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INTRODUCTION
rash, pain, Herpes zoster, HZ, PHN
POSTHERPETIC NEURALGIA, PHN, VIRUS INFECTION, DISEASE, HERPES ZOSTER, NEUROINFLAMMATORY RESPONSE, PATHOGENESIS, COMPLICATIONS
Herpes zoster (HZ) is a comment disease with distinctive clinical conditions, it is caused after varicella‐zoster virus infection. According to epidemiological investigation, one in four people might suffer from HZ during their lifetime, and for individuals aged over 50, the incidence for HZ increased to almost 50% (Da...
PMC10097047
METHODS
PIAN
This open‐label pilot study was undertaken in the Pian Center of Shanghai Changhai Hospital, China, from February 1, 2020 to January 30, 2022. The protocol is in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement. This trial was prospectively registered at Chictr.o...
PMC10097047
Study design
PHN, herpetic neuralgia, rash, pain
PHN, HERPETIC NEURALGIA, SYNDROME
This is a prospective, single‐arm, and single‐center pilot study to investigate autologous fat grafting to the thoracic paravertebral space for elders with herpetic neuralgia in the rash phase, the main object of this trail is to investigate the feasibility and safety of this treatment in preventing PHN. Participants w...
PMC10097047
Interventions
allodynia, Pain, hyperalgesia
All included patients were treated with autologous fat grafting to the thoracic paravertebral space with hyperalgesia and allodynia in related region. All procedures were performed by a skilled plastic surgeon. Before harvest, the region was injected by a tumescent solution (0.5% lidocaine + 0.0005% adrenaline). The fa...
PMC10097047
Electoral pain threshold assessment
pain
In this trial, we assessed the pain threshold based on patients’ response to a gradual increased electrical stimulus (0.1 mA, pulse width 0.3 ms, impulse frequency 50 Hz) using a pain vision detection device (PS‐2100, Nipro Corporation, Osaka, Japan). During each assessment, a 1‐inch square electrode was placed either ...
PMC10097047
Data collection and outcomes
neuropathic pain, skin eruption, pain, PHN, herpetic pain, herpetic neuralgia
PHN, HERPETIC NEURALGIA, SKIN ERUPTION
Baseline data collected included demographic information; pain level (as perceived by the patient using visual analog scale, VAS, a 10‐cm unmarked line, with anchors: 0 = no pain and 10 cm = worst pain imaginable); current medications; smoking status; and pain threshold of the patient's affected dermal area as well as ...
PMC10097047
Sample size and statistical methods
This is a hypothesis‐generating feasibility study; the collected data and information are supposed to identify the safety and treatment responses, and to calculate a preliminary sample size for a randomized controlled trial. We chose to include a total of eight patients in this trial. Data were analyzed using the SPSS ...
PMC10097047
RESULTS
PHN, pain, rash, abdominal pain
HERPES ZOSTER, PHN, EVENTS
Eight patients accept the intervention and complete all follow‐ups. All of them are female, with a mean age of 63.7 years (range from 50 to 76 years), while seven of them have a high school degree. All patients are suffered from chest, back or abdominal pain due to emerging herpes zoster, the mean duration for pain is ...
PMC10097047
DISCUSSION
neuropathic pain, mood disorders, rash, pain, PHN
ADVERSE EVENTS, PHN, PATHOGENESIS, SYNDROME
In this trial, we identify that autologous fat grafting to the paravertebral space of the algogenic segment is a potentially valid method to prevent PHN. Among the eight patients accepted fat grafting, most of them have experienced immediate pain relief after the intervention, while eight of them have a lasting allogen...
PMC10097047
CONCLUSION
PHN
ADVERSE EVENTS, PHN
In this prospective, single‐armed trial, we first report the feasibility and the safety of autologous fat transplantation to the paravertebral space in preventing PHN. More advantages of this technique including rich in fat content, easy to obtain, cost‐benefit as well as less adverse events makes it a promising treatm...
PMC10097047
AUTHOR CONTRIBUTIONS
XJ Li designed the trial and conducted the experiments, R Tao conducted the experiments, XY meng analyzed the data and wrote the manuscript, H Wang revised the manuscript, HD Bi conceived the study and conducted the experiments, YC Xiong conceived the study. All authors read and approved the final version.
PMC10097047
CONFLICT OF INTEREST STATEMENT
The authors declare that they have no competing interests.
PMC10097047
PEER REVIEW
The peer review history for this article is available at
PMC10097047
DATA AVAILABILITY STATEMENT
Data are available from the corresponding author with reasonable requesting.
