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1.
Contraception ; 123: 110008, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-2281946

ABSTRACT

OBJECTIVES: Self-administered subcutaneous (SC) depot medroxyprogesterone acetate (DMPA) can improve contraception access by eliminating a health center visit for administration. For patients at our New York City health centers who were offered a switch to self-administered DMPA-SC at the onset of the coronavirus 2019 (COVID-19) pandemic, we sought to understand their experience of choosing to switch, of accessing and using the method, and their method satisfaction. STUDY DESIGN: Individual interview study of 22 patients using intramuscular DMPA prior to the start of the pandemic. All had a telehealth visit to discuss switching to self-administered DMPA-SC and received a DMPA-SC prescription during the first months of COVID-19. We used a grounded theory analysis approach. RESULTS: Respondents viewed switching to self-administered DMPA-SC as a decision they had to make if they wanted to continue DMPA. Most respondents experienced logistical challenges acquiring DMPA-SC from their pharmacy. Issues around convenience were important to respondents; however what respondents found convenient varied. Despite all this, respondents appreciated having the option of DMPA-SC and felt it to be overall empowering. CONCLUSIONS: This study exploring patients' experience with self-administered DMPA-SC during the initial year of the COVID-19 pandemic found that, notwithstanding initial hesitation about self-administered injections and logistical challenges getting the SC formulation, many found the experience of trying self-administered DMPA-SC to be empowering and appreciated having this option. Thus, self-administered DMPA-SC should be included in clinicians' routine contraception counseling and provision, insurance companies should cover DMPA-SC without requiring prior authorization, and pharmacies should consistently stock DMPA-SC. IMPLICATIONS: Self-administered DMPA-SC is an acceptable contraception option that provides an opportunity to maintain contraception access while eliminating need for an in-person visit. Thus, self-administered DMPA-SC should be included in clinicians' routine contraception counseling and provision, insurance companies need to cover this contraceptive without need for prior authorization, and pharmacies should consistently stock DMPA-SC.


Subject(s)
COVID-19 , Contraceptive Agents, Female , Female , Humans , Medroxyprogesterone Acetate , Pandemics , Patient Satisfaction , Injections, Subcutaneous
2.
BMJ Open ; 13(3): e059288, 2023 03 16.
Article in English | MEDLINE | ID: covidwho-2269119

ABSTRACT

OBJECTIVES: This study aimed to compare the time required and concerns raised by various perspectives of participants regarding administering subcutaneous and intravenous trastuzumab for patients with breast cancer (BC). DESIGN: This observational time-motion study design with mixed-methods research (cross-sectional surveys and semistructured interviews) was conducted. The time spent on preparing or administering trastuzumab by different healthcare professionals (HCPs) was recorded. The data were analysed by descriptive/inferential statistical analyses, followed by thematic analyses. SETTING: Outpatient and inpatient administration units of a single medical centre in Taiwan. PARTICIPANTS: The study included patients with early-stage BC who received subcutaneous or intravenous trastuzumab (n=93), and HCPs including two attending physicians, a nurse practitioner, two pharmacists and two nurses. RESULT: Based on the perspectives of patients and HCPs, the subcutaneous form of trastuzumab was more efficient, less expensive and produced less discomfort in outpatient units than inpatient units. More participants preferred the subcutaneous form over the intravenous form in both outpatient and inpatient units. Pharmacists and nurse practitioners spent threefold more time on patients when preparing and administering the intravenous form in both outpatient and inpatient units. The concerns raised by patients and HCPs varied in certain aspects, including the injection skills, speed, mental distress (eg, needle phobia) and pain associated with the subcutaneous form. Almost all patients preferred receiving the subcutaneous form in outpatient units after the initial COVID-19 outbreak. CONCLUSION: Patients with early-stage BC preferred receiving subcutaneous trastuzumab in outpatient units rather than inpatient units or the intravenous form before and after the COVID-19 outbreak. Such findings may serve as real-world evidence to facilitate better quality of care regarding administration of subcutaneous or intravenous trastuzumab in medical settings, and its feasible resolutions to balance the quality, concerns and efficiency of anticancer administration during the COVID-19 pandemic.


Subject(s)
Breast Neoplasms , COVID-19 , Humans , Female , Trastuzumab/therapeutic use , Breast Neoplasms/drug therapy , Cross-Sectional Studies , Pandemics , Injections, Subcutaneous , Administration, Intravenous , Receptor, ErbB-2
3.
N Engl J Med ; 388(6): 518-528, 2023 02 09.
Article in English | MEDLINE | ID: covidwho-2234819

ABSTRACT

BACKGROUND: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 µg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. RESULTS: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).


