Search

Purpose The purpose of this article is to perform a literature review of current evidence studying the use of the Eat, Sleep, Console method of assessment for managing infants with Neonatal Opioid Withdrawal Syndrome, more commonly known as Neonatal Abstinence Syndrome. Results Four main themes emerged from the review. When Eat, Sleep, Console was utilized as the assessment method for infants with Neonatal Opioid Withdrawal Syndrome, a decrease in the pharmacological intervention was observed, length of hospitalization decreased along with the overall cost of treatment, and caregiver presence and involvement in the care of their infants improved. Conclusions Replacing traditional assessment tools with the ESC method for the management of newborn infants with NOWS has proven to have a positive impact on patient outcomes. Further research is needed to study the long-term outcomes of utilizing this method and to compare the impact of various pharmacotherapy drugs when employing the ESC method as the assessment tool. Multidisciplinary collaboration alongside extensive caregiver education and involvement is essential to the success of the ESC method.

Background Medication Assisted Treatment for Opioid Dependence (MATOD) is clinically effective and cost effective, yet a lack of MATOD prescribers in the community limits access to this treatment in Australia. These shortages are often greatest in regional and rural areas. Objective(s) The Enhancing Pharmacists Involvement in Care (EPIC)-MATOD study will evaluate clinical and implementation outcomes among people with opioid dependence receiving MATOD through a collaborative pharmacist-prescriber model of care across multiple sites in a regional location (encompassing a mix of metropolitan and non-metropolitan areas) of Victoria, Australia. Methods and analysis The EPIC-MATOD study is a prospective, multisite, implementation trial of collaborative MATOD care. Pharmacists and prescribers will be recruited through the local network of opioid pharmacotherapy providers. Patients will be recruited through participating healthcare providers. After induction into the collaborative care model, patients and healthcare professionals will be followed up over 6- (patients) and 12-months (pharmacists and prescribers) in a hybrid implementation-efficacy study, with outcomes mapped to the RE-AIM framework. The primary clinical efficacy endpoint is patient retention in treatment at 26 weeks. The primary implementation outcome is treatment capacity, based on prescriber time required to provide treatment through collaborative care compared with traditional care. Secondary clinical endpoints include attendance for dosing and clinical reviews, substance use, mental and physical health and overall well-being. Implementation costs, acceptability, and provider engagement in collaborative care will be used as secondary implementation outcome indicators. Time and costs associated with collaborative care, and health service utilisation, will also be estimated. Project impact The study will provide important information on outcomes and acceptability of collaborative care for MATOD, as well as the cost and key considerations in delivering a collaborative model of care in Australia and other countries where similar treatment barriers exist.

Background Little is known about the influence of hepatic artery infusion pump (HAIP) therapy in the setting of chemotherapy resistant hepatic disease in the era of modern systemic therapies. Methods Patients who underwent HAIP therapy for chemotherapy resistant and unresectable colorectal liver metastases (CRLM) were reviewed retrospectively. Results A total of 25 patients met inclusion criteria. 52% had isolated CRLM and 92% had five or more metastatic lesions. Partial response was noted in 40% of patients. Median hepatic progression-free survival (PFS) was 7 months in those with extrahepatic disease versus 6 months in those with isolated CRLM at the time of HAIP placement (p = 0.75). Median overall survival was 8 months in patients with extrahepatic disease and 14 months in patients with isolated CRLM (p = 0.06). Conclusions Our findings are comparable to published data and augment the literature which supports HAIP use in chemotherapy-resistant, liver-predominant metastatic colorectal cancer patients.

Background Weight loss medications have been shown to be effective for weight loss and reducing disease state risk in patients who are overweight or obese. However, it is unknown what impact pharmacists have on weight loss when providing medication management services. Objective To evaluate weight loss outcomes and clinic utilization of a pharmacist-run weight-loss pharmacotherapy service. Setting VA Tennessee Valley Healthcare System (TVHS) in Nashville, TN Practice description Patients enrolled in the MOVE! weight loss program were referred to a clinical pharmacy specialist (CPS) who was able to assess comorbidities, prescribe weight loss medication, and provide ongoing follow-up via telehealth visits. Practice innovation This is the first description of a pharmacist-run weight loss pharmacotherapy clinic. This model expanded the role of pharmacists at TVHS, where CPS involvement was previously limited to chart reviews when medication recommendations were requested. Evaluation This prospective quality improvement project evaluated patients seen by the CPS in the first 6 months of clinic implementation. Primary outcomes included change in weight and proportion of patients with at least 5% weight loss at the end of study period. Results were compared with patients seen by preventative medicine providers (PMPs) in the same time frame. Results A total of 79 patients were seen in the CPS clinic and 40 met inclusion criteria. The clinic utilization rate was 100%. Mean weight change was -3.6 ± 5.7 kg (p less than 0.0005) and 25% of patients followed by the CPS lost at least 5% body weight. In the PMP clinic, 29 patients demonstrated a mean weight change of -1.6 ± 6.0 kg (p=0.15 compared to baseline) and 17.2% lost at least 5% body weight. Conclusion This pharmacist-led weight loss clinic demonstrated statistically significant reductions in weight and was able to expand access to care for patients seeking weight loss services.

