Treatment with psychostimulants and atomoxetine in people with psychotic disorders: reassessing the risk of clinical deterioration in a real-world setting.

BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine. AIMS: To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before. METHOD: This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year. RESULTS: Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24-0.54; P < 0.0001). CONCLUSIONS: These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders.

Nanofiber-based wound dressing in wound healing of elderly patients.

Introduction: With the aging of the population, it has become a serious problem that the wounds of elderly patients are not easy to heal. Aim: To explore the application of nanofiber wound dressing in wound healing of elderly patients. Material and methods: In this article, 86 elderly patients with chronic wounds admitted to the Affiliated Hospital of Shaanxi University of Chinese Medicine from January 2023 to September 2023 were enrolled, and they were randomly divided into control and experimental groups, with 43 cases in each group. Controls used traditional wound dressings in care. The experimental group used nanofiber wound dressings. The wound healing efficacy, inflammatory factors, side effects, wound infection degree, healing time, and pain were compared between the two groups. Results: The total effective rate of the experimental group (97.67%) was higher as against controls (86.04%). Wound germiculture positive (7.14 ±2.76%) was lower in the experimental group as against controls (22.13 ±3.27%. The wound healing time of the experimental group (18.68 ±5.78 d) was shorter as against controls (30.24 ±6.19 d). The visual analogue scale (VAS) score of the experimental group (2.68 ±0.41 s) was lower as against controls (3.57 ±0.89 s) after 16 days of care (p < 0.05). Conclusions: The use of nanofiber dressings is an effective means to promote wound healing in elderly patients, which is worthy of application in practical care.

Informed consent for psychotherapy: Ethical illusion or clinical reality? A survey about psychotherapists' attitudes and practices in Germany.

OBJECTIVE: This study aimed to assess clinicians' attitudes and their current clinical practices regarding informed consent for psychotherapy. METHOD: A convenience sample of N = 530 clinicians in Germany (n = 418 licensed psychotherapists and n = 112 postgraduate psychotherapy trainees) took part in an online survey. RESULTS: Most clinicians (84%) reported obtaining informed consent for psychotherapy in their daily routine. However, many psychotherapists felt unsure about satisfactorily fulfilling the legal (63%) and ethical obligations (52%). The two most frequently reported components of information disclosure related to explaining the terms and conditions of psychotherapy (96%) and the psychotherapeutic approach (91%). Providing information about mechanisms of psychotherapy (33%) and the role of expectations (30%) were least practiced. One in five psychotherapists reported not informing clients about potential risks and side effects. A considerable proportion reported concern about inducing anxiety in patients by disclosing information about risks and side effects (52%). CONCLUSIONS: Although obtaining informed consent for psychotherapy seems to be the rule rather than the exception in clinical practice, the quality of its implementation in terms of legal, ethical and clinical demands remains questionable. Training psychotherapists in providing comprehensive informed consent enables informed decision-making and might have a positive influence on treatment expectations and outcomes.

Clinical study of interstitial brachytherapy for 72 cases of recurrent cervical cancer.

Objective: To determine the application value of interstitial brachytherapy in the treatment of recurrent cervical cancer. Methods: A retrospective analysis was conducted on the clinical data of 72 patients with recurrent cervical cancer admitted to The Fourth Hospital of Hebei Medical University from September 2017 to April 2022. They were divided into two groups according to different brachytherapy methods: conventional after-load radiotherapy group and interstitial brachytherapy group. After treatment, regular outpatient reviews or telephone follow-ups were conducted to evaluate the efficacy, related toxic and side effects and prognostic factors. Results: The short-term efficacy of the interstitial brachytherapy group was significantly higher than that of the interstitial brachytherapy group (p<0.05). The one-year LC and two-year LC of the interstitial brachytherapy group were 94% and 90.6%, respectively, while those of the conventional after-load group were 74.5% and 67.8%, respectively, with a statistically significant difference (p<0.05). The clinical efficacy of peripheral recurrence was 13.9% in the interstitial brachytherapy group, and that in the conventional after-load group was 2.7%, with a statistically significant difference (p<0.05). There was a statistically significant difference in late toxic and side effects between the two groups (p<0.05). Prognostic factors: Multivariate analysis of the COX regression model showed that only the maximum tumor diameter was an independent prognostic factor for OS and PFS, while the recurrence site and brachytherapy method were the independent prognostic factors for LC. Conclusion: Interstitial brachytherapy radiotherapy touts various benefits in the treatment of patients with recurrent cervical cancer, such as good short-term efficacy, high local control rate, reduced incidence of advanced bladder and rectal toxicity, and improved quality of life.

