on voiding diary criteria. Satisfaction with therapy was reported by 93% of subjects and 86% found their charging experience acceptable. Of the urinary incontinence Test Responders, 88% continued to be responders at 2 years, and 28% were completely dry. There were no unanticipated (AEs) or serious device‐related AEs.ConclusionsThe Axonics System® provides sustained clinically meaningful improvements in OAB subjects at 2 years. There were no serious device‐related AEs. Subjects reported continued satisfaction with their therapy. ]]> <![CDATA[Seroepidemiology of Chronic Fatigue Syndrome: A Case-Control Study]]> https://www.researchpad.co/article/Ndcb989ac-ac38-4613-bbc9-273d81e2c680 We performed serological testing for a large number of infectious agents in 26 patients from Atlanta who had chronic fatigue syndrome (CFS) and in 50 controls matched by age, race, and sex. We did not find any agent associated with CFS. In addition, we did not find elevated levels of antibody to any of a wide range of agents examined. In particular, we did not find elevated titers of antibody to any herpesvirus, nor did we find evidence of enteroviral exposure in this group of patients.

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<![CDATA[Return to the Past: The Case for Antibody-Based Therapies in Infectious Diseases]]> https://www.researchpad.co/article/N09e44abe-3ef9-459e-9dd3-e98619bbac11 In the preantibiotic era, passive antibody administration (serum therapy) was useful for the treatment of many infectious diseases. The introduction of antimicrobial chemotherapy in the 1940s led to the rapid abandonment of many forms of passive antibody therapy. Chemotherapy was more effective and less toxic than antibody therapy. In this last decade of the 20th century the efficacy of antimicrobial chemotherapy is diminishing because of the rapidly escalating number of immunocompromised individuals, the emergence of new pathogens, the reemergence of old pathogens, and widespread development of resistance to antimicrobial drugs. This diminishment in the effectiveness of chemotherapy has been paralleled by advances in monoclonal antibody technology that have made feasible the generation of human antibodies. This combination of factors makes passive antibody therapy an option worthy of serious consideration. We propose that for every pathogen there exists an antibody that will modify the infection to the benefit of the host. Such antibodies are potential antimicrobial agents. Antibody-based therapies have significant advantages and disadvantages relative to standard chemotherapy. The reintroduction of antibody-based therapy would require major changes in the practices of infectious disease specialists.

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<![CDATA[Spectrum of Clinical Illness in Hospitalized Patients with “Common Cold” Virus Infections]]> https://www.researchpad.co/article/Nc4c3169f-a14d-4e0d-8991-c36cc932de0a

Abstract

The viruses associated most frequently with the “common cold” are rhinoviruses and coronaviruses. The first prospective cohort study to determine the prevalence of rhinovirus and coronavirus infections in patients of all ages hospitalized for acute respiratory illnesses is described. Hospital admissions for acute respiratory illnesses were identified, and cell culture for rhinovirus and serologic assays on paired sera for coronaviruses 229E and OC43 were performed. A total of 61 infections with rhinoviruses and coronaviruses were identified from 1198 respiratory illnesses (5.1%); in addition, 9 additional infections associated with ≥1 other respiratory viruses were identified. Of those infected with only rhinovirus or coronavirus, underlying cardiopulmonary diseases were present in 35% of the patients aged <5 years, in 93% aged between 5 and 35 years, and in 73% aged >35 years. The predominant clinical syndromes varied by age: pneumonia and bronchiolitis in children aged <5 years; exacerbations of asthma in older children and young adults; and pneumonia and exacerbations of chronic obstructive pulmonary disease and congestive heart failure in older adults. Therefore, rhinovirus and coronavirus infections in hospitalized patients were associated with lower respiratory tract illnesses in all age groups.

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<![CDATA[Cough stress tests to diagnose stress urinary incontinence in women with pelvic organ prolapse with indication for surgical treatment]]> https://www.researchpad.co/article/N1a288052-617c-4b47-bdb8-ec5096d7d8f0

Abstract

Aims

To evaluate the diagnostic ability of different cough stress tests (CSTs) in women with pelvic organ prolapse (POP), performed during outpatient urogynaecological exams.

Methods

Prospective, multicentre observational study involving women on waiting lists for POP surgery. With a subjectively full bladder, patients were asked to perform five different CSTs: without prolapse reduction ([a] standing, followed by [b] semilithotomy position); keeping semilithotomy position with prolapse reduced (by [c] posterior speculum, followed by [d] pessary); [e] standing again with the pessary in place. Primary outcome was positive CST in at least one of the five CSTs. Bladder volume was measured and symptoms of stress urinary incontinence (SUI) were detected by two validated questionnaires.

