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Cureus Jul 2023The foot and the lower leg comprise the ankle joint complex. The foot is crucial for the maintenance of posture. Frequently, overuse or repeated microtrauma to the... (Review)
Review
The foot and the lower leg comprise the ankle joint complex. The foot is crucial for the maintenance of posture. Frequently, overuse or repeated microtrauma to the fascia causes plantar fasciitis. This review aims to suggest the efficacy of various plantar fasciitis (PF) interventions based on modifications in clinical results. This review included studies from 2019 to March 2023 identified through a systematic literature search. The measures used to predict improvement in pain, discomfort, and foot function symptoms included the Visual Analog scale, Numerical Pain Rating Scale, Pressure Point Threshold by algometer, Weight-Bearing Lunge Test by inch tape, and range of motion. The review included 20 studies that fulfilled the inclusion criteria. Therapeutic interventions included insoles, foot orthosis, foam roller stretching, manual stretching, muscle strengthening, intrinsic muscle activities, extracorporeal shock wave lithotripsy, dry needling, laser, ultrasound, and others, which resulted in pain reduction, improved foot function, and ease of everyday routine. All therapeutic strategies used impacts resulting from minimal to maximal recovery. Various advanced approaches are more effective than conventional physical therapy. In conclusion, conservative therapeutic strategies with manual techniques, orthoses, and alternative intervention strategies can be combined to effectively relieve pain and improve function and overall results. Further high-quality studies are essential to learn more about the ideal dose, treatment approaches, and long-term impacts of these therapies.
PubMed: 37654968
DOI: 10.7759/cureus.42740 -
Clinical Lymphoma, Myeloma & Leukemia Jan 2021Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subgroup of B-cell precursor ALL (BCP-ALL) with a gene expression profile analogous to... (Review)
Review
Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subgroup of B-cell precursor ALL (BCP-ALL) with a gene expression profile analogous to Philadelphia-positive ALL and recurrent IKAROS Family Zinc Finger 1 (IKZF1) gene deletion despite lacking BCR-ABL1 (Breakpoint cluster region-ABL protooncogene) translocation. Although recognized to occur at all ages, the proportion of cases among BCP-ALL varies (< 10% in children and up to 30% in adolescents). In all age groups, males are more commonly affected. Generally, Ph-like ALL is associated with adverse clinical features and an increased risk of treatment failure with conventional approaches. Genetic alterations such as aberrant expression, point mutations, or fusion translocations lead to activation of cytokine receptors and signaling kinases, which affect the ABL1 (ABL class fusion) or Janus Kinase (JAK) signaling pathways. Several clinical trials are being conducted to understand whether specific tyrosine kinase inhibitor therapy can improve cure rates. This review summarizes the current literature available about this entity.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult
PubMed: 33485429
DOI: 10.1016/j.clml.2020.08.011 -
Diabetes & Metabolic Syndrome Sep 2022Insulin icodec is currently the most advanced candidate insulin suitable for once-weekly administration. We aim to conduct a systematic review of the literature to find... (Review)
Review
BACKGROUND AND AIMS
Insulin icodec is currently the most advanced candidate insulin suitable for once-weekly administration. We aim to conduct a systematic review of the literature to find out the efficacy and safety of insulin icodec in patients with diabetes mellitus.
METHODS
We systematically searched the electronic database of PubMed, and Google Scholar from inception until August 20, 2022, using MeSH keywords. Ongoing trials of insulin icodec were additionally searched from the ClinicalTrials.Gov. We retrieved all the available granular details of phase 1 to phase 3 studies of insulin icodec in both type 1 and type 2 diabetes.
