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Journal of Veterinary Internal Medicine Mar 2023Evidence supporting the effectiveness of therapeutic protocols for nonassociative immune-mediated hemolytic anemia (na-IMHA) is weak.
BACKGROUND
Evidence supporting the effectiveness of therapeutic protocols for nonassociative immune-mediated hemolytic anemia (na-IMHA) is weak.
HYPOTHESIS/OBJECTIVES
Investigate the efficacy of various drugs in na-IMHA.
ANIMALS
Two hundred forty-two dogs.
METHODS
Multi-institutional retrospective study (2015-2020). Immunosuppressive effectiveness was determined by time to packed cell volume (PCV) stabilization and duration of hospitalization through analysis by mixed model linear regression. Occurrence of disease relapse, death, and antithrombotic effectiveness, were analyzed using mixed model logistic regression.
RESULTS
Use of corticosteroids vs a multi-agent protocol had no effect on time to PCV stabilization (P = .55), duration of hospitalization (P = .13), or case fatality (P = .06). A higher rate of relapse (P = .04; odds ratio: 3.97; 95% confidence interval [CI]: 1.06-14.8) was detected in dogs receiving corticosteroids (11.3%) during follow-up (median: 28.5 days, range: 0-1631 days) compared to multiple agents (3.1%) during follow up (median: 47.0 days, range: 0-1992 days). When comparing drug protocols, there was no effect on time to PCV stabilization (P = .31), relapse (P = .44), or case fatality (P = .08). Duration of hospitalization was longer, by 1.8 days (95% CI: 0.39-3.28 days), for the corticosteroid with mycophenolate mofetil group (P = .01) compared to corticosteroids alone. Use of clopidogrel vs multiple agents had no effect on development of thromboses (P ≥ .36).
CONCLUSIONS AND CLINICAL IMPORTANCE
Addition of a second immunosuppressive agent did not alter immediate outcome measures but might be associated with a reduction in relapse. Use of multiple antithrombotic agents did not reduce incidence of thrombosis.
Topics: Animals; Dogs; Adrenal Cortex Hormones; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Dog Diseases; Immunosuppressive Agents; Recurrence; Retrospective Studies
PubMed: 36809664
DOI: 10.1111/jvim.16652 -
American Journal of Hypertension Jul 2022To compare prevalence of hypertension and stage II hypertension assessed by 2 blood pressure (BP) observation protocols.
Differences in Hypertension and Stage II Hypertension by Demographic and Risk Factors, Obtained by Two Different Protocols in US Adults: National Health and Nutrition Examination Survey, 2017-2018.
BACKGROUND
To compare prevalence of hypertension and stage II hypertension assessed by 2 blood pressure (BP) observation protocols.
METHODS
Participants aged 18 years and older (n = 4,689) in the National Health and Nutrition Examination Survey (NHANES 2017-2018) had their BP measured following 2 protocols: the legacy auscultation protocol (AP) and oscillometric protocol (OP). The order of protocols was randomly assigned. Prevalence estimates for hypertension (BP ≥130/80 mm Hg or use of medication for hypertension) and stage II hypertension (BP ≥140/90 mm Hg) were determined overall, by demographics, and by risk factors for each protocol. Ratios (OP% ÷ AP%) and kappa statistics were calculated.
RESULTS
Age-adjusted hypertension prevalence was 44.5% (95% confidence interval [CI]: 41.1%-48.0%) using OP and 45.1% (95% CI: 41.5%-48.7%) using AP, prevalence ratio = 0.99 (95% CI = 0.94-1.04). Age-adjusted stage II hypertension prevalence was 15.8% (95% CI: 13.6%-18.2%) using AP and 17.1% (95% CI: 14.7%-19.7%) using OP, prevalence ratio = 0.92 (95% CI = 0.81-1.04). For both hypertension and stage II hypertension, the prevalence ratios by demographics and by risk factors all included unity in their 95% CI, except for stage II hypertension in adults 60+ years (ratio: 0.88 [95% CI: 0.78-0.98]). Kappa for agreement between protocols for hypertension and stage II hypertension was 0.75 (95% CI = 0.71-0.79) and 0.67 (95% CI = 0.61-0.72), respectively.