Subject(s)
COVID-19 Drug Treatment , COVID-19 , Interferon Lambda , Adult , Humans , Bayes Theorem , COVID-19/therapy , Double-Blind Method , Interferon Lambda/administration & dosage , Interferon Lambda/adverse effects , Interferon Lambda/therapeutic use , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Polyethylene Glycols/therapeutic use , SARS-CoV-2 , Treatment Outcome , Ambulatory Care , Injections, Subcutaneous , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , COVID-19 Vaccines/therapeutic use , Vaccination
4.
N Engl J Med ; 385(6): 503-515, 2021 08 05.
Article in English | MEDLINE | ID: covidwho-2160403

ABSTRACT

BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks. RESULTS: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.).


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Gastric Inhibitory Polypeptide/administration & dosage , Glucagon-Like Peptides/administration & dosage , Hypoglycemic Agents/administration & dosage , Blood Glucose/analysis , Diabetes Mellitus, Type 2/blood , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Gastric Inhibitory Polypeptide/adverse effects , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptides/adverse effects , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Incretins/therapeutic use , Injections, Subcutaneous , Male , Metformin/therapeutic use , Middle Aged , Nausea/chemically induced , Weight Loss/drug effects
5.
J Clin Rheumatol ; 28(7): 346-348, 2022 Oct 01.
Article in English | MEDLINE | ID: covidwho-2051770

ABSTRACT

BACKGROUND: With the arrival of the SARS-CoV-2 pandemic in 2020, it was proposed to make the change from intravenous (IV) tocilizumab (TCZ) to its subcutaneous formulation, in order to avoid rheumatological patients having to go to the day hospital and guarantee enough IV TCZ for those critical patients with COVID who needed it. The aim of this study was to describe the rate and reasons for switching back to IV TCZ from subcutaneous TCZ. METHODS: We included patients from the rheumatology service that were on treatment with IV TCZ in February 2020 and were followed up until March 2021. Patients that remained on subcutaneous TCZ were compared with those who switched back to IV TCZ (switch-back group). A subgroup analysis according to rheumatic disease was performed. RESULTS: Fifty-five patients switched to subcutaneous TCZ: 28 rheumatoid arthritis, 19 giant cell arteritis, 4 polymyalgia rheumatica, 2 juvenile idiopathic arthritis, and 2 systemic sclerosis. Seventeen patients switched back to IV TCZ due to ineffectiveness (n = 8), patient preference (n = 4), adverse events (n = 4), and difficulty with the SC administration route (n = 1). In the analysis by disease, 4 of 23 patients switched back to IV TCZ in giant cell arteritis/polymyalgia rheumatica group due to ineffectiveness (n = 2), injection site reaction (n = 1), or patient preference (n = 1). In rheumatoid arthritis group, 11 of 28 patients switched back to IV TCZ: ineffectiveness (n = 5), patient preference (n = 3), headache (n = 1), injection site reaction (n = 1), and due to difficulty with the SC administration route (n = 1). CONCLUSIONS: Mass switch from IV to subcutaneous TCZ during the SARS-CoV-2 pandemic has been safe, effective, and well tolerated after 1 year of follow-up.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , COVID-19 Drug Treatment , Giant Cell Arteritis , Polymyalgia Rheumatica , Antibodies, Monoclonal, Humanized , Arthritis, Rheumatoid/drug therapy , Giant Cell Arteritis/drug therapy , Humans , Injection Site Reaction/drug therapy , Injections, Subcutaneous , Pandemics , Polymyalgia Rheumatica/chemically induced , SARS-CoV-2 , Treatment Outcome
6.
N Engl J Med ; 387(6): 495-505, 2022 08 11.
Article in English | MEDLINE | ID: covidwho-2031919

