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About 30% of patients with major depressive disorder have treatment-resistant depression (TRD). Recently, intranasal esketamine was approved as a treatment option after the failure of two antidepressant trials. We report a patient with multiresistant depression that was successfully and safely treated with esketamine nasal spray. This 31-year-old inpatient with severe, chronic, and multi-TRD received an acute course of intranasal esketamine (84 mg). Previously, 14 different antidepressants, alone or in potentiation, and several neurostimulation techniques had been unsuccessful. Over 20 bi-weekly sessions, she had no significant adverse effects and was stabilized into remission. During the maintenance phase and 1 year after, she continues to be stable. This case report provides an example of a patient with severe TRD that showed significant improvement after treatment with intranasal esketamine.

BACKGROUND Benzodiazepines and electroconvulsive therapy (ECT) are standard treatment options for catatonia, a life-threatening psychomotor syndrome in people with serious mental illness. The purpose of this study was to discuss the use of ketamine in treatment-resistant catatonia, which has not been established in current literature. CASE REPORT A 63-year-old woman with schizoaffective disorder and many previous psychiatric hospitalizations was initially admitted to a psychiatric unit for severe catatonic condition, including mutism, psychomotor retardation, poor intake, and significant weight loss. She had historically failed many ECT treatments and a course of transcranial magnetic stimulation. She scored 12 on the Bush-Francis Catatonia Rating Scale. After she had no response to lorazepam or ECT, she was started on sublingual ketamine, 50 mg twice a week. She showed significant improvement and her Bush-Francis Catatonia Rating Scale score decreased steadily. She was successfully discharged home but had a quick readmission after missing a dose of ketamine. After it was resumed, she progressively improved and was again discharged home. She continued taking sublingual ketamine, until her insurance approved esketamine nasal spray. Due to a change in insurance approval, later she was switched to a combination of esketamine and sublingual ketamine. She steadily resumed her baseline activities and remained clinically stable. She did not require acute hospitalization in the months that followed. CONCLUSIONS This case highlights a potential use of sublingual ketamine and esketamine nasal spray as a treatment option in patients with chronic catatonia when other treatment choices fail to be effective.

Short-term memory loss is a common complication after intracranial hemorrhage or traumatic brain injury. FDA-approved cholinesterase inhibitors for memory symptoms of Alzheimer\'s disease have not been proven effective for improving memory impairment resulting from a hemorrhagic event. The purpose of this case study was to present the potential effectiveness of a compounded nasal spray containing methylcobalamin in improving short-term memory function in a patient post-intracranial hemorrhage. The patient started to administer the methylcobalamin nasal spray once daily after suffering from short-term memory loss for four years. His verbal memory, visual memory, and quality of life were assessed by the Hopkins Verbal Learning Test-Revised, Benton Visual Retention Test, and the 36-Item Short Form Survey, respectively, at baseline and 30 days after treatment. The delayed recall test was repeated after 60 days. After 30 days of treatment, the patient received improved scores in both verbal and visual memory tests, as well as improved self-reported quality of life. The patient became less dependent on phone reminders in daily life. The improvement in delayed recall remained significant after 60 days of treatment. This case report suggests a potentially safe and effective therapy for attenuating short-term memory impairment after intracranial hemorrhage.

Patients with treatment-resistant depression (TRD) treated with esketamine nasal spray commonly experience transient symptoms of dissociation. Manifestations of dissociation, such as feelings of detachment from the environment, can cause considerable anxiety for patients. Nonpharmacologic interventions may help clinicians to manage associated anxiety and confusion due to dissociation following administration of esketamine nasal spray. We present the case of a 64-year-old woman with major depressive disorder who participated in a clinical trial evaluating the efficacy and safety of esketamine nasal spray in conjunction with an oral antidepressant for TRD. The patient received flexible doses of esketamine nasal spray (56 or 84 mg) twice weekly for 4 weeks. On treatment day 1, the patient was administered 56 mg of esketamine nasal spray using two nasal spray devices (28 mg per device). Twenty minutes after the first esketamine nasal spray device was administered, the patient experienced a dissociative episode lasting 40 minutes that caused anxiety and confusion. The patient was encouraged to listen to music during treatment sessions, which resulted in notable improvement of her symptoms. Listening to music of choice immediately following esketamine nasal spray administration along with reassurance from staff may help manage confusion and anxiety associated with dissociation.

BACKGROUND: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development.
METHODS: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors.
RESULTS: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206).
CONCLUSIONS: IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.

