First-line Medication Research Articles

Comparing the medication costs of treating patients with schizophrenia who use cannabis with those who do not.

Cannabis use is more prevalent among people with schizophrenia than in the general population. This usage detrimentally impacts disease prognosis, contributing to escalated admissions, heightened severity of psychotic symptoms, and reduced medication response. The recent decriminalisation of cannabis in South Africa may lead to an upsurge in usage, consequently intensifying the strain on mental healthcare services. This study aimed to compare the medication costs of patients with schizophrenia depending on cannabis use. Weskoppies Hospital, Pretoria, South Africa, 2018-2019. Data pertaining to medication expenses during the 2018-2019 period were acquired from the hospital pharmacy. Data were collected from 114 patient records to form two equal cohorts: one exposed to cannabis and the other non-exposed, as indicated by urine drug screens or admission of cannabis use. Medications prescribed from admission to time of being ready for discharge were recorded and corresponding costs were calculated. Patients who were exposed to cannabis had higher medication costs (R 516.47) than patients who were non-exposed (R 328.69) (p = 0.0519), over the whole admission period. Cannabis exposure escalates the financial burden of treating schizophrenia at Weskoppies Hospital. This might be attributed to failure of cost-effective, first-line medications prompting the prescription of costlier, second-line alternatives or higher prescribed dosages. This study contributes to findings that it is more expensive to treat patients with schizophrenia who have relapsed, if they are using cannabis. This finding has future cost implications when budgeting for pharmacotherapeutic treatment.

Mechanistic insights into the conformational changes and alterations in residual communications due to the mutations in the pncA Gene of Mycobacterium tuberculosis: A computational perspective for effective therapeutic solutions

Due to its emerging resistance to first-line anti-TB medications, tuberculosis (TB) is one of the most contagious illness in the world. According to reports, the effectiveness of treating TB is severely impacted by drug resistance, notably resistance caused by mutations in the pncA gene-encoded pyrazinamidase (PZase) to the front-line drug pyrazinamide (PZA). The present study focused on investigating the resistance mechanism caused by the mutations D12N, T47A, and H137R to better understand the structural and molecular events responsible for the resistance acquired by the pncA gene of Mycobacterium tuberculosis (MTB) at the structural level. Bioinformatics analysis predicted that all three mutations were deleterious and located near the active centre of the pncA, affecting its functional activity. Furthermore, molecular dynamics simulation (MDS) results established that mutations significantly reduced the structural stability and caused the rearrangement of FE2+ in the active centre of pncA. Moreover, essential dynamics analysis, including principal component analysis (PCA) and free energy landscape (FEL), concluded variations in the protein motion and decreased conformational space in the mutants. Additionally, the mutations potentially impacted the network topologies and altered the residual communications in the network. The complex simulation study results established the significant movement of the flap region from the active centre of mutant complexes, further supporting the flap region’s significance in developing resistance to the PZA drug. This study advances our knowledge of the primary cause of the mechanism of PZA resistance and the structural dynamics of pncA mutants, which will help us to design new and potent chemical scaffolds to treat drug-resistant TB (DR-TB).

Prescribing medications for Parkinson's: part two

Around 10 million people worldwide have Parkinson's and in the UK the estimated figure is 153 000. The condition is characterised by motor symptoms including tremors, stiffness, slowness, balance problems and/or gait disorders, but people can develop a wide range of associated psychological and physical problems. Treatment for Parkinson's includes a combination of multidisciplinary input from specialists such as physiotherapy, speech and language therapy and occupational therapy, alongside the use of recognised medication regimens. Most first-line medication requires titration and is started at a low dose and increased gradually, to reduce the risk of side effects and to monitor response to treatment. Medications for Parkinson's are complex to manage, and many have side effects that could affect patient concordance. Any prescribing decisions should be discussed with the person with Parkinson's and their family members. There are a variety of medications available to manage motor and non-motor symptoms in Parkinson's, but this article will focus on levodopa, dopamine agonists, MAO-B inhibitors and catechol-O-methyltransferase inhibitors.

Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome induced by first-line antitubercular medication: A case series

Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome induced by first-line antitubercular medication: A case series

Body dysmorphia in a 23 year old patient with obsessive compulsive disorder: a case report

IntroductionBody dysmorphic disorder (BDD) was considered an anxiety disorder in the DSM-IV, but in the DSM-V was added to the obsessive-compulsive and related disorders category. BDD is a psychiatric disorder characterised by an excessive, persistent, and distressful preoccupation with a perceived defect in appearance. These perceived defects are slight and are unnoticed by others. People with BDD usually have poor insight and are preoccupied with a perceived physical defect which causes them to check on it repeatedly. This leads to an impairment in psychosocial functioning, depression, and an increase in suicide risk.ObjectivesReview how dismorphophobia (BDD) and obsessive compulsive syndrome intersect, the differences they present in symptomatology, prevalence and treatment.MethodsPresentation of a patient’s case and review of existing literature, in regards to body dysmorphic syndrome and its similarities and differences with respect to obsessive compulsive syndrome.ResultsThere are common features between both disorders, which are genetic overlap, physical past traumatic events, sex ratio, trait of perfectionism and body image disturbance.Studies have found the prevalence of BDD in patients with OCD in a large patient sample was 8.7% to 15% compared to 3% in non-OCD.The risk of comorbidity of OCD-BDD is three times higher in samples with a primary diagnosis of BDD compared to those with a primary diagnosis of OCD with 27.5% and 10.4%, respectively.BDD as well as OCD must be managed with pharmacological and psychotherapy treatment. A selective serotonin reuptake inhibitor is the recommended first-line medication for BDD, even if appearance beliefs are delusional in nature. Serotonin reuptake inhibitor (SRI) doses and trial durations are similar to those used for OCD; higher doses and a longer treatment trial are recommended than those typically used for depression and most other disorders. Cognitive-behavioral therapy that is specifically tailored to BDD is the psychosocial treatment of choice. Simply treating BDD as if it were OCD is not recommended.ConclusionsThere are limitations included a restricted number of studies overall, an absence of studies comparing biological parameters, and the frequent inclusion of participants with comorbid body dysmorphic disorder and obsessive-compulsive disorder. The current nosological status of body dysmorphic disorder is somewhat tenuous and requires further investigation, with particular focus on dimensional, biological and aetiological elements.Disclosure of InterestNone Declared

Brain magnetic resonance imaging outperforms clinical severity ratings in the prediction of treatment outcomes in major depressive disorder

IntroductionMajor depressive disorder (MDD) is a prevalent and disabling condition. Approximately 30-50% of patients do not respond to first-line medication or psychotherapy. Therefore, several studies have investigated the predictive potential of pretreatment severity rating or neuroimaging features to guide clinical approaches that can speed optimal treatment selection.ObjectivesTo evaluate the performance of 1) severity ratings (scores of Hamilton Depression/Anxiety Scale, illness duration, and sleep quality, etc.) and demographic characteristic and 2) brain magnetic resonance imaging (MRI) features in predicting treatment outcomes for MDD. Second, to assess performance variations among varied modalities and interventions in MRI studies.MethodsWe searched studies in PubMed, Embase, Web of Science, and Science Direct databases before March 22, 2023. We extracted a confusion matrix for prediction in each study. Separate meta-analyses were performed for clinical and MRI studies. The logarithm of diagnostic odds ratio [log(DOR)], sensitivity, and specificity were conducted using Reitsma’s random effect model. The area under curve (AUC) of summary receiver operating characteristic (SROC) curve was calculated.Subgroup analyses were conducted in MRI studies based on modalities: resting-state functional MRI (rsfMRI), task-based fMRI (tbfMRI), and structural MRI (sMRI), and interventions: antidepressant (including selective serotonin reuptake inhibitors [SSRI]) and electroconvulsive therapy (ECT). Meta-regression was conducted 1) between clinical and MRI studies and 2) among modality or intervention subgroups in MRI studies.ResultsWe included ten studies used clinical features covering 6494 patients, yielded a log(DOR) of 1.42, AUC of 0.71, sensitivity of 0.61, and specificity of 0.74. In terms of MRI, 44 studies with 2623 patients were included, revealing an overall log(DOR) of 2.53. The AUC, sensitivity, and specificity were 0.89, 0.78, and 0.75.Studies using MRI features had a higher sensitivity (0.89 vs. 0.61) in predicting treatment outcomes than clinical features (P < 0.001). RsfMRI had higher specificity (0.79 vs. 0.69) than tbfMRI subgroup (P = 0.01). No significant differences were found between sMRI and other modalities, nor between antidepressants (SSRIs and others) and ECT. Antidepressant studies primarily identified predictive imaging features in limbic and default mode networks, while ECT mainly focused on limbic network.ConclusionsOur findings suggest a robust promise for pretreatment brain MRI features in predicting treatment outcomes in MDD, offering higher accuracy than clinical studies. While tasks in tbfMRI studies differed, those studies overall had less predictive utility than rsfMRI data. For MRI studies, overlapping but distinct network level measures predicted outcomes for antidepressants and ECT.Disclosure of InterestNone Declared