Knee osteoarthritis (OA) is a common and morbid condition. No disease-modifying therapies exist; hence the goals of current treatment are to palliate pain and to retain function. OA is significantly influenced by the placebo effect. Nonpharmacologic interventions are essential and have been shown to improve outcomes. Canes, unloading braces, and therapeutic heating/cooling may be valuable. Pharmacotherapy options include topical and oral nonsteroidal anti-inflammatory drugs, duloxetine, and periodic intra-articular glucocorticoids and hyaluronans. Opioids, intra-articular stem cells, and platelet-rich plasma are not recommended. Novel targets such as nerve growth factor are under investigation and may be approved soon for OA pain.

Introduction: Due to functional hypogammaglobulinemia, multiple myeloma patients are at increased risk for infection and generally have poorer responses to vaccines. In this study, we examined antibody responses after complete COVID-19 vaccination in patients with plasma cell dyscrasias, most of whom were receiving treatment. Patients and Methods: Real world study of consecutive patients with multiple myeloma and other plasma cell dyscrasias (PCD) were evaluated after complete vaccination with either the 2-shot mRNA vaccines from BioNTech and Moderna or the 1-shot adenoviral vector vaccine from Johnson & Johnson (J&J). Patients received vaccines 1-4 months before antibody testing without controlling for the type of vaccine or the timing of drug therapy. Patients with a clinical history or antibody evidence of prior infection were excluded. Anti-nucleocapsid and quantitative anti-spike antibody levels were measured with the Roche Elecys assay. Results: 95% of patients had detectable antibody responses. Multivariate analysis showed that higher age, ongoing anti-CD38 monoclonal antibody therapy and the J&J vaccine negatively affected quantitative response. A small number of ineffectively vaccinated patients receiving IVIG subsequently had detectable nucleocapsid and spike antibodies confirming the presence of the latter in currently administered IVIG. Conclusions: Nearly all PCD had detectable anti-spike antibodies after vaccination but age, anti-CD38 monoclonal antibody therapy, and the single-shot J&J vaccine negatively affected responses. In patients who received the J&J vaccine, second doses or heterologous mRNA vaccines should be tested. Quantitative antibody testing might make future management more rational, particularly in patients with poor responses.

Aim: To assess relations between Valsalva- and phenylephrine test-derived measures and outcome in reduced ejection fraction heart failure (HFrEF) patients receiving comprehensive neurohormonal blockade pharmacotherapy. Methods: Data from 56 HFrEF patients (LVEF: 32±6%; mean±SD) subjected to Valsalva and phenylephrine tests were analyzed retrospectively. Baroreflex-related (Valsalva-ratio [cBRSVR] and BP-RRI slope from phase IV [cBRSIV_SLOPE]) and non-baroreflex-related measures (systolic BP rise in phase IV [ΔSBPPHASE_IV], and pulse-amplitude-ratio [PAR]) were calculated from Valsalva. Short-term outcome (HF-related hospitalization, ICD shock or all-cause death within 24-months from examination) and long-term outcome (ICD shock or all-cause death within 60-months) were analyzed. Results: The endpoint occurred in 16 and 18 patients, for short- and long-term outcome, respectively. Low ΔSBPPHASE_IV identified patients at risk in long-term perspective, as evidenced by low- vs. high ΔSBPPHASE_IV comparison (square-wave response patients assigned to low ΔSBPPHASE_IV group, P=0.002), and Cox model (HR: 0.91, CI: 0.86-0.96, P Conclusions: Non-baroreflex-related measures obtained from Valsalva: ΔSBPPHASE_IV and PAR, might carry prognostic value in HFrEF patients receiving neurohormonal blockade pharmacotherapy.

Clostridioides difficile infection (CDI) is a major public health concern for pediatric and adult patients. The management of pediatric CDI poses a challenge to healthcare providers due to lack of strong randomized controlled trials to guide pharmacological management. Additionally, recent updates to CDI guidelines recommend oral vancomycin over metronidazole for the management of CDI in adults, leaving questions regarding how to best manage pediatric patients. This continuing education pharmacotherapy review describes available evidence for the safety and efficacy of medications used in the treatment and management of pediatric CDI and aims to clarify discrepancies between pediatric and adult recommendations.

