scholarly journals Naltrexone Treatment for Prolonged Grief Disorder: Study Protocol for a Randomized, Triple-Blinded, Placebo-Controlled Trial

2020 ◽  
Author(s):  
James Gang ◽  
James Kocsis ◽  
Jonathan Avery ◽  
Paul Maciejewski ◽  
Holly Prigerson
Keyword(s):  
Symptom Severity ◽  
Pharmacological Treatment ◽  
Controlled Trial ◽  
Prolonged Grief Disorder ◽  
Prolonged Grief ◽  
Increased Risk ◽  
Oral Naltrexone ◽  
Naltrexone Treatment ◽  
Reward Pathway

Abstract BACKGROUNDThere is a lack of effective pharmacotherapy for prolonged grief disorder (PGD). Evidence suggests that the neurobiology of PGD involves the same circuitry as the reward pathway. Based upon this evidence, we hypothesize that PGD can be conceptualized as a disorder of addiction, and therefore could benefit from being treated with medications that are currently used to treat such disorders. One such medication is naltrexone, which is currently used to treat alcohol and opioid dependence. Oral naltrexone was chosen for its mechanism of action, safety, and convenience. The primary aim of this study is to establish the efficacy of using oral naltrexone as a pharmacological treatment for PGD. Specifically, we hypothesize that participants receiving naltrexone will demonstrate reduced PGD symptoms when compared to placebo.METHODS/DESIGNThis is a randomized, placebo-controlled, triple-blinded (to healthcare professionals, participants, and data analysts) in which we propose to enroll 46 participants who meet criteria for Prolonged Grief Disorder (PGD). Participants will be randomly assigned to the naltrexone 50 mg oral arm or placebo arm; medications will be over-encapsulated to appear identical. Participants will take their assigned medication for 8 weeks, with monthly clinic visits to assess symptom severity, social closeness, and adverse reactions. Weekly surveys of Prolonged Grief-13-Revised (PG-13-R) will be used to relate naltrexone use to changes in PGD symptom severity. Follow-up 4 weeks after their last visit will assess the longevity of treatment, as well as any lingering adverse reactions.DISCUSSIONThis study is the first to investigate the use of oral naltrexone as pharmacological treatment for PGD. The acute and debilitating nature of the disorder, in addition to the evidence demonstrating the increased risk of comorbidities, highlights the need for pharmacological treatment like naltrexone that can act more rapidly, may help those for whom psychotherapy may not be effective, and/or may augment psychotherapy to promote PGD symptom grief resolution.TRIAL REGISTRATIONClinicalTrials.gov, NCT04547985. Registered on 8/31/2020, https://clinicaltrials.gov/ct2/show/NCT04547985.

scholarly journals Naltrexone treatment for prolonged grief disorder: study protocol for a randomized, triple-blinded, placebo-controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
James Gang ◽  
James Kocsis ◽  
Jonathan Avery ◽  
Paul K. Maciejewski ◽  
Holly G. Prigerson
Keyword(s):  
Symptom Severity ◽  
Pharmacological Treatment ◽  
Adverse Reactions ◽  
Controlled Trial ◽  
Prolonged Grief Disorder ◽  
Prolonged Grief ◽  
Link Type ◽  
Increased Risk ◽  
Oral Naltrexone ◽  
Grief Resolution