PMC10097047
REFERENCES
PMC10097047
ABSTRACT
infusion-site, pain
RHD, SECONDARY, RHEUMATIC HEART DISEASE
The authors declare no conflict of interest.Since 1955, the recommended strategy for rheumatic heart disease (RHD) secondary prophylaxis has been benzathine penicillin G [BPG; 1.2 MU (900 mg)] injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is...
PMC10720493
KEYWORDS
PMC10720493
INTRODUCTION
skin infections, throat, infections, ARF
ARF, AUTOIMMUNE RESPONSE, INFECTIONS, SKIN INFECTION, SECONDARY, ACUTE RHEUMATIC FEVER
Acute rheumatic fever (ARF) results from an abnormal autoimmune response to inadequately treated throat or skin infections with Group A Streptococcus (There is no specific treatment for ARF. However, the mainstay of current therapy, benzathine penicillin G (BPG), which is a long-acting formulation, is directed at preve...
PMC10720493
RESULTS
PMC10720493
Participants
Seventy-seven adults were screened for eligibility, and 24 eligible participants were recruited; four were females. The median (range) screening age and body mass index (BMI) were 26.9 (18.0–54.1) years and 25.1 (21.9–34.0) kg/mConsort diagram for trial participants.
PMC10720493
Study infusion
pain
Three participants did not receive the planned dose of BPG. The first two participants in cohort 1 received 3.1 MIU because ~1 mL infusate failed to progress through the flow control extension tubing, while one participant in cohort 3 received 8.2 MIU as the infusion after a period of cessation due to pain. All other p...
PMC10720493
Pain scores
NRS, pain
Reported numerical rating scale (NRS) pain scores ranged from 0 to 8 with the greatest intensity recorded during the infusion, but the median (range) pain scores were 2.5 (0–6), 3 (0–8), and 2.5 (0–6) for cohorts 1, 2, and 3, respectively. Moderate pain (NRS 4–7) was not experienced beyond 2 days, and no pain was repor...
PMC10720493
Modified Skindex-16 scores
Normalized overall Skindex-17 scores ranged from 0 to 61 with the highest scores reported in the first 2 days after infusion. Scores decreased thereafter with only four participants reporting scores beyond Day 14. The highest normalized domain (symptoms) score was 75 reported by a cohort 2 participant on Day 2. The nor...
PMC10720493
Adverse events
swelling, erythema, pain, infusion-site, tenderness/pain
ADVERSE EVENTS, ERYTHEMA, HYPERPIGMENTATION
There were 101 adverse events reported during the study with no serious adverse events (Table S5). All participants experienced some infusion-site reaction including erythema, swelling, tenderness/pain, and pigmentation ranging in duration from less than 1 day (pain) to 217 days (hyperpigmentation). There were two off-...
PMC10720493
Pharmacokinetic modeling
From the 24 individuals, there were 400 samples included in the PK analysis. The fraction of samples below the limit of quantification (LOQ) (BLQ) was low (11%), those measured between the LOQ and limit of detection (LOD), Visual inspection of the population data demonstrated a change in the terminal phase occurring af...
PMC10720493
DISCUSSION
hyperpigmentation, Hyperpigmentation, erythema, pain, PD, bruising, infusion-site, NRS
HYPERPIGMENTATION, HYPERPIGMENTATION, ERYTHEMA, RHD, HYPERMELANOSIS
Subcutaneous infusion of high-dose BPG (SCIP) is tolerable and safe. Despite all participants experiencing some degree of infusion-site reaction, they all resolved spontaneously with no serious adverse outcomes. While pain is a subjective experience, the maximum reported pain at injection was severe (NRS 8), requiring ...
PMC10720493
MATERIALS AND METHODS
PMC10720493
Study design
SECONDARY
We conducted a phase 1 open-label study using three cohorts with increasing doses of BPG, with the primary objective of assessing the safety and tolerability of SCIP. The secondary objectives were to characterize the PK, including the time above the current accepted pharmacological surrogate for protection against
PMC10720493
Participants
Twenty-four healthy participants were recruited into the study from eligible adults aged 18–65 years, without significant co-morbidities. Full eligibility/exclusion criteria are provided (Table S6). To explore the effect of body composition, 12 participants with an ideal BMI (20–24.9 kg/m
PMC10720493
Study intervention
ADVERSE EVENTS, RECRUITMENT, SKIN NECROSIS
Participants received a single SC infusion of 3.6 (2,700 mg, 9 mL), 7.2 (5,400 mg, 13.8 mL), or 10.8 MIU (8,100 mg, 20.7 mL) of BPG (Bicillin L-A, Pfizer, Sydney, Australia) delivered under ultrasound guidance. To achieve sustained plasma penicillin concentrations of 73% and 99% for a 3-month period above target concen...
