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CNS Drugs Jun 2022The objective of this study was to determine which symptoms measured by the Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS)... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of Individual Items of the Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS) in Adults with Treatment-Resistant Depression Treated with Esketamine Nasal Spray Combined with a New Oral Antidepressant.
OBJECTIVE
The objective of this study was to determine which symptoms measured by the Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS) improve in those treated with esketamine nasal spray in combination with oral antidepressant (AD) compared with those treated with placebo plus AD for adult patients with treatment-resistant depression (TRD). These results complement the interpretation of PHQ-9 and MADRS total scores.
METHODS
The TRANSFORM 2 study evaluated the efficacy and safety of esketamine nasal spray in combination with AD. This post-hoc analysis used PHQ-9 and MADRS data to evaluate symptom changes. The total scores change and proportions of individual item change scores on the PHQ-9 and MADRS were evaluated at days 15 and 28; analysis of variance was used to test differences on total scores. Generalized estimation equations of logistic regression models were used to estimate the likelihood of improvement on instrument items.
RESULTS
The mean total score reduction of the PHQ-9, indicating improvement, was greater in the esketamine plus AD arm compared with placebo plus AD at day 15 (- 1.8; p = 0.045) and day 28 (- 2.8; p = 0.006). Proportions of those who improved (≥ 1 point on a 4-point scale and ≥ 2 points on a 7-point scale for the PHQ-9 and MADRS, respectively) was greater in the esketamine plus AD group compared with the placebo plus AD group across all items. The odds of improving for those in the esketamine plus AD group compared with the placebo plus AD group were over two times greater on the PHQ-9 items: "Little interest/pleasure in things" (OR 2.252, 95% CI 1.165-4.355); "Feeling down, depressed, or hopeless" (OR 2.767, 95% CI 1.400-5.470); and "Feeling tired or having little energy" (OR 2.171, 95% CI 1.153-4.087). The mean reduction in total scores on the MADRS, indicating improvement, was numerically greater at day 15 (- 2.0; p = 0.189) and statistically significantly greater at day 28 (- 4.4; p = 0.017) in the esketamine plus AD arm compared with placebo plus AD. The odds of improving for those in the esketamine plus AD group compared with the placebo plus AD group were over two times greater on the MADRS items measuring "Apparent sadness" (OR 2.007, 95% CI 1.096-3.674); and "Inability to feel" (OR 2.099, 95% CI 1.180-3.735).
CONCLUSION
Improvement in mean total scores in those treated with esketamine plus AD compared with placebo plus AD are important results to confirm efficacy. The odds of improving in those treated with esketamine plus AD was at least two times greater than with placebo plus AD on three patient- and two clinician-reported individual symptoms of TRD. These findings provide patient-relevant quantification of the esketamine plus AD treatment benefit, adding understanding as to which symptoms are most improved with treatment.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT02418585; first posted 16 April 2015.
Topics: Adult; Antidepressive Agents; Depression; Double-Blind Method; Humans; Ketamine; Nasal Sprays; Patient Health Questionnaire; Treatment Outcome
PubMed: 35441931
DOI: 10.1007/s40263-022-00916-2 -
European Journal of Pharmaceutics and... Aug 2023Low oral absorption and extensive first pass metabolism of progesterone is reported for many oral formulations which warrants investigation into other routes of...