RESULTS
Phase 1 study showed insulin icodec having a half-life of 196 h (>1 week) while a steady state is achieved after 3 to 4 weekly injections. Phase 2 studies compared once-weekly icodec to insulin glargine (U-100) and found a similar glucose control with no significantly greater hypoglycemia risks. Top-line results from the five phase 3 studies reported better glucose control with once-weekly icodec compared to both once-daily insulin glargine (ONWARDS 1) and once-daily degludec (in both ONWARDS 2 and 4) with similar rates of hypoglycemia in type 2 diabetes, although there was a higher hypoglycemic event with insulin icodec in type 1 diabetes (ONWARDS 6) compared to once-daily degludec despite a similar glycemic control.
CONCLUSION
A brighter prospect of once-weekly insulin icodec is on the card in particular in type 2 diabetes in terms of reducing injection pricks by >85% vs. once-daily basal insulin analogs, although few unknowns still exist.
Topics: Humans; Insulin Glargine; Diabetes Mellitus, Type 2; Blood Glucose; Hypoglycemic Agents; Hypoglycemia; Glycated Hemoglobin
PubMed: 36108418
DOI: 10.1016/j.dsx.2022.102615 -
Brazilian Journal of Physical Therapy 2021Therapeutic ultrasound (US) is a widely used intervention in physical therapy to manage pain and to aid in the healing of soft tissue. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Therapeutic ultrasound (US) is a widely used intervention in physical therapy to manage pain and to aid in the healing of soft tissue.
OBJECTIVE
This systematic review aimed to determine the effects of therapeutic US on knee osteoarthritis (KOA) symptoms.
METHODS
PubMed, MEDLINE, EMBASE, Google Scholar, and the Cochrane databases were searched from inception to April 2019. Randomized controlled trials (RCTs) involving adults with symptomatic KOA that compared therapeutic US with a sham or other control were included. The methodological quality of the trials was assessed at the study level using the Cochrane Risk of Bias tool. The quality of evidence at the outcome level- and overall- was assessed using GRADE methodology. Meta-analyses were conducted using random effects models, and heterogeneity was assessed using the I statistic.
RESULTS
Four studies (N = 234 participants) were eligible for inclusion in our primary analyses assessing therapeutic US versus sham. The methodological quality of the included RCTs ranged from moderate to very low. Treatment with therapeutic US resulted in small, statistically significant benefits for pain (approximate 9.6% improvement on a 0-100 visual analog scale [95% confidence interval: 2, 17.4%]) and self-reported measures of function (approximate 12.8% improvement on a 0-100 visual analog scale [0.4, 25.2%]). The overall quality of the evidence was very low. No adverse events were reported in any of the included studies.
CONCLUSIONS
The use of therapeutic US may provide additional benefits to physical therapy regimens in terms of symptom relief in individuals with KOA. However, it is not possible to make any meaningful recommendations for clinical practice due to the small number of applicable RCTs and the low methodological quality of the RCTs deemed eligible for this study.
Topics: Adult; Humans; Osteoarthritis, Knee; Pain; Pain Measurement; Ultrasonic Therapy
PubMed: 34535411
DOI: 10.1016/j.bjpt.2021.07.003 -
The Cochrane Database of Systematic... Jun 2023Pain is a common symptom in people with cancer; 30% to 50% of people with cancer will experience moderate-to-severe pain. This can have a major negative impact on their... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pain is a common symptom in people with cancer; 30% to 50% of people with cancer will experience moderate-to-severe pain. This can have a major negative impact on their quality of life. Opioid (morphine-like) medications are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. Pain is not sufficiently relieved by opioid medications in 10% to 15% of people with cancer. In people with insufficient relief of cancer pain, new analgesics are needed to effectively and safely supplement or replace opioids.
OBJECTIVES
To evaluate the benefits and harms of cannabis-based medicines, including medical cannabis, for treating pain and other symptoms in adults with cancer compared to placebo or any other established analgesic for cancer pain.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 26 January 2023.
