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Journal of the Academy of... 2024Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available... (Review)
Review
Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.
Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.
Topics: Humans; Administration, Intravenous; Psychomotor Agitation; Aggression; Antipsychotic Agents; Prospective Studies
PubMed: 38309683
DOI: 10.1016/j.jaclp.2024.01.004 -
Advanced Drug Delivery Reviews 2020Microneedles (MNs) have been used to deliver drugs for over two decades. These platforms have been proven to increase transdermal drug delivery efficiency dramatically...
Microneedles (MNs) have been used to deliver drugs for over two decades. These platforms have been proven to increase transdermal drug delivery efficiency dramatically by penetrating restrictive tissue barriers in a minimally invasive manner. While much of the early development of MNs focused on transdermal drug delivery, this technology can be applied to a variety of other non-transdermal biomedical applications. Several variations, such as multi-layer or hollow MNs, have been developed to cater to the needs of specific applications. The heterogeneity in the design of MNs has demanded similar variety in their fabrication methods; the most common methods include micromolding and drawing lithography. Numerous materials have been explored for MN fabrication which range from biocompatible ceramics and metals to natural and synthetic biodegradable polymers. Recent advances in MN engineering have diversified MNs to include unique shapes, materials, and mechanical properties that can be tailored for organ-specific applications. In this review, we discuss the design and creation of modern MNs that aim to surpass the biological barriers of non-transdermal drug delivery in ocular, vascular, oral, and mucosal tissue.
Topics: Administration, Topical; Biological Transport; Drug Delivery Systems; Equipment Design; Humans; Microinjections; Microtechnology; Polymers; Prostheses and Implants
PubMed: 31837356
DOI: 10.1016/j.addr.2019.11.010 -
Journal of Surgical Oncology Feb 2018The field of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has suffered from a lack of clinical trials to validate its expanding use. (Review)
Review
BACKGROUND
The field of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has suffered from a lack of clinical trials to validate its expanding use.
OBJECTIVE
To evaluate published and ongoing clinical trials seeking to better define role of CRS/HIPEC in the treatment of peritoneal surface malignancies.
METHODS
Systematic review by PubMed search was performed using terms "Clinical trial," "intraperitoneal chemotherapy," and "HIPEC." ClinicalTrials.gov and EudraCT registries were searched for active clinical trials. Eligibility included CRS/HIPEC trials investigating adult patient populations from published clinical reports and/or trials currently accruing or at completion.
RESULTS
Thirteen published trials and 57 active clinical trials were included for review.
CONCLUSIONS
Published and ongoing U.S. and international clinical trials for CRS and HIPEC are defining important parameters that include improving patient selection, strategic sequences of treatment, cytoreductive strategies, chemotherapeutics, optimal hyperthermic temperature and timing, and toxicity profiles. Main barriers or limitations to trial development remain patient enrollment, trial design, and oncologic community collaboration. Overall progress is positive with increasing number of clinical trials throughout the world. Collaboration between surgeons and the wider oncologic community will be crucial to validate this important treatment strategy.
Topics: Chemotherapy, Cancer, Regional Perfusion; Clinical Trials as Topic; Cytoreduction Surgical Procedures; Humans; Hyperthermia, Induced; Meta-Analysis as Topic; Peritoneal Neoplasms; Prognosis; Survival Rate
PubMed: 29120491
DOI: 10.1002/jso.24813 -
Farmacia Hospitalaria : Organo Oficial... 2024The off-label use in clinical practice of non-approved syringes for intravitreal drug administration has resulted in the detection of silicone oil drops in the vitreous... (Review)
Review
OBJECTIVE
The off-label use in clinical practice of non-approved syringes for intravitreal drug administration has resulted in the detection of silicone oil drops in the vitreous of some patients. This situation derives from the lack of approved syringes for intraocular use in the Spanish market. The aim of this work is to review the use of syringes for intraocular administration, as well as to search for alternatives that meet the legal requirements for these unmet needs.
METHOD
A systematic review was performed following the PRISMA 2020 guidelines by searching PubMed with the descriptors: (silicone) AND (syringes) AND ((intraocular) OR (intravitreal)) and filtering all existing publications from January 2006 to December 2023, including all those articles dealing with silicone oil release in intravitreal injections and analysing the possible consequences.
RESULTS
Sixty-eight results were found, 23 of which were excluded because they did not deal with the subject under study, leaving a total of 45 articles for the systematic review. These were classified according to the conclusions obtained in 4 groups: the adverse reactions produced by silicone; the administration technique; the physicochemical aspects of silicone release; and the characteristics of the medical device. After reviewing the current manufacturers and technical data sheets of commercialised syringes, the existing syringes for this use have been collected, finding 2 that will probably be commercialised in Spain at the beginning of 2024: Zero Residual™ 0.2 ml SiO-free and VitreJect® Ophthalmic.