Low oral absorption and extensive first pass metabolism of progesterone is reported for many oral formulations which warrants investigation into other routes of administration. It is the aim of this study to investigate the generation of inhaled formulations of progesterone though a spray drying approach with a focus on how spray drying impacts the physicochemical properties of progesterone. Formulations of progesterone with L-leucine and hydroxypropyl methylcellulose acetate succinate (HPMCAS) are reported to this aim. X-ray diffraction, spectroscopy and thermal analysis were used to characterise these formulations and confirmed that progesterone crystallises as the Form II polymorph during spray drying regardless of the solvent used. The resultant formulations showed higher aqueous solubility than progesterone Form I starting material and the addition of HPMCAS was shown to temporarily enable a supersaturated state. Thermal analysis was used to show that the Form II polymorph was sensitive to transformation to Form I during heating. The addition of L-leucine to the formulations reduced the temperature for the polymorphic transformation by ∼ 10 °C. However, when HPMCAS was added to the formulation, the Form II polymorph was prevented from transforming to the Form I polymorph. Cascade impaction was used to determine the aerosol performance of the spray dried powders and showed promising lung deposition profiles (mass median aerodynamic diameter 5 µm) with significant variation depending on the organic solvent used and the ratio of organic to aqueous phase in the feedstock. However, further optimisation of formulations was required to direct more progesterone into the alveolar regions. The addition of HPMCAS was seen to increase the alveolar deposition and therefore formed a formulation with a lower fine particle fraction and mass median aerodynamic diameter. The most suitable formulation for inhalation was formed from a 50:50 acetone:water mixture and showed an ED, FPF and FPD of 81.7%, 44.5% and 7.3 mg respectively. Therefore, HPMCAS is suggested as a suitable excipient to increase solubility, prevent polymorphic transformation and improve inhalation properties of spray dried progesterone formulations. This study highlights the use of spray drying to form inhalable progesterone powders with higher solubility which may broaden the application of this medicine.
Topics: Powders; Progesterone; Leucine; Excipients; Administration, Inhalation; Aerosols; Solvents; Particle Size; Dry Powder Inhalers
PubMed: 37392870
DOI: 10.1016/j.ejpb.2023.06.018 -
Medical Devices (Auckland, N.Z.) 2018There is a need for fast-acting, non-oral medication options for migraine because some attacks develop rapidly and some are accompanied by nausea, vomiting, and... (Review)
Review
There is a need for fast-acting, non-oral medication options for migraine because some attacks develop rapidly and some are accompanied by nausea, vomiting, and gastroparesis, which can hinder oral medication uptake and absorption. The most commonly prescribed migraine medications are oral triptans, with sumatriptan as the most common. However, oral triptans are associated with adverse events (AEs) of atypical sensations that may be problematic for patients. Subcutaneous (SC) injectable sumatriptan and conventional liquid triptan nasal spray formulations are also available, but the frequency of atypical sensations is the highest with SC sumatriptan, and the intense bitter taste of conventional liquid triptan nasal spray discourages use. AVP-825 (ONZETRA Xsail) is an intranasal medication delivery system containing 22 mg sumatriptan nasal powder that is now available in the USA for the acute treatment of migraine with or without aura in adults. The objective of this review is to summarize the development of AVP-825, which utilizes unique features of nasal anatomy to achieve efficient absorption and reduced systemic exposure. Literature searches for "sumatriptan nasal powder", "AVP-825", and "sumatriptan intranasal" were conducted. Review articles and pharmacokinetic, Phase II and Phase III studies were evaluated. AVP-825 demonstrates an earlier onset of efficacy and lower rate of atypical sensations than the oral standard of care, which can be attributed to its fast absorption and low systemic exposure. AEs of abnormal taste are predominantly mild. These results confirm the initial design concept for AVP-825, which aligned pharmacokinetics, anatomy, and drug presentation in a novel device to achieve optimal outcomes for the acute treatment of migraine.
PubMed: 29760572
DOI: 10.2147/MDER.S130900 -
MBio Apr 2021SARS-CoV-2 infection causing the COVID-19 pandemic calls for immediate interventions to avoid viral transmission, disease progression, and subsequent excessive...