BACKGROUND. Older adults with late-life depression (LLD) often experience incomplete or lack of response to first-line pharmacotherapy. The treatment of LLD could be improved using objective biological measures to predict response. Transcranial magnetic stimulation (TMS) can be used to measure cortical excitability, inhibition, and plasticity, which have been implicated in LLD pathophysiology, and associated with brain stimulation treatment outcomes in younger adults with depression. TMS measures have not yet been investigated as predictors of treatment outcomes in LLD, or pharmacotherapy outcomes in adults of any age with depression. METHODS. We assessed whether pre-treatment single-pulse and paired-pulse TMS measures, combined with clinical and demographic measures, predict venlafaxine treatment response in 76 outpatients with LLD. We compared the predictive performance of machine learning models including or excluding TMS predictors. RESULTS. Two single-pulse TMS measures predicted venlafaxine response: cortical excitability (neuronal membrane excitability), and the variability of cortical excitability (dynamic fluctuations in excitability levels). In cross-validation, models using a combination of these TMS predictors, clinical markers of treatment resistance, and age, classified patients with 73±11% balanced accuracy (average correct classification rate of responders and non-responders; permutation testing, p

BACKGROUND The STOP AF First trial recently demonstrated that initial treatment with cryoballoon ablation (CBA) is safe and superior to antiarrhythmic drug (AAD) therapy for preventing atrial arrhythmia recurrence in patients with symptomatic atrial fibrillation (AF). OBJECTIVE The purpose of this study was to evaluate the change in quality of life (QoL) and symptoms after first-line CBA vs AAD therapy. METHODS Patients with symptomatic AF not previously receiving rhythm control therapy were randomized to AAD (class I or III) or CBA (Arctic Front Advance, Medtronic, Mounds View, MN). QoL was evaluated at baseline and at 6 and 12 months by using the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and the European Quality of Life-5 Dimensions questionnaires. A review of AF-associated symptoms was conducted at baseline and at 1, 3, 6, and 12 months. RESULTS In total, 203 subjects received either CBA (n = 104 [51.2%]) or AAD therapy (n = 99 [48.8%]). Improvements in the AFEQT summary and subscale scores were significantly larger with CBA than with AAD therapy at 6 and 12 months (P 5 points) in the AFEQT summary score from baseline to 12 months was observed in 96.0% (100) of patients in the CBA arm vs 72.2% (71) of patients in the AAD arm (P < .001). No significant between-group differences were observed in the change in the European Quality of Life-5 Dimensions index or visual analog scale scores. Overall, 54.4% (57) of the CBA group vs 29.7% (29) of the AAD group reported no AF-specific symptom recurrence after a 90-day blanking period (P = .0005). CONCLUSION First-line CBA vs AAD therapy is associated with larger improvements in AF-specific QoL and a higher rate of symptom resolution.

OBJECTIVES This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction. BACKGROUND The estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized. METHODS We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor-neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]). RESULTS We identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses. CONCLUSIONS In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i. (J Am Coll Cardiol HF 2022;10:73-84) (c) 2022 by the American College of Cardiology Foundation.

Left ventricular (LV) pseudoaneurysm is a rare complication after postinfarction repair of ventricular septal rupture (VSR), and surgical treatment of this condition due to mycosis has rarely been reported. We report a rare case of successful surgical treatment of delayed LV pseudoaneurysm related to Candida albicans infection after repair of VSR due to myocardial infarction. A 75-year-old woman was admitted for fever and severe inflammatory reaction. Two and a half years previously, she had undergone postinfarct VSR repair and was treated for mycotic infective endocarditis due to C. albicans. Transthoracic echocardiography and computed tomography revealed a LV pseudoaneurysm (maximum transverse diameter 6.2 cm). The cause of the LV pseudoaneurysm was suspected to be infectious, and broad-spectrum antibiotic treatment was started. Fourteen days after admission, she developed acute abdominal pain and an elevated β-D-glucan level because the LV pseudoaneurysm ruptured. Emergency surgical treatment was performed with antimycotic drug therapy. The LV wall defect was reconstructed using bovine pericardium under cardiopulmonary support. Her postoperative course was good, and she was discharged to home. Echocardiography revealed no recurrence of the LV pseudoaneurysm at 4 months postoperatively. During 1 year of follow-up, the patient had been doing well without any infection or adverse event.

Temporomandibular joint disorder is defined by pain and/or loss of function of the temporomandibular joint and its associated muscles and structures. Treatments include noninvasive pharmacologic therapies, minimally invasive muscular and articular injections, and surgery. Conservative therapies include nonsteroidal anti-inflammatory drugs, muscle relaxants, benzodiazepines, antidepressants, and anticonvulsants. Minimally invasive injections include botulinum toxin, corticosteroids, platelet-rich plasma, hyaluronic acid, and prolotherapy with hypertonic glucose. With many pharmacologic treatment options and modalities available to the oral and maxillofacial surgeon, mild to moderate temporomandibular joint disorder can be managed safely and effectively to improve symptoms of pain and function of the temporomandibular joint.