SELECTION CRITERIA
We selected double-blind randomised, controlled trials (RCT) of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment for cancer pain in adults, with any treatment duration and at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. The primary outcomes were 1. proportions of participants reporting no worse than mild pain; 2. Patient Global Impression of Change (PGIC) of much improved or very much improved and 3. withdrawals due to adverse events. Secondary outcomes were 4. number of participants who reported pain relief of 30% or greater and overall opioid use reduced or stable; 5. number of participants who reported pain relief of 30% or greater, or 50% or greater; 6. pain intensity; 7. sleep problems; 8. depression and anxiety; 9. daily maintenance and breakthrough opioid dosage; 10. dropouts due to lack of efficacy; 11. all central nervous system adverse events. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We identified 14 studies involving 1823 participants. No study assessed the proportions of participants reporting no worse than mild pain on treatment by 14 days after start of treatment. We found five RCTs assessing oromucosal nabiximols (tetrahydrocannabinol (THC) and cannabidiol (CBD)) or THC alone involving 1539 participants with moderate or severe pain despite opioid therapy. The double-blind periods of the RCTs ranged between two and five weeks. Four studies with a parallel design and 1333 participants were available for meta-analysis. There was moderate-certainty evidence that there was no clinically relevant benefit for proportions of PGIC much or very much improved (risk difference (RD) 0.06, 95% confidence interval (CI) 0.01 to 0.12; number needed to treat for an additional beneficial outcome (NNTB) 16, 95% CI 8 to 100). There was moderate-certainty evidence for no clinically relevant difference in the proportion of withdrawals due to adverse events (RD 0.04, 95% CI 0 to 0.08; number needed to treat for an additional harmful outcome (NNTH) 25, 95% CI 16 to endless). There was moderate-certainty evidence for no difference between nabiximols or THC and placebo in the frequency of serious adverse events (RD 0.02, 95% CI -0.03 to 0.07). There was moderate-certainty evidence that nabiximols and THC used as add-on treatment for opioid-refractory cancer pain did not differ from placebo in reducing mean pain intensity (standardised mean difference (SMD) -0.19, 95% CI -0.40 to 0.02). There was low-certainty evidence that a synthetic THC analogue (nabilone) delivered over eight weeks was not superior to placebo in reducing pain associated with chemotherapy or radiochemotherapy in people with head and neck cancer and non-small cell lung cancer (2 studies, 89 participants, qualitative analysis). Analyses of tolerability and safety were not possible for these studies. There was low-certainty evidence that synthetic THC analogues were superior to placebo (SMD -0.98, 95% CI -1.36 to -0.60), but not superior to low-dose codeine (SMD 0.03, 95% CI -0.25 to 0.32; 5 single-dose trials; 126 participants) in reducing moderate-to-severe cancer pain after cessation of previous analgesic treatment for three to four and a half hours (2 single-dose trials; 66 participants). Analyses of tolerability and safety were not possible for these studies. There was low-certainty evidence that CBD oil did not add value to specialist palliative care alone in the reduction of pain intensity in people with advanced cancer. There was no difference in the number of dropouts due to adverse events and serious adverse events (1 study, 144 participants, qualitative analysis). We found no studies using herbal cannabis.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that oromucosal nabiximols and THC are ineffective in relieving moderate-to-severe opioid-refractory cancer pain. There is low-certainty evidence that nabilone is ineffective in reducing pain associated with (radio-) chemotherapy in people with head and neck cancer and non-small cell lung cancer. There is low-certainty evidence that a single dose of synthetic THC analogues is not superior to a single low-dose morphine equivalent in reducing moderate-to-severe cancer pain. There is low-certainty evidence that CBD does not add value to specialist palliative care alone in the reduction of pain in people with advanced cancer.
Topics: Adult; Humans; Analgesics, Opioid; Cancer Pain; Cannabis; Carcinoma, Non-Small-Cell Lung; Codeine; Lung Neoplasms; Medical Marijuana; Morphine; Randomized Controlled Trials as Topic
PubMed: 37283486
DOI: 10.1002/14651858.CD014915.pub2 -
Journal of Rehabilitation Medicine Oct 2019To compare the efficacy of kinesio taping on chronic non-specific low back pain with that of other general physical therapies. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the efficacy of kinesio taping on chronic non-specific low back pain with that of other general physical therapies.