Results

A total of 297 women completed all CSTs and were included in the analyses. Mean (SD) age, parity, and body mass index were 64.8 (9.9) years, 2.7 (1.3) deliveries, and 26.6 (3.4) kg/m2, respectively. In total, 99 women (33.3%) reported SUI symptoms. At least one positive CST was recorded in 152 patients (51.1%), and in 90 (59.2%) of these 152, a positive CST was observed only when POP was reduced (occult SUI). The CST was positive in 92 (92.9%) of the 99 patients with coexisting SUI symptoms and in 60 (30.3%) of the 205 asymptomatic patients. The percentage of patients with a positive CST was significantly lower when bladder volume was <200 mL vs ≥200 mL (P = .046).

Conclusions

The identification of urinary leakage cases with CSTs is best achieved using multiple different patient positions, different prolapse reduction methods, and bladder volumes ≥200 mL.

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<![CDATA[Postpartum hemorrhage care bundles to improve adherence to guidelines: A WHO technical consultation† ]]> https://www.researchpad.co/article/N79ff44fa-cea3-42b3-9901-147a36620e56

Abstract

Objective

To systematically develop evidence‐based bundles for care of postpartum hemorrhage (PPH).

Methods

An international technical consultation was conducted in 2017 to develop draft bundles of clinical interventions for PPH taken from the WHO's 2012 and 2017 PPH recommendations and based on the validated “GRADE Evidence‐to‐Decision” framework. Twenty‐three global maternal‐health experts participated in the development process, which was informed by a systematic literature search on bundle definitions, designs, and implementation experiences. Over a 6‐month period, the expert panel met online and via teleconferences, culminating in a 2‐day in‐person meeting.

Results

The consultation led to the definition of two care bundles for facility implementation. The “first response to PPH bundle” comprises uterotonics, isotonic crystalloids, tranexamic acid, and uterine massage. The “response to refractory PPH bundle” comprises compressive measures (aortic or bimanual uterine compression), the non‐pneumatic antishock garment, and intrauterine balloon tamponade (IBT). Advocacy, training, teamwork, communication, and use of best clinical practices were defined as PPH bundle supporting elements.

Conclusion

For the first response bundle, further research should assess its feasibility, acceptability, and effectiveness; and identify optimal implementation strategies. For the response to refractory bundle, further research should address pending controversies, including the operational definition of refractory PPH and effectiveness of IBT devices.

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<![CDATA[First‐in‐human high‐cumulative‐dose stem cell therapy in idiopathic pulmonary fibrosis with rapid lung function decline]]> https://www.researchpad.co/article/N66a40bd5-fd77-4f7c-94c2-84781b22a0e9

Abstract

Previous phase I studies demonstrated safety and some beneficial effects of mesenchymal stem cells (MSCs) in patients with mild to moderate idiopathic pulmonary fibrosis (IPF). The aim of our study was to evaluate the safety, tolerability, and efficacy of a high cumulative dose of bone marrow MSCs in patients with rapid progressive course of severe to moderate IPF. Twenty patients with forced ventilation capacity (FVC) ≥40% and diffusing capacity of the lung for carbon monoxide (DLCO) ≥20% with a decline of both >10% over the previous 12 months were randomized into two groups: one group received two intravenous doses of allogeneic MSCs (2 × 108 cells) every 3 months, and the second group received a placebo. A total amount of 1.6 × 109 MSCs had been administered to each patient after the study completion. There were no significant adverse effects after administration of MSCs in any patients. In the group of MSC therapy, we observed significantly better improvement for the 6‐minute walk distance in 13 weeks, for DLCO in 26 weeks, and for FVC in 39 weeks compared with placebo. FVC for 12 months in the MSCs therapy group increased by 7.8% from baseline, whereas it declined by 5.9% in the placebo group. We did not find differences between the groups in mortality (two patients died in each group) or any changes in the high‐resolution computed tomography fibrosis score. In patients with IPF and a rapid pulmonary function decline, therapy with high doses of allogeneic MSCs is a safe and promising method to reduce disease progression.