Time to re-evaluate the risks and benefits of valproate and a call for action.

Valproate is widely used in psychiatry and neurology, including off-label use. Here we consider its potential benefits and risks, particularly for women of childbearing potential, and the evidence that clinical guidelines are adhered to. Finally, we consider the implications for clinical practice and research into its efficacy in off-label indications.

Cannabinoids in psychiatry: they are here to stay.

Cannabinoids are commonly perceived by the public as safe and effective for improving mental health, despite limited evidence to support their use. We discuss reasons why cannabinoids may be particularly compelling for our patients and provide strategies for how psychiatrists can counsel and educate patients on the evidence regarding cannabinoids.

Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications.

Metformin is the oldest and most commonly used first-line antidiabetic drug because of its good clinical efficacy, high safety, low cost and easy access. At the same time, in recent years, we have found that its role as a therapeutic drug is gradually expanding. A large number of basic studies have shown that metformin may become a promising attractive candidate for drug repurposing. Therefore, it is extremely beneficial to conduct an in-depth discussion on the main mechanism of metformin. As early as the year 1950, studies showed that metformin played a biological role by regulating mitochondria. Then, ground-breaking studies showed that metformin functions by inhibiting complex I in the mitochondrial respiratory chain. Although there are still many controversies about the key molecular targets of metformin, with the emergence of more and more evidence, it gradually came to be concluded that mitochondria play a central role in the application of metformin. Mitochondria are important fulcrums for cell functions. The exact mechanism of action in mitochondria of this pleiotropic anti-hyperglycaemic molecule is still unclear. This review article explores the core role of mitochondria in the pharmacological and toxicological effects of metformin, and summarises the mechanism of action if metformin in mitochondria. It also provides ideas and supporting evidence for the re-development and reuse of metformin as an old drug, as well as new insight into the treatment of human diseases.

A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health.

Curcumin is the most important active component in turmeric extracts. Curcumin, a natural monomer from plants has received a considerable attention as a dietary supplement, exhibiting evident activity in a wide range of human pathological conditions. In general, curcumin is beneficial to human health, demonstrating pharmacological activities of anti-inflammation and antioxidation, as well as antitumor and immune regulation activities. Curcumin also presents therapeutic potential in neurodegenerative, cardiovascular and cerebrovascular diseases. In this review article, we summarize the advancements made in recent years with respect to curcumin as a biologically active agent in malignant tumors, Alzheimer's disease (AD), hematological diseases and viral infectious diseases. We also focus on problems associated with curcumin from basic research to clinical translation, such as its low solubility, leading to poor bioavailability, as well as the controversy surrounding the association between curcumin purity and effect. Through a review and summary of the clinical research on curcumin and case reports of adverse effects, we found that the clinical transformation of curcumin is not successful, and excessive intake of curcumin may have adverse effects on the kidneys, heart, liver, blood and immune system, which leads us to warn that curcumin has a long way to go from basic research to application transformation.

Clozapine-induced myocarditis: electronic health register analysis of incidence, timing, clinical markers and diagnostic accuracy.