CONCLUSIONS
From the results obtained, it can be interpreted that the use of syringes and needles with silicone for intravitreal use is a concern for health professionals due to the implications and consequences that may arise in patients, the most important being adverse reactions, so it is necessary to have silicone-free syringes on the market that are specific for intraocular use. Safety and legality in the use of intraocular syringes and needles is essential to guarantee ocular integrity and patient health.
Topics: Syringes; Humans; Silicone Oils; Intravitreal Injections; Off-Label Use; Spain
PubMed: 38705829
DOI: 10.1016/j.farma.2024.04.011 -
European Neuropsychopharmacology : the... Jun 2024Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment... (Meta-Analysis)
Meta-Analysis Review
Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase.
Topics: Humans; Antipsychotic Agents; Administration, Oral; Schizophrenia; Delayed-Action Preparations; Network Meta-Analysis; Randomized Controlled Trials as Topic; Injections; Treatment Outcome
PubMed: 38490016
DOI: 10.1016/j.euroneuro.2024.03.003 -
Plants (Basel, Switzerland) May 2022The use of and cannabinoid products for the treatment of neuropathic pain is a growing area of research. This type of pain has a high prevalence, limited response to... (Review)
Review
The use of and cannabinoid products for the treatment of neuropathic pain is a growing area of research. This type of pain has a high prevalence, limited response to available therapies and high social and economic costs. Systemic cannabinoid-based therapies have shown some unwanted side effects. Alternative routes of administration in the treatment of neuropathic pain may provide better acceptance for the treatment of multiple pathologies associated with neuropathic pain. To examine the efficacy, tolerability, and safety of cannabinoids (individualized formulations, phytocannabinoids, and synthetics) administered by routes other than oral or inhalation compared to placebo and/or conventional medications in the management of neuropathic pain. This systematic review of the literature reveals a lack of clinical research investigating cannabis by routes other than oral and inhalation as a potential treatment for neuropathic pain and highlights the need for further investigation with well-designed clinical trials. There is a significant lack of evidence indicating that cannabinoids administered by routes other than oral or inhaled may be an effective alternative, with better tolerance and safety in the treatment of neuropathic pain. Higher quality, long-term, randomized controlled trials are needed to examine whether cannabinoids administered by routes other than inhalation and oral routes may have a role in the treatment of neuropathic pain.
PubMed: 35631782
DOI: 10.3390/plants11101357 -
The Cochrane Database of Systematic... Apr 2016This is the third updated version of a Cochrane review first published in Issue 4, 2003 of The Cochrane Library and first updated in 2007. Morphine has been used for... (Review)
Review
BACKGROUND
This is the third updated version of a Cochrane review first published in Issue 4, 2003 of The Cochrane Library and first updated in 2007. Morphine has been used for many years to relieve pain. Oral morphine in either immediate release or modified release form remains the analgesic of choice for moderate or severe cancer pain.
OBJECTIVES
To determine the efficacy of oral morphine in relieving cancer pain, and to assess the incidence and severity of adverse events.
SEARCH METHODS
We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9); MEDLINE (1966 to October 2015); and EMBASE (1974 to October 2015). We also searched ClinicalTrials.gov (1 October 2015).
SELECTION CRITERIA
Published randomised controlled trials (RCTs) using placebo or active comparators reporting on the analgesic effect of oral morphine in adults and children with cancer pain. We excluded trials with fewer than 10 participants.
DATA COLLECTION AND ANALYSIS
One review author extracted data, which were checked by another review author. There were insufficient comparable data for meta-analysis to be undertaken or to produce numbers needed to treat (NNTs) for the analgesic effect. We extracted any available data on the number or proportion of participants with 'no worse than mild pain' or treatment success (very satisfied, or very good or excellent on patient global impression scales).