Abstract Background There is a lack of effective pharmacotherapy for prolonged grief disorder (PGD). Evidence suggests that the neurobiology of PGD involves the same circuitry as the reward pathway. Based upon this evidence, we hypothesize that PGD can be conceptualized as a disorder of addiction and therefore could benefit from being treated with medications that are currently used to treat such disorders. One such medication is naltrexone, which is currently used to treat alcohol and opioid dependence. Oral naltrexone was chosen for its mechanism of action, safety, and convenience. The primary aim of this study is to establish the efficacy of using oral naltrexone as a pharmacological treatment for PGD. Specifically, we hypothesize that participants receiving naltrexone will demonstrate reduced PGD symptoms when compared to placebo. Methods/design This is a randomized, placebo-controlled, triple-blinded (to healthcare professionals/study staff, participants, and data analysts) study in which we propose to enroll 48 participants who meet criteria for Prolonged Grief Disorder (PGD). Participants will be randomly assigned to the naltrexone 50 mg oral arm or placebo arm; medications will be over-encapsulated to appear identical. Participants will take their assigned medication for 8 weeks, with clinic visits every 4 weeks to assess symptom severity, social closeness, and adverse reactions. Weekly surveys of Prolonged Grief-13-Revised (PG-13-R) will be used to relate naltrexone use to changes in PGD symptom severity. Follow-up 4 weeks after their last visit will assess the longevity of treatment, as well as any lingering adverse reactions. Discussion This study is the first to investigate the use of oral naltrexone as pharmacological treatment for PGD. The acute and debilitating nature of the disorder, in addition to the increased risk of comorbidities, highlights the need for pharmacological treatment like naltrexone that can act more rapidly, may help those for whom psychotherapy may not be effective, and/or may augment psychotherapy to promote PGD symptom grief resolution. Trial registration ClinicalTrials.govNCT04547985. Registered on 8/31/2020.

Lower perception of pharmacological treatment increases risk of non-adherence to medication

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
CB Graversen ◽  
JB Valentin ◽  
ML Larsen ◽  
S Riahi ◽  
T Holmberg ◽  
...  
Keyword(s):  
Pharmacological Treatment ◽  
Poisson Regression ◽  
Drug Class ◽  
Angiotensin Receptor Blockers ◽  
Adverse Outcomes ◽  
Adherence To Medication ◽  
Increased Risk ◽  
Patient Reported ◽  
High Level

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Background A large proportion of patients fail to reach optimal adherence to medication following incident ischemic heart disease (IHD) despite amble evidence of the beneficial effect of medication. Non-adherence to medication increases risk of disease-related adverse outcomes but none has explored how perception about pharmacological treatment detail on non-adherence using register-based follow-up data. Purpose To investigate the association between patients’ perception of pharmacological treatment and risk of non-initiation and non-adherence to medication in a population with incident IHD. Methods This cohort study followed 871 patients until 365 days after incident IHD. The study combined patient-reported survey data on perception about pharmacological treatment (categorised by ‘To a high level’, ‘To some level’, and ‘To a lesser level’) with register-based data on reimbursed prescription of cardiovascular medication (antithrombotics, statins, ACE-inhibitors/angiotensin receptor blockers, and β-blockers). Non-initiation was defined as no pick-up of medication in the first 180 days following incident IHD and analysed by Poisson regression. Two different measures evaluated non-adherence in patients initiating treatment: 1) proportion of days covered (PDC) analysed by Poisson regression, and 2) risk of discontinuation analysed by Cox proportional hazard regression. All analyses were adjusted for confounding variables (age, sex, ethnicity, income, educational level, civil status, occupation, charlson comorbidity index, supportive relatives, and individual consultation in medication) identified by directed acyclic graph and obtained from national registers and the survey. Item non-response was handled by multiple imputation and item consistency was evaluated by McDonalds omega. Results Lower perceptions about pharmacological treatment was associated with increased risk of non-initiation and non-adherence to medication irrespectively of drug class and adherence measure in the multiple adjusted analyses (please see figure illustrating results on antithrombotics). A dose-response relationship was observed both at 180- and 365-days of follow-up, but the steepest decline in adherence differed when comparing the two adherence measures (results not shown). Moderate internal consistency was found for the summed measure of perception (McDonalds omega = 0.67). Conclusion Lower perception of pharmacological treatment was associated with subsequent non-initiation and non-adherence to medication, irrespectively of measurement method and drug class. Abstract Figure. Figre: Multiple adjusted analyses

scholarly journals Stroke in hemodialysis patients randomized to different intravenous iron strategies: a prespecified analysis from the PIVOTAL trial

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0004272021
Author(s):  
Patrick B. Mark ◽  
Pardeep S. Jhund ◽  
Matthew R. Walters ◽  
Mark C. Petrie ◽  
Albert Power ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stroke Risk ◽  
Controlled Trial ◽  
Intravenous Iron ◽  
Hemodialysis Patients ◽  
High Dose ◽  
Pivotal Trial ◽  
Increased Risk ◽  
Iv Iron