SARS-CoV-2 infection causing the COVID-19 pandemic calls for immediate interventions to avoid viral transmission, disease progression, and subsequent excessive inflammation and tissue destruction. Primary normal human bronchial epithelial cells are among the first targets of SARS-CoV-2 infection. Here, we show that ColdZyme medical device mouth spray efficiently protected against virus entry, excessive inflammation, and tissue damage. Applying ColdZyme to fully differentiated, polarized human epithelium cultured at an air-liquid interphase (ALI) completely blocked binding of SARS-CoV-2 and increased local complement activation mediated by the virus as well as productive infection of the tissue model. While SARS-CoV-2 infection resulted in exaggerated intracellular complement activation immediately following infection and a drop in transepithelial resistance, these parameters were bypassed by single pretreatment of the tissues with ColdZyme mouth spray. Crucially, our study highlights the importance of testing already evaluated and safe drugs such as ColdZyme mouth spray for maintaining epithelial integrity and hindering SARS-CoV-2 entry within standardized three-dimensional (3D) models mimicking the human airway epithelium. Although our understanding of COVID-19 continuously progresses, essential questions regarding prophylaxis and treatment remain open. A hallmark of severe SARS-CoV-2 infection is a hitherto-undescribed mechanism leading to excessive inflammation and tissue destruction associated with enhanced pathogenicity and mortality. To tackle the problem at the source, transfer of SARS-CoV-2, subsequent binding, infection, and inflammatory responses have to be avoided. In this study, we used fully differentiated, mucus-producing, and ciliated human airway epithelial cultures to test the efficacy of ColdZyme medical device mouth spray in terms of protection from SARS-CoV-2 infection. Importantly, we found that pretreatment of the airway cultures using ColdZyme mouth spray resulted in significantly shielding the epithelial integrity, hindering virus binding and infection, and blocking excessive intrinsic complement activation within the airway cultures. Our data suggest that ColdZyme mouth spray may have an impact in prevention of COVID-19.
Topics: Antiviral Agents; Bronchi; COVID-19; Complement C3; Epithelial Cells; Humans; Immunity, Innate; Nasal Mucosa; Oral Sprays; Respiratory Mucosa; SARS-CoV-2; Virus Attachment
PubMed: 33906927
DOI: 10.1128/mBio.00904-21 -
The Journal of Hospital Infection Feb 2022The highest viral loads of severe acute respiratory syndrome coronavirus-2 are detectable in the oral cavity, so a potential reduction of infectious virus by nasal and...
The highest viral loads of severe acute respiratory syndrome coronavirus-2 are detectable in the oral cavity, so a potential reduction of infectious virus by nasal and oral sprays could reduce transmission. Therefore, the inactivation capacity of nine nasal and oral sprays was evaluated according to EN 14476. One nasal spray based on sodium hypochlorite and one oral spray containing essential oils reduced viral titres by two to three orders of magnitude. Although clinical data are still sparse, nasal and oral sprays display a more convenient application for elderly people or those who are unable to rinse/gargle.
Topics: Aged; COVID-19; Humans; Mouth; Mouthwashes; Nasal Sprays; SARS-CoV-2
PubMed: 34752803
DOI: 10.1016/j.jhin.2021.10.019 -
BMC Veterinary Research Feb 2018Newcastle disease (ND) is a highly infectious disease causing considerable economic losses to poultry farmers worldwide. Conventional vaccine delivery methods are not... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Newcastle disease (ND) is a highly infectious disease causing considerable economic losses to poultry farmers worldwide. Conventional vaccine delivery methods are not suitable for smallholder and rural poultry producers, and thus appropriate vaccination methods need to be sought. This study was carried out with the main objective of evaluating the efficacy of ND I2 vaccine delivered via drinking water and spray under smallholder farmers' condition in Minjar-Shenkora district, central Ethiopia. Twenty households were randomly assigned to intervention and control groups. Chickens owned by the selected households were randomly assigned to one of the three intervention groups. Blood samples were collected regularly for antibody assay from individual chicken vaccinated with ND I2 vaccine using different routes.