ABSTRACT

BACKGROUND: Teclistamab is a T-cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 1-2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Patients received a weekly subcutaneous injection of teclistamab (at a dose of 1.5 mg per kilogram of body weight) after receiving step-up doses of 0.06 mg and 0.3 mg per kilogram. The primary end point was the overall response (partial response or better). RESULTS: Among 165 patients who received teclistamab, 77.6% had triple-class refractory disease (median, five previous therapy lines). With a median follow-up of 14.1 months, the overall response rate was 63.0%, with 65 patients (39.4%) having a complete response or better. A total of 44 patients (26.7%) were found to have no minimal residual disease (MRD); the MRD-negativity rate among the patients with a complete response or better was 46%. The median duration of response was 18.4 months (95% confidence interval [CI], 14.9 to not estimable). The median duration of progression-free survival was 11.3 months (95% CI, 8.8 to 17.1). Common adverse events included cytokine release syndrome (in 72.1% of the patients; grade 3, 0.6%; no grade 4), neutropenia (in 70.9%; grade 3 or 4, 64.2%), anemia (in 52.1%; grade 3 or 4, 37.0%), and thrombocytopenia (in 40.0%; grade 3 or 4, 21.2%). Infections were frequent (in 76.4%; grade 3 or 4, 44.8%). Neurotoxic events occurred in 24 patients (14.5%), including immune effector cell-associated neurotoxicity syndrome in 5 patients (3.0%; all grade 1 or 2). CONCLUSIONS: Teclistamab resulted in a high rate of deep and durable response in patients with triple-class-exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2. (Funded by Janssen Research and Development; MajesTEC-1 ClinicalTrials.gov numbers, NCT03145181 and NCT04557098.).


Subject(s)
Antibodies, Bispecific , Antineoplastic Agents, Immunological , B-Cell Maturation Antigen , CD3 Complex , Multiple Myeloma , Antibodies, Bispecific/administration & dosage , Antibodies, Bispecific/adverse effects , Antibodies, Bispecific/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B-Cell Maturation Antigen/antagonists & inhibitors , CD3 Complex/antagonists & inhibitors , Humans , Injections, Subcutaneous , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/drug therapy , Recurrence , T-Lymphocytes/drug effects , T-Lymphocytes/immunology
7.
Expert Rev Clin Immunol ; 18(2): 105-114, 2022 02.
Article in English | MEDLINE | ID: covidwho-1978089

ABSTRACT

INTRODUCTION: In recent years, different studies have highlighted the importance of B cells in the pathophysiology of multiple sclerosis (MS): they secrete cytokines to modulate the inflammatory environment, present antigens for the activation of T lymphocytes, and they secrete antibodies contributing to the destruction of the myelin sheath. Combined, these findings have lead to new possible means for treating MS. AREAS COVERED: In this review, we provide an up-to-date overview of the characteristics of ofatumumab (aka Kesimpta), and the differences between this drug and the other anti-CD20 monoclonal antibodies used to treat MS. EXPERT OPINION: The evolution of disease-modifying treatment algorithms in MS underlines the importance of starting treatment as soon as the diagnosis is defined, and with adequate 'treatment intensity.' Monoclonal antibodies and other aggressive treatments are now considered as an option at the clinical presentation of the disease, based to the prognostic profile emerging through clinical and paraclinical investigations. The recent adoption of new diagnostic criteria allows for the early diagnosis of MS. This, together with the availability of disease-modifying therapies (DMTs), such as ofatumumab, with a good efficacy/safety profile and which are easy to administer, could contribute to significant improvements in the long-term prognosis of MS.


Subject(s)
Multiple Sclerosis , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Humans , Injections, Subcutaneous , Multiple Sclerosis/diagnosis , Multiple Sclerosis/drug therapy
8.
BMJ Glob Health ; 7(7)2022 07.
Article in English | MEDLINE | ID: covidwho-1950117

ABSTRACT

Subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is an innovative contraceptive method aimed at meeting women's unique circumstances and needs, largely due to its ability to be self-injected. Substantial research and advocacy investments have been made to promote roll-out of DMPA-SC across sub-Saharan Africa. To date, research on the demand for DMPA-SC as a self-injectable method has been conducted largely with healthcare providers, via qualitative research, or with highly specific subsamples that are not population based. Using three recent rounds of data from Performance Monitoring for Action, we examined population-representative trends in demand, use, and preference for self-injection among current non-users in Burkina Faso, the Democratic Republic of Congo (Kinshasa and Kongo Central regions), Kenya, and Nigeria (Lagos and Kano States). We found that while over 80.0% of women had heard of injectables across settings, few women had heard of self-injection (ranging from 13.0% in Kenya to 24.8% in Burkina Faso). Despite initial increases in DMPA-SC prevalence, DMPA-SC usage began to stagnate or even decrease in all settings in the recent three years (except in Nigeria-Kano). Few (0.0%-16.7%) current DMPA-SC users were self-injecting, and the majority instead were relying on a healthcare provider for administration of DMPA-SC. Among current contraceptive non-users wishing to use an injectable in the future, only 1.5%-11.4% preferred to self-inject. Our results show that self-injection is uncommon, and demand for self-injection is very limited across six settings, calling for further qualitative and quantitative research on women's views on DMPA-SC and self-injection and, ultimately, their contraceptive preferences and needs.