CONCLUSIONS
In adults and for nearly all subcategories there were no significant differences in prevalence of hypertension and stage II hypertension between protocols, indicating that protocol change may not affect the national prevalence estimates of hypertension and stage II hypertension.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Nutrition Surveys; Prevalence; Risk Factors; United States
PubMed: 35333925
DOI: 10.1093/ajh/hpac042 -
Anales Del Sistema Sanitario de Navarra 2003There are discordant guides and protocols when it comes to treating a patient who has ingested a caustic substance. Different ideas or tendencies speak in favour of... (Review)
Review
There are discordant guides and protocols when it comes to treating a patient who has ingested a caustic substance. Different ideas or tendencies speak in favour of dilution, neutralization, provoking vomiting, carrying out stomach washes, etc., depending on the milieu where the problem arises: at home, at the health centre, emergency service or hospital. The same occurs with the type of diluent or neutralizing agent to be used, how and when to start the treatment pattern with corticoids and/or antibiotics and antisecretory, if indeed this is necessary. We have carried out an exhaustive bibliographical study, an experimental work and a study of the different diagnosis and treatment guides and protocols used in different Spanish hospitals. At the experimental level it was found that there are histopathological markers that advise against the use of diluent substances following the ingestion of caustic alkali. Except in the cases of ingestion of solid caustic substances -crystalline or granulated- categorical contraindications are given against dilution. Corticoids are not efficient when a caustic acid is ingested; their use is more than questionable following the ingestion of caustic alkali. Diagnosis and quality of treatment are based on endoscopy. There is no single criterion that defines which moment (the time following ingestion) is the most convenient for carrying this out, although the period between the first 6-12 hours is the most suitable. We present an independent protocol of diagnosis and treatment -in the form of algorithms- that must be followed after the ingestion of caustic acids or caustic alkali.
Topics: Acute Disease; Caustics; Humans; Poisoning
PubMed: 12813486
DOI: No ID Found -
BMC Oral Health May 2022To evaluate the effect of amalgam contamination, different surface treatments, and adhesive protocols on dentin microleakage to bulk-fill composite resin material.
BACKGROUND
To evaluate the effect of amalgam contamination, different surface treatments, and adhesive protocols on dentin microleakage to bulk-fill composite resin material.
METHODS
Forty teeth were fixed in (polyvinyl siloxane) PVS molds, and the Class II cavities were placed on mesial and distal aspects. Thirty teeth were restored by amalgam and thermocycled to 10,000 cycles (5 and 55 °C, 30-s dwell time). The rest were restored with Filtek one Bulk Fill composite without amalgam predecessor. Samples were divided into: G1 (dentin pretreated with 2% chlorhexidine gluconate), G2 (0.5 mm of dentin was removed), G3 (no surface modification), and G4 (control, where composite was bonded to sound dentin without amalgam predecessor.). Single Bond Universal Adhesive system was used to bond the composite material, by using the etch-and-rinse protocol in the mesial cavity preparation and self-etch protocol in the distal. Specimens underwent thermocycling for 5000 cycles, then embedded in silver nitrate and sectioned for stereomicroscope examination. Descriptive statistics, Mann-Whitney U test, and Kruskal-Wallis test were used to analyze the results at p < 0.05.
RESULTS
The highest microleakage score values (4.00) were found in the G2, and G4 in etch-and-rinse protocol. While the lowest scores were found in G2 when using self-etching protocol (1.5). Lower microleakage values were associated with the chlorhexidine treatment group for both adhesive protocols. No significant differences were found between amalgam contaminated and non-contaminated groups.
CONCLUSIONS
Amalgam contamination did not affect microleakage. Self-etching adhesive protocol significantly reduced microleakage for all groups irrespective of the surface treatment. Chlorhexidine pretreatment improved microleakage for both adhesive protocols but had no significant effect.
Topics: Chlorhexidine; Composite Resins; Dental Cavity Preparation; Dental Cements; Dental Leakage; Dental Restoration, Permanent; Dentin; Dentin-Bonding Agents; Humans; Materials Testing; Resin Cements
PubMed: 35585533
DOI: 10.1186/s12903-022-02214-1 -
Frontiers in Veterinary Science 2022Etorphine is widely used in zoological medicine for the immobilization of large herbivores. All reported immobilization protocols for kulans use etorphine as the primary...