Background: People with kidney failure treated with hemodialysis (HD) are at increased risk of stroke compared to similarly aged people with normal kidney function. One concern is that treatment of renal anemia might increase stroke risk. We studied risk factors for stroke in a prespecified secondary analysis of a randomized controlled trial of intravenous iron treatment strategies in HD. Methods: We analyzed data from the Proactive IV IrOn Therapy in HaemodiALysis Patients (PIVOTAL) trial focusing on variables associated with risk of stroke. The trial randomized 2,141 adults, who had started hemodialysis <12 months earlier and who were receiving an erythropoiesis-stimulating agent (ESA), to high-dose IV iron administered proactively or low-dose IV iron administered reactively in a 1:1 ratio. Possible stroke events were independently adjudicated. We performed analyses to identify variables associated with stroke during follow-up and assessed survival following stroke. Results: During a median 2.1 years follow-up, 69 (3.2%) patients experienced a first post randomization stroke. 57 (82.6%) were ischemic strokes and 12 (17.4%) hemorrhagic strokes. There were 34 post randomization strokes in the proactive arm and 35 in the reactive arm (hazard ratio (95% confidence interval): 0.90 (0.56, 1.44), p=0.66). In multivariable models, female gender, diabetes, history of prior stroke at baseline, higher baseline systolic blood pressure, lower serum albumin and higher C-reactive protein were independently associated with stroke events during follow up. Hemoglobin, total iron or ESA dose were not associated with risk of stroke. 58% of patients with a stroke event died during follow-up, compared to 23% without a stroke. Conclusions: In hemodialysis patients, stroke risk is broadly associated with risk factors previously described to increase cardiovascular risk in this population. Proactive intravenous iron does not increase stroke risk.

scholarly journals P001 IS PROPHYLACTIC MESH IS ROUTINELY REQUIRED FOR STOMA CONSTRUCTION? IDENTIFICATION OF THE ‘TARGET GROUP’

2021 ◽  
Vol 108 (Supplement_8) ◽  
Author(s):  
Ahmed Hassan ◽  
Wei Toh ◽  
James Ayathamattam ◽  
Zachary Thomas ◽  
Ondrej Ryska
Keyword(s):  
Controlled Trial ◽  
Cost Benefit ◽  
Prophylactic Mesh ◽  
Nice Guidelines ◽  
Prophylactic Measures ◽  
Increased Risk ◽  
End Colostomy ◽  
Randomised Controlled

Abstract Background Evidence to support routine prophylactic mesh insertion during stoma construction is conflicting. The PREVENT randomised controlled trial (RCT) suggested lower incidence of parastomal hernia (PSH) with prophylactic mesh but with no quality of life or cost benefit. Another two RCTs has shown no prophylactic benefit (STOMAMESH & STOMA-const). Although European Hernia guidelines recommends routine prophylactic mesh in end-colostomy, NICE guidelines suggest mesh on individual basis not routinely. Aim To identify the group with higher risk to develop a symptomatic PSH when prophylactic mesh should be considered Material and Methods A single center retrospective review of all stoma formed. Younger patient than 18 years and patients who had less than 6 months’ follow-up were excluded. Development of PSH was confirmed by radiological evidence or direct intra-operative visualization Results 194 patients between January 2015 till December 2019 were included with mean follow-up of 15.7±13.5 months where 91 patients developed PSH. On multivariate analysis, older age (&gt;65) (OR 2.3, 95% CI 1.08 – 4.99, p 0.03) and Obesity (OR 5.8, 95% CI 2.53 – 13.57, p 0.00) were risk factors of developing PSH. Among the PSH group, 28 were symptomatic (31%). Symptomatic subgroup had higher ASA (ASA &gt;2) than asymptomatic subgroup (50% Vs 27%, p 0.05) Conclusions Obese patients older than 65 years are at increased risk of PSH. IF their ASA &gt;2 this PSH is likely to become symptomatic. This is the group who should benefit the most from prophylactic measures including mesh insertion and should be targeted for future trials

scholarly journals Randomized Controlled Trial of Family Therapy in Advanced Cancer Continued Into Bereavement