Subject(s)
Contraceptive Agents, Female , Medroxyprogesterone Acetate , Democratic Republic of the Congo , Female , Humans , Injections, Subcutaneous , Nigeria , Self Administration
9.
Endocrinol Diabetes Metab ; 5(4): e352, 2022 07.
Article in English | MEDLINE | ID: covidwho-1919273

ABSTRACT

INTRODUCTION: The aim of this study was to compare glycemic control and body mass index standard deviation score (BMI-SDS) before and after implementation of intensive insulin therapy using multiple daily injection (MDI) or continuous subcutaneous insulin infusion (CSII) in adolescents with type 1 diabetes (T1D) attending a large multidisciplinary paediatric diabetes clinic in Australia. METHODS: Prospective data were collected for cross-sectional comparison of youth aged 10.0-17.9 years (n = 669) from routine follow-up visits to the diabetes clinic in 2004, 2010, and 2016. Outcome measures included HbA1c; BMI-SDS; and insulin regimen. RESULTS: BMI-SDS remained stable between 2004 to 2016 in the 10-13 and 14-17 year age group (0.7 vs. 0.5, p = .12 and 0.7 vs. 0.7, p = .93, respectively). BMI-SDS was not different across HbA1c groups; <53 mmol/mol (7.0%), 53 to <75 mmol/mol (<7.0 to <9.0%) and >75 mmol/mol (>9.0%) in 2004 (p = .873), 2010 (p = .10) or 2016 (p = .630). Mean HbA1c decreased from 2004 to 2016 in the 10-13 year (69 mmol/mol (8.4%) vs. 57 mmol/mol (7.4%), p = <.001) and 14-17 year group (72 mmol/mol (8.7%) vs. 63 mmol/mol (7.9%), p = <.001). Prior to the implementation of MDI and CSII in 2004 only 10% of 10-13 year olds and 8% of 14-17 year olds achieved the international target for glycemic control (HbA1c 53 mmol/mol [<7.0%]). In 2016, this increased to 31% of 10-13 year olds and 21% of 14-17 year olds. CONCLUSIONS: BMI-SDS did not increase with the change to intensive insulin therapy despite a doubling in the number of adolescents achieving the recommended glycemic target of <7.0% (53 mmol/mol). HbA1c was not associated with weight gain.


Subject(s)
Diabetes Mellitus, Type 1 , Adolescent , Blood Glucose , Child , Cross-Sectional Studies , Diabetes Mellitus, Type 1/drug therapy , Glycated Hemoglobin , Humans , Hypoglycemic Agents/therapeutic use , Injections, Subcutaneous , Insulin/therapeutic use , Insulin, Regular, Human/therapeutic use , Prospective Studies , Weight Gain
10.
Mult Scler ; 28(6): 910-924, 2022 05.
Article in English | MEDLINE | ID: covidwho-1883453

ABSTRACT

BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). OBJECTIVE: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. METHODS: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. RESULTS: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. CONCLUSION: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.


Subject(s)
Multiple Sclerosis , Antibodies, Monoclonal , Antibodies, Monoclonal, Humanized/adverse effects , Humans , Injections, Subcutaneous , Multiple Sclerosis/chemically induced
11.
JAMA ; 327(17): 1679-1687, 2022 05 03.
Article in English | MEDLINE | ID: covidwho-1843805

