Median Oxycodone Research Articles

Post-mortem oxycodone blood concentrations of hospitalized cancer and surgery patients compared with fatal poisonings

Oxycodone is a strong opioid drug commonly used to treat acute, cancer, and chronic non-malignant pain. In this study, all oxycodone-related medico-legal cases where death had occurred in a hospital or nursing home in Finland were investigated to determine the range of post-mortem (PM) oxycodone blood concentrations in a therapeutic setting. All toxicology cases in which oxycodone was detected in PM femoral blood during the 4-year period of 2016–2019 in Finland were retrieved from the national PM toxicology database. In this material, the 365 deceased hospital patient cases that met the study inclusion criteria were divided into four groups according to the cause and manner of death. The reference group of 121 fatal oxycodone poisoning cases comprised two groups: those with verified associated drug abuse and those without drug abuse. The median oxycodone concentration in PM blood was significantly higher in cancer patients (0.10 mg/L) than in patients with recent surgery (0.07 mg/L) or other disease (0.06 mg/L) (p < 0.05). In addition, the median oxycodone concentration was significantly lower in all hospital patient groups than in the poisoning groups, the latter displaying 0.38 mg/L (abuse) and 0.64 mg/L (no abuse) (p < 0.001). This study shows that half of the subjects in the cancer patient group had PM blood oxycodone concentrations above the typical clinical therapeutic plasma concentration range (0.005–0.10 mg/L). Appropriate medication of hospitalized surgery and cancer patients can result in concentrations of up to 0.2 and 0.6 mg/L, respectively, while higher concentrations are exceptional.

Postoperative pain in a prospectively assessed surgical short-stay cohort: A subgroup analysis.

There is sparse information about postoperative pain after short stay surgery. We explored the incidence of immediate postoperative pain and its relationship with persistent pain or opioid use 2 weeks after surgery. This was a subgroup analysis of prospective and controlled data from adult patients (n=931) who underwent short-stay surgery in a tertiary care hospital. Data comprised patient demographics, surgical category, pain scores and analgesic management during the recovery unit stay, before discharge on the postoperative morning after surgery and again 2 weeks after surgery. Half of the patients had severe dynamic pain in the recovery unit. It was commonest after orthopaedic (70% of patients), followed by gynaecological (54%), gastrointestinal (51%) and spine surgery (49%). Multimodal pain management was used for most patients (n=811, 87%) with opioid use predominant. The median oxycodone dose during short-stay was the highest after orthopaedic surgery (39 mg). The first individual dynamic pain score after surgery was associated with follow-up pain score at rest (OR=1.37), dynamic pain (OR=1.35) and pain interference (OR=1.34) at 2 weeks after surgery. Maximum dynamic pain reported in the recovery unit was associated with pain at rest (OR=1.56), dynamic pain (OR=1.65) and pain interference (OR=1.45) at 2 weeks after surgery. Pain scores at 2 weeks were highest and analgesic use greatest in those patients who underwent spinal surgery. Intense postoperative pain remains common after short-stay surgery in some surgical categories including orthopaedic surgery and is associated with a greater likelihood of pain at 2 weeks.

Brace versus cast following surgical treatment of distal radial fracture: a prospective randomised study comparing quality of recovery

Background:Immobilisation following surgical treatment of distal radial fractures (DRF) is traditionally performed with a dorsal cast splint. There is an interest in changing the rigid cast to a removable brace. This can reduce the risk for cast-corrections, complications and improve recovery of function. The aim of the study was to compare quality of recovery (QoR) between brace and traditional cast for immobilisation during the first postoperative week. Methods:60 patients with American Society of Anesthesiologists (ASA) physical status 1-3, scheduled for surgical treatment of DRF under a supraclavicular block (SCB) in a day-surgery setting were randomised into two groups of immobilisation post-surgery; brace (n=30) versus traditional cast (n=30). Study objectives were: differences in self-assessed QoR using the QoR-15 questionnaire, postoperative oral oxycodone consumption, perioperative time events and unplanned healthcare contacts one week postoperatively. Results:54 patients, 46 females/eight males were included in the analysis; 27 with brace and 27 with traditional cast. QoR-15 median scores improved significantly from baseline/preoperative to day 7 (brace p=0.001, cast p=0.001) with no differences between the two groups. The only difference found was that patients in the brace group had significantly worse pain score 24-hours post-surgery (p=0.022). No significant differences were seen in total median oxycodone consumption the first three postoperative days. No differences were found in perioperative events or unplanned healthcare contacts. Conclusions:Brace appears to be a feasible option to traditional cast for immobilisation following surgical treatment of DRF. The early QoR was similar in both groups apart from more pain in the brace group the first 24 postoperative hours.