Etorphine is widely used in zoological medicine for the immobilization of large herbivores. All reported immobilization protocols for kulans use etorphine as the primary immobilizing agent. However, etorphine can trigger severe side effects and is highly toxic for humans, its availability is occasionally limited for use in wildlife medicine. Therefore, two different alpha-2 agonist-based protocols for the general anesthesia of kulans were investigated and compared with the standard etorphine immobilization. In total, 21 immobilizations were performed within the scope of routine husbandry management at the Serengeti-Park Hodenhagen. Kulans were darted using a ketamine-medetomidine-midazolam-butorphanol (KMMB) protocol ( = 8, treatment group (TG) 1), a tiletamine-zolazepam-medetomidine-butorphanol (TZMB) protocol ( = 7, treatment group (TG) 2), or an etorphine-acepromazine-detomidine-butorphanol (EADB) protocol ( = 6, control group). Vital parameters included heart rate, respiratory rate, arterial blood pressure (invasive), end tidal CO (etCO), electromyography and core body temperature, which were all assessed every 10 min. For blood gas analysis, arterial samples were collected 15, 30, 45 and 60 min after induction. Subjective measures of quality and efficacy included quality of induction, immobilization, and recovery. Time to recumbency was longer for TG 1 (9.00 ± 1.67 min) and TG 2 (10.43 ± 1.79 min) compared to the induction times in the control group (5.33 ± 1.93 min). Treatment group protocols resulted in excellent muscle relaxation, normoxemia and normocapnia. Lower pulse rates combined with systolic arterial hypertension were detected in the alpha-2 agonist-based protocols. However, only in TZMB-immobilized kulans, sustained severe systolic arterial hypertension was observed, with significantly higher values than in the TG 1 and the normotensive control group. At 60 min following induction, medetomidine and detomidine were antagonized with atipamezole IM (5 mg/mg medetomidine or 2 mg/mg detomidine), etorphine and butorphanol with naltrexone IV (2 mg/mg butorphanol or 50 mg/mg etorphine), and midazolam and zolazepam with flumazenil IV (0.3 mg per animal). All three combinations provided smooth and rapid recoveries. To conclude, the investigated treatment protocols (KMMB and TZMB) provided a safe and efficient general anesthesia in kulans with significantly better muscle relaxation, higher respiration rates and improved arterial oxygenation compared with the immobilizations of the control group. However, the control group (EADB) showed faster recoveries. Therefore, EADB is recommended for ultra-short immobilizations (e.g., microchipping and collaring), especially with free-ranging kulans where individual recovery is uncertain, whereas the investigated treatment protocols are recommended for prolonged medical procedures on captive kulans.
PubMed: 36213408
DOI: 10.3389/fvets.2022.885317 -
The Oncologist May 2017Combining targeted and cytotoxic agents has the potential to improve efficacy and attenuate resistance for metastatic cancer. Information regarding safe starting doses... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Combining targeted and cytotoxic agents has the potential to improve efficacy and attenuate resistance for metastatic cancer. Information regarding safe starting doses for clinical trials of novel three-drug combinations is lacking.
MATERIALS AND METHODS
Published phase I-III adult oncology clinical trials of three-drug combinations involving a targeted agent were identified by PubMed search (January 1, 2010 to December 31, 2013). A dose percentage was calculated to compare the dose used in combination to the single agent recommended dose: (U.S. Food and Drug Administration-approved/recommended phase II dose/maximum tolerated dose). The additive dose percentage was the sum of the dose percentages for each drug in the combination.
RESULTS
A total of 37,763 subjects and 243 drug combinations were included. Only 28% of studies could give each of the three agents at 100%. For combinations involving two targeted agents and a cytotoxic agent, the lowest starting additive dose percentage was 133%, which increased to 250% if two antibodies were included. For combinations of one targeted agent and two cytotoxic agents, the lowest additive safe dose percentage was 137%. When both cytotoxic agents were held at 100%, as occurred in 56% of studies (which generally used cytotoxic doublets with known combination safety dosing), the lowest safe dose percentage was 225% (providing that a histone deacetylase inhibitor was not the targeted agent).
