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BMJ (Clinical Research Ed.) Jan 2021To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying... (Meta-Analysis)
Meta-Analysis
Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.
OBJECTIVE
To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk.
DESIGN
Network meta-analysis.
DATA SOURCES
Medline, Embase, and Cochrane CENTRAL up to 11 August 2020.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias.
MAIN OUTCOME MEASURES
Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review.
RESULTS
764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes.
CONCLUSIONS
In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019153180.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Mortality; Network Meta-Analysis; Randomized Controlled Trials as Topic; Renal Insufficiency; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33441402
DOI: 10.1136/bmj.m4573 -
Journal of Ophthalmic & Vision Research 2020Conjunctivitis is a commonly encountered condition in ophthalmology clinics throughout the world. In the management of suspected cases of conjunctivitis, alarming signs... (Review)
Review
Conjunctivitis is a commonly encountered condition in ophthalmology clinics throughout the world. In the management of suspected cases of conjunctivitis, alarming signs for more serious intraocular conditions, such as severe pain, decreased vision, and painful pupillary reaction, must be considered. Additionally, a thorough medical and ophthalmic history should be obtained and a thorough physical examination should be done in patients with atypical findings and chronic course. Concurrent physical exam findings with relevant history may reveal the presence of a systemic condition with involvement of the conjunctiva. Viral conjunctivitis remains to be the most common overall cause of conjunctivitis. Bacterial conjunctivitis is encountered less frequently and it is the second most common cause of infectious conjunctivitis. Allergic conjunctivitis is encountered in nearly half of the population and the findings include itching, mucoid discharge, chemosis, and eyelid edema. Long-term usage of eye drops with preservatives in a patient with conjunctival irritation and discharge points to the toxic conjunctivitis as the underlying etiology. Effective management of conjunctivitis includes timely diagnosis, appropriate differentiation of the various etiologies, and appropriate treatment.
PubMed: 32864068
DOI: 10.18502/jovr.v15i3.7456 -
The Cochrane Database of Systematic... Jan 2015Neck pain is common, disabling and costly. Exercise is one treatment approach. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neck pain is common, disabling and costly. Exercise is one treatment approach.
OBJECTIVES
To assess the effectiveness of exercises to improve pain, disability, function, patient satisfaction, quality of life and global perceived effect in adults with neck pain.
SEARCH METHODS
We searched MEDLINE, MANTIS, ClinicalTrials.gov and three other computerized databases up to between January and May 2014 plus additional sources (reference checking, citation searching, contact with authors).
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing single therapeutic exercise with a control for adults suffering from neck pain with or without cervicogenic headache or radiculopathy.
DATA COLLECTION AND ANALYSIS
Two review authors independently conducted trial selection, data extraction, 'Risk of bias' assessment and clinical relevance. The quality of the evidence was assessed using GRADE. Meta-analyses were performed for relative risk and standardized mean differences (SMD) with 95% confidence intervals (CIs) after judging clinical and statistical heterogeneity.
MAIN RESULTS
Twenty-seven trials (2485 analyzed /3005 randomized participants) met our inclusion criteria.For acute neck pain only, no evidence was found.For chronic neck pain, moderate quality evidence supports 1) cervico-scapulothoracic and upper extremity strength training to improve pain of a moderate to large amount immediately post treatment [pooled SMD (SMDp) -0.71 (95% CI: -1.33 to -0.10)] and at short-term follow-up; 2) scapulothoracic and upper extremity endurance training for slight beneficial effect on pain at immediate post treatment and short-term follow-up; 3) combined cervical, shoulder and scapulothoracic strengthening and stretching exercises varied from a small to large magnitude of beneficial effect on pain at immediate post treatment [SMDp -0.33 (95% CI: -0.55 to -0.10)] and up to long-term follow-up and a medium magnitude of effect improving function at both immediate post treatment and at short-term follow-up [SMDp -0.45 (95%CI: -0.72 to -0.18)]; 4) cervico-scapulothoracic strengthening/stabilization exercises to improve pain and function at intermediate term [SMDp -14.90 (95% CI:-22.40 to -7.39)]; 5) Mindfulness exercises (Qigong) minimally improved function but not global perceived effect at short term. Low evidence suggests 1) breathing exercises; 2) general fitness training; 3) stretching alone; and 4) feedback exercises combined with pattern synchronization may not change pain or function at immediate post treatment to short-term follow-up. Very low evidence suggests neuromuscular eye-neck co-ordination/proprioceptive exercises may improve pain and function at short-term follow-up.For chronic cervicogenic headache, moderate quality evidence supports static-dynamic cervico-scapulothoracic strengthening/endurance exercises including pressure biofeedback immediate post treatment and probably improves pain, function and global perceived effect at long-term follow-up. Low grade evidence supports sustained natural apophyseal glides (SNAG) exercises.For acute radiculopathy, low quality evidence suggests a small benefit for pain reduction at immediate post treatment with cervical stretch/strengthening/stabilization exercises.