2016 ◽  
Vol 34 (16) ◽  
pp. 1921-1927 ◽  
Author(s):  
David W. Kissane ◽  
Talia I. Zaider ◽  
Yuelin Li ◽  
Shira Hichenberg ◽  
Tammy Schuler ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Family Therapy ◽  
Advanced Cancer ◽  
Standard Care ◽  
Controlled Trial ◽  
Significant Treatment ◽  
Prolonged Grief Disorder ◽  
Prolonged Grief ◽  
Randomized Controlled ◽  
High Conflict

Purpose Systematic family-centered cancer care is needed. We conducted a randomized controlled trial of family therapy, delivered to families identified by screening to be at risk from dysfunctional relationships when one of their relatives has advanced cancer. Patients and Methods Eligible patients with advanced cancer and their family members screened above the cut-off on the Family Relationships Index. After screening 1,488 patients or relatives at Memorial Sloan Kettering Cancer Center or three related community hospice programs, 620 patients (42%) were recruited, which represented 170 families. Families were stratified by three levels of family dysfunction (low communicating, low involvement, and high conflict) and randomly assigned to one of three arms: standard care or 6 or 10 sessions of a manualized family intervention. Primary outcomes were the Complicated Grief Inventory-Abbreviated (CGI) and Beck Depression Inventory-II (BDI-II). Generalized estimating equations allowed for clustered data in an intention-to-treat analysis. Results On the CGI, a significant treatment effect (Wald χ2 = 6.88; df = 2; P = .032) and treatment by family-type interaction was found (Wald χ2 = 20.64; df = 4; P < .001), and better outcomes resulted from 10 sessions compared with standard care for low-communicating and high-conflict groups compared with low-involvement families. Low-communicating families improved by 6 months of bereavement. In the standard care arm, 15.5% of the bereaved developed a prolonged grief disorder at 13 months of bereavement compared with 3.3% of those who received 10 sessions of intervention (Wald χ2 = 8.31; df = 2; P =.048). No significant treatment effects were found on the BDI-II. Conclusion Family-focused therapy delivered to high-risk families during palliative care and continued into bereavement reduced the severity of complicated grief and the development of prolonged grief disorder.

scholarly journals Use of Oral and Implantable Naltrexone in the Management of the Opioid-Impaired Physician

2003 ◽  
Vol 31 (2) ◽  
pp. 196-201 ◽  
Author(s):  
G. K. Hulse ◽  
G. O'Neil ◽  
M. Hatton ◽  
M. J. Paech
Keyword(s):  
Previous Treatment ◽  
Opioid Antagonist ◽  
Opioid Use ◽  
Medical Board ◽  
Prescription Drug Use ◽  
Increased Risk ◽  
Oral Naltrexone ◽  
Patients At Risk ◽  
Ongoing Monitoring

Doctors are at an increased risk for prescription drug use, particularly opioids and benzodiazpines. This use can interfere with work function and has major potential negative implications for patient safety. Oral naltrexone, an opioid antagonist, has been used as part of a management strategy for opioid-dependent physicians. While some patients stabilize on oral naltrexone, others relapse to opioid use. An alternative method of naltrexone maintenance involves the injection or surgical insertion of a sustained release preparation of naltrexone. This approach dramatically improves compliance, removing the onus from the previously opioid impaired physician to use daily oral naltrexone. This article describes the cases of four opioid-impaired doctors who received naltrexone (either oral or implant) as part of their management. The authors conclude that monitoring daily oral naltrexone use and detecting early opioid relapse is difficult, placing both the opioid impaired physician and their patients at risk. In contrast, by using implantable naltrexone, compliance is assured and opioid abstinence can virtually be guaranteed for five months. It is argued that naltrexone implants offer a level of protection not achieved with any previous treatment. It is recommended that management should involve early and close collaboration between the treating doctor and the Medical Board, with initial treatment, ongoing monitoring and follow-up being a Medical Board requirement for registration.