Brace versus cast following surgical treatment of distal radial fracture: a prospective randomised study comparing quality of recovery

Background: Immobilisation following surgical treatment of distal radial fractures (DRF) is traditionally performed with a dorsal cast splint. There is an interest in changing the rigid cast to a removable brace. This can reduce the risk for cast-corrections, complications and improve recovery of function. The aim of the study was to compare quality of recovery (QoR) between brace and traditional cast for immobilisation during the first postoperative week. Methods: 60 patients with American Society of Anesthesiologists (ASA) physical status 1–3, scheduled for surgical treatment of DRF under a supraclavicular block (SCB) in a day-surgery setting were randomised into two groups of immobilisation post-surgery; brace (n=30) versus traditional cast (n=30). Study objectives were: differences in self-assessed QoR using the QoR-15 questionnaire, postoperative oral oxycodone consumption, perioperative time events and unplanned healthcare contacts one week postoperatively. Results: 54 patients, 46 females/eight males were included in the analysis; 27 with brace and 27 with traditional cast. QoR-15 median scores improved significantly from baseline/preoperative to day 7 (brace p=0.001, cast p=0.001) with no differences between the two groups. The only difference found was that patients in the brace group had significantly worse pain score 24-hours post-surgery (p=0.022). No significant differences were seen in total median oxycodone consumption the first three postoperative days. No differences were found in perioperative events or unplanned healthcare contacts. Conclusions: Brace appears to be a feasible option to traditional cast for immobilisation following surgical treatment of DRF. The early QoR was similar in both groups apart from more pain in the brace group the first 24 postoperative hours.

Brace versus cast following surgical treatment of distal radial fracture: a prospective randomised study comparing quality of recovery.

Background:Immobilisation following surgical treatment of distal radial fractures (DRF) is traditionally performed with a dorsal cast splint. There is an interest in changing the rigid cast to a removable brace. This can reduce the risk for cast-corrections, complications and improve recovery of function. The aim of the study was to compare quality of recovery (QoR) between brace and traditional cast for immobilisation during the first postoperative week. Methods:60 patients with American Society of Anesthesiologists (ASA) physical status 1-3, scheduled for surgical treatment of DRF under a supraclavicular block (SCB) in a day-surgery setting were randomised into two groups of immobilisation post-surgery; brace (n=30) versus traditional cast (n=30). Study objectives were: differences in self-assessed QoR using the QoR-15 questionnaire, postoperative oral oxycodone consumption, perioperative time events and unplanned healthcare contacts one week postoperatively. Results:54 patients, 46 females/eight males were included in the analysis; 27 with brace and 27 with traditional cast. QoR-15 sum median scores improved significantly from baseline/preoperative to day 7 (brace p=0.001, cast p=0.001) with no differences between the two groups. The only difference found was that patients in the brace group had significantly worse pain score 24-hours post-surgery (p=0.022). No significant differences were seen in sum median oxycodone consumption the first three postoperative days. No differences were found in perioperative events or unplanned healthcare contacts. Conclusions:Brace appears to be a feasible option to traditional cast for immobilisation following surgical treatment of DRF. The early QoR was similar in both groups apart from more pain in the brace group the first 24 postoperative hours.

Introduction of a modified analgesic ladder in the emergency depart-ment: Effect on oxycodone use for back pain.