ABSTRACT

Importance: Lipoprotein(a) (Lp[a]) is an important risk factor for atherothrombotic cardiovascular disease and aortic stenosis, for which there are no treatments approved by regulatory authorities. Objectives: To assess adverse events and tolerability of a short interfering RNA (siRNA) designed to reduce hepatic production of apolipoprotein(a) and to assess associated changes in plasma concentrations of Lp(a) at different doses. Design, Setting, and Participants: A single ascending dose study of SLN360, an siRNA targeting apolipoprotein(a) synthesis conducted at 5 clinical research unit sites located in the US, United Kingdom, and Australia. The study enrolled adults with Lp(a) plasma concentrations of 150 nmol/L or greater at screening and no known clinically overt cardiovascular disease. Participants were enrolled between November 18, 2020, and July 21, 2021, with last follow-up on December 29, 2021. Interventions: Participants were randomized to receive placebo (n = 8) or single doses of SLN360 at 30 mg (n = 6), 100 mg (n = 6), 300 mg (n = 6), or 600 mg (n = 6), administered subcutaneously. Main Outcomes and Measures: The primary outcome was evaluation of safety and tolerability. Secondary outcomes included change in plasma concentrations of Lp(a) to a maximum follow-up of 150 days. Results: Among 32 participants who were randomized and received the study intervention (mean age, 50 [SD, 13.5] years; 17 women [53%]), 32 (100%) completed the trial. One participant experienced 2 serious adverse event episodes: admission to the hospital for headache following SARS-CoV-2 vaccination and later for complications of cholecystitis, both of which were judged to be unrelated to study drug. Median baseline Lp(a) concentrations were as follows: placebo, 238 (IQR, 203-308) nmol/L; 30-mg SLN360, 171 (IQR, 142-219) nmol/L; 100-mg SLN360, 217 (IQR, 202-274) nmol/L; 300-mg SLN360, 285 (IQR, 195-338) nmol/L; and 600-mg SLN360, 231 (IQR, 179-276) nmol/L. Maximal median changes in Lp(a) were -20 (IQR, -61 to 3) nmol/L, -89 (IQR, -119 to -61) nmol/L, -185 (IQR, -226 to -163) nmol/L, -268 (IQR, -292 to -189) nmol/L, and -227 (IQR, -270 to -174) nmol/L, with maximal median percentage changes of -10% (IQR, -16% to 1%), -46% (IQR, -64% to -40%), -86% (IQR, -92% to -82%), -96% (IQR, -98% to -89%), and -98% (IQR, -98% to -97%), for the placebo group and the 30-mg, 100-mg, 300-mg, and 600-mg SLN360 groups, respectively. The duration of Lp(a) lowering was dose dependent, persisting for at least 150 days after administration. Conclusions and Relevance: In this phase 1 study of 32 participants with elevated Lp(a) levels and no known cardiovascular disease, the siRNA SLN360 was well tolerated, and a dose-dependent lowering of plasma Lp(a) concentrations was observed. The findings support further study to determine the safety and efficacy of this siRNA. Trial Registration: ClinicalTrials.gov Identifier: NCT04606602; EudraCT Identifier: 2020-002471-35.


Subject(s)
Apoprotein(a) , Hyperlipoproteinemias , RNA, Small Interfering , Adult , Apoprotein(a)/adverse effects , Apoprotein(a)/biosynthesis , Apoprotein(a)/blood , Cardiovascular Diseases/etiology , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Hyperlipoproteinemias/blood , Hyperlipoproteinemias/genetics , Hyperlipoproteinemias/metabolism , Hyperlipoproteinemias/therapy , Injections, Subcutaneous , Lipoprotein(a)/adverse effects , Lipoprotein(a)/biosynthesis , Lipoprotein(a)/blood , Male , Middle Aged , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/adverse effects , RNA, Small Interfering/therapeutic use , Treatment Outcome
13.
Hum Vaccin Immunother ; 18(5): 2042136, 2022 11 30.
Article in English | MEDLINE | ID: covidwho-1730550

ABSTRACT

A 60-year-old woman presented with a depressed lesion at the site of her first COVID-19 (Astra Zeneca) vaccine injection. The lesion was diagnosed as a case of injection related localized lipoatrophy as markers of autoimmune disease were negative and biopsy differentiated it from localized involutional lipoatrophy. This case of localized lipoatrophy was likely due to inadvertent subcutaneous injection of the COVID-19 vaccine with a 16 mm long needle.