METHODS
Relevant studies published up to 31 July 2018 were searched in electronic databases (PubMed, Web of Science, Science Direct, Physiotherapy Evidence Database (PEDro), Cochrane Library, Wanfang Data, Vip Data and China National Knowledge Infrastructure). The quality of included studies was assessed using a risk of bias assessment tool, as recommended by the Cochrane Collaboration. Data from visual analogue scales and Oswestry Disability Index were extracted as selected outcome indicators. Tests of heterogeneity were performed. Weight-ed mean difference (WMD) data with its 95% confidence intervals (95% CI) were used as a measure of effect sizes, in order to pool the results from each included study using either a fixed or random effects model (where appropriate and possible).
RESULTS
Eight studies fulfilled the inclusion and exclusion criteria. The quality of included studies was moderate. Patients with chronic non-specific low back pain in the kinesio taping group achieved better pain relief (WMD = -1.22; 95% CI -1.49 to -0.96, I2 = 91%, p < 0.00001) and activities of daily living (WMD = -7.11; 95% CI -8.70 to -5.51, I2 = 77%, p < 0.0001) than those in the control group.
CONCLUSION
Kinesio taping may be a new, simple and convenient choice for intervention in low back pain. In the future, we can measure the efficacy about kinesio taping via clinical application in order to prove the possibility of treatment for low back pain.
Topics: Athletic Tape; Humans; Low Back Pain; Physical Therapy Modalities
PubMed: 31544952
DOI: 10.2340/16501977-2605 -
Value in Health : the Journal of the... Feb 2022This study aimed to assess the effectiveness of virtual reality (VR) in managing different types of pain in different age groups and to provide evidence for the clinical... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study aimed to assess the effectiveness of virtual reality (VR) in managing different types of pain in different age groups and to provide evidence for the clinical application of new alternative strategy for pain management.
METHODS
Electronic databases, including the Cochrane Library, PubMed, EMBASE, and the Web of Science, were searched for studies published up to October 2020. Randomized controlled trials that reported on VR for pain management were included.
RESULTS
A total of 31 randomized controlled trials were included. As for the pain intensity, the increase of visual analog scale score in the VR group was 1.62 scores less than that in the control group. In juvenile patients, the VR group had 1.79 scores lower than that in control group. For adult patients, the VR group had 1.34 scores lower than that in control group. As for other pain-related indicators, the VR group had lower levels of anxiety, lower pain unpleasantness, lower pulse rate, and shorter duration of dressing change and spent less time thinking about pain. Nevertheless, there was no statistical difference in pain tolerance. VR can effectively alleviate acute pain. In terms of chronic low back pain and cancer-related pain, there was no statistical difference between VR therapy and standard therapy.
CONCLUSIONS
VR is a feasible alternative therapy for both juveniles and adults in pain management, and it has a greater potential for juveniles. VR can effectively alleviate acute pain. Nevertheless, VR showed little effectiveness in increasing pain tolerance, which may explain in part the ineffectiveness of VR therapy in pain management for chronic pain.
Topics: Adolescent; Adult; Aged; Cancer Pain; Child; Chronic Pain; Female; Humans; Low Back Pain; Male; Middle Aged; Pain Management; Pain Measurement; Randomized Controlled Trials as Topic; Time Factors; Virtual Reality; Virtual Reality Exposure Therapy; Visual Analog Scale; Young Adult
PubMed: 35094802
DOI: 10.1016/j.jval.2021.04.1285 -
The American Journal of Drug and... Mar 2023Although the misuse of ketamine constitutes a worldwide issue, ketamine is quickly taking its place as a therapeutic option in the management of several mental...