PMC10720493
Study infusion
Prior to infusion, participants underwent an ultrasound examination (Acuson S3000 and Acuson 18L6 probe, Siemens Medical Solutions, Malvern, USA) to assess SC fat using a validated protocol (The prescribed BPG dose was transferred to a 30 mL syringe (JMS Co. Ltd, Hiroshima, Japan) and delivered into a single injection ...
PMC10720493
Pharmacokinetic samples
Pharmacokinetic samples consisted of serial dried blood spots and venous samples. DBSs were collected 2, 6, 12, 24, 48, and 72 hours pre-dose and 5, 7, 14, 21, 28, 42, 56, 70, 84, 98, and 112 days post-dose, and two venous blood samples were collected at 12 hours and 14 days post-dose. Three to five drops of mixed capi...
PMC10720493
Safety monitoring
NRS, pain
Safety and tolerability were assessed using the numerical rating scale for pain (The NRS with scores from 0 to 10 was used for its ease of application and validity in assessing acute and change in pain over time, with 0 and 10 representing “no pain” and “worst pain imaginable,” respectively. The minimally clinically im...
PMC10720493
Population pharmacokinetic analysis
LogThe principal structure of the pharmacokinetic modeling was based on our previous published population of PK models (Inter-individual variability as well as correlations between IIV terms was then evaluated for each parameter. The IIV was exponentially modeled for all parameters. Given the wide range of participant ...
PMC10720493
Simulations
Once a final population pharmacokinetic model was established, simulations were performed based on weight and BMI data from the CDC for 20-year-olds (Penicillin concentrations were determined every 6 hours for all simulations. Four-weekly doses of 1.2 MIU of BPG given IM at steady state (
PMC10720493
ACKNOWLEDGMENTS
INFECTIOUS DISEASES, STREP
We gratefully acknowledge the assistance of Elizabeth Eadie-Mirams, Renae Barr, Christine Everest, Rebecca Trowman, Jana Ilievski, David Pham, and Evelyn Carapetis in the planning, administration, and conduct of the study. We also acknowledge Lara Hatchuel, Nicola Norton, and the Linear Clinical Research team for their...
PMC10720493
SUPPLEMENTAL MATERIAL
The following material is available online at
PMC10720493
aac.00962-23-s0001.docx
Supplemental material.Click here for additional data file.ASM does not own the copyrights to Supplemental Material that may be linked to, or accessed through, an article. The authors have granted ASM a non-exclusive, world-wide license to publish the Supplemental Material files. Please contact the corresponding author ...
PMC10720493
REFERENCES
PMC10720493
1. Introduction
HS.Hidradenitis suppurativa, TNF-α, psoriasis
DISEASE, PATHOPHYSIOLOGY, PSORIASIS, SKIN CONDITION, ABSCESSES, HIDRADENITIS SUPPURATIVA, SCARRING, PATHOLOGY, PATHOGENESIS
Janus kinase (JAK)/signal transducer and activator of transcription signaling (STAT) has been implicated in the pathophysiology of hidradenitis suppurativa (HS). This study evaluated treatment-related transcriptomic and proteomic changes in patients with moderate-to-severe HS treated with the investigational oral JAK1-...
PMC10139090
2. Results
PMC10139090
2.1. Transcriptomics
Lesional skin punch biopsies from 12 sample pairs taken from the edge of an active HS lesion [In the pathway enrichment analysis, a number of inflammatory pathways were found to be enriched in the Week 8 DEGs from the 30 mg povorcitinib QD group (We previously reported on a 128-gene signature of HS [Treatment-related c...
PMC10139090
2.2. Proteomics
Based on paired comparisons and the significance cutoff, a total of 33 differentially expressed proteins (DEPs) of interest were selected (6 upregulated and 27 downregulated proteins), representing the union of statistically significant upregulated and downregulated proteins for each treatment at Weeks 4 and 8 (FDR < 0...
PMC10139090
3. Discussion
Hidradenitis suppurativa, tissue damage
HIDRADENITIS SUPPURATIVA, DISEASE, SCARRING
Hidradenitis suppurativa is a chronic, painful disease that can lead to permanent tissue damage and scarring, and it has a significant negative impact on quality of life [Treatment with povorcitinib QD over 8 weeks was associated with a dose-dependent modulation of several proteins of interest, some of which have been ...