BACKGROUND: Clozapine is associated with increased risk of myocarditis. However, many common side-effects of clozapine overlap with the clinical manifestations of myocarditis. As a result, there is uncertainty about which signs, symptoms and investigations are important in distinguishing myocarditis from benign adverse effects of clozapine. Clarity on this issue is important, since missing a diagnosis of myocarditis or discontinuing clozapine unnecessarily may both have devastating consequences. AIMS: To examine the clinical characteristics of clozapine-induced myocarditis and to identify which signs and symptoms distinguish true myocarditis from other clozapine adverse effects. METHOD: A retrospective analysis of the record database for 247 621 patients was performed. A natural language processing algorithm identified the instances of patients in which myocarditis was suspected. The anonymised case notes for the patients of each suspected instance were then manually examined, and those whose instances were ambiguous were referred for an independent assessment by up to three cardiologists. Patients with suspected instances were classified as having confirmed myocarditis, myocarditis ruled out or undetermined. RESULTS: Of 254 instances in 228 patients with suspected myocarditis, 11.4% (n = 29 instances) were confirmed as probable myocarditis. Troponin and C-reactive protein (CRP) had excellent diagnostic value (area under the curve 0.975 and 0.896, respectively), whereas tachycardia was of little diagnostic value. All confirmed instances occurred within 42 days of clozapine initiation. CONCLUSIONS: Suspicion of myocarditis can lead to unnecessary discontinuation of clozapine. The 'critical period' for myocarditis emergence is the first 6 weeks, and clinical signs including tachycardia are of low specificity. Elevated CRP and troponin are the best markers for the need for further evaluation.

Selective serotonin reuptake inhibitor 'discontinuation syndrome' or withdrawal.

Attempts to define selective serotonin reuptake inhibitor (SSRI) withdrawal with the term 'discontinuation syndrome' are not supported by evidence. Acknowledging that SSRI use can result in dependence and withdrawal allows patients to be better informed around decisions related to these drugs, and helps inform strategies for safe tapering as appropriate.

Towards safer risperidone prescribing in Alzheimer's disease.

BACKGROUND: In the treatment of psychosis, agitation and aggression in Alzheimer's disease, guidelines emphasise the need to 'use the lowest possible dose' of antipsychotic drugs, but provide no information on optimal dosing. AIMS: This analysis investigated the pharmacokinetic profiles of risperidone and 9-hydroxy (OH)-risperidone, and how these related to treatment-emergent extrapyramidal side-effects (EPS), using data from The Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease study (Clinicaltrials.gov identifier: NCT00015548). METHOD: A statistical model, which described the concentration-time course of risperidone and 9-OH-risperidone, was used to predict peak, trough and average concentrations of risperidone, 9-OH-risperidone and 'active moiety' (combined concentrations) (n = 108 participants). Logistic regression was used to investigate the associations of pharmacokinetic biomarkers with EPS. Model-based predictions were used to simulate the dose adjustments needed to avoid EPS. RESULTS: The model showed an age-related reduction in risperidone clearance (P < 0.0001), reduced renal elimination of 9-OH-risperidone (elimination half-life 27 h), and slower active moiety clearance in 22% of patients, (concentration-to-dose ratio: 20.2 (s.d. = 7.2) v. 7.6 (s.d. = 4.9) ng/mL per mg/day, Mann-Whitney U-test, P < 0.0001). Higher trough 9-OH-risperidone and active moiety concentrations (P < 0.0001) and lower Mini-Mental State Examination (MMSE) scores (P < 0.0001), were associated with EPS. Model-based predictions suggest the optimum dose ranged from 0.25 mg/day (85 years, MMSE of 5), to 1 mg/day (75 years, MMSE of 15), with alternate day dosing required for those with slower drug clearance. CONCLUSIONS: Our findings argue for age- and MMSE-related dose adjustments and suggest that a single measure of the concentration-to-dose ratio could be used to identify those with slower drug clearance.

Benzodiazepines: it's time to return to the evidence.

SUMMARY: We propose that discussions of benzodiazepines in the current psychiatric literature have become negatively biased and have strayed from the scientific evidence base. We advocate returning to the evidence in discussing benzodiazepines and adhering to clear definitions and conceptual rigour in commentary about them.

Cisplatin combined with capecitabine-induced chemotherapy for local nasopharyngeal carcinoma can improve the quality of life and reduce toxic and side effects.