Although the misuse of ketamine constitutes a worldwide issue, ketamine is quickly taking its place as a therapeutic option in the management of several mental disorders. However, the use of ketamine and/or its analogues, as well as combinations with other drugs, can be fatal. To outline the cases of overdoses and deaths related to the use of ketamine and/or its analogues, as reported in the scientific literature. To investigate if ketamine is safe in a therapeutic context, particularly in its use as an antidepressant. Electronic searches were performed on three medical databases. Articles describing cases of overdose and/or death associated with ketamine and/or its analogues were included. After the removal of duplicates, title analysis and full-text analysis, 34 articles were included in this review. Eighteen articles described fatal cases and sixteen described overdoses. Poly-substance use was mentioned in 53% of the selected articles. Most cases were males and the ages varied from two to 65 years old. A total of 312 overdose cases and 138 deaths were reported. In both death reports and overdose cases, ketamine was preponderant: 89.1% and 79%, respectively. No cases of overdose or death related to the use of ketamine as an antidepressant in a therapeutic setting were found; most of the deaths occurred in the circumstances of polydrug use and overdoses left no sequelae. There is legitimate concern about the risks involving the use of ketamine and its analogues, especially in recreational settings. On the other hand, ketamine as medicine is considered safe and it is listed as an essential medicine by the World Health Organization. Although clinicians must remain vigilant, this should not deter appropriate prescription.
Topics: Male; Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Female; Ketamine; Drug Overdose; Substance-Related Disorders; Analgesics, Opioid
PubMed: 36410032
DOI: 10.1080/00952990.2022.2132506 -
The Cochrane Database of Systematic... Jun 2020Worldwide, there is an increasing incidence of type 2 diabetes mellitus (T2DM). Metformin is still the recommended first-line glucose-lowering drug for people with T2DM.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Worldwide, there is an increasing incidence of type 2 diabetes mellitus (T2DM). Metformin is still the recommended first-line glucose-lowering drug for people with T2DM. Despite this, the effects of metformin on patient-important outcomes are still not clarified.
OBJECTIVES
To assess the effects of metformin monotherapy in adults with T2DM.
SEARCH METHODS
We based our search on a systematic report from the Agency for Healthcare Research and Quality, and topped-up the search in CENTRAL, MEDLINE, Embase, WHO ICTRP, and ClinicalTrials.gov. Additionally, we searched the reference lists of included trials and systematic reviews, as well as health technology assessment reports and medical agencies. The date of the last search for all databases was 2 December 2019, except Embase (searched up 28 April 2017).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with at least one year's duration comparing metformin monotherapy with no intervention, behaviour changing interventions or other glucose-lowering drugs in adults with T2DM.
DATA COLLECTION AND ANALYSIS
Two review authors read all abstracts and full-text articles/records, assessed risk of bias, and extracted outcome data independently. We resolved discrepancies by involvement of a third review author. For meta-analyses we used a random-effects model with investigation of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall certainty of the evidence by using the GRADE instrument.
