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The Journal of Urology Jul 2022This guideline provides direction to clinicians and patients regarding how to recognize interstitial cystitis/bladder pain syndrome (IC/BPS), conduct a valid diagnostic...
PURPOSE
This guideline provides direction to clinicians and patients regarding how to recognize interstitial cystitis/bladder pain syndrome (IC/BPS), conduct a valid diagnostic process, and approach treatment with the goals of maximizing symptom control and patient quality of life while minimizing adverse events and patient burden.
METHODS
An initial systematic review of the literature using the MEDLINE® database (search dates 1/1/83-7/22/09) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of IC/BPS. The review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. In July 2013, the Guideline underwent an Update Literature Review, a process in which an additional literature search is conducted and a systematic review is produced in order to maintain guideline currency with newly published literature. The 2013 review identified an additional 31 articles relevant to treatment. An Update Literature Review in 2022 (search dates: 06/2013-01/2021) identified 63 studies, 53 of which were added to the evidence base.
RESULTS
In contrast to the prior versions, the 2022 updated Guideline no longer divides treatments into first-line through sixth-line tiers. Instead, treatment is categorized into behavioral/non-pharmacologic, oral medicines, bladder instillations, procedures, and major surgery. This approach reinforces that the clinical approach for IC/BPS needs to be individualized and based on the unique characteristics of each patient. In addition, new statements were written to provide guidance on cystoscopy for patients with Hunner lesions, shared decision-making, and potential adverse events from pentosan polysulfate. The supporting text on major surgery also has been completely revised.
CONCLUSION
IC/BPS is a heterogeneous clinical syndrome. Even though patients present with similar symptoms of bladder/pelvic pain and pressure/discomfort associated with urinary frequency and strong urge to urinate, there are subgroups or phenotypes within IC/BPS. Except for patients with Hunner lesions, initial treatment should typically be nonsurgical. Concurrent, multi-modal therapies may be offered.
Topics: Cystitis, Interstitial; Cystoscopy; Humans; Pelvic Pain; Quality of Life; Urinary Bladder
PubMed: 35536143
DOI: 10.1097/JU.0000000000002756 -
Survey of Ophthalmology 2022Pentosan polysulfate sodium (PPS), a semisynthetic sulfated polysaccharide, is the only FDA-approved oral therapy for interstitial cystitis. Recent studies have... (Review)
Review
Pentosan polysulfate sodium (PPS), a semisynthetic sulfated polysaccharide, is the only FDA-approved oral therapy for interstitial cystitis. Recent studies have described a progressive, vision-threatening macular condition associated with long-term PPS use. We reviewed all publications concerning PPS maculopathy to consolidate known clinical features and to evaluate the strength of this association. Current literature supports a strong dose-dependent association between PPS exposure and a progressive maculopathy impacting the retinal pigment epithelium (RPE) and RPE-photoreceptor interface that may worsen even after drug cessation. Initial symptoms may include prolonged dark adaptation and difficulty reading with relative visual acuity preservation. Fundus examination often shows macular pigment clumps corresponding to lesions of focal RPE thickening. Fundus autofluorescence most clearly depicts the condition, with a distinctive pattern of hypo- and hyperautofluorescent spots in the posterior pole that sometimes extends to the retinal periphery. Many cases also show a characteristic peripapillary hypoautofluorescent halo. Near infrared reflectance may aid in early detection. RPE atrophy, cystoid macular edema, and macular neovascularization may also occur, potentially resulting in loss of central acuity. This newly described association implies significant public health risk. Ophthalmologists should screen PPS users with multimodal retinal imaging, and prescribers should minimize dose and duration of PPS use.
Topics: Anticoagulants; Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Retinal Diseases; Retinal Pigment Epithelium
PubMed: 34000253
DOI: 10.1016/j.survophthal.2021.05.005 -
Handbook of Clinical Neurology 2018Arguably the most important goal of prion research is the discovery of a safe and effective treatment for the human diseases. The final stages of the pathway to develop...
Arguably the most important goal of prion research is the discovery of a safe and effective treatment for the human diseases. The final stages of the pathway to develop a treatment require clinical trials. Choices about how a trial is designed and conducted have a large impact on the chances of success. The gold-standard large randomized double-blind placebo-controlled study, which minimizes sources of bias and has been incredibly successful in other diseases, has been hard to achieve in Creutzfeldt-Jakob disease principally because of the rarity and rapidity of the clinical syndrome. To date, clinical trials have been restricted to repurposed compounds, doxycycline, quinacrine, pentosan polysulfate (PPS), and flupertine. In most cases, these trials have used survival as an endpoint, which, whilst clearcut, has limitations. Biomarkers have played a strong role in diagnosis and entry criteria, but only a limited role as secondary outcome measures. Recent developments suggest some possible improvements in trial design by use of new outcome measures that have more favorable properties, and biomarkers of neuronal damage and/or prion seeding activity. Alternative patient populations, including those at risk of genetic forms of prion disease, warrant more consideration. In the future, improved trial designs will be employed to test compounds designed specifically to treat prion diseases.