Subject(s)
COVID-19 , Lipodystrophy , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Humans , Injections, Subcutaneous , Lipodystrophy/chemically induced , Lipodystrophy/drug therapy , Middle Aged
14.
Am J Health Syst Pharm ; 79(15): 1236-1244, 2022 07 22.
Article in English | MEDLINE | ID: covidwho-1692258

ABSTRACT

PURPOSE: To discuss the potential implications of obesity for drug administration and absorption from subcutaneous (SC) and intramuscular (IM) injection sites. SUMMARY: The SC and IM routes are useful for the parenteral administration of medications to optimize pharmacokinetic properties such as time to onset and duration of effect, for cost considerations, or for ease of administration, such as when intravenous access is unavailable. The choice of SC or IM injection depends on the specific medication, with SC administration preferred for products such as insulin where a slower and more sustained response is desirable, while IM administration is usually preferred for products such as vaccines where more rapid absorption leads to a more rapid antibody response. Obesity has the potential to influence the rate and extent of absorption, as well as adverse effects, of medications administered by the SC or IM route through changes in SC tissue composition and depth or by inadvertent administration of IM medications into SC tissue because of improper needle length. Potential adverse effects associated with IM or SC injections in addition to pain, bruising, and hematoma formation include sciatic nerve injury, particularly with IM injection in the upper outer quadrant of the buttock; bone contusion or rarely osteonecrosis if the IM injection is excessively deep; and granulomas, fat necrosis, and calcification with SC injection. CONCLUSION: Issues related to medication absorption in obese patients are likely to become more prominent in the future with increasing approvals of a wide range of biotherapeutic agents administered by SC injection. Studies should be directed toward these and other agents to assist with dosing decisions in this challenging population.


Subject(s)
Insulin , Subcutaneous Tissue , Humans , Injections, Intramuscular/adverse effects , Injections, Subcutaneous , Obesity
15.
Biomed Pharmacother ; 146: 112572, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1588216

ABSTRACT

BACKGROUND: Interferon-ß is an attractive drug for repurposing and use in the treatment of COVID-19, based on its in vitro antiviral activity and the encouraging results from clinical trials. The aim of this study was to analyze the impact of early interferon-ß treatment in patients admitted with COVID-19 during the first wave of the pandemic. METHODS: This post hoc analysis of a COVID-19@Spain multicenter cohort included 3808 consecutive adult patients hospitalized with COVID-19 from 1 January to 17 March 2020. The primary endpoint was 30-day all-cause mortality, and the main exposure of interest was subcutaneous administration of interferon-ß, defined as early if started ≤ 3 days from admission. Multivariate logistic and Cox regression analyses were conducted to identify the associations of different variables with receiving early interferon-ß therapy and to assess its impact on 30-day mortality. A propensity score was calculated and used to both control for confounders and perform a matched cohort analysis. RESULTS: Overall, 683 patients (17.9%) received early interferon-ß therapy. These patients were more severely ill. Adjusted HR for mortality with early interferon-ß was 1.03 (95% CI, 0.82-1.30) in the overall cohort, 0.96 (0.82-1.13) in the PS-matched subcohort, and 0.89 (0.60-1.32) when interferon-ß treatment was analyzed as a time-dependent variable. CONCLUSIONS: In this multicenter cohort of admitted COVID-19 patients, receiving early interferon-ß therapy after hospital admission did not show an association with lower mortality. Whether interferon-ß might be useful in the earlier stages of the disease or specific subgroups of patients requires further research.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19 Drug Treatment , COVID-19/diagnosis , Interferon-beta/administration & dosage , SARS-CoV-2/drug effects , Time-to-Treatment/trends , Aged , Aged, 80 and over , COVID-19/mortality , Cohort Studies , Female , Hospitalization/trends , Humans , Injections, Subcutaneous , Male , Prognosis , Retrospective Studies , Spain/epidemiology , Treatment Outcome
16.
Clin J Oncol Nurs ; 25(6): 663-671, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1533298

ABSTRACT

BACKGROUND: The subcutaneous (SC) route has evolved significantly. More than two dozen chemotherapy and supportive therapies have been approved for use in the oncology setting. Several IV therapies have been approved for the SC route and require a significantly higher volume than historical maximum limits. Differences exist in how these drugs are administered as compared to older chemotherapy agents. OBJECTIVES: The purpose of this article is to provide a brief history of the SC route and describe its role in cancer treatment. The use of recombinant hyaluronidase is reviewed within the context of SC monoclonal antibodies. Proper administration techniques and interventions for reducing patient discomfort are discussed. METHODS: Sentinel medical texts, pharmacokinetic studies, manufacturer's recommendations, and peer-reviewed articles were examined. FINDINGS: The SC route offers several advantages over the oral and IV routes. A clear understanding of anatomical site selection and injection techniques is beneficial for providing requisite patient education.