MAIN RESULTS
We included 18 RCTs with multiple study arms (N = 10,680). The percentage of participants finishing the trials was approximately 58% in all groups. Treatment duration ranged from one to 10.7 years. We judged no trials to be at low risk of bias on all 'Risk of bias' domains. The main outcomes of interest were all-cause mortality, serious adverse events (SAEs), health-related quality of life (HRQoL), cardiovascular mortality (CVM), non-fatal myocardial infarction (NFMI), non-fatal stroke (NFS), and end-stage renal disease (ESRD). Two trials compared metformin (N = 370) with insulin (N = 454). Neither trial reported on all-cause mortality, SAE, CVM, NFMI, NFS or ESRD. One trial provided information on HRQoL but did not show a substantial difference between the interventions. Seven trials compared metformin with sulphonylureas. Four trials reported on all-cause mortality: in three trials no participant died, and in the remaining trial 31/1454 participants (2.1%) in the metformin group died compared with 31/1441 participants (2.2%) in the sulphonylurea group (very low-certainty evidence). Three trials reported on SAE: in two trials no SAE occurred (186 participants); in the other trial 331/1454 participants (22.8%) in the metformin group experienced a SAE compared with 308/1441 participants (21.4%) in the sulphonylurea group (very low-certainty evidence). Two trials reported on CVM: in one trial no CVM was observed and in the other trial 4/1441 participants (0.3%) in the metformin group died of cardiovascular reasons compared with 8/1447 participants (0.6%) in the sulphonylurea group (very low-certainty evidence). Three trials reported on NFMI: in two trials no NFMI occurred, and in the other trial 21/1454 participants (1.4%) in the metformin group experienced a NFMI compared with 15/1441 participants (1.0%) in the sulphonylurea group (very low-certainty evidence). One trial reported no NFS occurred (very low-certainty evidence). No trial reported on HRQoL or ESRD. Seven trials compared metformin with thiazolidinediones (very low-certainty evidence for all outcomes). Five trials reported on all-cause mortality: in two trials no participant died; the overall RR was 0.88, 95% CI 0.55 to 1.39; P = 0.57; 5 trials; 4402 participants). Four trials reported on SAE, the RR was 0,95, 95% CI 0.84 to 1.09; P = 0.49; 3208 participants. Four trials reported on CVM, the RR was 0.71, 95% CI 0.21 to 2.39; P = 0.58; 3211 participants. Three trial reported on NFMI: in two trials no NFMI occurred and in one trial 21/1454 participants (1.4%) in the metformin group experienced a NFMI compared with 25/1456 participants (1.7%) in the thiazolidinedione group. One trial reported no NFS occurred. No trial reported on HRQoL or ESRD. Three trials compared metformin with dipeptidyl peptidase-4 inhibitors (one trial each with saxagliptin, sitagliptin, vildagliptin with altogether 1977 participants). There was no substantial difference between the interventions for all-cause mortality, SAE, CVM, NFMI and NFS (very low-certainty evidence for all outcomes). One trial compared metformin with a glucagon-like peptide-1 analogue (very low-certainty evidence for all reported outcomes). There was no substantial difference between the interventions for all-cause mortality, CVM, NFMI and NFS. One or more SAEs were reported in 16/268 (6.0%) of the participants allocated to metformin compared with 35/539 (6.5%) of the participants allocated to a glucagon-like peptide-1 analogue. HRQoL or ESRD were not reported. One trial compared metformin with meglitinide and two trials compared metformin with no intervention. No deaths or SAEs occurred (very low-certainty evidence) no other patient-important outcomes were reported. No trial compared metformin with placebo or a behaviour changing interventions. Four ongoing trials with 5824 participants are likely to report one or more of our outcomes of interest and are estimated to be completed between 2018 and 2024. Furthermore, 24 trials with 2369 participants are awaiting assessment.
AUTHORS' CONCLUSIONS
There is no clear evidence whether metformin monotherapy compared with no intervention, behaviour changing interventions or other glucose-lowering drugs influences patient-important outcomes.
Topics: Adult; Carbamates; Cardiovascular Diseases; Cause of Death; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin; Metformin; Myocardial Infarction; Piperidines; Quality of Life; Randomized Controlled Trials as Topic; Stroke; Sulfonylurea Compounds
PubMed: 32501595
DOI: 10.1002/14651858.CD012906.pub2 -
The Lancet. Gastroenterology &... Nov 2021Gastrointestinal angiodysplasias are vascular malformations that often cause red blood cell transfusion-dependent anaemia. Several studies suggest that somatostatin... (Meta-Analysis)
Meta-Analysis
Effectiveness and predictors of response to somatostatin analogues in patients with gastrointestinal angiodysplasias: a systematic review and individual patient data meta-analysis.