Background Although community pharmacists have been actively engaged in patient care, their role in deprescribing is still restricted. Objectives This study aimed to assess the effectiveness of a new educational approach designed to catalyze deprescribing in community pharmacies. Methods In this 4-month, randomized, controlled trial, 108 community pharmacies in Egypt were randomly and equally distributed to either the active or the control groups. Participants from the active group pharmacies received 31 deprescribing-related clinical case scenarios, designed according to the available deprescribing guideline and clinical experiences of an expert panel members, and delivered through WhatsApp. Then participants from both groups reported the incidence of potentially inappropriate medicines (PIMs), the frequency of deprescribing opportunities, and related pharmacist interventions. Results Pharmacists from the active group reported a considerably higher incidence of PIMs (20.87%) than that reported by pharmacists from the control group (5.03%). In addition, they made 1326 deprescribing-related interventions, of which 1022 (77.07%) were accepted and 641 (48.34%) were significant interventions. The proportions of cessation of drug therapy, reducing the dose, and persuasion of patients to accept deprescribing pharmacist interventions in the active group were 37.85%, 22.09%, and 10.63%, respectively. In contrast, 150 of 268 deprescribing-related interventions (55.97%) in the active group were accepted. The clinical value and type of deprescribing decision were statistically significant determinants for the acceptance of deprescribing decisions. The mean time needed to persuade the patient about deprescribing and the cost saved per patient across the active and the control groups were 5.09 ± 3.54 minutes versus 10.03 ± 6.19 minutes and 17.88 ± 9.60 U.S. dollars versus 4.49 ± 2.44 U.S. dollars, respectively. Conclusion The intervention proposed improved the frequency and clinical value of deprescribing decisions.

Purpose This report from VitalSign6 project describes treatment selection, follow-up rates and remission outcomes by initial depression severity using the PCP-FIRST model. Methods This retrospective analysis included 32,106 patients aged ≥12 years screened with the Patient Health Questionnaire 2-item (PHQ-2) from November 2016 to July 2019 across 37 primary care clinics. PHQ-2 positive-screen patients (PHQ-2 ≥ 3) received 9-item PHQ (PHQ-9) and 7-item Generalized Anxiety Disorder scales, clinician assessments, and evaluation for pharmacotherapy management with measurement-based care (MBC). Results Of PHQ-2 screened patients, 18.7% (5994/32,106) were positive and received a PHQ-9. Of 5994 patients with PHQ-9, 2571 received a clinical diagnosis of depression of whom, 333 had none-mild depression (PHQ-9 Conclusions Despite this being a real-world, usual care sample, remission outcomes exceed real world remission rate expectations of 6% in primary care.

Background Medical emergency teams use medications to rescue deteriorating patients. Medication management is the system of steps and processes, including prescribing, distribution, administration, and monitoring, to achieve the best outcomes from medication use. Systems or standards for medication management by medical emergency teams have not been defined. Objectives The aim of the study was to propose potential solutions to improve medical emergency team medication management by evaluating medication supply and related medication management practices during medical emergency team activations and understanding clinicians' perceptions about medical emergency team medication management in acute hospitals. Methods A prospective multicentre audit of intensive care unit–equipped hospitals in Victoria, Australia, was conducted. After advertisement and invitation via scheduled email newsletters to hospitals, a representative of the medical emergency team from each hospital self-administered an online audit tool during December 2019 and January 2020. Audit data were analysed descriptively, and perceptions were analysed using content analysis. Results Responses were received from 32 of the 44 (72.7%) eligible hospitals. At 17 of the 32 (53.1%) hospitals, arrest trolleys provided medications for medical emergency team activations, in addition to arrest calls. At 15 of the 32 (46.9%) hospitals, separate, dedicated medical emergency team medication supplies were used to care for deteriorating patients. Dedicated medical emergency team supplies contained a median of 20 (range = 8–37) medications, predominantly cardiovascular (median = 8, mode = 7, range = 4–16) and neurological medications (median and mode = 6, range = 0–11). Variation was observed in all storage and other supply-related medication management practices studied. The four most frequent categories of clinicians' perceptions described systematic challenges with availability of the right medication in the right place at the right time. Conclusions Current supply and related medication management practices and clinicians' perceptions demonstrated further development is necessary for medication management to meet the needs of medical emergency team clinicians and their patients.

In the United States, alcohol is the most common substance used and the spectrum of unhealthy alcohol use is highly prevalent. Complications of unhealthy alcohol use affect nearly every organ system. One of the most frequent and potentially life-threatening of these complications is alcohol withdrawal syndrome for which benzodiazepines remain first-line therapy. Pharmacologic treatment of alcohol use disorder, the most severe form of unhealthy alcohol use, is underutilized despite the availability of multiple effective medications. Although behavioral therapies are an important component of treatment, they are overemphasized at the expense of pharmacotherapy.