BACKGROUND: This study was designed to probe into the effect of cisplatin combined with capecitabine on nasopharyngeal carcinoma (NPC). METHODS: A total of 136 NPC patients treated for the first time in our hospital from January 2016 to March 2017 were collected and divided into two groups: A and B. Among them, 66 in group A were treated with cisplatin intravenous drip, while 70 in group B were treated with capecitabine on the basis of group A. The efficacy, toxic and side effects, and quality of life of the two groups were observed. RESULTS: The short-term efficacy of group B was better than that of group A (p<0.05). The toxic and side effects of group B were lower than that of group A (p<0.05). The quality of life in group B was higher than that in group A (p<0.05). CONCLUSIONS: Cisplatin combined with capecitabine-induced chemotherapy for local NPC can improve the quality of life and reduce the toxic and side effects.

Selective Antifungal Activity and Fungal Biofilm Inhibition of Tryptophan Center Symmetrical Short Peptide.

Candida albicans, an opportunistic fungus, causes dental caries and contributes to mucosal bacterial dysbiosis leading to a second infection. Furthermore, C.albicans forms biofilms that are resistant to medicinal treatment. To make matters worse, antifungal resistance has spread (albeit slowly) in this species. Thus, it has been imperative to develop novel, antifungal drug compounds. Herein, a peptide was engineered with the sequence of RRFSFWFSFRR-NH2; this was named P19. This novel peptide has been observed to exert disruptive effects on fungal cell membrane physiology. Our results showed that P19 displayed high binding affinity to lipopolysaccharides (LPS), lipoteichoic acids (LTA) and the plasma membrane phosphatidylinositol (PI), phosphatidylserine (PS), cardiolipin, and phosphatidylglycerol (PG), further indicating that the molecular mechanism of P19 was not associated with the receptor recognition, but rather related to competitive interaction with the plasma membrane. In addition, compared with fluconazole and amphotericin B, P19 has been shown to have a lower potential for resistance selection than established antifungal agents.

Treatment concerns for psychiatric symptoms in patients with COVID-19 with or without psychiatric disorders.

Many psychiatric patients have been infected with COVID-19, and patients with COVID-19 may develop psychiatric symptoms after treatment with antiviral drugs. Given the tolerability and minimal P450 interactions, antidepressants (i.e., citalopram, escitalopram etc.), antipsychotics (i.e., olanzapine) and valproate can be considered to be safe in combination with antiviral drugs.

Barriers to monitoring and management of cardiovascular and metabolic health of patients prescribed antipsychotic drugs: a systematic review.

BACKGROUND: The use of atypical antipsychotics which currently form the primary choice pharmacotherapy for several mental health conditions have been linked to cardiovascular and metabolic side effects. This systematic review aimed to investigate the barriers to monitoring and management of cardiovascular co-morbidities in patients prescribed antipsychotic medicines. METHODS: A protocol-led (CRD-42018106002) systematic literature review was conducted by searching Medline, Embase, and PsycINFO databases 2003 until October 2019. Cochrane, Centre for Review and Dissemination (CRD) and PRISMA guidelines were followed. Studies investigating barriers to monitoring and management of cardiovascular co-morbidities in patients prescribed antipsychotic medicines were included. RESULTS: A total of 23 records were included. Key barriers included a) health-care system-related factors such as lack of knowledge and expertise amongst care providers, available resources, confusion around remit and roles, fragmentation of care such as across general practitioners and psychiatrists, and time constraints and b) patient-related factors such as disability resulting from mental health conditions, knowledge and skills of the patients. CONCLUSION: Barriers to monitoring and management of cardiovascular and metabolic health of patients taking antipsychotic medicines are multidimensional. Apart from educational interventions directed to both patients and health-care professionals, the results suggest a need for the improvement of wider system-related factors to improve physical health of patients prescribed antipsychotic medicines. Clearer guidelines, clarity of remit and roles amongst service providers are necessary in addition to educational interventions directed at patients and health-care professionals in improving physical health monitoring, counselling and management of patients prescribed antipsychotic medicines. TRIAL REGISTRATION: A protocol was developed and registered with PROSPERO as per PRISMA-P guidelines ( CRD 42018106002 ).