Fármacos antipsicóticos de segunda generación y su impacto en el tejido adiposo

Schizophrenia is a chronic neuropsychiatric disorder that affects 21 million people worldwide. Currently, second-generation or atypical antipsychotics (SGAs) are the first-line medications for the treatment of this disease. However, despite its high efficacy in counteracting the neuropsychiatric symptoms of schizophrenia, recent clinical investigations in patients treated with SGAs show an increase in the prevalence of pivotal metabolic alterations, including increased body weight, hyperglycemia and dyslipidemia. Although the molecular mechanisms responsible for these side effects are not fully understood, cumulative evidences associate SGA administration with alterations in the different adipose tissue depots of white, brown and beige adipocytes. In this review, we have recapitulated the current knowledge in this area with a particular focus on the molecular aspects of the adipocyte biology, including differentiation, lipid metabolism, thermogenic function and browning processes. Keywords: antipsychotics; schizophrenia; adipose tissue; thermogenesis; browning; lipid; metabolism

Oral Pharmacokinetic Drug-drug Interactions between Amifampridine and Acetaminophen in Rats

Amifampridine, the first-line medication for Lambert-Eaton myasthenic syndrome (LEMS), is extensively metabolized by N-acetyltransferase 2 (NAT2). Drug-drug interactions (DDIs) can occur when co-administered with a NAT2 inhibitor and amifampridine. Acetaminophen is a widely used analgesic for mild to moderate pain, which is also known as a NAT2 inhibitor. In this work, we studied the effects of acetaminophen on the amifampridine pharmacokinetics in rats. Both acetaminophen (300 mg/kg) and amifampridine (2 mg/kg) were administered orally. In acetaminophen-treated rats, the systemic exposure to amifampridine significantly increased, and the ratio of the area under the plasma concentration-time curve for 3-N-acetylamifampridine to amifampridine (AUCm/AUCp) decreased markedly, which is likely due to the inhibition of NAT2 by acetaminophen. Also, the urinary amount excreted was increased in the acetaminophen-treated group, but the renal clearance remained unchanged. This oral pharmacokinetic drug-drug interaction study showed that orally administered acetaminophen significantly inhibits the NAT2-based metabolism of amifampridine and may cause meaningful DDIs.

Prescribing cascades of antigout medications from thiazide diuretics in gout-naïve hypertensive adults receiving first-line pharmacological management