Background United States population-level data on asthma morbidity and mortality are available primarily through state-level surveys. We hypothesize that significant county-level heterogeneity may be obscured by state-level data, thus impeding focused initiatives to improve asthma outcomes. Objective To assess heterogeneity in the prevalence of uncontrolled, severe, and severe uncontrolled asthma by examining state- and county-level morbidity reflected in large administrative claims datasets and identify relationships between pharmacotherapy-based morbidity and the Centers for Disease Control and Prevention's asthma mortality data. Methods Asthma prevalence and morbidity were identified using medical and pharmacy claims from the IQVIA Longitudinal Access and Adjudication Data database (7/2015-6/2018). Heatmaps ranked prevalence of severe uncontrolled asthma by deciles in all 50 states and the District of Columbia, plus 2935 counties. Mortality in states (2016) and 3147 counties (1999-2018) was similarly mapped and ranked and contrasted with claims-based morbidity. Results Among 4,506,527 individuals with asthma, 640,936 (14.2%) received agespecific therapy for severe asthma. Of those with severe asthma, 144,232 (22.5%) filled ≥2 annual courses of systemic steroids and were designated as having severe uncontrolled asthma. Most states with high mortality had relatively few patients with severe uncontrolled asthma. A significant correlation between mortality and morbidity and trends by urban/rural and metropolitan status were found at the county level. Conclusion: Intra-state heterogeneity in the morbidity and mortality of severe uncontrolled asthma at the county level is not evident in state-level analyses. Increased local awareness of systemic corticosteroid use as an indicator of uncontrolled asthma should prompt regional educational and public health efforts to improve outcomes.

Pharmacotherapy may be indicated to treat a variety of conditions for patients living with human immunodeficiency virus. It is important for nurse practitioners (NPs) to be aware of clinically significant interactions involving antiretroviral therapy and other prescribed drugs or over-the-counter products, herbal therapies, and dietary supplements. Drug interactions may result in adverse clinical outcomes by increasing or decreasing drug levels, which subsequently may compromise viral control, enhance risk of toxicity, or have other unintended effects. Various clinical resources are available for NPs to make safer prescribing decisions.

Summary Neonatal invasive candidiasis is an important cause of morbidity and mortality in preterm infants. The incidence of invasive candidiasis in this population has been declining in high-income settings, largely due to preventive measures, although there are still considerable variations in incidence between health-care centres. Surveillance data and large, multicentre studies in lower-income settings are not available, although preventive measures in these settings have been shown to decrease the incidence of neonatal invasive candidiasis. Understanding risk factors and pathogenesis are key to the prevention of invasive candidiasis. The difficulty of a definitive diagnosis of invasive candidiasis and the high risk for death or substantial neurodevelopmental impairment, even with appropriate treatment, further increase the need for effective preventive measures. In this Review, we examine the pathogenesis, clinical presentation, and diagnosis of invasive candidiasis. We highlight commonly used and emerging preventive and prophylactic measures, including standardised central line care, antibiotic stewardship, antifungal prophylaxis, and probiotics. Finally, we provide updates on empirical treatment, clinical management in confirmed cases of invasive candidiasis, and antifungal pharmacotherapy.

Background Exercise is indicated as a monotherapy for depression, as well as an augmentation strategy alongside standard treatments. However, it is not yet clear how exercise and standard treatments interact with regards to patient outcomes. The primary aim of the current systematic review and meta-analysis was to compare the antidepressant effects of exercise combined with standard treatment to standard treatment alone. Method A systematic search was conducted for trials comparing the efficacy of standard treatments alone or in combination with exercise for reducing symptoms of depression. Random effects meta-analysis was used to estimate pooled standardized mean difference for standard treatment alone versus standard treatment with exercise. Results Twenty-two studies were included in the meta-analysis. There was a moderate pooled effect in favour of exercise combined with standard treatment compared to standard treatment alone (SMD = -0.62, p Limitations There was considerable heterogeneity between trials. Uneven covariate distributions within subgroups limited our ability to explore the sources of heterogeneity. Conclusions Exercise combined with standard treatments leads to significantly greater antidepressant effects over standard treatment alone. Patients and clinicians should consider using exercise alongside standard treatments to enhance therapeutic efficacy for depression.