The aim of this study was to assess the introduction of an analgesic ladder and targeted education on oxycodone use for patients presenting to the emergency department (ED). A retrospective pre-post implementation study was conducted. Data were extracted for patients presenting from June to July 2016 (preintervention) and June to July 2017 (post-intervention). The EDs of a major metropolitan health service and an affiliated community-based hospital. Patients with back pain where nonpharmacological interventions such as mobilization and physiotherapy are recommended as the mainstay of treatment. A modified analgesic ladder introduced in May 2017. The ladder promoted the use of simple analgesics such as paracetamol and nonsteroidal anti-inflammatory drug (NSAIDs) prior to opioids and tramadol in preference to oxycodone in selected patients. The proportion of patients prescribed oxycodone and total doses administered. There were 107 patients pre and 107 post-intervention included in this study. After implementation of the analgesic ladder, 78 (72.9 percent) preintervention patients and 55 (51.4 percent) post-intervention patients received oxycodone in ED (p = 0.001). The median oxycodone doses administered in the ED was 14 mg (interquartile range: 5-20 mg) and 5 mg (interquartile range: 5-10 mg; p < 0.001), respectively. On discharge from hospital, a prescription for oxycodone was issued for 36 (33.6 percent) patients preintervention and 26 (24.3 percent) patients post-intervention (p = 0.13). Among patients with back pain, implementation of a modified analgesic ladder was associated with a statistically significant but modest reduction in oxycodone prescription. Consideration of multifaceted interventions to produce major and sustained changes in opioid prescribing is required.

Do Socioeconomic Disparities Exist in Postoperative Opioid Prescription and Consumption?

Since 1999, >200 000 people in the United States have died from a prescription opioid overdose. Lower socioeconomic status (SES) is one important risk factor. This study investigates socioeconomic disparities in postoperative opioid prescription and consumption. September 2018-April 2019, 128 patients were surveyed postoperatively regarding opioid consumption. The neighborhood disadvantage was calculated using area deprivation index (ADI). The top 3 quartiles were "high SES" and the bottom quartile "low SES." The study population included 96 high SES patients, median ADI 6 (2-12.3) and 32 low SES, median ADI 94.5 (81.3-97.3). For both, median Oxycodone 5 mg prescribed was 20 pills. 29.2% of high SES consumed 0 pills, 40.6% consumed 1-9 pills, and 27.1% consumed 10+ pills. 25.0% of low SES consumed 0 pills, 46.9% consumed 1-9 pills, and 18.8% consumed 10+ pills. No significant difference in opioid prescription (P = .792) or consumption (P = .508) between SES groups. Patients of all SES are prescribed and consumed opioids in similar patterns with no significant difference in postoperative pain following ambulatory surgery.

Self-Reported Non-Steroidal Anti-Inflammatory Drug Allergy and Postpartum Pain Management [36M

INTRODUCTION: Patients with a self-reported NSAID allergy (SRNA) are limited in the medications available to treat postpartum pain. Our objective was to determine the frequency of SRNA, how it affects the medications administered for inpatient postpartum analgesia, and whether it is associated with obstetrical outcomes. METHODS: Retrospective cohort study of singleton deliveries at ≥37 weeks of gestation at a tertiary university hospital from 2013-2016. Patients were excluded for self-reported opioid allergies, drug abuse history, positive urine toxicology, general anesthesia for delivery, and incomplete records. The primary outcomes evaluated were the postpartum pain medications received, including the total amount in milligrams. Demographic and clinical characteristics were reviewed to identify any associations with SRNA. RESULTS: A total of 20,920 deliveries were included: 235 with SRNA and 20,685 without SRNA. SRNA was documented in 1.12% of the study population. After cesarean delivery, median oxycodone use was 19.4 (IQR 6.6-36.7) and 15.4 (IQR 2.6-28.6) mg/day among women with and without SRNA, respectively (P&lt;.04). After vaginal delivery, median oxycodone use was 10.4 (IQR 0-32.9) and 0 (IQR 0-17.9) mg/day among women with and without SRNA, respectively (P&lt;.001). Acetaminophen use (P&lt;.0001) and total postpartum days (P&lt;.05) were also increased in women with SRNA compared to women without SRNA. No demographic or clinical factors differed between groups. CONCLUSION: SRNA is documented in approximately 1% of obstetrical patients and affects the medications administered for inpatient postpartum analgesia; both oxycodone and acetaminophen use are increased among SRNA patients, regardless of mode of delivery.

Oxycodone for pain management in the latent phase of labour - A pragmatic trial.