AUTHORS' CONCLUSIONS
No high quality evidence was found, indicating that there is still uncertainty about the effectiveness of exercise for neck pain. Using specific strengthening exercises as a part of routine practice for chronic neck pain, cervicogenic headache and radiculopathy may be beneficial. Research showed the use of strengthening and endurance exercises for the cervico-scapulothoracic and shoulder may be beneficial in reducing pain and improving function. However, when only stretching exercises were used no beneficial effects may be expected. Future research should explore optimal dosage.
Topics: Acute Pain; Adult; Chronic Pain; Female; Headache; Humans; Male; Manipulation, Chiropractic; Neck; Neck Pain; Pain Management; Physical Therapy Modalities; Radiculopathy; Randomized Controlled Trials as Topic
PubMed: 25629215
DOI: 10.1002/14651858.CD004250.pub5 -
Clinical Optometry 2023Artificial tears are the mainstay of dry eye disease management, but also have a role in corneal abrasion and wound healing, pain and inflammation management,... (Review)
Review
Artificial tears are the mainstay of dry eye disease management, but also have a role in corneal abrasion and wound healing, pain and inflammation management, conjunctivitis, keratitis, contact lens rewetting and removal, and foreign body removal. A systematic review of randomized controlled trials (PROSPERO registration CRD42022369619) comparing the efficacy of artificial tears in patients with dry eye to inform prescribing choices using Web of Science, PubMed and Medline databases identified 64 relevant articles. There is good evidence that artificial tears improve symptoms of dry eye disease within a month of regular use, applied about four times a day, but signs generally take several months to improve. Not all patients with dry eye disease benefit from artificial tears, so if there is no benefit over a month, alternative management should be considered. Combination formulations are more effective than single active ingredient artificial tears. Artificial tears containing polyethylene glycol are more effective than those containing carboxymethylcellulose/carmellose sodium and hydroxypropyl methylcellulose. Those classified as having evaporative dry eye disease, benefit from artificial tears with liposomes, especially of higher concentration. The data available is limited by the definition of dry eye disease applied in published studies being variable, as well as the disease severity examined and compliance with artificial tears being rarely quantified.
PubMed: 36647552
DOI: 10.2147/OPTO.S350185 -
Clinical Reviews in Allergy & Immunology Aug 2023Vernal keratoconjunctivitis (VKC) is a chronic, bilateral corneal and conjunctival problem which typically presents in young individuals. VKC is characterized by... (Review)
Review
Vernal keratoconjunctivitis (VKC) is a chronic, bilateral corneal and conjunctival problem which typically presents in young individuals. VKC is characterized by itching, photophobia, white mucous discharge, lacrimation, foreign body sensation, and pain due to corneal involvement of shield ulcers. Vernal keratoconjunctivitis is categorized within ocular diseases. The diagnosis is clinical, as no sure biomarkers pathognomonic of the disease have yet been identified. The VKC therapy relies on different types of drugs, from antihistamines and topical steroids to cyclosporine or tacrolimus eye drops. In extremely rare cases, there is also the need for surgical treatment for the debridement of ulcers, as well as for advanced glaucoma and cataracts, caused by excessive prolonged use of steroid eye drops. We performed a systematic review of the literature, according to PRISMA guideline recommendations. We searched the PubMed database from January 2016 to June 2023. Search terms were Vernal, Vernal keratoconjunctivitis, and VKC. We initially identified 211 articles. After the screening process, 168 studies were eligible according to our criteria and were included in the review. In this study, we performed a systematic literature review to provide a comprehensive overview of currently available diagnostic methods, management of VKC, and its treatments.