Gambling disorder creates a significant public health burden. Despite decades of clinical trials, there are no licensed pharmacological treatments for gambling disorder. Contributing factors to this are the high placebo response rates seen in clinical trials, the heterogeneity of the disorder and high rates of psychiatric comorbidities. Indeed, a number of demographic and clinical variables have previously been associated with altered responses to pharmacotherapy, psychotherapy and placebo. Which variables are likely to predict response to one modality over another remains uncertain. We carried out multiple linear regression analyses in a pooled dataset from six treatment studies in gambling disorder with the aim of identifying predictors of treatment response. Potential predictors were identified a priori through hypothesis and entered into models including all patients, and subsequently for those randomized to active medication or placebo separately. We found that baseline severity of gambling symptoms and number of weeks completed in a trial were predictors of active medication response, while decreased baseline symptoms of anxiety, increased baseline symptoms of depression, and non-Caucasian ethnicity were associated with placebo response. Sensitivity analyses showed that these associations were robust to choices made during the analysis. Further research is required to understand whether controlling for these variables, or using enriched samples, improves assay sensitivity in placebo-controlled clinical trials for gambling disorder.

OBJECTIVE: To examine the use of pharmacotherapy in obesity treatment in the United States from 2011 to 2016 using a large, nationally representative sample. PATIENTS AND METHODS: Data were obtained over six years, 2011 to 2016, from the National Ambulatory Medical Care Survey. There were three types of visits identified: patients with obesity and an anti-obesity drug mention, patients with obesity and no anti-obesity drug mention, and patients without obesity and with anti-obesity drug mention. Chi-square tests were used to compare characteristics across each type of visit. To predict the odds of an anti-obesity medication mention for patients with obesity, a logistic regression analysis was conducted. RESULTS: Of the overall weighted 196,872,870 office-based physician visits made by patients with obesity from 2011 to 2016, one percent mentioned an anti-obesity drug. Additionally, there were 760,470 office-based physician visits by patients without obesity but with an anti-obesity medication mention. An anti-obesity drug mention was more likely for those ages 51 or older and those residing in the South (AOR: 5.31 95% CI: 1.19-23.59). CONCLUSION: There was a slight increase in anti-obesity medication mentions, from 0.26% in 2011 to 0.28% in 2016, but only one percent of office-based visits for patients with obesity received a prescription for an anti-obesity medication. Physicians tended to prescribe anti-obesity medications to those with obesity ages 51 or older and residing in the South. Anti-obesity medication as treatment for obesity is significantly underutilized.

Introduction Physicians play a critical role in tobacco treatment, being a frequent link to smokers and a trusted source of information. Unfortunately, barriers exist that limit physicians’ implementation of evidence-based interventions. This study examines the implementation and predictors of the Ask, Advise, Assess, Assist, Arrange model of tobacco treatment clinical guidelines among U.S. physicians. Methods A national sample of 1,058 U.S. physicians from 6 specialties (family medicine, internal medicine, obstetrics and gynecology, cardiology, pulmonology, and oncology) were surveyed in 2018 (51.8% response rate). Survey domains included demographics, awareness of the guidelines, tobacco treatment practices (i.e., Ask, Advise, Assess, Assist, Arrange model), perceived barriers to treatment, and perceived efficacy of various treatments. Multiple logistic regression analyzed the predictors of implementing guideline activities. Results Mean age was 51.3 years, with the majority male (64.4%) and non-Hispanic White (63.9%). Nearly all physicians reported asking patients whether they smoke (95.6%) and advising them to stop (94.8%), slightly fewer assessed the readiness to quit (86.5%), and only a minority assisted with a quit plan (27.4%) or arranged a follow-up (18.6%). Only 18% reported using the U.S. Public Health Service Guidelines in clinical practice. Time-related factors were the most common barriers (53.4%), with patient factors (36.9%) and financial/resource factors (35.1%) cited less frequently. The predictors of implementing aspects of the Ask, Advise, Assess, Assist, Arrange model included physician awareness and utilization of the U.S. Public Health Service Guidelines, specialty, and to a smaller degree, graduating before 1990, not reporting time as a barrier, patient barriers, sex, and higher perceived effectiveness of pharmacotherapy. Conclusions This national survey highlights the need for increased implementation of all aspects of the latest guidelines for evidence-based tobacco treatments, including community-based resources.

Obesity is an alarming medical condition, whereby, its prevalence has escalated tremendously across the globe. The aetiology of obesity is obscure and multifactorial, which primarily involves complex interactions between genetic background, social and environmental factors, as well as developmental and biological factors. Multiple comorbidities have been linked with obesity, such as hypertension, diabetes, cancer, and stroke. Therefore, appropriate behavioural and lifestyle modifications are essential to achieve weight loss in obese patients. There are several conventional drugs and pharmacological modalities available for the therapeutic management of obesity. Nevertheless, many of these conventional anti-obesity agents are associated with severe adverse effects and long-term complications. These factors have prompted extensive research for the discovery and development of novel anti-obesity agents. A vast range of natural products have been explored and studied for their anti-obesity potential. Compounds from plant sources have demonstrated improved toxicological profiles and multipronged synergistic actions. In this review, we have discussed the influence of various natural products on obesity. We have also elaborated the various mechanisms of action underlying the anti-obesity effects of notable natural substances.