PMC10139090
4. Materials and Methods
PMC10139090
4.1. Study Design and Patients
Clinical samples were collected from two phase 2 studies of patients with moderate-to-severe HS [Serum was collected from all participants at baseline and Weeks 4 and 8 for proteomic analysis. Availability of skin biopsy samples for transcriptomic analysis was limited to 12 sample pairs (15 mg povorcitinib once daily [...
PMC10139090
4.2. Transcriptomic Analyses
RNA sequencing was conducted on frozen samples at the Beijing Genomics Institute using the Illumina HiSeq 4000 system (Illumina, Inc., San Diego, CA, USA), and sequences were aligned by using the Human Genome B38 library (National Center for Biotechnology Information) and the Gencode.V29 gene model (Gencode Project, EM...
PMC10139090
4.3. Proteomic Analyses
BLOOD
Blood samples were obtained at baseline, Week 4, and Week 8 from multiple dose groups (15 mg povorcitinib QD,
PMC10139090
4.4. Statistical Analyses
For transcriptomic analyses, a paired
PMC10139090
5. Conclusions
DISEASE, PATHOLOGY
In conclusion, based on findings observed in skin biopsies and blood of patients with moderate-to-severe HS, 8 weeks of treatment with the JAK1 inhibitor povorcitinib was associated with the reversal of a previously identified HS transcriptomic signature, as well as dose-dependent changes in a number of circulating pro...
PMC10139090
Supplementary Materials
The following supporting information can be downloaded at: Click here for additional data file.
PMC10139090
Author Contributions
Conceptualization: H.L., L.L.S. and S.H.S.; Data curation: H.L., L.L.S. and S.H.S.; Formal analysis: H.L., L.L.S. and S.H.S.; Resources: H.L., L.L.S. and S.H.S.; Software: H.L.; Visualization: H.L., L.L.S. and S.H.S.; Writing—reviewing & editing: H.L., L.L.S. and S.H.S. All authors have read and agreed to the published...
PMC10139090
Institutional Review Board Statement
Ethikkommission der Universität zu Lübeck, Ethik-Kommission der Medizinischen
The clinical studies were conducted in accordance with the Declaration of Helsinki and approved by the institutional review board (IRB) or institutional ethics committee (IEC) at each participating site (United States and Canada central IRB/IEC: Advarra; United States local IRBs/IECs: Penn State College of Medicine IRB...
PMC10139090
Informed Consent Statement
All patients provided written informed consent.
PMC10139090
Data Availability Statement
Access to individual patient-level data is not available for this study. Information on Incyte’s clinical trial data sharing policy and instructions for submitting clinical trial data requests are available at:
PMC10139090
Conflicts of Interest
H.L., L.L.S. and S.H.S. are employees and shareholders of Incyte Research Institute/Incyte Corporation. Incyte was involved in the design of the study; the collection, analysis, and interpretation of data; and in writing the manuscript.
PMC10139090
Methods
MINOR
We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (
PMC10645316
Results
muscle mass
Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (m...
PMC10645316
Conclusion
These data suggest that polymorphic variation in the
PMC10645316
Data Availability
The data are provided in the attached Excel file.
PMC10645316
Introduction
muscle mass, sarcopenia, Sarcopenia, sarcopenic
SARCOPENIA, ATROPHIC, SARCOPENIA
The maintenance of a healthy muscle mass is important in giving individuals the strength to perform the tasks of daily living. Muscle protein is continually turned over such that muscle mass is maintained by balancing the rates of protein synthesis and degradation within relatively tight windows [Sarcopenia, is defined...
PMC10645316
Materials and methods
PMC10645316
Participants and physiological analysis
sarcopenia
SARCOPENIA
Participants aged 70 years and over with sarcopenia, according to the EWGSOP definition (2010) [
PMC10645316
DNA analysis
Whole blood samples were taken at the first study visit and frozen. DNA was extracted from the first 110 whole blood samples received using the QIAamp DNA blood mini kit according to the manufacturer’s instructions. This set of samples were the first batches received from the various trial sites by the laboratory, and ...
PMC10645316
Statistical analysis
All of the data used in this analysis is available in Whether the alleles were in Hardy-Weinberg equilibrium was determined by Chi squared test using allele frequencies published for the European Caucasian population (rs10783486, MAF = 0.26 and rs2854464, MAF = 0.26) [The threshold for statistical significance (alpha) ...