BACKGROUND: The management of chronic rhinosinusitis (CRS) in patients with cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) is still a challenge. At our institution we have used gentamycin nasal spray, extemporaneously produced, for prophylactic treatment of moderate-to-severe CRS. The aim of this study was to investigate the gentamycin susceptibility of bacteria in sputum samples in CF and PCD patients treated for CRS.
METHODS: Patients with CF and PCD who were prescribed gentamycin nasal spray for CRS and had sputum bacterial cultures taken pre-treatment and followed-up at least once after ≥6 months were retrospectively included. Microbiological data were descriptively analysed in terms of bacterial species and resistance to gentamycin.
RESULTS: A case series of 17 CF and 12 PCD patients passed the inclusion criteria. Of those cases, three (18%) CF patients and one (8%) PCD patient developed resistance to gentamycin during treatment with gentamycin nasal spray. In all four cases, the resistant bacterial isolates were <i>P. aeruginosa</i>. Additionally, two CF patients already had <i>P. aeruginosa </i> isolates resistant to gentamycin in the pre-treatment culture. In further two CF patients, the multi-resistant <i>Burgdorferi cepacia </i>complex, including gentamycin resistance, was identified. <i>P. aeruginosa </i> and <i>S. aureus </i> in CF and <i>P. aeruginosa</i> and <i>H. influenza </i> in PCD were the predominant bacterial species.
CONCLUSIONS: The study showed that there was moderate incidence of gentamycin resistance in CF and PCD patients at our institution. However, further prospective studies are needed to confirm the outcomes.

Background: A spray pattern (SP) test is one of the most challenging in vitro tests for nasal spray products (NSPs) associated with a high degree of variation. The total results variation observed in such studies should be in major part representative of product performance to assure high confidence when making conclusions based on obtained results. Analytical methods should be developed in a way to minimize variation contribution of random factors. A systematic statistical assessment of sources of variation is encouraged to be performed during any method development. Methods: This study includes the development of a product-shaking procedure, definition of in vivo relevant actuation parameters, and the development of a robust SP method considering NSP behavior. The final SP method is tested on different days and in different laboratories to evaluate the contribution of individual factors and interactions to the observed variance in SP using a gauge repeatability and reproducibility (GRR) model. Results: It was found that the time lag between consecutive actuations significantly influences the variability of the SP area, suggesting the importance of determining a recovery period. Factor analyst was not found to be important. Factor day was found to have the potential to impact results, mostly through interactions with other factors, suggesting that one should pay attention when performing any comparative studies within the same laboratory on different days. Significant differences were observed when the same product was tested in different laboratories. Conclusion: Key random factors, which significantly contribute to total variation, were identified using a GRR approach. By applying an appropriate control strategy over these factors, one can assure that assessed total variation can be representative of product performance. The same general approach is not only applicable to development of SP method for NSP but to all types of analytical testing as well.

Opioid overdose is a growing concern in the United States and internationally. Prehospital or pre-medical personnel (layperson) administration of naloxone, an opioid antagonist, to reverse overdose, is an expanding mode of harm reduction. Recently, community clinics, methadone clinics, needle exchanges, some pharmacies, and other health care facilities have made naloxone available to the community.
This case describes heroin overdose reversal of a 28-year-old male who had been using about a gram of heroin intravenously for 3 years but recently reduced frequency of use in an attempt to stop. He was seen initially 1 week prior to a buprenorphine induction in our clinic. After the initial intake, he used intravenous heroin, a larger amount than over the past several weeks in anticipation of abstinence, lost consciousness, and was difficult to arouse. A friend with him noted the patient\'s respirations to become shallow and administered naloxone nasal spray that the patient had obtained from a needle exchange, but did so intravenously by attaching an unused drug needle to the syringe barrel in place of the nasal atomizer. The patient\'s overdose was reversed and he recovered.
This is the first known published case of a community-distributed naloxone nasal spray being used intravenously by a layperson (bystander). The case emphasizes the efficacy of naloxone in overdose reversal and also the need for education or instructions on naloxone use by others (not just the user). Finally, it highlights the risk of overdose in those entering treatment, seeking intoxication one last time.

The objective of the present study was to design and develop drug-device combination product in particular flunisolide nasal spray (FNS) using quality by design (QbD) approach. Quality target product profile (QTPP) of FNS was defined and critical quality attributes (CQAs), i.e. viscosity (cp) (Y1) and D50 droplet size distribution (DSD) (μm) (Y2) were identified. Potential risk factors were identified using a fish bone diagram and failure mode effect analysis (FMEA) tools. Plackett-Burman and Box-Behnken designs were used for screening the significant factors and optimizing the variables range, respectively. It was observed that viscosity (cp) (Y1) was significantly impacted by formulation variables X1: propylene glycol (PG) (%) and X2: polyethylene glycol (PEG) 3350 (%), while D50 DSD (μm) (Y2) was significantly impacted by formulation variables X1: PG (%), X2: PEG 3350 (%) and device variable X8: delivery volume (μl). A design space plot within which the CQAs remained unchanged was established at laboratory scale. In conclusion, this study demonstrated how QbD based development approach can be applied to the development of drug-device combination products with enhanced understanding of the impact of formulation, process and device variables on CQAs of drug-device combination products.