Topical anesthesia.

Topical anesthetics are being widely used in numerous medical and surgical sub-specialties such as anesthesia, ophthalmology, otorhinolaryngology, dentistry, urology, and aesthetic surgery. They cause superficial loss of pain sensation after direct application. Their delivery and effectiveness can be enhanced by using free bases; by increasing the drug concentration, lowering the melting point; by using physical and chemical permeation enhancers and lipid delivery vesicles. Various topical anesthetic agents available for use are eutectic mixture of local anesthetics, ELA-max, lidocaine, epinephrine, tetracaine, bupivanor, 4% tetracaine, benzocaine, proparacaine, Betacaine-LA, topicaine, lidoderm, S-caine patch™ and local anesthetic peel. While using them, careful attention must be paid to their pharmacology, area and duration of application, age and weight of the patients and possible side-effects.

Analysis of clozapine prescribing in the over-65s: 5-year retrospective study.

AIMS AND METHOD: Patients prescribed clozapine are increasingly living into old age. However, there is a lack of studies to guide prescribing in this age group. We sought to identify all clozapine patients in Hertfordshire Partnership NHS Foundation Trust over a 5-year period and review side-effect burden and co-prescribing in all patients aged over 65 years. RESULTS: We identified 69 patients. The majority (61%) were stable in terms of mental state; 94% of cases had experienced a side-effect within the past year, with constipation occurring most commonly (65% of cases). CLINICAL IMPLICATIONS: Our findings reveal a significant side-effect burden, particularly in relation to constipation. Clozapine-induced gastrointestinal hypomotility (CIGH) can be fatal; however, increasing age has not been a recognised risk factor for constipation in clozapine patients to date. This raises questions about increasing risk to physical health as patients age and adds to concerns about the lack of monitoring for CIGH.

Clozapine and Sweet's syndrome: case report.

A patient developed fever, raised inflammatory markers and a maculopapular rash following commencement of clozapine for treatment of his schizoaffective disorder. Skin biopsy confirmed Sweet's syndrome. Identification of the cause was challenging, with a number of possible considerations including infection, malignancy and various potential drug triggers.This case highlights the difficulties in the diagnosis of Sweet's syndrome, as well as in identifying the original trigger, which can have significant consequences for management. Withdrawal of potentially causative drugs must be balanced with their benefits, and decisions must be made in the best interests of the patient. Following two courses of prednisolone and withdrawal of clozapine, the patient's rash and systemic symptoms resolved. This confirmed the diagnosis of drug-induced Sweet's syndrome, with clozapine as the offending agent. His mental state stabilised on an alternative antipsychotic.

The Promises of Proteomics and Metabolomics for Unravelling the Mechanism and Side Effect Landscape of Beta-Adrenoceptor Antagonists in Cardiovascular Therapeutics.

Cardiovascular medicine witnessed notable advances for the past decade. Multiomics research offers a new lens for precision/personalized medicine for existing and emerging drugs used in the cardiovascular clinic. Beta-blockers are vital in treating hypertension and chronic heart failure. However, clinical use of beta-blockers is also associated with side effects and person-to-person variations in their pharmacokinetics and pharmacodynamics. A comprehensive understanding of the mechanisms that underpin the side effect landscape of beta-blockers is imperative to optimize their therapeutic value. In addition, current research emphasizes the circadian clock's vital roles in regulating pharmacological parameters. Administration of the beta-blockers at specific dosing times could potentially improve their effectiveness and reduce their toxic effects. The rapid development of mass spectrometry technologies with chemical proteomics and thermal proteome profiling methods has also substantially advanced our understanding of underlying side effects mechanisms by unbiased deconvolution of drug targets and off-targets. Metabolomics is steadily demonstrating its utility for conducting mechanistic and toxicological analyses of pharmacological compounds. This article discusses the promises of cutting-edge proteomics and metabolomics approaches to investigate the molecular targets, mechanism of action, adverse effects, and dosing time dependency of beta-blockers.