Parenteral opioids are used for pain relief in labour but there are little data for oxycodone in this context. The aim of this study was to evaluate the efficacy, foetal exposure and safety of subcutaneous oxycodone in the latent phase of labour. This pragmatic trial included 76 parturients, who received subcutaneous oxycodone for pain relief in the latent phase of labour according to the hospital protocol: an initial dose 0.1mg/kg, and a second dose, 0.05mg/kg, could be administered four hours later. Pain intensity and pain relief were assessed using a numerical rating scale of 0-10. After delivery, blood samples from the maternal and umbilical veins were collected, and plasma concentrations of oxycodone and its main metabolites were quantified using UPLC-MS/MS. The Apgar scores and maternal and neonatal adverse effects were recorded. The foetal exposure at birth was low, the median oxycodone and oxymorphone umbilical vein plasma concentrations were 1.2ng/mL (range 0.21-7.8) and 0.14ng/mL (0-0.26), respectively. Pain scores decreased substantially, from a median pain score of 7/10 before oxycodone to median scores of 5/10 at 30minutes after administration, 5/10 at 60minutes and 6/10 at 120minutes. The median Apgar score was 9 (range 2-10) at 1minute and 9 (6-10) at 5minutes. Maternal adverse effects were mild, and there were no oxycodone-related neonatal adverse effects. Subcutaneous oxycodone provided effective analgesia during the latent phase of labour. Newborn exposure at birth was low, and oxycodone was well-tolerated.

Continuous surgical multi-level extrapleural block for video-assisted thoracoscopic surgery: a retrospective study assessing its efficacy as pain relief following lobectomy and wedge resection

Background: Video-assisted thoracoscopic surgery (VATS) causes less postoperative pain than thoracotomy; however, adequate analgesia remains vital. As part of a multi-modal postoperative analgesia, a continuous surgeon-placed extrapleural block catheter is an option. The aim of this retrospective study was to evaluate the analgesic efficacy of a continuous extrapleural block as part of a multimodal analgesic regimen after VATS in general, and VATS lobectomy and wedge resection in particular. Methods: Case records for patients having undergone VATS surgery and been provided a multi-level continuous extrapleural block with an elastomeric pump infusing levobupivacaine 2.7 mg/ml at a rate of 5 ml/h during 2015 and 2016 were reviewed. Pain (Numeric Rating Scale) at rest and mobilisation as well as opioid requirement (daily, postoperative days 0-3, as well as accumulated) were analysed. Results: In all, 454 records were reviewed: 150 wedge resections, 264 lobectomies and 40 miscellaneous cases. At rest, pain was mild median NRS rated 3-3-1-1 for postoperative day (POD) 0 to 3, during movement, pain was rated moderate during POD 0 and 1 and mild the remaining days (median NRS 4-4-3-3 for POD 0-3). The proportion of patients exhibiting mild pain at rest increased from 55% on POD 0 to 81 % on POD 3. The percentage of patients experiencing severe pain at rest decreased from 15% to 6%. Median oxycodone consumption was 10 mg per day for POD 1-3. Pain after VATS wedge resection was significantly lower at POD 1 and 3 compared to pain after VATS lobectomy. Conclusion: We found a continuous surgeon-placed extrapleural catheter block to be a valuable and seemingly safe addition to our multimodal procedure specific analgesia after VATS. Whether the efficacy of the block can be improved by increasing local anaesthetic and/or adding adjuncts warrants further investigation.

Continuous surgical multi-level extrapleural block for video-assisted thoracoscopic surgery: a retrospective study assessing its efficacy as pain relief following lobectomy and wedge resection.

Background: Video-assisted thoracoscopic surgery (VATS) causes less postoperative pain than thoracotomy; however, adequate analgesia remains vital. As part of a multi-modal postoperative analgesia, a continuous surgeon-placed extrapleural block catheter is an option. The aim of this retrospective study was to evaluate the analgesic efficacy of a continuous extrapleural block as part of a multimodal analgesic regimen after VATS in general, and VATS lobectomy and wedge resection in particular. Methods: Case records for patients having undergone VATS surgery and been provided a multi-level continuous extrapleural block with an elastomeric pump infusing levobupivacaine 2.7 mg/ml at a rate of 5 ml/h during 2015 and 2016 were reviewed. Pain (Numeric Rating Scale) at rest and mobilisation as well as opioid requirement (daily, postoperative days 0-3, as well as accumulated) were analysed. Results: In all, 454 records were reviewed: 150 wedge resections, 264 lobectomies and 40 miscellaneous cases. At rest, pain was mild median NRS rated 3-3-1-1 for postoperative day (POD) 0 to 3, during movement, pain was rated moderate during POD 0 and 1 and mild the remaining days (median NRS 4-4-3-3 for POD 0-3). The proportion of patients exhibiting mild pain at rest increased from 55% on POD 0 to 81 % on POD 3. The percentage of patients experiencing severe pain at rest decreased from 15% to 6%. Median oxycodone consumption was 10 mg per day for POD 1-3. Pain after VATS wedge resection was significantly lower at POD 1 and 3 compared to pain after VATS lobectomy. Conclusion: We found a continuous surgeon-placed extrapleural catheter block to be a valuable and seemingly safe addition to our multimodal procedure specific analgesia after VATS. Whether the efficacy of the block can be improved by increasing local anaesthetic and/or adding adjuncts warrants further investigation.