CONCLUSION
These findings serve as a safe starting point for dosing novel three-drug combinations involving a targeted agent in clinical trials and practice. 2017;22:576-584 IMPLICATIONS FOR PRACTICE: Targeted and cytotoxic drug combinations can improve efficacy and overcome resistance. More knowledge of safe starting doses would facilitate use of combinations in clinical trials and practice. Analysis of 37,763 subjects (243 combinations) showed three drugs could be safely administered, but less than 30% of combinations could include all three drugs at full dose. Dose reductions to 45% of the dose of each single agent may be required. Combinations involving two antibodies required fewer dose reductions, and the use of established cytotoxic doublets made initial dose assignment easier.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Dose-Response Relationship, Drug; Histone Deacetylase Inhibitors; Humans; Neoplasms
PubMed: 28424323
DOI: 10.1634/theoncologist.2016-0357 -
PLoS Computational Biology Oct 2022Language interfaces with many other cognitive domains. This paper explores how interactions at these interfaces can be studied with deep learning methods, focusing on...
Language interfaces with many other cognitive domains. This paper explores how interactions at these interfaces can be studied with deep learning methods, focusing on the relation between language emergence and visual perception. To model the emergence of language, a sender and a receiver agent are trained on a reference game. The agents are implemented as deep neural networks, with dedicated vision and language modules. Motivated by the mutual influence between language and perception in cognition, we apply systematic manipulations to the agents' (i) visual representations, to analyze the effects on emergent communication, and (ii) communication protocols, to analyze the effects on visual representations. Our analyses show that perceptual biases shape semantic categorization and communicative content. Conversely, if the communication protocol partitions object space along certain attributes, agents learn to represent visual information about these attributes more accurately, and the representations of communication partners align. Finally, an evolutionary analysis suggests that visual representations may be shaped in part to facilitate the communication of environmentally relevant distinctions. Aside from accounting for co-adaptation effects between language and perception, our results point out ways to modulate and improve visual representation learning and emergent communication in artificial agents.
Topics: Language; Communication; Semantics; Cognition; Visual Perception
PubMed: 36315590
DOI: 10.1371/journal.pcbi.1010658 -
The Cochrane Database of Systematic... Nov 2015Gonadotrophin-releasing hormone agonists (GnRHa) are commonly used in assisted reproduction technology (ART) cycles to prevent a luteinising hormone surge during... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gonadotrophin-releasing hormone agonists (GnRHa) are commonly used in assisted reproduction technology (ART) cycles to prevent a luteinising hormone surge during controlled ovarian hyperstimulation (COH) prior to planned oocyte retrieval, thus optimising the chances of live birth.
OBJECTIVES
To evaluate the effectiveness of the different GnRHa protocols as adjuncts to COH in women undergoing ART cycles.
SEARCH METHODS
We searched the following databases from inception to April 2015: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2015, Issue 3), MEDLINE, EMBASE, CINAHL, PsycINFO, and registries of ongoing trials. Reference lists of relevant articles were also searched.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing any two protocols of GnRHa used in in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles in subfertile women.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed trial eligibility and risk of bias, and extracted the data. The primary outcome measure was number of live births or ongoing pregnancies per woman/couple randomised. Secondary outcome measures were number of clinical pregnancies, number of oocytes retrieved, dose of gonadotrophins used, adverse effects (pregnancy losses, ovarian hyperstimulation, cycle cancellation, and premature luteinising hormone (LH) surges), and cost and acceptability of the regimens. We combined data to calculate odds ratios (OR) for dichotomous variables and mean differences (MD) for continuous variables, with 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methods.