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<![CDATA[Trends in mesenchymal stem cell clinical trials 2004‐2018: Is efficacy optimal in a narrow dose range?]]> https://www.researchpad.co/article/N2f8205be-ba95-460e-88e8-896bff9ee826

Abstract

The number of clinical trials using mesenchymal stem cells (MSCs) has increased since 2008, but this trend slowed in the past several years and dropped precipitously in 2018. Previous reports have analyzed MSC clinical trials by disease, phase, cell source, country of origin, and trial initiation date, all of which can be downloaded directly from http://clinicaltrials.gov. We have extended analyses to a larger group of 914 MSC trials reported through 2018. To search for potential factors that may influence the design of new trials, we extracted data on routes of administration and dosing from individual http://clinicaltrials.gov records as this information cannot be downloaded directly from the database. Intravenous (IV) injection is the most common, least invasive and most reproducible method, accounting for 43% of all trials. The median dose for IV delivery is 100 million MSCs/patient/dose. Analysis of all trials using IV injection that reported positive outcomes indicated minimal effective doses (MEDs) ranging from 70 to 190 million MSCs/patient/dose in 14/16 trials with the other two trials administering much higher doses of at least 900 million cells. Dose‐response data showing differential efficacy for improved outcomes were reported in only four trials, which indicated a narrower MED range of 100‐150 million MSCs/patient with lower and higher IV doses being less effective. The results suggest that it may be critical to determine MEDs in early trials before proceeding with large clinical trials.

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<![CDATA[Vesomni improves the quality of life in men with lower urinary tract symptoms in routine clinical practice in Europe]]> https://www.researchpad.co/article/N82be2c4e-40c8-426b-affa-8470c52c1a87

Abstract

Aim

To evaluate the impact of Vesomni/Urizia/Volutsa, a fixed‐dose combination tablet containing 6 mg solifenacin (antimuscarinic) and 0.4 mg tamsulosin (α‐blocker), on health‐related quality of life (HRQoL) and treatment satisfaction in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in routine clinical practice.

Methods

EUROPA was a noninterventional study of men with LUTS/BPH not responding to monotherapy who were prescribed Vesomni in routine clinical practice. Data were collected retrospectively (1 year) and prospectively (1 year). Assessments were performed at baseline, weeks 4 to 8, weeks 9 to 18 (optional), weeks 19 to 39 (optional), and Weeks 40 to 52. The primary endpoint was change from baseline in HRQoL, as assessed by the Overactive Bladder Questionnaire (OAB‐q) symptom bother subscale score. Change from baseline in OAB‐q total and coping, sleep, and social interaction subscale scores, treatment satisfaction‐visual analog scale (TS‐VAS), International Prostate Symptom Score (IPSS), and European Quality of Life 5‐Dimension‐5‐Level (EQ‐5D‐5L) questionnaire were also evaluated.

Results

Five hundred and eighty‐nine patients were enrolled. The mean changes in adjusted mean (95% confidence interval [CI]) OAB‐q symptom bother subscale scores were −16.40 (−24.31, −8.49) at weeks 4 to 8 and −19.59 (−28.26, −10.92) at weeks 40 to 52; at weeks 40 to 52, changes were clinically meaningful in 84.6% of patients. Adjusted mean (95% CI) change from baseline to weeks 40 to 52 were 15.02 (7.35, 22.69), 19.37 (10.86, 27.89), 18.65 (7.44, 29.86), 9.85 (3.90, 15.81), and 16.09 (9.07, 23.11) for concern, coping, sleep, social interaction, and total, respectively. TS‐VAS, IPSS, and EQ‐5D‐5L all improved, and treatment persistence at weeks 40 to 52 was 77.1%. Urinary retention was reported in four (0.7%) patients.

Conclusions

Vesomni was well‐tolerated and improved HRQoL and treatment satisfaction in patients with LUTS/BPH.

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<![CDATA[Abnormal vaginal microbiome associated with vaginal mesh complications]]> https://www.researchpad.co/article/N8a1b5b38-aaf3-4da4-a6c1-c85bdf54e5f7

Abstract

Aims

To identify differences in the vaginal microbiomes of women after transvaginal mesh (TVM) surgery for pelvic organ prolapse with and without mesh‐associated complications.

Methods

Patients with complications were eligible as cases, patients without as controls. DNA was isolated and the V1‐2 region of the 16S ribosomal RNA gene was amplified and sequenced. Overall richness was quantified using Chao1. Overall diversity was expressed as Shannon diversity and screened for group differences using analysis of variance. Multivariate differences among groups were evaluated with functions from R.