MAIN RESULTS
We identified seven new studies in this update. We excluded six, and one study is ongoing so also not included in this update. This review contains a total of 62 included studies, with 4241 participants. Thirty-six studies used a cross-over design ranging from one to 15 days, with the greatest number (11) for seven days for each arm of the trial. Overall we judged the included studies to be at high risk of bias because the methods of randomisation and allocation concealment were poorly reported. The primary outcomes for this review were participant-reported pain and pain relief.Fifteen studies compared oral morphine modified release (Mm/r) preparations with morphine immediate release (MIR). Fourteen studies compared Mm/r in different strengths; six of these included 24-hour modified release products. Fifteen studies compared Mm/r with other opioids. Six studies compared MIR with other opioids. Two studies compared oral Mm/r with rectal Mm/r. Three studies compared MIR with MIR by a different route of administration. Two studies compared Mm/r with Mm/r at different times and two compared MIR with MIR given at a different time. One study was found comparing each of the following: Mm/r tablet with Mm/r suspension; Mm/r with non-opioids; MIR with non-opioids; and oral morphine with epidural morphine.In the previous update, a standard of 'no worse than mild pain' was set, equivalent to a score of 30/100 mm or less on a visual analogue pain intensity scale (VAS), or the equivalent in other pain scales. Eighteen studies achieved this level of pain relief on average, and no study reported that good levels of pain relief were not attained. Where results were reported for individual participants in 17 studies, 'no worse than mild pain' was achieved by 96% of participants (362/377), and an outcome equivalent to treatment success in 63% (400/638).Morphine is an effective analgesic for cancer pain. Pain relief did not differ between Mm/r and MIR. Modified release versions of morphine were effective for 12- or 24-hour dosing depending on the formulation. Daily doses in studies ranged from 25 mg to 2000 mg with an average of between 100 mg and 250 mg. Dose titration was undertaken with both instant release and modified release products. A small number of participants did not achieve adequate analgesia with morphine. Adverse events were common, predictable, and approximately 6% of participants discontinued treatment with morphine because of intolerable adverse events.The quality of the evidence is generally poor. Studies are old, often small, and were largely carried out for registration purposes and therefore were only designed to show equivalence between different formulations.
AUTHORS' CONCLUSIONS
The conclusions have not changed for this update. The effectiveness of oral morphine has stood the test of time, but the randomised trial literature for morphine is small given the importance of this medicine. Most trials recruited fewer than 100 participants and did not provide appropriate data for meta-analysis. Only a few reported how many people had good pain relief, but where it was reported, over 90% had no worse than mild pain within a reasonably short time period. The review demonstrates the wide dose range of morphine used in studies, and that a small percentage of participants are unable to tolerate oral morphine. The review also shows the wide range of study designs, and inconsistency in cross-over designs. Trial design was frequently based on titration of morphine or comparator to achieve adequate analgesia, then crossing participants over in cross-over design studies. It was not clear if these trials were sufficiently powered to detect any clinical differences between formulations or comparator drugs. New studies added to the review for the previous update reinforced the view that it is possible to use modified release morphine to titrate to analgesic effect. There is qualitative evidence that oral morphine has much the same efficacy as other available opioids.
Topics: Administration, Oral; Adult; Analgesics, Opioid; Child; Humans; Morphine; Neoplasms; Pain; Randomized Controlled Trials as Topic
PubMed: 27105021
DOI: 10.1002/14651858.CD003868.pub4 -
Archives of Dermatological Research Aug 2022Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is... (Review)
Review
Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is available about the feasibility and efficacy of therapies alternative to systemic treatment and surgical excision, both of which often lead to unsatisfactory results or complications. We conducted a systematic review to evaluate the efficacy and safety of topical and intralesional sodium thiosulfate, extracorporeal shock-wave lithotripsy (ESWL), and laser for calcinosis cutis. PubMed, Embase, and Web of Science were searched. Reports of calciphylaxis and treatment combined with systemic medications were excluded. A total of 40 studies including 136 patients were analysed. Partial or complete remission after monotherapy was observed in 64% to 81% of cases. Self-applied topical sodium thiosulfate required patient's adherence (mean treatment duration, 4.9 months; range 2-24). Laser therapy enabled complete remission of microcalcifications after a single procedure (57%; 12/21). ESWL and intralesional sodium thiosulfate injections decreased calcinosis-associated pain (median reduction in VAS score, 3; range 0-9 and 1; range 0-5, respectively). The most common adverse event was scarring and hyperkeratosis, observed after CO laser (56%; 10/18). Intralesional sodium thiosulfate injections caused transient pain in over 11% of patients. Recurrences within the follow-up were rare (2%; 3/136). This study provides an overview of minimally invasive and local therapies that in selected cases might transcend conventional treatment. The limitation of this study is the poor level of evidence, which emerges mainly from non-randomized studies at high risk of bias.
Topics: Administration, Cutaneous; Calcinosis; Humans; Immunotherapy; Pain; Remission Induction
PubMed: 34165603
DOI: 10.1007/s00403-021-02264-5 -
British Journal of Clinical Pharmacology Jul 2016The size of the placebo response in type 2 diabetes (T2DM) treatment and its relation to the route of drug administration have not been systematically reviewed. We aimed... (Comparative Study)
Comparative Study Meta-Analysis Review
AIMS
The size of the placebo response in type 2 diabetes (T2DM) treatment and its relation to the route of drug administration have not been systematically reviewed. We aimed to determine weight loss, change in HbA1c and incidence of adverse events after treatment with injectable placebo GLP-1 receptor agonist (GLP-1ra), compared with oral placebo DPP-4 inhibitor (DPP-4i) and placebo SGLT-2 inhibitor (SGLT-2i).