Prescribing cascade is a significant clinical problem but is often overlooked. We explore the incidence of the prescribing cascades of antigout medications related to thiazide treatment in gout-naïve hypertensive adults newly exposed to the pharmacological treatment. This population-based, retrospective cohort study used the Taiwan National Health Insurance Registry Database. Gout-naïve hypertensive adults who were newly dispensed first-line antihypertensive drugs between January 1, 2000, and December 31, 2016, were enrolled. Patients were divided into the thiazide group (n = 4192) and the non-thiazide group (n = 81,083). The non-thiazide group included patients who received an angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker, or beta-blocker. The study utilized propensity score matching and multivariable Cox regression models to investigate the prescribing cascade of antigout agents following antihypertensive treatment, adjusting for factors like age, sex, comorbidities, and concurrent medications. After propensity score matching, each group consisted of 4045 patients, with the thiazide group exhibiting a higher risk of being prescribed antigout medications across different time intervals post-treatment initiation. Specifically, adjusted hazard ratios (aHRs) for the thiazide group were 2.23, 2.07, and 2.41 for < 30 days, 31–180 days, and > 180 days, respectively, indicating a sustained and significant risk over time. Comparative analyses revealed thiazide diuretics were associated with a higher risk of antigout medication prescriptions compared to other antihypertensive classes, particularly evident after 180 days. Subgroup analyses across various demographics and comorbidities consistently showed an increased risk in the thiazide cohort. Gout-naïve hypertensive adults newly dispensed thiazide had a higher risk of subsequently adding antigout agents than those taking other first-line antihypertensive medications. The awareness and interruption of these prescribing cascades are critical to improving patient safety.

Resolving neuroinflammatory and social deficits in ASD model mice: Dexmedetomidine downregulates NF-κB/IL-6 pathway via α2AR

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that severely affects individuals’ daily life and social development. Unfortunately, there are currently no effective treatments for ASD. Dexmedetomidine (DEX) is a selective agonist of α2 adrenergic receptor (α2AR) and is widely used as a first-line medication for sedation and hypnosis in clinical practice. In recent years, there have been reports suggesting its potential positive effects on improving emotional and cognitive functions. However, whether dexmedetomidine has therapeutic effects on the core symptoms of ASD, namely social deficits and repetitive behaviors, remains to be investigated. In the present study, we employed various behavioral tests to assess the phenotypes of animals, including the three-chamber, self-grooming, marble burying, open field, and elevated plus maze. Additionally, electrophysiological recordings, western blotting, qPCR were mainly used to investigate and validate the potential mechanisms underlying the role of dexmedetomidine. We found that intraperitoneal injection of dexmedetomidine in ASD model mice-BTBR T+ Itpr3tf/J (BTBR) mice could adaptively improve their social deficits. Further, we observed a significant reduction in c-Fos positive signals and interleukin-6 (IL-6) expression level in the prelimbic cortex (PrL) of the BTBR mice treated with dexmedetomidine. Enhancing or inhibiting the action of IL-6 directly affects the social behavior of BTBR mice. Mechanistically, we have found that NF-κB p65 is a key pathway regulating IL-6 expression in the PrL region. In addition, we have confirmed that the α2AR acts as a receptor switch mediating the beneficial effects of dexmedetomidine in improving social deficits. This study provides the first evidence of the beneficial effects of dexmedetomidine on core symptoms of ASD and offers a theoretical basis and potential therapeutic approach for the clinical treatment of ASD.

An International Survey of the Management of Atrial Fibrillation in Critically Unwell Patients.

To evaluate the current management of new-onset atrial fibrillation and compare differences in practice regionally. Cross-sectional survey. United States, Canada, United Kingdom, Europe, Australia, and New Zealand. Critical care attending physicians/consultants and fellows. None. A total of 386 surveys were included in our analysis. Rate control was the preferred treatment approach for hemodynamically stable patients (69.1%), and amiodarone was the most used antiarrhythmic medication (70.9%). For hemodynamically unstable patients, a strategy of electrolyte supplementation and antiarrhythmic therapy was most common (54.7%). Physicians responding to the survey distributed by the Society of Critical Care Medicine were more likely to prescribe beta-blockers as a first-line antiarrhythmic medication (38.4%), use more transthoracic echocardiography than respondents from other regions (82.4%), and more likely to refer patients who survive their ICU stay for cardiology follow-up if they had new-onset atrial fibrillation (57.2%). The majority of survey respondents (83.0%) were interested in participating in future studies of atrial fibrillation in critically ill patients. Significant variation exists in the management of new-onset atrial fibrillation in critically ill patients, as well as geographic variation. Further research is necessary to inform guidelines in this population and establish if differences in practice impact long-term outcomes.

Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission.

Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1-/- mice but partially terminated SE in IL1R1-/- mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1β pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.

A Breakthrough in the Treatment of Necrobiosis Lipoidica? Update on Treatment, Etiopathogenesis, Diagnosis, and Clinical Presentation.