Correlation of Subjective Effects with Systemic Opioid Exposure from Fixed-Dose Combinations of Oxycodone/Acetaminophen in Recreational Users of Prescription Drugs.

To correlate abuse-related pharmacodynamic measures and pharmacokinetic measures after administering immediate-release/extended-release and immediate-release oxycodone/acetaminophen fixed-dose combination analgesicsDesign. Randomized, double-blind, active- and placebo-controlled, 7-way crossover studySetting. Contract research organizationSubjects. Nondependent recreational users of prescription opioids. Participants received single doses of intact immediate-release/extended-release and immediate-release oxycodone/acetaminophen 15/650 mg, intact immediate-release/extended-release and immediate-release oxycodone/acetaminophen 30/1,300 mg, crushed immediate-release/extended-release and immediate-release oxycodone/acetaminophen 30/1,300 mg, and placebo. Measures of pharmacodynamics (pupillometry, drug liking, drug high, good drug effects) and pharmacokinetics were assessed predose and up to 24 hours postdose, and correlations between pharmacokinetic parameters and pharmacodynamic data were explored. Of 61 participants, 55 completed all 7 treatments. Intact immediate-release/extended-release oxycodone/acetaminophen produced 50% lower oxycodone peak plasma concentration (Cmax) than immediate-release oxycodone/acetaminophen. Median oxycodone time to Cmax (tmax) was significantly longer (P<0.001) for intact immediate-release/extended-release oxycodone/acetaminophen than immediate-release oxycodone/acetaminophen. The pharmacokinetics of crushed immediate-release/extended-release and immediate-release oxycodone/acetaminophen (30/1,300 mg) followed a similar pattern. Crushing did not shorten the median oxycodone tmax for immediate-release/extended-release oxycodone/acetaminophen (30/1,300 mg). Strong correlations were observed between oxycodone Cmax and area under the curve from time 0 to time x peak effects and area under the subjective effect curve from time 0 to time x for all subjective effects (R2=0.711-0.997). Immediate-release/extended-release oxycodone/acetaminophen produced lower oxycodone Cmax and longer tmax than immediate-release oxycodone/acetaminophen. Lower oxycodone concentrations, particularly at earlier time points, were strongly correlated with lesser positive subjective drug effects.

Relative Bioavailability Study of an Abuse-Deterrent Formulation of Extended-Release Oxycodone with Sequestered Naltrexone (ALO-02) Versus Immediate-Release Oxycodone Tablets in Healthy Volunteers