The National Cancer Database: Survival Between Head and Neck Melanoma and Melanoma of Other Regions

2021 ◽  
pp. 019459982110532
Author(s):  
Claudia I. Cabrera ◽  
Shawn Li ◽  
Rosalynn Conic ◽  
Brian R. Gastman
Keyword(s):  
Head And Neck ◽  
Survival Data ◽  
Controlled Trial ◽  
Additional Patient ◽  
National Cancer Database ◽  
Risk Of Death ◽  
Increased Risk ◽  
Head And Neck Melanoma ◽  
Over Time

Objective Primary site is considered an important prognostic factor for cutaneous malignant melanoma (CMM); however, opinions vary regarding its influence on survival. This study compares overall survival between head and neck melanoma (HNM) and melanoma of other regions (MOR), as well as between melanoma of the scalp and neck (MSN) and melanoma of other head regions (MOHR). Study Design Level III retrospective cohort study. Setting Patients from Commission on Cancer–accredited cancer programs affiliated to the National Cancer Database (NCDB). Methods Patients with HNM (MSN and MOHR included) and MOR, stages I to IV (n = 39,754), and their linked survival data using the NCDB were identified. Survival was analyzed using propensity score matching methods. Results After matching using propensity scores, allowing this observational study to mimic a randomized controlled trial, subjects with HNM showed a 22% increased mortality when compared to MOR ( P < .01). Among those with HNM, hazard was not proportional over time. Overall, subjects with MSN in the first 3.5 years of follow-up (75% of subjects) showed a 15% increased mortality when compared to MOHR ( P < .01); however, after 3.5 years, no difference in survival was noted ( P = .5). Conclusion Patients with HNM showed a higher mortality when compared to MOR. The risk of death of primary sites within the head and neck varies over time, showing a higher risk of mortality for scalp and neck during the first 3.5 years of follow-up. This increased risk was not evident after the 3.5-year threshold. Further research is needed to evaluate additional patient factors or differences in treatment approaches.

Causes and Relevance of Unsatisfactory and Satisfactory but Limited Smears of Liquid-Based Compared With Conventional Cervical Cytology

2012 ◽  
Vol 136 (1) ◽  
pp. 76-83 ◽  
Author(s):  
Albertus G Siebers ◽  
Paul JJM Klinkhamer ◽  
Judith EM Vedder ◽  
Marc Arbyn ◽  
Johan Bulten
Keyword(s):  
Controlled Trial ◽  
Papanicolaou Test ◽  
Design Data ◽  
Detection Rates ◽  
Transformation Zone ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Underlying Causes ◽  
Liquid Based Cytology

Context.—Recent randomized controlled trials have shown a significant decrease in unsatisfactory rates for liquid-based cytology (LBC) compared with conventional Papanicolaou test (CP). The underlying causes and relevance of unsatisfactory results for LBC and CP have never been compared within the setting of a randomized controlled trial. Objective.—To examine differences in causes and relevance of unsatisfactory and satisfactory but limited by (SBLB) results for LBC and CP. Design.—Data from the Netherlands ThinPrep Versus Conventional Cytology (NETHCON) trial were used, involving 89 784 women. Causes and relevance of unsatisfactory and SBLB results were analyzed. Results.—The primary cause for unsatisfactory results for CP and LBC was scant cellularity. Other causes for unsatisfactory CPs were virtually eliminated with LBC. The same was true for SBLB subcategories, with the exception of SBLB absence of transformation zone component and SBLB scant cellularity. The SBLB absence of transformation zone component showed a statistically significant 22% and SBLB scant cellularity a 12% nonsignificant increase with LBC. The detection rates of abnormalities found during 18 months of follow-up of unsatisfactory test results did not differ significantly between the 2 study arms, nor did they differ from the initial test positivity rates from the NETHCON trial. Conclusions.—Liquid-based cytology shows an almost complete elimination of most causes for unsatisfactory CP, with scant cellularity remaining as the sole cause for unsatisfactory LBC. On the other hand, with LBC a significant increase of smears without a transformation zone component was noted. Women with an unsatisfactory test result are not at increased risk for cervical abnormalities either with LBC or with CP. Trial Registration.—Nederlands Trial Register, NTR1032, www.trialregister.nl.

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