MAIN RESULTS
We included 37 RCTs (3872 women), one ongoing trial, and one trial awaiting classification. These trials made nine different comparisons between protocols. Twenty of the RCTs compared long protocols and short protocols. Only 19/37 RCTs reported live birth or ongoing pregnancy.There was no conclusive evidence of a difference between a long protocol and a short protocol in live birth and ongoing pregnancy rates (OR 1.30, 95% CI 0.94 to 1.81; 12 RCTs, n = 976 women, I² = 15%, low quality evidence). Our findings suggest that in a population in which 14% of women achieve live birth or ongoing pregnancy using a short protocol, between 13% and 23% will achieve live birth or ongoing pregnancy using a long protocol. There was evidence of an increase in clinical pregnancy rates (OR 1.50, 95% CI 1.18 to 1.92; 20 RCTs, n = 1643 women, I² = 27%, moderate quality evidence) associated with the use of a long protocol.There was no evidence of a difference between the groups in terms of live birth and ongoing pregnancy rates when the following GnRHa protocols were compared: long versus ultrashort protocol (OR 1.78, 95% CI 0.72 to 4.36; one RCT, n = 150 women, low quality evidence), long luteal versus long follicular phase protocol (OR 1.89, 95% CI 0.87 to 4.10; one RCT, n = 223 women, low quality evidence), when GnRHa was stopped versus when it was continued (OR 0.75, 95% CI 0.42 to 1.33; three RCTs, n = 290 women, I² = 0%, low quality evidence), when the dose of GnRHa was reduced versus when the same dose was continued (OR 1.02, 95% CI 0.68 to 1.52; four RCTs, n = 407 women, I² = 0%, low quality evidence), when GnRHa was discontinued versus continued after human chorionic gonadotrophin (HCG) administration in the long protocol (OR 0.89, 95% CI 0.49 to 1.64; one RCT, n = 181 women, low quality evidence), and when administration of GnRHa lasted for two versus three weeks before stimulation (OR 1.14, 95% CI 0.49 to 2.68; one RCT, n = 85 women, low quality evidence). Our primary outcomes were not reported for any other comparisons.Regarding adverse events, there were insufficient data to enable us to reach any conclusions except about the cycle cancellation rate. There was no conclusive evidence of a difference in cycle cancellation rate (OR 0.95, 95% CI 0.59 to 1.55; 11 RCTs, n = 1026 women, I² = 42%, low quality evidence) when a long protocol was compared with a short protocol. This suggests that in a population in which 9% of women would have their cycles cancelled using a short protocol, between 5.5% and 14% will have cancelled cycles when using a long protocol.The quality of the evidence ranged from moderate to low. The main limitations in the evidence were failure to report live birth or ongoing pregnancy, poor reporting of methods in the primary studies, and imprecise findings due to lack of data. Only 10 of the 37 included studies were conducted within the last 10 years.
AUTHORS' CONCLUSIONS
When long GnRHa protocols and short GnRHa protocols were compared, we found no conclusive evidence of a difference in live birth and ongoing pregnancy rates, but there was moderate quality evidence of higher clinical pregnancy rates in the long protocol group. None of the other analyses showed any evidence of a difference in birth or pregnancy outcomes between the protocols compared. There was insufficient evidence to make any conclusions regarding adverse effects.
Topics: Buserelin; Clinical Protocols; Drug Administration Schedule; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Live Birth; Luteinizing Hormone; Ovulation Induction; Pituitary Gland; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted; Triptorelin Pamoate
PubMed: 26558801
DOI: 10.1002/14651858.CD006919.pub4 -
BMC Geriatrics Apr 2022To manage the rapidly growing incidence of, and related medical burden resulting from hip fractures in older adults in an aging society, studies involving orthogeriatric...
BACKGROUND
To manage the rapidly growing incidence of, and related medical burden resulting from hip fractures in older adults in an aging society, studies involving orthogeriatric co-management treatment models have reported improved outcomes, including reduced medical costs. The treatment gap for osteoporosis was however seldom emphasized in the published treatment protocols. Aiming to improve the existing orthogeriatric protocol, we have established a patient-centered protocol for elderly patient hip fractures, which simultaneously focuses on fracture care and anti-osteoporosis agent prescription in regarding to healthcare quality and medical expense.
METHODS
This was a retrospective study comparing patients who enrolled in the multidisciplinary co-managed protocol for geriatric hip fractures and those who did not. The inclusion criteria for this study were: (a) single-sided hip fractures treated from 1 to 2018 to 30 June 2020, (b) patients who were 60-years or older (c) trauma treated within 3 days from time of injury, and (d) minimal follow-up period of 12 months after surgery.
RESULTS
From 1 to 2018 to 30 June 2020, 578 patients were included (267 patients in the protocol group vs. 331 patients in the conventional group). The protocol group was associated with significantly reduced lengths of hospital stay (p = 0.041), medical expenditures (p = 0.006), and mortality (p = 0.029) during their acute in-hospital admission period. Early osteoporosis diagnosis and anti-osteoporosis agent prescription were achieved in the protocol group, with a significantly wider coverage for BMD assessment (p < 0.001) and prescriptions for anti-osteoporosis medication (p < 0.001). Yet, there was no significant decline in the one-year refracture rate in the protocol group.