Topics: Clinical Trials as Topic; Drug Discovery; Humans; Prion Diseases
PubMed: 29887150
DOI: 10.1016/B978-0-444-63945-5.00024-6 -
Der Ophthalmologe : Zeitschrift Der... Dec 2020Toxic retinopathies are most frequently induced by external stimulants (e.g. nicotine, poppers, methanol) and are less frequently undesired side effects of systemic...
Toxic retinopathies are most frequently induced by external stimulants (e.g. nicotine, poppers, methanol) and are less frequently undesired side effects of systemic drugs (e.g. hydroxychloroquine, ethambutol, MEK, ERK, FLT3 or checkpoint inhibitors, didanosine, pentosan polysulfate sodium) or intravitreally applied drugs. The clinical symptoms of undesired side effects of drugs are often similar to retinal diseases from other causes, which interferes with the recognition of the undesired side effects of drugs. Clinical findings, pathophysiological mechanisms and if advisable strategies for screening are discussed. The focus is on the presentation of confirmed undesirable side effects with established associations for medications which have long been approved. For novel medications, in addition potential but not proven associations are presented to facilitate the recognition of additional cases with side effects for these medications.
Topics: Humans; Pentosan Sulfuric Polyester; Retinal Diseases
PubMed: 33211161
DOI: 10.1007/s00347-020-01260-w -
The Canadian Journal of Urology Dec 2023Interstitial cystitis (IC) is a chronic disease with urinary tract symptoms and pain. Pentosan polysulfate (PPS) is the only U.S. Food and Drug Administration approved... (Review)
Review
INTRODUCTION
Interstitial cystitis (IC) is a chronic disease with urinary tract symptoms and pain. Pentosan polysulfate (PPS) is the only U.S. Food and Drug Administration approved oral medication for the treatment of IC pain and symptoms. Recently, articles described a pigmentary maculopathy in IC patients on long term PPS therapy. Currently, there is no definitive study directly linking PPS as the cause of the pigmentary maculopathy. The aim of this review is to evaluate if PPS is the causative factor of the pigmentary maculopathy or if PPS use is only associated with the pigmentary maculopathy.
MATERIALS AND METHODS
A comprehensive review of peer reviewed journals using the search terms IC, maculopathy, mast cells, immune inflammatory components, Tamm-Horsfall protein, cations and tight junctions was performed to examine the pathophysiology and role of chronic inflammation in IC and known retinal maculopathies.
RESULTS
Chronic inflammatory cells have been reported in age-related macular degeneration choroid blood vessels and in bladder submucosal and detrusor layers in IC patients. Studies in IC and maculopathies demonstrate a significant milieu of activated chronic inflammatory and immunologic responses that cause a more "leaky" epithelium and a subsequent cascade of inflammatory events that results in the pathological changes seen in these two conditions.
CONCLUSIONS
After an analysis of the literature describing a pigmentary maculopathy in IC patients on long term PPS, a causal relationship does not appear to be present. An alternate model is proposed postulating that the causative factor for the pigmentary maculopathy is the underlying inflammatory state associated with IC and not PPS use.
Topics: Humans; Pentosan Sulfuric Polyester; Macular Degeneration; Cystitis, Interstitial; Pain; Inflammation
PubMed: 38104330
DOI: No ID Found -
Pharmaceuticals (Basel, Switzerland) Feb 2022With the increased prevalence of new SARS-CoV-2 variants of concern, such as Delta and Omicron, the COVID-19 pandemic has become an ongoing human health disaster,...
With the increased prevalence of new SARS-CoV-2 variants of concern, such as Delta and Omicron, the COVID-19 pandemic has become an ongoing human health disaster, killing millions worldwide. SARS-CoV-2 invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition, heparan sulfate (HS) on the surface of host cells plays an important role as a co-receptor for this viral pathogen-host cell interaction. Our previous studies demonstrated that many sulfated glycans, such as heparin, fucoidans, and rhamnan sulfate have anti-SARS-CoV-2 activities. In the current study, a small library of sulfated glycans and highly negatively charged compounds, including pentosan polysulfate (PPS), mucopolysaccharide polysulfate (MPS), sulfated lactobionic acid, sulodexide, and defibrotide, was assembled and evaluated for binding to the S-proteins and inhibition of viral infectivity in vitro. These compounds inhibited the interaction of the S-protein receptor-binding domain (RBD) (wild type and different variants) with immobilized heparin, a highly sulfated HS, as determined using surface plasmon resonance (SPR). PPS and MPS showed the strongest inhibition of interaction of heparin and S-protein RBD. The competitive binding studies showed that the IC of PPS and MPS against the S-protein RBD binding to immobilized heparin was ~35 nM and ~9 nM, respectively, much lower than the IC for soluble heparin (IC = 56 nM). Both PPS and MPS showed stronger inhibition than heparin on the S-protein RBD or spike pseudotyped lentiviral particles binding to immobilized heparin. Finally, in an in vitro cell-based assay, PPS and MPS exhibited strong antiviral activities against pseudotyped viral particles of SARS-CoV-2 containing wild-type or Delta S-proteins.