BACKGROUND
Gastrointestinal angiodysplasias are vascular malformations that often cause red blood cell transfusion-dependent anaemia. Several studies suggest that somatostatin analogues might decrease rebleeding rates, but the true effect size is unknown. We therefore aimed to investigate the efficacy of somatostatin analogues on red blood cell transfusion requirements of patients with gastrointestinal angiodysplasias and to identify subgroups that might benefit the most from somatostatin analogue therapy.
METHODS
We did a systematic review and individual patient data meta-analysis. We searched MEDLINE, Embase, and Cochrane on Jan 15, 2016, with an updated search on April 25, 2021. All published randomised controlled trials and cohort studies that reported on somatostatin analogue therapy in patients with gastrointestinal angiodysplasias were eligible for screening. We excluded studies without original patient data, single case reports, small case series (ie, <10 participants), studies in which patients had a specific aetiology of gastrointestinal angiodysplasias, and studies in which somatostatin analogue therapy was initiated simultaneously with other treatment modalities. Authors of eligible studies were invited to share individual patient data. Aggregated data was used if individual patient data were not provided. The primary outcome was the mean reduction in the number of red blood cell transfusions during somatostatin analogue therapy, compared with baseline, expressed as the incidence rate ratio (IRR) and absolute mean decrease. We defined patients as either good responders (≥50% reduction in the number of red blood cell transfusions) or poor responders (<50% reduction). A mixed-effects negative binomial regression was used to account for clustering of patients and skewness in data. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42020213985.
FINDINGS
We identified 11 eligible studies (one randomised controlled trial and ten cohort studies) of moderate-to-high quality and obtained individual patient data from the authors of nine (82%) studies. The remaining two (18%) studies provided sufficient information in the published manuscript to extract individual patient data. In total, we analysed data from 212 patients. Somatostatin analogues reduced the number of red blood cell transfusions with an IRR of 0·18 (95% CI 0·14-0·24; p<0·0001) during a median treatment duration of 12 months (IQR 6·0-12·0) and follow-up period of 12 months (12·0-12·0), correlating with a mean absolute decrease in the number of red blood cell transfusions from 12·8 (95% CI 10·4-15·8) during baseline to 2·3 (1·9-2·9) during follow-up-ie, a reduction of 10·5 red blood cell transfusions (p<0·0001). 177 (83%) of 212 patients had a good response to somatostatin analogue therapy (defined as at least a 50% reduction in the number of red blood cell transfusions). Heterogeneity across studies was moderate (I=53%; p=0·02). Location of gastrointestinal angiodysplasias in the stomach compared with angiodysplasias in the small bowel and colon (IRR interaction 1·92 [95% CI 1·13-3·26]; p=0·02) was associated with worse treatment response. Octreotide was associated with a better treatment response than lanreotide therapy (IRR interaction 2·13 [95% CI 1·12-4·04]; p=0·02). The certainty of evidence was high for the randomised controlled trial and low for the ten cohort studies. Adverse events occurred in 38 (18%) of 212 patients receiving somatostatin analogue therapy, with ten (5%) discontinuing this therapy because of adverse events. The most common adverse events were loose stools (seven [3%] of 212), cholelithiasis (five [2%]), flatulence (four [2%]), and administration site reactions (erythema, five [2%]).
INTERPRETATION
Somatostatin analogue therapy is safe and effective in most patients with red blood cell transfusion-dependent bleeding due to gastrointestinal angiodysplasias. Somatostatin analogue therapy is more effective in patients with angiodysplasias located in the small bowel and colon, and octreotide therapy seems to be more effective than lanreotide therapy.
FUNDING
The Netherlands Organisation for Health Research and Development and the Radboud University Medical Center.
Topics: Angiodysplasia; Erythrocyte Transfusion; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Octreotide; Peptides, Cyclic; Somatostatin; Treatment Outcome
PubMed: 34508668
DOI: 10.1016/S2468-1253(21)00262-4