CONCLUSIONS
The implementation of a multidisciplinary co-managed care protocol for geriatric proximal femur fractures successfully improved patient outcomes with significantly reduced lengths of stay, medical expenditures, and mortality during the acute in-hospital admission period. The high prescription rate of anti-osteoporosis medication after hip fractures in the protocol group was not associated with a significantly lower re-fracture rate in the 12-month follow-up. However, the association between early anti-osteoporosis agent prescription and reduced long-term medical expenses in this group of patients has provided a direction for future research.
Topics: Aged; Femoral Fractures; Femur; Hip Fractures; Humans; Osteoporosis; Retrospective Studies
PubMed: 35410173
DOI: 10.1186/s12877-022-03014-6 -
Trials May 2021Chemoprophylactics against emerging epidemic and pandemic infectious diseases offer potential for prevention but require efficacy and safety analysis before widespread... (Review)
Review
BACKGROUND
Chemoprophylactics against emerging epidemic and pandemic infectious diseases offer potential for prevention but require efficacy and safety analysis before widespread use can be recommended. Chemoprophylaxis with repurposed drugs enables deployment ahead of development of novel vaccines. It may have particular utility as a stopgap ahead of vaccine deployment or when vaccines become less effective on virus variants, in countries where there may be structural inaccessibility to vaccines or in specific risk-groups. Rapid implementation of robust trial designs is a persistent challenge in epidemics. We systematically reviewed SARS-CoV-2 and COVID-19 chemoprophylaxis trial registrations from the first 21 weeks of the pandemic to critically appraise significant design features and alignment of study populations to clinical and public health uses, and describe candidate chemoprophylactic agents.
METHODS
We searched online international trial databases from 31 Dec 2019 to 26 May 2020 using keywords "proph*" or "prevention". Trial protocols assessing efficacy of chemoprophylactic agents for COVID-19 were included. Trial components were screened for eligibility and relevant studies extracted. Key trial design features were assessed.
RESULTS
We found 76 chemoprophylaxis study registrations, proposing enrolment of 208,367 people with median size of 490 (IQR 262-1710). A randomised design was specified for 63 trials, 61 included a control group and total proposed enrolment size was 197,010, median 600 (IQR 236-1834). Four protocols provided information on effect size sought. We estimate that for a control group attack rate of 10%, 66% of trials would be underpowered to detect a 50% effect size, and 97% of trials would be underpowered to detect a 30% effect size (at the 80% level). We found evidence of adaptive design in one trial registration only. Laboratory-confirmed infection with or without symptoms was the most common primary outcome. Polymerase chain reaction testing alone was used in 46% of trials, serological testing in 6.6% and 14.5% used both testing methods. Healthcare workers were the target population in 52/79 (65.8%) trials: 49 pre-exposure prophylaxis (PrEP) and 3 post-exposure prophylaxis (PEP). Sixteen trials (20.3%) planned PEP in close contacts. Five studies (6.3%) considered chemoprophylaxis in clinical-risk patients. Older adults were the focus of recruitment in only 3 (3.8%) studies (all long-term care facilities). Two (2.5%) studies of PrEP in the general population included older adults. Hydroxychloroquine was the most common candidate agent in 55/79 trials (69.6%), followed by chloroquine (4/79, 5.0%) and lopinavir/ritonavir (3/79, 3.8%).
CONCLUSION
Many registered COVID-19 chemoprophylaxis efficacy trials were underpowered to detect clinically meaningful protection at epidemiologically informed attack rates. This, compounded with the time that has taken to organise these trials as compared to the rapid development of COVID-19 vaccines, has rendered these trials of marginal importance. International coordination mechanisms and collaboration is required. Supporting the design of feasible chemoprophylaxis trials, large enough to generate strong evidence, early on in an epidemic using adaptive platform trial designs will allow structured entry and exit of candidate agents and rapid stand-up of trial infrastructure.
REVIEW PROTOCOL REGISTRATION
Our protocol is registered at https://www.osf.io/vp56f on May 20, 2020.
Topics: Aged; Antiviral Agents; COVID-19; COVID-19 Vaccines; Chemoprevention; Humans; Pandemics; SARS-CoV-2; Treatment Outcome
PubMed: 34051840
DOI: 10.1186/s13063-021-05323-4