PMC10645316
GTEX data
NINDS
The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the GTEx analyses described in this manuscript were obtained from: the GTEx Portal (
PMC10645316
Results
The demographics of participants included in this analysis are given in
PMC10645316
Baseline demographics of the study population.
CONTRACTION
BMI: body mass index, cv: coefficient of variation, SARC-F: Strength, assistance with walking, rising from a chair, climbing stairs, and falls questionnaire score, SPPB: Short Physical Performance Battery score: QMVC: Quadriceps Maximal Voluntary contraction. For normally distributed data values are given as mean ± SD ...
PMC10645316
rs10783486
muscle mass
Given population differences in body composition and strength between males and females, the sexes were analysed separately. There were no associations of genotype with strength, total body muscle mass (quantified by bioimpedance) or limb muscle mass (quantified by DXA) in either sex (
PMC10645316
Associations of rs10783846 with height and limb fat mass in individuals in the LACE study.
MINOR
Height and limb fat were compared in males and females possessing the minor allele for rs10783846 with those homozygous for the major allele. Median height (A, p = 0.023), arm fat mass (B, p = 0.008) and leg fat mass (C, p = 0.046) were higher in males with the minor allele than their counterparts homozygous for the ma...
PMC10645316
Effect of the minor allele of rs10783846 on body composition and strength in females and males at baseline.
CONTRACTION
BMI: body mass index, SARC-F: Strength, assistance with walking, rising from a chair, climbing stairs, and falls questionnaire score, SPPB: Short Physical Performance Battery score: QMVC: Quadriceps Maximal Voluntary contraction. For normally distributed data values are given as mean ± SD and for data that did not show...
PMC10645316
Association of height with limb fat mass in individuals in the LACE study.
Height was compared with limb fat mass in males and females from the LACE study. In males there was a weak association of leg fat mass with height (r = 0.31, p = 0.025) but not in females. Arm fat mass was not associated with height in males or females.
PMC10645316
Association of height with limb muscle mass in individuals in the LACE study.
muscle mass
Height was compared with limb muscle mass in males and females from the LACE study. In both males (r = 0.57 p<0.001) and females (r = 0.61, p<0.001) there was a strong association of leg muscle mass with height. Arm muscle mass was also associated with height in both males (r = 0.51, p<0.001) and females (r = 0.52, p<0...
PMC10645316
Arm and leg fat mass in LACE males adjusted for height.
Limb fat mass was log
PMC10645316
rs2854464
muscle mass or limb muscle mass
Analysis of the rs2854464 allele showed a similar pattern to that described for rs10783486 both with no associations with total muscle mass or limb muscle mass (
PMC10645316
Associations of rs2854464 with height and limb fat mass in males and females in the LACE study.
MINOR
Height and limb fat were compared in males and females possessing the minor allele for rs2854464 with those homozygous for the major allele. Median height (A, p = 0.023), arm fat mass (B, p = 0.008) and leg fat mass (C, p = 0.046) were higher in males with the minor allele than their counterparts homozygous for the maj...
PMC10645316
Effect of the minor allele of rs2854464 on body composition and strength in females and males at baseline.
CONTRACTION
BMI: body mass index, SARC-F: Strength, assistance with walking, rising from a chair, climbing stairs, and falls questionnaire score, SPPB: Short Physical Performance Battery score: QMVC: Quadriceps Maximal Voluntary contraction. For normally distributed data values are given as mean ± SD and for data that did not show...
PMC10645316
Expression of different alleles in skeletal muscle
MINOR
Previous data have suggested that the rs2854464 polymorphism is located in a miR-24 binding site and that the major A allele has greater affinity for miR-24 leading to a reduction in ACVR1B mRNA. If this hypothesis was correct, it might be expected that there would be differential expression of the two ACVR1B alleles w...
PMC10645316
Discussion
PROLIFERATION, GIANT, MINOR
These data show that males in the LACE cohort with at least one minor allele for either rs10783486 or rs2854464 were taller than those homozygous for the major allele and had more arm fat but we did not see any associations of these alleles with body composition in females. Previous studies have shown that polymorphism...
PMC10645316
Limitations of the study
muscle mass, sarcopenia, appendicular muscle mass
RECRUITMENT, SARCOPENIA
This analysis is limited by the size of the study populations and by the lack of a control group of individuals of similar age who did not have sarcopenia. Both these limitations arise from the samples coming from the LACE clinical trial. Firstly, the trial was placebo-controlled trial within the sarcopenia population,...