Subject(s)
Antineoplastic Agents, Immunological , Antineoplastic Agents , Antibodies, Monoclonal , Antineoplastic Agents/therapeutic use , Humans , Hyaluronoglucosaminidase/therapeutic use , Injections, Subcutaneous
17.
Obstet Gynecol ; 138(4): 574-577, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1462516

ABSTRACT

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, health care professionals have made swift accommodations to provide consistent and safe care, including emphasizing remote access to allow physical distancing. Depot medroxyprogesterone acetate intramuscular injection (DMPA-IM) prescription is typically administered by a health care professional, whereas DMPA-subcutaneous has the potential to be safely self-injected by patients, avoiding contact with a health care professional. However, DMPA-subcutaneous is rarely prescribed despite its U.S. Food and Drug Administration approval in 2004 and widespread coverage by both state Medicaid providers and many private insurers. Depot medroxyprogesterone acetate users are disproportionately non-White, and thus the restriction in DMPA-subcutaneous prescribing may both stem from and contribute to systemic racial health disparities. We review evidence on acceptability, safety, and continuation rates of DMPA-subcutaneous, consider sources of implicit bias that may impede prescription of this contraceptive method, and provide recommendations for implementing DMPA-subcutaneous prescribing.


Subject(s)
COVID-19 , Contraceptive Agents, Female/administration & dosage , Family Planning Services/statistics & numerical data , Medroxyprogesterone Acetate/administration & dosage , Patient Acceptance of Health Care/statistics & numerical data , Contraception/statistics & numerical data , Drug Prescriptions/statistics & numerical data , Family Planning Services/methods , Female , Health Services Accessibility/statistics & numerical data , Healthcare Disparities/statistics & numerical data , Humans , Injections, Subcutaneous , SARS-CoV-2 , Self Administration , United States
18.
Vet Surg ; 50(2): 410-417, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1455661

ABSTRACT

OBJECTIVE: To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses. STUDY DESIGN: prospective, randomized, blinded, crossover trial. ANIMALS: Six adult horses weighing 494 ± 33 kg. METHODS: Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were collected at various time points for 24 hours. Accelerometry data were obtained for 8 hours to measure locomotor activity. Data were analyzed with a mixed effects model, and α was set at .05. RESULTS: Meperidine terminal half-life (T1/2 ), maximal plasma concentrations, and time to maximal concentration were 186 ± 59 and 164 ± 56 minutes, 265.7 ± 47.2 and 243.1 ± 80.1 ng/mL at 17 ± 6, and 24 ± 13 minutes for IM at subcutaneous administration, respectively. No effect of treatment or time was observed on thermal or mechanical thresholds, heart rate, respiratory rate, locomotor activity, frequency of defecations, or fecal weight (P > .2 for all). CONCLUSION: Maximum meperidine concentrations were achieved quickly with a short T1/2 in both treatment groups. Neither IM nor subcutaneous meperidine influenced thermal or mechanical threshold or physiological variables. CLINICAL SIGNIFICANCE: The short half-life and lack of detectable antinociceptive effect do not support IM or subcutaneous administration meperidine at 1 mg/kg for analgesia in horses.


Subject(s)
Analgesics, Opioid/pharmacology , Horses/metabolism , Meperidine/pharmacology , Analgesics, Opioid/pharmacokinetics , Animals , Female , Injections, Intramuscular/veterinary , Injections, Subcutaneous/veterinary , Male , Meperidine/pharmacokinetics
19.
Cochrane Database Syst Rev ; 6: CD008077, 2021 06 08.
Article in English | MEDLINE | ID: covidwho-1453524