Necrobiosis lipoidica (NL) is a rare granulomatous disease of a not fully understood etiopathogenesis. Classically, NL is associated with insulin-dependent diabetes mellitus. The disease often fails to respond to conventional treatments and adversely affects patients' quality of life. First-line medications are usually topical corticosteroids, but patients respond to them with varying degrees of success. Other options include tacrolimus, phototherapy, cyclosporine, fumaric acid esters, and biologics (adalimumab, etanercept, and infliximab). Our review aims to present new therapeutic approaches potentially effective in patients with refractory lesions, describe the presumed etiopathogenesis, and provide diagnostic guidance for clinicians. The review concludes that Janus kinase inhibitors and biologics such as ustekinumab and secukinumab can be used effectively in patients with recalcitrant NL. Another promising treatment option is tapinarof (an aryl hydrocarbon receptor agonist). However, studies on larger groups of patients are still needed to evaluate the effectiveness of different therapeutic options and to define consistent treatment regimens for NL. It is advisable to improve the awareness of physicians of various specialties regarding necrobiosis lipoidica as lesions diagnosed earlier usually have a better response to treatment.

A Comprehensive Review of Novel FDA-Approved Psychiatric Medications (2018-2022).

Mental health disorders are among the top leading causes of disease burden worldwide and many patients have high levels of treatment resistance. Even though medications offer improvement to some patients, antidepressants are only effective in about half of those treated, and schizophrenia is treatment-refractory in about one-third of patients. One way to combat this disparity is to improve medication development and discovery for psychiatric disorders through evidence-based research. Recently, most psychiatric medications approved by the United States Food and Drug Administration (FDA) are for increased tolerability or extended release. Because of the slow, incremental progress, there is a pressing need to explore novel medications with new indications or mechanisms of action to treat the expanding population with mental disorders, especially in those who are fully or partially recalcitrant to first-line medication options. This review aims to present the newest FDAmedications with new indications, establish the clinical need for each, and discuss future directions in drug development. We searched and reviewed novel psychiatric medications approved by the FDA from 2018 to 2022. We then analyzed each medication in the United States Clinical Trials Registry and gathered updated results for efficacy and safety information. We also searched PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, Web of Science, Elsevier, and Google Scholar to understand how these new indications met current clinical needs. Finally, we inquired about related technological implications that will lead the field of psychopharmacology now and in the years to come. We found 12 novel psychiatric medications approved by the FDA from 2018 to 2022, representing a very small percentage of the total FDA approvals during thatperiod. These psychiatric medications with novel mechanisms or improved efficacy and safety are expected to provide further options for treating mental health disorders; promising results will lead to new patterns of research.

Abstract P318: Provider Barriers and Facilitators to Treatment Intensification for Patients With Uncontrolled Blood Pressure

Background: Hypertension is the leading cause of cardiovascular disease and premature death worldwide, however, therapeutic inertia, failure to intensify pharmacotherapy when blood pressure (BP) is not at goal, is a key obstacle to hypertension control. We aimed to identify barriers and facilitators to increasing the dose or adding a different antihypertensive medication class for patients with uncontrolled BP. Methods: We conducted a qualitative study of healthcare providers from Kaiser Permanente Southern California (KPSC). Using a stratified purposeful sampling approach, we identified 300 providers across 15 medical centers and specialties and with a mix of treatment intensification rates. In 2 separate waves, we emailed a letter of invitation to 150 eligible providers followed by 2 reminder emails each two weeks apart. We sought to conduct 30 semi-structured interviews about management of patients newly diagnosed with hypertension including use of single-pill combination therapy (SPC) (the recommended first-line therapy within KPSC), barriers to therapeutic intensification and use of home BP monitoring for treatment intensification decision making. We used rapid analysis methods to code responses and develop themes. Results: A total of 11 interviews were completed with providers from family medicine (n=7), internal medicine (n=3) and cardiology (n=1) who had an average of 6 years of practice within KPSC. The majority of providers reported using monotherapy as first-line treatment while SPC therapy was reserved for younger patients and those with baseline systolic BP &gt;160 mm Hg. Monotherapy was often preferred to help providers determine if the first-line medication is causing side effects. Nearly all providers reported maximizing the dose of one medication before adding another medication class. Providers ranked the barriers to intensifying patients’ treatment in order of importance as 1) side effects such as frequent urination, hyperkalemia, and hypotension, 2) nonadherence to the current antihypertensive medication regimen and patient preference/hesitancy, 3) comorbidities (e.g., kidney function), and 4) age-related factors such as memory loss and ability to complete follow-up labs. All providers reported using patients’ home BP readings for treatment decision-making with most recognizing that patients’ out-of-clinic BP may be lower than clinic BP. Conclusion: Providers embraced stepped-care treatment for newly diagnosed patients with hypertension with most preferring monotherapy as first-line treatment. Concerns with side effects, nonadherence to the medication regimen and shared decision-making are key factors in providers’ decisions to intensify therapy for patients with uncontrolled BP. Targeted interventions to address provider barriers to treatment intensification may be needed.