Background: ALO-02, an opioid formulation intended to deter abuse, comprising capsules filled with pellets of extended-release oxycodone hydrochloride, an opioid, surrounding sequestered naltrexone hydrochloride, an opioid antagonist. This study compared oxycodone pharmacokinetics following ALO-02 (oxycodone/naltrexone 40 mg/4.8 mg) versus immediate-release oxycodone (IRO) tablets (20 mg). Methods: This was an institutional review board–approved, open-label, single-dose, randomized, two-way crossover study in 14 healthy fasted adults (aged 18 to 55 years). Plasma concentrations of oxycodone, naltrexone, and 6-β-naltrexol were determined. Maximum plasma concentration (Cmax), area under the plasma concentrationtime profile from time 0 to infinity (AUCinf) and to the last quantifiable concentration (AUClast), time to Cmax (Tmax), and terminal half-life (t1/2) were determined. Adverse events (AEs) were recorded throughout the study. Results: Median oxycodone Tmax was prolonged (12 versus 1 hours) and mean t1/2 was longer (7.2 versus 4.6 hours) for ALO-02 versus IRO. ALO-02/IRO ratio (90% confidence interval [CI]) of adjusted geometric means for dose-normalized AUCinf was 107.2% (96.7%, 118.8%), with CI contained within equivalence limits of 80%–125%. Dose-normalized ALO-02/IRO Cmax ratio (90% CI) was 33.0% (28.8%, 37.9%). Following ALO-02 administration, plasma naltrexone concentrations were below the limit of quantification (BLQ; 4.00 pg/mL), and 6-β-naltrexol concentrations were BLQ (4.00 pg/mL) in >50% of participants or generally low (<50.0 pg/mL). Most AEs were mild, with nausea and dizziness being most frequent. Conclusion: Pharmacokinetic comparisons indicate equivalent oxycodone bioavailability under fasted conditions. The lower Cmax and longer Tmax and t1/2 observed for ALO-02 versus IRO are consistent with the extended-release profile of ALO-02 formulation. Low naltrexone and 6-β-naltrexol concentrations indicated successful sequestration of naltrexone in ALO-02.

Central nervous system penetration of oxycodone after intravenous and epidural administration

BackgroundDespite being increasingly used for pain management, only two studies, with controversial results, have evaluated the epidural use of oxycodone. MethodsTwenty-four women, aged 26–64 yr, undergoing elective gynaecological surgery were enrolled in this randomized, double-blinded, parallel group study. The subjects were administered either i.v. oxycodone and epidural placebo (IV group; n=12) or epidural oxycodone and i.v. placebo (EPI group; n=12) after operation. Oxycodone was administered as a single dose of 0.1 mg kg−1. An epidural catheter for drug administration was placed at T12/L1 and a spinal catheter for cerebrospinal fluid (CSF) sampling at L3/4. Plasma and CSF were frequently collected for the analysis of oxycodone and its major metabolites. The primary outcomes were the peak concentration (Cmax), time to peak concentration (Tmax), and the exposure (AUClast) of oxycodone in CSF and plasma. The secondary outcome was the analgesic efficacy, measured as the total dose of rescue fentanyl during the first four postoperative hours. ResultsIn the EPI group, the median oxycodone Cmax and AUClast in the CSF were 320- and 120-fold higher, respectively, compared with the IV group. The total dose of rescue fentanyl was significantly lower in the EPI group (seven subjects needed 16 doses) than in the IV group [12 subjects needed 71 doses (P=0.001)]. No serious or unexpected adverse events were reported. ConclusionsEpidural oxycodone provides much higher CSF concentrations and possibly better analgesic efficacy than does i.v. oxycodone. Clinical trial registrationEudraCT reference number: 2011-000125-76.

Remifentanil Infusion Does Not Induce Opioid Tolerance After Cardiac Surgery

Remifentanil is being used increasingly during fast-track cardiac surgery. Postoperative hyperalgesia and opioid tolerance have been reported in volunteer studies and in patients after major abdominal surgery with remifentanil infusion. In the present study, the authors evaluated whether high-dose remifentanil infusion induces opioid tolerance in 90 patients undergoing coronary artery bypass surgery with sternotomy. Prospective, randomized, and double-blind study. Single-institution, tertiary level, university hospital. Ninety patients undergoing coronary artery bypass surgery. Patients were randomized to receive a 3-hour infusion of remifentanil (0.3 microg/kg/min, n = 45) or placebo (n = 45) intraoperatively as adjunct to a standardized sufentanil/propofol-based general anesthesia. Opioid consumption, pain, and sedation scores, as well as adverse events and patients' satisfaction with pain therapy, were recorded for 48 postoperative hours. There were no differences in postoperative opioid consumption between the groups (median oxycodone consumption in the remifentanil group, 98 mg [range, 29-166] and in the placebo group, 99 mg [42-219]). Pain scores were comparable at rest, but during a deep breath pain scores were lower in the remifentanil group (p = 0.020). Sedation scores, satisfaction with analgesia, and adverse events were similar between the 2 groups. The most common adverse event was nausea, with a 33% incidence in the placebo and 40% incidence in the remifentanil group. Three-hour remifentanil infusion did not increase postoperative pain or opioid consumption in cardiac surgery patients. The present results suggest that high-dose remifentanil does not elicit opioid tolerance when given during cardiac surgery.