Topics: Humans; Conjunctivitis, Allergic; Ulcer; Cyclosporine; Tacrolimus; Ophthalmic Solutions
PubMed: 37658939
DOI: 10.1007/s12016-023-08970-4 -
Frontiers in Neurology 2020Neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are autoimmune inflammatory disorders of the... (Review)
Review
Neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are autoimmune inflammatory disorders of the central nervous system (CNS). Pain is highly prevalent and debilitating in NMOSD and MOGAD with a severe impact on quality of life, and there is a critical need for further studies to successfully treat and manage pain in these rare disorders. In NMOSD, pain has a prevalence of over 80%, and pain syndromes include neuropathic, nociceptive, and mixed pain, which can emerge in acute relapse or become chronic during the disease course. The impact of pain in MOGAD has only recently received increased attention, with an estimated prevalence of over 70%. These patients typically experience not only severe headache, retrobulbar pain, and/or pain on eye movement in optic neuritis but also neuropathic and nociceptive pain. Given the high relevance of pain in MOGAD and NMOSD, this article provides a systematic review of the current literature pertaining to pain in both disorders, focusing on the etiology of their respective pain syndromes and their pathophysiological background. Acknowledging the challenge and complexity of diagnosing pain, we also provide a mechanism-based classification of NMOSD- and MOGAD-related pain syndromes and summarize current treatment strategies.
PubMed: 33473247
DOI: 10.3389/fneur.2020.00778 -
Journal of Cosmetic Dermatology May 2022The overall effects of Carboxytherapy, defined as the administration of carbon dioxide, have been studied for many years. It has been suggested that by improving... (Review)
Review
INTRODUCTION
The overall effects of Carboxytherapy, defined as the administration of carbon dioxide, have been studied for many years. It has been suggested that by improving oxygenation, interacting with the tissue perfusion regulators, and disrupting the adipose cell membranes, the method can lead to notable improvements in different esthetic and pathological conditions. Therefore, we aimed to systematically review the available studies evaluating the potential benefits of carboxytherapy in dermatological conditions and how it objectively stands against scientific scrutiny.
METHODS
We searched the PubMed, Scopus, Embase, and Web of Science databases, including the studies exploring the method's efficacy in managing any dermatological condition.
RESULTS
A total 27 of studies were identified (with a pooled sample of over 700 cases), most of which were clinical trials. Facial wrinkles, periorbital hyperpigmentation, skin laxity deficiency, scars, striae distensae, localized lipolysis and cellulite, alopecia, chronic diabetic wounds, and psoriatic plaques comprised the package of the dermatological conditions that were studied. Except for a few studies, the method mainly demonstrated significant improvements on all of the mentioned conditions. The inter- and post-operational adverse events were mild and transient, including erythema, pain, crepitus, and ecchymoses.
DISCUSSION
Carboxytherapy can provide those practicing in the field with sustainably favorable results. However, the numbers of cases on whom the fat-reducing capabilities of the method were studied and experienced varying degrees of recurrence caught our eye. In addition, we observed a notable disparity between the outcome measures utilized in the studies. The modest sample size in each condition also added to the injury, as the conditions on which the method was evaluated are pretty common in the general population. Therefore, for a definite conclusion, more randomized controlled trials with the shortcomings mentioned well addressed need to be conducted.
Topics: Cellulite; Dermatology; Erythema; Humans; Skin Aging; Striae Distensae
PubMed: 35124882
DOI: 10.1111/jocd.14834 -
RMD Open 2019To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League Against Rheumatism treatment recommendations.