In a previously healthy asymptomatic 18-year old male, Wolff-Parkinson-White syndrome (WPW) with left ventricular hypertrabeculation/noncompaction (LVHT) and systolic dysfunction was detected. Holter monitoring disclosed multiple long episodes of supraventricular tachycardia with a heart rate of about 110/min. After radiofrequency ablation of an epicardial posteroseptal accessory pathway with ante- and retrograde conduction, systolic function gradually normalized without any pharmacotherapy. After 32 months of follow-up, the patient remains asymptomatic with normal systolic function. WPW-induced tachycardiomyopathy may even occur in asymptomatic patients, who are so adapted to their arrhythmias that they do not recognize them. Learning objective: Tachycardiomyopathy in Wolff-Parkinson-White syndrome may even occur in asymptomatic patients. They seem so adapted to their tachyarrhythmia that they do not recognize them. Radiofrequency ablation of the accessory pathway may lead to complete normalization of systolic function. If left ventricular hypertrabeculation/noncompaction in the presented patient is causal or a coincidence remains unknown. Genetic testing revealed no variants. Because of left ventricular hypertrabeculation/noncompaction cardiologic follow-up is indicated.

Purpose To elucidate strategies for and controversies surrounding the use of anti-inflammatory medications after uneventful cataract surgery, with a focus on the prevention of irreversible vision loss due to cystoid macular edema (CME). Design Perspective. Methods Expert commentary on the management of inflammation after cataract surgery. Discussion includes combination therapy with corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), dosing strategies, and emerging therapies. Results While prescribing both NSAIDs and corticosteroids for cataract surgery is common, these classes have overlapping mechanisms. Combination therapy may speed visual recovery, but there remains little evidence for improved long-term visual outcomes from NSAIDs. The last 2 decades have seen increasing data on potential benefits of pretreatment with NSAIDs 1-3 days prior to cataract surgery. Simultaneously, newly approved “dropless” delivery systems hold promise, and clinical trials are ongoing to assess outcomes of such formulations. Conclusions Optimal pharmacologic treatment for inflammation after cataract surgery remains controversial. A consensus definition for clinically significant CME may facilitate the comparison of anti-inflammatory drugs. And there remains a need for well-designed trials examining both topical and extended-release drug-delivery systems to refine the treatment paradigm.

The association between central nervous (CNS) stimulants used to treat attention deficit hyperactivity disorder (ADHD) and Raynaud's phenomenon (RP) has received little attention to date. Our aim was to map the existing literature on aetiopathogenesis, clinical presentation and management of peripheral vasculopathy, with a focus on RP, secondary to drug therapy for ADHD. We searched the PubMed® database (01/11/1951 to 01/08/2020) and included articles written in English, which focussed on CNS stimulants used to treat ADHD and RP. The search identified 150 articles 9 of which were eligible for inclusion (70 patients). The majority of studies (n = 6) related to children or adolescents; however, adult cases were also identified. Peripheral vascular manifestations included attacks of RP (new and worsening) and cold sensitivity (acrocyanosis and perniosis). Irreversible ischaemic complications including digital autoamputation and lower limb critical digital ischaemia have also been reported. The implicated causative CNS stimulants were Methylphenidate (n = 5), Dextroamphetamine (n = 4), Atomoxetine (n = 2), and Lisdexamphetamine (n = 2). Complete resolution of RP symptoms was observed in half (n = 5) of studies upon drug cessation. Other therapeutic strategies have included dose reduction and switching to an alternative drug therapy. A potential autoimmune association has also been postulated including drug-induced autoimmunity and new cases of systemic sclerosis which have been potentially attributed to treatment. Future research is required to understand the association between CNS stimulant drug therapies for ADHD and peripheral vascular manifestations, including RP.

Critical illness could result in altered pharmacokinetic profiles of many commonly administered medications in ICU settings. Pharmacokinetic, which consists of a multistage process containing absorption, distribution, metabolism, and elimination, could be significantly altered in critically ill patients that emphasize the importance of individualized pharmacotherapy. The most important pharmacokinetic parameters that would be altered in critically ill patients are volume of distribution, clearance, trough concentration, peak concentration, and area under the curve. In this review, the most commonly administered drugs in critically ill patients have been discussed in detail based on the pharmacokinetic aspects of drugs and patients. The contents of this paper have been designed as a brief guideline for professionals who are practicing in ICU settings. Clinical data regarding precise drug dosing, renal dose adjustments, and dialyzability considerations have been included. The major goal of this review was to summarize the commonly prescribed drugs in ICU to facilitate the accessibility of various data need during the management of ICU admitted patients by the professional in this unit to minimize drug dosing errors.