Results

We recruited 14 patients after mesh exposure, 5 after contraction, and 21 as controls. The average number of operational taxonomic unit was 74.79 (SD ± 63.91) for controls, 57.13 (SD ± 58.74) after exposures, and 92.42 (SD ± 50.01) after contractions. Total 89.6% of bacteria in controls, 86.4% in previous exposures, and 81.3% in contractions were classified as either Firmicutes, Proteobacteria, or Actinobacteria (P < .001). Veillonella spp. was more abundant in patients after contraction (P = .045). The individual microbiomes varied, and we did not detect any significant differences in richness but a trend towards higher diversity with complications.

Conclusions

The presence of Veillonella spp. could be associated with mesh contraction. Our study did not identify vaginal microbiotic dysbiosis as a factor associated with exposure. Larger cohort studies would be needed to distinguish the vaginal microbiome of women predisposed to mesh‐related complications for targeted phenotyping of patients who could benefit from TVM surgery.

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<![CDATA[Scientific evidence for pelvic floor devices presented at conferences: An overview]]> https://www.researchpad.co/article/Naacac44d-7447-4367-b9eb-f2a26b84cc91

Abstract

Aims

An increasing number of diagnostic and therapeutic medical devices are available to help patients and physicians manage pelvic floor symptoms in women. Many of these are presented at scientific conferences, and in the absence of a gold standard for evaluation, marketing has become more prominent than scientific evaluation. The goal of this study was to (a) provide an overview of pelvic floor devices for women that have been presented at recent annual meetings of leading scientific societies and (b) to summarize and review the scientific evidence underpinning these devices.

Methods

Manual searches were performed of all abstracts presented in 2016 and 2017 at annual meetings of the International Continence Society, the International Urogynecological Association, the European Association of Urology, and the American Urological Association. The exhibition floor of the 2017 International Continence Society was also searched. Subsequently, literature searches of both the MEDLINE and Embase databases were performed in November 2018 to identify original full‐text publications related to the identified devices.

Results

We identified 11 devices from these sources, which were mainly used for the control of urinary incontinence. Only seven of these pelvic floor devices were covered by publications, with no full‐text records identified for the remaining four devices.

Conclusions

Sample sizes were small and there was a lack of convincing evidence for most devices. Despite this, many devices were available in the market. Our findings indicate that the process for introducing these new devices is in stark contrast with the strict requirements for introducing new drug classes.

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<![CDATA[Low Frequency of Opportunistic Infections in Patients Receiving Vedolizumab in Clinical Trials and Post-Marketing Setting]]> https://www.researchpad.co/article/5c8ad878d5eed0c48499f7af

Abstract

Background

Vedolizumab (ENTYVIO) is a humanized α4β7 integrin antagonist approved for the treatment of inflammatory bowel disease, which selectively blocks gut-specific lymphocyte trafficking. We evaluated the risk of opportunistic infections of interest in patients treated with vedolizumab.

Methods

We determined the frequency of opportunistic infections and tuberculosis in patients receiving vedolizumab in phase 3 clinical trials and post-marketing settings. We also evaluated adverse events reported in the post-marketing setting in patients with a history of or concurrent hepatitis B/C virus infection.

Results

The incidence of opportunistic infections in patients receiving vedolizumab was 0.7 (GEMINI 1 and 2 clinical trials) and 1.0 (long-term safety study) per 100 patient-years, with 217 events reported in approximately 114,071 patient-years of exposure (post-marketing setting). Most opportunistic infections were nonserious and the majority of patients continued treatment with vedolizumab. Clostridium difficile was the most commonly reported infection, with an incidence rate of 0.5 per 100 patient-years (clinical trials). Tuberculosis was reported at 0.1 per 100 patient-years (clinical trials), with 7 events in the post-marketing setting. No tuberculosis-related deaths were reported in either setting. No cases of progressive multifocal leukoencephalopathy were reported. In 29 patients with a history of or concurrent hepatitis B/C infection in the post-marketing setting, no viral reactivation was observed.

Conclusions

Clinical trials and post-marketing data showed that the rate of serious opportunistic infections in patients receiving vedolizumab was low and most patients could continue vedolizumab treatment. The frequency of tuberculosis infection was also low and no hepatitis B/C viral reactivation was reported.

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<![CDATA[Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib]]> https://www.researchpad.co/article/5c8ad85dd5eed0c48499f499

Abstract

Background

Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). Tofacitinib is approved for rheumatoid arthritis and psoriatic arthritis, where it has been shown to increase herpes zoster (HZ) risk. We evaluated HZ risk among UC patients using tofacitinib.

Methods

HZ cases were identified in tofacitinib phase II/III/ongoing, open-label, long-term extension (OLE) UC trials. We calculated HZ incidence rates (IRs) per 100 patient-years of tofacitinib exposure within phase III maintenance (Maintenance Cohort) and phase II/III/OLE (Overall Cohort) studies, stratified by baseline demographics and other factors. HZ risk factors were evaluated in the Overall Cohort using Cox proportional hazard models.