METHODS
The MEDLINE, EMBASE and Cochrane databases were searched for case-control/prospective cohort studies, randomised controlled trials (RCTs) and systematic reviews.
RESULTS
Current evidence in primary SjS patients fulfilling the 2002 criteria is based on the data from 9 RCTs, 18 prospective cohort studies and 5 case-control studies. Two Cochrane systematic literature reviews (SLRs) have reported that topical treatments for dry mouth and dry eye are safe and effective. Ocular cyclosporine A was safe and effective in two RCTs including 1039 patients with dry eye syndrome. Two Cochrane SLRs on serum tear drops and plugs showed inconsistency in possible benefits, both for symptoms and objective measures. Five RCTs reported significant improvements in oral dryness and salivary flow rates for pilocarpine and cevimeline. An RCT showed no significant placebo-differences for hydroxychloroquine 400 mg/day for the primary outcome (visual analogue scale (VAS) composite of dryness, fatigue and pain). We identified seven RCTs carried out in primary SjS patients. RCTs using infliximab, anakinra and baminercept found no placebo-differences for the primary outcomes. The two largest RCTs randomised 255 patients to receive rituximab or placebo and reported no significant results in the primary outcome (VAS composite), while prospective studies suggested efficacy in systemic disease.
CONCLUSION
The current evidence supporting the use of the main topical therapeutic options of primary SjS is solid, while limited data from RCTs are available to guide systemic therapies.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Humans; Sjogren's Syndrome; Treatment Outcome
PubMed: 31749986
DOI: 10.1136/rmdopen-2019-001064 -
The Cochrane Database of Systematic... Oct 2022Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such... (Review)
Review
BACKGROUND
Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks).
OBJECTIVES
To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 8); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The date of the last search was 20 August 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which topical corticosteroids, alone or in combination with tobramycin, were compared with no treatment, artificial tears (AT), vehicles, AT plus tobramycin, or cyclosporine A (CsA).
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We identified 22 RCTs conducted in the USA, Italy, Spain, China, South Korea, and India. These RCTs reported outcome data from a total of 4169 participants with DED. Study characteristics and risk of bias All trials recruited adults aged 18 years or older, except one trial that enrolled children and adolescents aged between 3 and 14 years. Half of these trials involved predominantly female participants (median 79%, interquartile range [IQR] 76% to 80%). On average, each trial enrolled 86 participants (IQR 40 to 158). The treatment duration of topical steroids ranged between one week and three months; trial duration lasted between one week and six months. Eight trials were sponsored exclusively by industry, and four trials were co-sponsored by industry and institutional or governmental funds. We assessed the risk of bias of both subjective and objective outcomes using RoB 2, finding nearly half of the trials to be at high risk of bias associated with selective outcome reporting. Findings Of the 22 trials, 16 evaluated effects of topical steroids, alone or in combination with tobramycin, as compared with lubricants (AT, vehicle), AT plus tobramycin, or no treatment. Corticosteroids probably have a small to moderate effect on improving patient-reported symptoms by 0.29 standardized mean difference (SMD) (95% confidence interval [CI] 0.16 to 0.42) as compared with lubricants (moderate certainty evidence). Topical steroids also likely have a small to moderate effect on lowering corneal staining scores by 0.4 SMDs (95% CI 0.18 to 0.62) (moderate certainty evidence). However, steroids may increase tear film break-up time (TBUT) slightly (mean difference [MD] 0.70 s, 95% CI 0.06 to 1.34; low certainty evidence) but not tear osmolarity (MD 1.60 mOsm/kg, 95% CI -10.47 to 13.67; very low certainty evidence). Six trials examined topical steroids, either alone or in combination with CsA, against CsA alone. Low certainty evidence indicates that steroid-based interventions may have a small to moderate effect on improving participants' symptoms (SMD -0.33, 95% CI -0.51 to -0.15), but little to no effect on corneal staining scores (SMD 0.05, 95% CI -0.25 to 0.35) as compared with CsA. The effect of topical steroids compared to CsA alone on TBUT (MD 0.37 s, 95% CI -0.13 to 0.87) or tear osmolarity (MD 5.80 mOsm/kg, 95% CI -0.94 to 12.54; loteprednol etabonate alone) is uncertain because the certainty of the evidence is low or very low. None of the included trials reported on quality of life scores. Adverse effects The evidence for adverse ocular effects of topical corticosteroids is very uncertain. Topical corticosteroids may increase participants' risk of intraocular pressure (IOP) elevation (risk ratio [RR] 5.96, 95% CI 1.30 to 27.38) as compared with lubricants. However, when compared with CsA, steroids alone or combined with CsA may decrease or increase IOP elevation (RR 1.45, 95% CI 0.25 to 8.33). It is also uncertain whether topical steroids may increase risk of cataract formation when compared with lubricants (RR 0.34, 95% CI 0.01 to 8.22), given the short-term use and study duration (four weeks or less) to observe longer-term adverse effects. AUTHORS' CONCLUSIONS: Overall, the evidence for the specified review outcomes was of moderate to very low certainty, mostly due to high risk of bias associated with selective results reporting. For dry eye patients whose symptoms require anti-inflammatory control, topical corticosteroids probably provide small to moderate degrees of symptom relief beyond lubricants, and may provide small to moderate degrees of symptom relief beyond CsA. However, the current evidence is less certain about the effects of steroids on improved tear film quality or quantity. The available evidence is also very uncertain regarding the adverse effects of topical corticosteroids on IOP elevation or cataract formation or progression. Future trials should generate high certainty evidence to inform physicians and patients of the optimal treatment strategies with topical corticosteroids in terms of regimen (types, formulations, dosages), duration, and its time-dependent adverse profile.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Adrenal Cortex Hormones; Cataract; Cyclosporine; Dry Eye Syndromes; Glucocorticoids; Loteprednol Etabonate; Lubricant Eye Drops; Randomized Controlled Trials as Topic; Tobramycin
PubMed: 36269562
DOI: 10.1002/14651858.CD015070.pub2 -
Journal of Cosmetic Dermatology Dec 2016Hyaluronic acid is a widely available, biocompatible, polysaccharide with distinguishing physiochemical properties which inspire its application throughout several... (Review)
Review
BACKGROUND
Hyaluronic acid is a widely available, biocompatible, polysaccharide with distinguishing physiochemical properties which inspire its application throughout several fields of medicine.
OBJECTIVE
We aim to investigate the application of hyaluronic acid and its effectiveness throughout several fields of medicine, including several therapies administered and prescribed by general health practitioners.
METHODS
We conducted a systematic review on randomized controlled trials about the physiochemical properties of hyaluronic acid and its application through primary care. Studies included in this review were peer reviewed and met our inclusion criteria.
FINDINGS
Factors were clustered into the following: uses throughout several fields of medicine, physiochemical properties, bioavailability, tolerance, effectiveness, and adverse effects. Therapies with hyaluronic acid provided long-lasting, pain relieving, moisturizing, lubricating, and dermal filling effect. Tissue hydration, elasticity, and durability improved.
CONCLUSIONS
Adjunct therapy with hyaluronic acid provides longer-lasting therapeutic effect when compared to the use of glucocorticosteroids and NSAIDs in osteoarthritic chronic diseases, is well-established in ophthalmology due to its lubricating properties for the corneal endothelium, and improves tissue hydration and cellular resistance to mechanical damage in aesthetic dermatology, and has marginal adverse effects. Several trials indicated its role in tumor markers, liver diseases, and in pharmaceuticals, but further research would be necessary to draw conclusive results in those fields.
Topics: Biological Availability; Cosmetic Techniques; Dermal Fillers; Dry Eye Syndromes; Humans; Hyaluronic Acid; Neoplasms; Osteoarthritis; Randomized Controlled Trials as Topic; Viscosupplements
PubMed: 27324942
DOI: 10.1111/jocd.12237