Abstract P326: Patient Predictors of Antihypertensive Medications Prescription Classes Revealed by the All of Us Research Project (AOURP) Registry

Hypertension (HTN) treatment guidelines recommend five general classes (ACEi, ARB, CCB, diuretics, beta-blockers) of medications with minimal guidance regarding specific classes for different types of patients. Understanding heterogeneity in HTN treatment and demographic and clinical traits of individuals receiving different medication classes may provide insights into outcome disparities and enable the development of more tailored treatment recommendations. Using EHR data from the national All of Us Research Project (AOURP) registry, we examined patient predictors of first-line HTN medication class usage. From the AOURP we selected: 1) patients aged 18+ and diagnosed with new-onset HTN between 2010 and 2021 which is determined by having no HTN medication prescription prior to diagnosis date; 2) patients not pregnant within a year before and after the HTN diagnosis. We restricted our analyses to individuals receiving routine care within the EHR database as defined by having at least one in-person visit in the year prior to the first HTN diagnosis and prescribed with a single class of HTN medications within a year of their HTN diagnosis. We performed multivariate regression analysis on the outcome of whether a certain class of first-line medication was prescribed another class. Our covariates include age, sex, race/ethnicity, comorbidities (diabetes, CVD, CKD), and household income. All reported odds ratios below have a p-value of less than 0.05. Among 5,521 AOURP participants, ACEi was the most prescribed class (29%), followed by CCB (23%), Diuretic (22%), Beta-blocker (17%), and ARB (9%). We found ACEi were more likely to prescribed for females (OR: 0.74) while diuretics were less likely to be prescribed for males (OR: 1.45). We found CCB (OR: 2.73) and diuretics (OR: 1.54) were more likely to be prescribed for Blacks than their White counterparts. We also found that ACEi (OR: 2.75) were more likely prescribed for diabetics. In terms of household income, we found that ARB (OR: 1.67) were prescribed more frequently for those in higher income brackets (&lt;$25,000 vs $100,000+) compared to other classes of medication. This corresponds to the fact that ARB are relatively newer and more expensive class of HTN medications. Our findings show that although there are levels of clinical equipoise in terms of prescribed medication classes among the general population, evidence-based guidance on personalized antihypertension treatments may be needed.

Current vision on mechanism of action of bisphosphonates. The effect of long-term administration of bisphosphonates on bone tissue (preclinical studies)

Osteoporosis (OP) is one of the common chronic diseases in the elderly, which requires long–term therapy. Bisphosphonates (BP) belong to the first-line choice medications for the treatment of OP, however, prolonged period of bisphosphonates use has been associated with increased risk of atypical femoral fractures (AFFs), medication-related osteonecrosis of the jaw (MRONJ) and the impact on fracture healing, which attracts increased attention to the current widespread use of them.The article presents the existing classes of BP according to their chemical structure and mechanism of action, differences in their antiresorptive potencies. The data of studies on animal models on the effect of BP on the mechanical properties of bone, fracture repair, as well as the development of MRONJ are presented.

Naldemedine and Magnesium Oxide as First-Line Medications for Opioid-Induced Constipation: A Comparative Database Study in Japanese Patients With Cancer Pain.