Results

Overall, 65 (5.6%) patients developed HZ. Eleven patients had multidermatomal involvement (2 nonadjacent or 3–6 adjacent dermatomes), and 1 developed encephalitis (resolved upon standard treatment). Five (7.7%) events led to treatment discontinuation. HZ IR (95% confidence interval [CI]) in the Overall Cohort was 4.07 (3.14–5.19) over a mean (range) of 509.1 (1–1606) days, with no increased risk observed with increasing tofacitinib exposure. IRs (95% CI) were highest in patients age ≥65 years, 9.55 (4.77–17.08); Asian patients, 6.49 (3.55–10.89); patients with prior tumor necrosis factor inhibitor (TNFi) failure, 5.38 (3.86–7.29); and patients using tofacitinib 10 mg twice daily, 4.25 (3.18–5.56). Multivariate analysis identified older age and prior TNFi failure as independent risk factors.

Conclusions

In tofacitinib-treated UC patients, there was an elevated risk of HZ, although complicated HZ was infrequent. Increased HZ rates occurred in patients who were older, Asian, or had prior TNFi failure (NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612).

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<![CDATA[Patient-specific 3D models aid planning for triplane proximal femoral osteotomy in slipped capital femoral epiphysis]]> https://www.researchpad.co/article/5b3cd89f463d7e2aeccb4686

Abstract

Purpose

Slipped capital femoral epiphysis (SCFE) can result in a complex three-dimensional (3D) deformity of the proximal femur. A three-plane proximal femoral osteotomy (TPFO) has been described to improve hip mechanics. The purpose of this study was to evaluate the benefits of using 3D print technology to aid in surgical planning.

Patients and Methods

Fifteen children treated with TPFO for symptomatic proximal femoral deformity due to SCFE were included in this study. Ten patients were treated by a single surgeon with (model group, n = 5) or without (no-model group, n = 5) a 3D model for pre-operative planning, and compared with patients treated by two senior partners without the use of a model (senior group, n = 5) to evaluate for a learning curve. Peri-operative data including patient body mass index (BMI), surgical time and fluoroscopy time were recorded.

Results

Children in all three groups had similar BMIs at the time of the TPFO. Post-operative radiographic parameters were equally improved in all three groups. On average, surgical time decreased by 45 minutes and 38 minutes, and fluoroscopy time decreased by 50% and 25%, in the model group compared with the no-model and senior groups, respectively.

Conclusions

Patient-specific 3D models aid in surgical planning for complex 3D orthopaedic deformities by enabling practice of osteotomies. Results suggest that 3D models may decrease surgical time and fluoroscopy time while allowing for similar deformity correction. These models may be especially useful to overcome steep learning curves for complex procedures or in trainee education through mock surgical procedures.

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<![CDATA[Binary and analogue markers of skeletal maturity: clinical utility of the thenar and plantar sesamoids]]> https://www.researchpad.co/article/5b4aee8f463d7e6db07a9e2b

Abstract

Purpose

We investigate the thenar and plantar sesamoids as markers of skeletal maturity, and grade appearance using two scales, a binary system (absent or present), and an analogue system that relies upon judging regular changes in morphological appearance.

Methods

We studied 94 healthy children (49 female and 45 male patients) between ages three and 18 years who had approximately 700 serially acquired sets of radiographs and physical examinations. The children had at least annual radiographs taken of the left hand and left foot. Velocity of growth was calculated and curves were fit to a cubic spline model to determine age of maximum height velocity, or peak height velocity (PHV). Appearance of the plantar and thenar sesamoids was recorded using a binary system classifying the sesamoids as absent or present and an analogue system classifying the sesamoid as absent, present as a small ossification centre or larger than a small ossification centre.

Results

The plantar sesamoids appear 1.67 years before PHV and reach mature size 1.02 years after PHV. The thenar sesamoids appear 0.32 years before PHV and reach mature size 2.25 years after PHV. The plantar sesamoids are present and thenar sesamoids are absent at a mean 1.5 years prior to PHV. No patients had the thenar sesamoids present while the plantar sesamoids were absent.

Conclusion

As binary markers, when the plantar and thenar sesamoids are considered together it is possible to localize maturity. As analogue markers, they offer more information. The sesamoids also allow clarification of the calcaneal and Sanders stages.

Level of Evidence

Not Applicable.

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