PMC10645316
Conclusions
muscle mass, obesity, sarcopenic, sarcopenia, sarcopenic obesity
OBESITY, OBESE, SARCOPENIA
Our data suggest that polymorphisms in the activin I B receptor locus are associated with height and limb fat mass rather than muscle mass and strength in older men with sarcopenia. These findings are potentially of clinical significance; interventions that target the activin/myostatin pathway could potentially exert b...
PMC10645316
Supporting information
PMC10645316
All data used.
(XLSX)Click here for additional data file.
PMC10645316
SPSS statistics output from ANCOV analysis.
(XLSX)Click here for additional data file.
PMC10645316
Genotype frequencies in sarcopenia.
(DOCX)Click here for additional data file.
PMC10645316
Associations of rs10783846 with limb muscle mass in individuals in the LACE study.
MINOR
Arm and leg muscle masses were compared in males and females possessing the minor allele for rs10783846 with those homozygous for the major allele. Median arm muscle mass and leg muscle mass did not differ based on possession of the minor allele of rs10783846 in either gender.(TIF)Click here for additional data file.
PMC10645316
Associations of rs2854464 with limb muscle mass in individuals in the LACE study.
MINOR
Arm and leg muscle masses were compared in males and females possessing the minor allele for rs2854464 with those homozygous for the major allele. Median arm muscle mass and leg muscle mass did not differ based on possession of the minor allele of rs2854464in either gender.(TIF)Click here for additional data file.
PMC10645316
Association of polymorphisms in the ACVR1B locus with height and arm fat in the UK biobank study.
The UK biobank data set ((TIF)Click here for additional data file.
PMC10645316
eQTL analysis of rs2854464 and rs10783846 in skeletal muscle.
MINOR
The GTEx data set was analysed to determine whether either polymorphism showed differential expression. In skeletal muscle both minor alleles of rs2854464 and rs10783846 were more highly expressed than the major alleles. The data are shown in violin plot form taken from the GTEx portal.(TIF)Click here for additional da...
PMC10645316
Tissue eQTL analysis of rs2854464.
The GTEx data set was analysed for eQTL associations with rs2854464. The strongest effects of the polymorphism on expression were observed in the lung and in skeletal muscle.(TIF)Click here for additional data file.
PMC10645316
STROBE statement—Checklist of items that should be included in reports of observational studies.
(DOCX)Click here for additional data file.(DOCX)Click here for additional data file.AAS, TA, and MDW acknowledge support from the NIHR Newcastle Biomedical Research Centre. AA acknowledges support from the Health Services Research Unit, which is core funded by the Chief Scientist Office of the Scottish Government Healt...
PMC10645316
References
PMC10645316
Subject terms
knee osteoarthritis, human abuse, KOA
CHRONIC PAIN, KNEE OSTEOARTHRITIS
The potential synergistic effects of combining cannabinoids and opioids for analgesia has received considerable attention. No studies to date have evaluated this combination in patients with chronic pain. The present study aimed to evaluate the combined analgesic and drug effects of oral opioid (hydromorphone) and delt...
PMC10516978
Introduction
chronic pain, pain
ADVERSE EVENTS, ADVERSE EFFECTS, CHRONIC PAIN, DRUG EFFECT
The potential synergistic effects of combining cannabinoids and opioids for analgesia have drawn significant attention following preclinical evidence that cannabinoids and opioid combinations have additive nociceptive benefit with limited adverse effects [Evidence for the cannabinoid-opioid synergistic effects in human...
PMC10516978
Materials and methods
PMC10516978
Participants
KOA
Individuals with KOA were recruited between 11/2017 and 12/2020 using locally posted and online flyers and print/radio advertisements. A CONSORT flow diagram is depicted in Fig. 
PMC10516978
Study consort diagram.
A/E
ADVERSE EVENT
A/E adverse event.
PMC10516978
Study design and procedure
This Phase II study used a randomized, double-blind, placebo-controlled, within-subject study design. Potential participants completed a phone and in-person screening, during which they provided a urine sample that was tested for recent drug exposure and pregnancy (for premenopausal females) and were excluded if they r...
PMC10516978
Experimental study sessions
Eligible participants completed four experimental study sessions scheduled ≥7 days apart. All sessions started around 0800. Participants were asked to refrain from over-the-counter medications on session days and maintain steady doses of prescribed and non-contraindicated medications throughout participation. After pro...
PMC10516978
Measures
PMC10516978