METHODS
PubMed, EMBASE and Central were searched up to September 2014 for randomized placebo controlled trials investigating GLP-1ra, DPP-4i or SGLT2-i. Data on placebo groups were extracted and pooled using a generic inverse variance random effects model.
RESULTS
Sixty-seven trials were included, involving 2522, 5290 and 2028 patients randomized to placebo GLP-1ra, placebo DPP-4i and placebo SGLT-2i, respectively. Body weight decreased by -0.67 kg (95% CI -1.03, -0.31) after treatment with placebo GLP-1ra (-0.76 kg [95% CI -1.10, -0.43] with placebo short acting GLP-1ra and -0.32 kg [95% CI -1.75, 1.10] with placebo long acting GLP-1ra) and by -0.31 kg (95% CI -0.64, 0.01) with placebo DPP-4i (P = 0.06 for difference with placebo short acting GLP-1ra). Placebo SGLT-2i resulted in an intermediate -0.48 kg (95% CI -0.81, -0.15) weight loss. Weight loss with placebo showed a strong correlation with the active comparator drug (r(2) = 0.40-0.78). HbA1c changed little with placebo treatment (-0.23%, 0.10% and -0.13% for placebo GLP-1ra, DPP-4i and SGLT-2i). Adverse events occurred frequently with placebo, were often similar to the active comparator drug and led to drop-out in 2.0-2.7% of cases.
CONCLUSIONS
The response to placebo treatment was related to its active comparator, with injectable placebo GLP-1ra showing a relevant response on weight, whereas oral placebo DPP4i showed no significant response. These findings may suggest that subjective expectations influence T2DM treatment efficacy, which can possibly be employed therapeutically.
Topics: Administration, Oral; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Injections; Placebo Effect; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Weight Loss
PubMed: 26935973
DOI: 10.1111/bcp.12925 -
Annals of Internal Medicine Dec 2017Naloxone is effective for reversing opioid overdose, but optimal strategies for out-of-hospital use are uncertain. (Review)
Review
BACKGROUND
Naloxone is effective for reversing opioid overdose, but optimal strategies for out-of-hospital use are uncertain.
PURPOSE
To synthesize evidence on 1) the effects of naloxone route of administration and dosing for suspected opioid overdose in out-of-hospital settings on mortality, reversal of overdose, and harms, and 2) the need for transport to a health care facility after reversal of overdose with naloxone.
DATA SOURCES
Ovid MEDLINE (1946 through September 2017), PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, U.S. Food and Drug Administration (FDA) materials, and reference lists.
STUDY SELECTION
English-language cohort studies and randomized trials that compared different doses of naloxone, administration routes, or transport versus nontransport after reversal of overdose with naloxone. Main outcomes were mortality, reversal of overdose, recurrence of overdose, and harms.
DATA EXTRACTION
Dual extraction and quality assessment of individual studies; consensus assessment of overall strength of evidence (SOE).
DATA SYNTHESIS
Of 13 eligible studies, 3 randomized controlled trials and 4 cohort studies compared different administration routes. At the same dose (2 mg), 1 trial found similar efficacy between higher-concentration intranasal naloxone (2 mg/mL) and intramuscular naloxone, and 1 trial found that lower-concentration intranasal naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was associated with decreased risk for agitation (low SOE). Evidence was insufficient to evaluate other comparisons of route of administration. Six uncontrolled studies reported low rates of death and serious adverse events (0% to 1.25%) in nontransported patients after successful naloxone treatment.
LIMITATION
There were few studies, all had methodological limitations, and none evaluated FDA-approved autoinjectors or highly concentrated intranasal formulations.
CONCLUSION
Higher-concentration intranasal naloxone (2 mg/mL) seems to have efficacy similar to that of intramuscular naloxone for reversal of opioid overdose, with no difference in adverse events. Nontransport after reversal of overdose with naloxone seems to be associated with a low rate of serious harms, but no study evaluated risks of transport versus nontransport.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality. (PROSPERO: CRD42016053891).
Topics: Administration, Intranasal; Analgesics, Opioid; Drug Overdose; Emergency Medical Services; Humans; Injections, Intramuscular; Naloxone; Narcotic Antagonists
PubMed: 29181532
DOI: 10.7326/M17-2224