PubMed: 35215371
DOI: 10.3390/ph15020258 -
CMAJ : Canadian Medical Association... Jul 2021
Review
Topics: Humans; Macular Degeneration; Pentosan Sulfuric Polyester
PubMed: 34312174
DOI: 10.1503/cmaj.201900-f -
JAMA Ophthalmology Jan 2022Case series have identified a macular condition hypothesized to be associated with the use of pentosan polysulfate sodium (PPS). Observational studies seeking to...
IMPORTANCE
Case series have identified a macular condition hypothesized to be associated with the use of pentosan polysulfate sodium (PPS). Observational studies seeking to quantify this association have yielded equivocal results.
OBJECTIVE
To estimate the association between PPS exposure and maculopathy.
DESIGN, SETTING, AND PARTICIPANTS
This disproportionality analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System from January 2013 through June 2020.
EXPOSURE
Adverse event reports for pentosan polysulfate were selected and compared with adverse event reports associated with drugs taken for the following indications: interstitial cystitis, cystitis, bladder disorder, or bladder pain.
MAIN OUTCOME MEASURES
Retinal adverse events were identified using the retinal disorders Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query, which includes conditions associated with retinal damage attributable to blockage of its blood supply, nutritional deficiencies, toxins, and diseases affecting the retina.
RESULTS
There were 2775 reports available for analysis in the PPS group (of which 1966 were for women [70.9%]) and 6833 reports in the other drugs group (of which 4036 [59.1%] were for women). The proportion of adverse events for any macular event relative to all other events was elevated for the users of PPS compared with those using other interstitial cystitis and bladder pain drugs (proportionate reporting ratio [PRR], 1.21 [95% CI, 1.01-1.44]). With respect to specific retinal conditions, macular degeneration (20 [0.8%] vs 15 [0.2%]), maculopathy (83 [3.4%] vs 2 [0.03%]), retinal dystrophy (3 [0.1%] vs 0), retinal injury (5 [0.2%] vs 0), and retinal toxicity (3 [0.1%] vs 0) were proportionately more common among users of PPS compared with those using other interstitial cystitis and bladder pain drugs, respectively.
CONCLUSIONS AND RELEVANCE
The results of the current study add to the growing evidence that PPS use is associated with an increased risk of maculopathy. Studies that rule out prevalent retinal abnormalities prior to the initiation of PPS would strengthen the current body of literature.
Topics: Anticoagulants; Cystitis, Interstitial; Female; Humans; Macular Degeneration; Male; Pain; Pentosan Sulfuric Polyester; Retinal Dystrophies
PubMed: 34792558
DOI: 10.1001/jamaophthalmol.2021.4778 -
Joint Bone Spine Apr 2024Osteoarthritis (OA) is the most prevalent arthritis-type and is a major contributor to chronic joint pain, impaired physical function, and limited mobility. By the end...
Osteoarthritis (OA) is the most prevalent arthritis-type and is a major contributor to chronic joint pain, impaired physical function, and limited mobility. By the end of 2020, a total of 595 million, equal to 7·6% of the global population, had OA; this figure is expected to rise exponentially by 2050. Even while the disorder's intricate pathophysiology is starting to appear intelligible, we are yet to have a cure for the disorder. OA is typically managed with traditional palliative measures, such as topical and systemic analgesics, including non-steroidal anti-inflammatory drugs, therapeutic exercise, and braces. Sometimes, intra-articular glucocorticoids, viscosupplementation, or regenerative interventions provide short-term pain relief and functional improvement; some may require arthroplasty. Researchers continue their efforts to unveil a new therapeutic target to be effective in OA that modifies symptoms and arrests disease progression as well. In the present literature review, insights into new therapeutic strategies in OA, for example, liposome-based dexamethasone, microspore-based triamcinolone, nerve growth factor antagonist, anti-ADAMTS-5 (A Disintegrin And Metalloproteinase Thrombospoidin Motifs - 5), pentosan polysulfate sodium, allogeneic stem cells, C-C chemokine receptor type-4 (CCR4) ligand 17 inhibitor, Wnt-signaling inhibitor, and anti-obesity medications are provided.
PubMed: 38685527
DOI: 10.1016/j.jbspin.2024.105739