ABSTRACT

BACKGROUND: Heparin is an anticoagulant medication that is usually injected subcutaneously. Subcutaneous administration of heparin may result in complications such as bruising, haematoma, and pain at the injection site. One of the factors that may affect pain, haematoma, and bruising is injection speed. Several studies have been carried out to determine if speed of injection affects the amount of pain and bruising where the injection is given; however, the results of these studies have differed, and study authors have not reached a clear final conclusion. This is the second update of a review first published in 2014. OBJECTIVES: To assess the effects of duration (speed) of subcutaneous heparin injection on pain and bruising at the injection site in people admitted to hospitals or clinics who require treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). We also looked at haematoma at the injection site. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 22 June 2020. We undertook reference checking of included studies to identify additional studies. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) comparing the effects of different durations of subcutaneous injection of heparin on pain, bruising, and haematoma at the injection site. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently selected studies and extracted data via Covidence software and assessed methodological quality using Cochrane's risk of bias tool. The primary outcomes of interest were pain intensity at injection site and size and incidence of bruising. The secondary outcomes of interest were size and incidence of haematoma at injection site. We calculated the odds ratio (OR), mean difference (MD), or standardised mean difference (SMD) with corresponding 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE criteria. MAIN RESULTS: We identified one new study for this update, resulting in a total of five included studies with 503 participants who received subcutaneous injections of LMWH into the abdomen. Given the nature of the intervention, it was not possible to blind participants and caregivers (personnel) in any of the included studies. Two studies described blinding of outcome assessors. Overall, the methodological quality of included studies was moderate. The duration of the fast injection was 10 seconds, and the duration of the slow injection was 30 seconds in all included studies. Four studies reported site pain intensity after each injection at different time points. Two studies assessed site pain intensity immediately after each injection; meta-analysis showed no evidence of a difference in site pain intensity immediately after slow injection when compared to fast injection (MD -1.52, 95% CI -3.56 to 0.53; 140 participants; low-certainty evidence). Meta-analysis of three studies indicated that site pain intensity may be slightly reduced 48 hours after the slow heparin injection compared to fast injection (MD -1.60, 95% CI -2.69 to -0.51; 103 participants; low-certainty evidence). Five studies assessed bruise size at 48 hours, and two studies assessed bruise size at 60 hours. Meta-analysis showed there may be a reduction in bruise size 48 hours (SMD -0.54, 95% CI -1.05 to -0.02; 503 participants; 5 studies; very low-certainty evidence) and 60 hours (SMD -0.49, 95% CI -0.93 to -0.06; 84 participants; 2 studies; low-certainty evidence) after slow injection compared to fast injection. There was no evidence of a difference in bruise size 72 hours after slow injection compared to fast injection (SMD -0.27, 95% CI -0.61 to 0.06; 140 participants; 2 studies; low-certainty evidence). Three studies evaluated incidence of bruising and showed there may be a reduction in bruise incidence 48 hours (OR 0.39, 95% CI 0.26 to 0.60; 444 participants; low-certainty evidence) and 60 hours (OR 0.25, 95% CI 0.10 to 0.65; 84 participants; 2 studies; low-certainty evidence) after slow injection compared to fast injection. We downgraded the certainty of the evidence due to risk of bias concerns, imprecision, and inconsistency. None of the included studies measured size or incidence of haematoma. AUTHORS' CONCLUSIONS: Administering medication safely and enhancing patient comfort are the main aims of clinical nurses. In this review, we identified five RCTs that evaluated the effect of subcutaneous heparin injection duration on pain intensity, bruise size and incidence. We found that pain may be slightly reduced 48 hours after slow injection. Similarly, there may be a reduction in bruise size and incidence after slow injection compared to fast injection 48 and 60 hours postinjection. We downgraded the certainty of the evidence for all outcomes to low or very low due to risk of bias concerns, imprecision, and inconsistency. Accordingly, new trials with a more robust design, more participants, and a focus on different injection speeds will be useful in strengthening the certainty of the available evidence.


Subject(s)
Anticoagulants/administration & dosage , Contusions/prevention & control , Heparin, Low-Molecular-Weight/administration & dosage , Injections, Subcutaneous/methods , Pain, Procedural/prevention & control , Anticoagulants/adverse effects , Bias , Contusions/chemically induced , Contusions/pathology , Hematoma/chemically induced , Hematoma/pathology , Heparin, Low-Molecular-Weight/adverse effects , Humans , Injections, Subcutaneous/adverse effects , Middle Aged , Pain Measurement/methods , Pain, Procedural/etiology , Randomized Controlled Trials as Topic , Time Factors
20.
Inflamm Res ; 70(10-12): 1233-1246, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1442067

ABSTRACT

OBJECTIVE AND DESIGN: The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19. SUBJECTS: The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia. TREATMENT: 206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy. METHODS: The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders. RESULTS: 63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (P = .0017). The frequency of adverse drug reactions was comparable between the groups. CONCLUSION: In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate. TRAIL REGISTRATION: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Drug Treatment , Receptors, Interleukin-6/antagonists & inhibitors , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Double-Blind Method , Endpoint Determination , Female , Humans , Injections, Subcutaneous , Male , Middle Aged , Oxygen Inhalation Therapy , Respiration, Artificial , Treatment Outcome , Young Adult
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