RESULTS
At baseline, there was no difference in antibody titer among the experimental groups. After the first and booster vaccinations, the three vaccinated groups had significantly higher antibody titer (P < 0.001) than the unvaccinated control group. Interestingly, there was no statistically significant difference in antibody titer among the vaccinated groups. Out of the 40 chicken in the unvaccinated control only 14 had antibody titter≥ log. Similarly 19/37 of chicken in the drinking water group, 19/37 of chicken in the eye drop group and 20/40 chicken in the spray group had antibody titer ≥ log. Two weeks after the first vaccination the proportion of chicken with antibody titer ≥ log rose to 23/37, 30/37 and 29/40 in the group vaccinated via drinking water, eye drop and spray, respectively. The proportion remained low in unvaccinated group. Hundred percent of the vaccinated chicken survived after infection with the virulent ND virus (Alemaya strain); whereas only 40% survived from the unvaccinated control group.
CONCLUSION
The results of this study showed that ND I2 vaccine administered via drinking water and spray under smallholder farmers' situation provoked protective antibody level similar to the eye drop method. The use of ND I2 vaccine could contribute to food security if used by rural poultry farmers properly.
Topics: Administration, Oral; Aerosols; Animals; Antibodies, Viral; Chickens; Drinking Water; Ethiopia; Newcastle Disease; Newcastle disease virus; Viral Vaccines
PubMed: 29439696
DOI: 10.1186/s12917-018-1355-x -
Pain Medicine (Malden, Mass.) Apr 2022To compare the effectiveness, safety, and tolerability of add-on nabiximols (NBX) oromucosal spray vs typical oral long-acting opioid (LAO) analgesics in patients with...
Effectiveness, Safety, and Tolerability of Nabiximols Oromucosal Spray vs Typical Oral Long-Acting Opioid Analgesics in Patients with Severe Neuropathic Back Pain: Analysis of 6-Month Real-World Data from the German Pain e-Registry.
OBJECTIVE
To compare the effectiveness, safety, and tolerability of add-on nabiximols (NBX) oromucosal spray vs typical oral long-acting opioid (LAO) analgesics in patients with severe (± chronic) peripheral neuropathic back pain poorly responsive to other treatments.
METHODS
Retrospective analysis of anonymized, propensity score-matched data from the German Pain e-Registry of adult outpatients who initiated NBX or LAO between March 2017 and March 2020.
RESULTS
Data were analyzed from propensity score-matched patients treated with NBX (n = 655) or LAO (n = 655): mean age ≈51 years; 57% female; mean pain duration ≈2.6 years; chronic pain 61%; severe dysfunctional pain 93%. At 6 months, NBX was noninferior to LAO for overall symptom relief, based on the least-squares mean difference between cohorts in change from baseline in patient-reported, pain-related aggregated nine-item scale scores (-27.84%; 95% confidence interval [CI] -29.71 to -25.96; P < 0.001) and individual pain-related scale scores. Subsequent prespecified superiority analysis of the primary endpoint showed that NBX was superior to LAO: all secondary endpoints measuring symptoms of pain and physical function improved significantly with NBX and LAO, with between-group differences favoring NBX (all P < 0.001). Fewer patients treated with NBX than LAO experienced treatment-related adverse events (25.5% vs 76.0%; P < 0.001) or discontinued treatment because of treatment-related adverse events (7.9% vs 29.3%; P < 0.001).
CONCLUSION
Within study limitations (e.g., observational design, all potential biases), add-on NBX was superior to and better tolerated than add-on treatment with typical oral LAO analgesics in patients with neuropathic back pain inadequately controlled by recommended/established systemic therapies.