Introduction Naldemedine and magnesium oxide are common first-line early laxative medications used in the real-world scenario in Japan, for patients with cancer pain who receive opioid prescriptions, as per a nationwide hospital claims database study. However, the real-world prescription patterns and associated outcomes are unknown. Methods In this retrospective, cohort study using the Medical Data Vision (MDV) database (January 2018 to December 2020), data were collected from eligible patients (who had a long-term prescription of strong opioids, for >30 days) in Japan with naldemedine or magnesium oxide as the first-line laxative prescription, for a long-term opioid prescription for cancer pain with ≥6 months post-opioid observation period. A laxative prescription within three days after the opioid prescription date was termed an "early" prescription. The composite incidence of dose increase or addition/change of laxatives at three months after the start of the opioid prescription was the primary endpoint after adjusting baseline characteristics between the treatment arms by propensity score matching. Results After propensity score matching, 1717 and 544 patients who were prescribed naldemedine and magnesium oxide each were included in the early prescription and non-early prescription groups, respectively. Even after matching, the incidence of death was not adjusted enough and was significantly higher in the naldemedine arm than in the magnesium oxide arm in the non-early group but comparable in the early group. The incidence of addition, change, or dose increase was significantly higher in the naldemedine arm than in the magnesium oxide arm of the early prescription group (hazard ratio (95% confidence interval), 1.08 (1.00, 1.17); p=0.0402); the incidence was comparable between the arms of the non-early group. Conclusion These findings may provide valuable insights into real-world clinical treatment patterns and preliminary evidence for the selection of first-line medications to mitigate opioid-induced constipation in Japanese patients with cancer pain.

Pain in the Context of Sensory Deafferentation.

Pain that accompanies deafferentation is one of the most mysterious and misunderstood medical conditions. Prevalence rates for the assorted conditions vary considerably but the most reliable estimates are greater than 50% for strokes involving the somatosensory system, brachial plexus avulsions, spinal cord injury, and limb amputation, with controversy surrounding the mechanistic contributions of deafferentation to ensuing neuropathic pain syndromes. Deafferentation pain has also been described for loss of other body parts (e.g., eyes and breasts) and may contribute to between 10% and upwards of 30% of neuropathic symptoms in peripheral neuropathies. There is no pathognomonic test or sign to identify deafferentation pain, and part of the controversy surrounding it stems from the prodigious challenges in differentiating cause and effect. For example, it is unknown whether cortical reorganization causes pain or is a byproduct of pathoanatomical changes accompanying injury, including pain. Similarly, ascertaining whether deafferentation contributes to neuropathic pain, or whether concomitant injury to nerve fibers transmitting pain and touch sensation leads to a deafferentation-like phenotype can be clinically difficult, although a detailed neurologic examination, functional imaging, and psychophysical tests may provide clues. Due in part to the concurrent morbidities, the physical, psychologic, and by extension socioeconomic costs of disorders associated with deafferentation are higher than for other chronic pain conditions. Treatment is symptom-based, with evidence supporting first-line antineuropathic medications such as gabapentinoids and antidepressants. Studies examining noninvasive neuromodulation and virtual reality have yielded mixed results.

Metformin hydrochloride: The most prescribed treatment for type II diabetes -gets banned

Metformin hydrochloride (MH) is synthesis of N, N-dimethylguanidine medicament which is used for the treat of type-II diabetes which was discovered by Emil Werner and James Bell, which belongs to BCS class III. MH is chosen first-line oral blood glucose-lowering medication for the treatment of type-II diabetes, almost around 120 million patients are using worldwide. It works by decreasing the hepatic glucose production through a mild inhibition of mitochondrial respiration chain complex. MH which has been further tested and also proven that it can be used for various treatments such as, weight loss, improving fertility, slow the growth of tumour, anti-malaria, and few others. MH is synthesis from Galega officinalis which is a perennial plant that blooms in the summer and is native to most temperate areas. In this study, complete information about the drug history, drug profile, pharmacokinetic, drug interaction, clinical symptoms, advantages &amp; disadvantages of MH and reason why its getting banned has been explained in detail.