Topics: Adult; Analgesics; Analgesics, Opioid; Back Pain; Cannabidiol; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Neuralgia; Registries; Retrospective Studies
PubMed: 34480564
DOI: 10.1093/pm/pnab263 -
International Journal of Environmental... Sep 2022Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a global and evolving pandemic associated with heavy health and financial burdens. Considering the oral... (Meta-Analysis)
Meta-Analysis Review
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a global and evolving pandemic associated with heavy health and financial burdens. Considering the oral cavity as the major reservoir for SARS-CoV-2, a systematic review and meta-analysis were conducted to assess the efficacy of mouth rinses and nasal sprays in reducing the salivary viral load of SARS-CoV-2. All and studies that assessed the virucidal efficacy of mouth rinses and nasal sprays against SARS-CoV-2 and were published in the English language from December 2019 to April 2022 were considered for analyses. Special Medical Subject Headings terms were used to search Pubmed, Scopus, Embase Ovid, and Web of Science databases. The toxicological data reliability assessment tool (ToxRToool) was used to assess the quality of the included studies. Thirty-three studies (11 and 22 ) were deemed eligible for inclusion in this analysis. Results of the pooled data showed that povidone-iodine is the most efficacious intervention in terms of reducing the SARS-CoV-2 salivary viral load, followed by chlorhexidine. The mean difference in the viral load was 86% and 72%, respectively. Similarly, povidone-iodine was associated with the highest log reduction value (LRV) , followed by cetylpyridinium chloride, (LRV = 2.938 ( < 0.0005) and LRV = 2.907 ( = 0.009), respectively). Povidone-iodine-based oral and nasal preparations showed favourable results in terms of reducing SARS-CoV-2 viral loads both and . Considering the limited number of patients , further studies among larger cohorts are recommended.
Topics: COVID-19; Cetylpyridinium; Chlorhexidine; Humans; Mouthwashes; Nasal Sprays; Povidone-Iodine; Reproducibility of Results; SARS-CoV-2
PubMed: 36231450
DOI: 10.3390/ijerph191912148 -
Future Microbiology Jan 2021A review of nasal sprays and gargles with antiviral properties suggests that a number of commonly used antiseptics including povidone-iodine, Listerine,... (Review)
Review
A review of nasal sprays and gargles with antiviral properties suggests that a number of commonly used antiseptics including povidone-iodine, Listerine, iota-carrageenan and chlorhexidine should be studied in clinical trials to mitigate both the progression and transmission of SARS-CoV-2. Several of these antiseptics have demonstrated the ability to cut the viral load of SARS-CoV-2 by 3-4 log in 15-30 s . In addition, hypertonic saline targets viral replication by increasing hypochlorous acid inside the cell. A number of clinical trials are in process to study these interventions both for prevention of transmission, prophylaxis after exposure, and to diminish progression by reduction of viral load in the early stages of infection.
Topics: Anti-Infective Agents, Local; COVID-19; Carrageenan; Chlorhexidine; Drug Combinations; Hydrogen Peroxide; Nasal Sprays; Oils, Volatile; Povidone-Iodine; SARS-CoV-2; Salicylates; Terpenes; Viral Load
PubMed: 33464122
DOI: 10.2217/fmb-2020-0286 -
Microorganisms Feb 2023Microalgae are promising host organisms for the production of encapsulated recombinant proteins such as vaccines. However, bottlenecks in bioprocess development, such as...
Microalgae are promising host organisms for the production of encapsulated recombinant proteins such as vaccines. However, bottlenecks in bioprocess development, such as the drying stage, need to be addressed to ensure feasibility at scale. In this study, we investigated the potential of spray drying to produce a recombinant vaccine in microalgae. A transformant line of carrying a subunit vaccine against salmonid alphavirus was created via chloroplast engineering. The integrity of the recombinant protein after spray drying and its stability after 27 months storage at -80 °C, +4 °C and room temperature were assessed by immunoblotting. The protein withstood spray drying without significant losses. Long-term storage at +4 °C and room temperature resulted in 50% and 92% degradation, respectively. Optimizing spray drying and storage conditions should minimize degradation and favour short-term storage at positive temperatures. Using data on yield and productivity, the economics of spray drying- and freeze drying-based bioprocesses were compared. The drying stage corresponded to 41% of the total production cost. Process optimization, genetic engineering and new market strategies were identified as potential targets for cost reduction. Overall, this study successfully demonstrates the suitability of spray drying as a process option for recombinant protein production in microalgae at the industrial scale.
PubMed: 36838478
DOI: 10.3390/microorganisms11020512