BACKGROUND: Cryoballoon ablation (CBA) as a first-line rhythm control strategy is superior to antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrence; the impact of first-line CBA on quality of life (QoL) and symptoms has not been well characterized. METHODS: Patients aged 18 to 75 with symptomatic paroxysmal AF naïve to rhythm control therapy were randomized (1:1) to CBA (Arctic Front Advance, Medtronic) or AAD (Class I or III). Symptoms and QoL were assessed at baseline, 1, 3, 6, 9, and 12 months using the EHRA classification and Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and SF-36v2 questionnaires. Symptomatic palpitations were evaluated via patient diary. RESULTS: Overall, 107 patients were randomized to CBA and 111 to AAD; crossovers occurred in 9%. Larger improvements in the AFEQT summary, subscale and treatment satisfaction scores were observed at 12 months with CBA vs AAD (all P

Background This study investigated the individual and combined effects of self-reported resilience and serum ghrelin levels on 12-week remission in outpatients with depressive disorders who received antidepressant treatment. Methods The Connor-Davidson Resilience Scale (CDRS) score and serum ghrelin levels were assessed at baseline in 1,094 patients. The patients initially received antidepressant monotherapy. Patients with an insufficient response or uncomfortable side effects received alternative treatments every 3 weeks (at 3, 6, and 9 weeks). Subsequently, 12-week remission, defined as a Hamilton Depression Rating Scale (HAMD) score of ≤ 7, was evaluated. The individual and combined effects of the CDRS score (low vs. high) and serum ghrelin level (low vs. high) on 12-week remission were analyzed using logistic regression models after adjusting for relevant covariates. Results The individual effects of the CDRS score and serum ghrelin level on 12-week remission were not statistically significant. However, the high-CDRS, high-ghrelin group had a significantly higher 12-week remission rate compared to the low-CDRS, low-ghrelin group. Conclusions The combination of the CDRS score and serum ghrelin level is useful for predicting 12-week remission in patients with depressive disorders receiving pharmacotherapy.

Oral lichen planus (OLP) is a chronic non-infectious, inflammatory, immunological disease. In contrast to skin lesions, which are often self-limiting, oral lesions rarely heal on their own and can be resistant to local and systemic treatments. In this clinical trial, hyaluronic acid (HA) was mixed with triamcinolone for intralesional injection to reduce side effects in the treatment of OLP. This randomized clinical trial with a split-mouth design was performed on 28 patients with OLP. The mouth was divided randomly into two sides: a test side, which received HA combined with triamcinolone, and a control side, which received triamcinolone alone. The rate of symptom recurrence was 74.1% on the control side and 11.1% on the test side (significant difference, P

Background Despite the paucity of prospective evidence, stereotactic radiotherapy (SRT) is increasingly being considered in the setting of oligoprogression to delay the need to change systemic therapy. Objective To determine the local control (LC), progression-free survival (PFS), cumulative incidence of changing systemic therapy, and overall survival (OS) after SRT to oligoprogressive metastatic renal cell carcinoma (mRCC) lesions in patients who are on tyrosine kinase inhibitor (TKI) therapy. Design, setting, and participants A prospective multicenter study was performed to evaluate the use of SRT in oligoprogressive mRCC patients. Patients with mRCC who had previous stability or response after ≥3 mo of TKI therapy were eligible if they developed progression of five of fewer metastases. Thirty-seven patients with 57 oligoprogressive tumors were enrolled. Intervention Oligoprogressive tumors were treated with SRT, and the same TKI therapy was continued afterward. Outcome measurements and statistical analysis Competing risk analyses and the Kaplan-Meir methodology were used to report the outcomes of interest. Results and limitations The median duration of TKI therapy prior to study entry was 18.6 mo; 1-yr LC of the irradiated tumors was 93% (95% confidence interval [CI] 71–98%). The median PFS after SRT was 9.3 mo (95% CI 7.5–15.7 mo). The cumulative incidence of changing systemic therapy was 47% (95% CI 32–68%) at 1 yr, with a median time to change in systemic therapy of 12.6 mo (95% CI 9.6–17.4 mo). One-year OS was 92% (95% CI 82–100%). There were no grade 3–5 SRT-related toxicities. Conclusions LC of irradiated oligoprogressive mRCC tumors was high, and the need to change systemic therapy was delayed for a median of >1 yr. Patient summary The use of stereotactic radiotherapy in metastatic kidney cancer patients, who develop growth of a few tumors while on oral targeted therapy, can significantly delay the need to change to the next line of drug therapy.

This article summarizes and critiques the evidence for use of available pharmacotherapies (vasoactive, psychoactive, and hormonal medications) and energy-based therapies (laser, radiofrequency, shockwave, and neurostimulation) for treatment of female sexual dysfunction. The enthusiasm with which energy-based treatments for sexual dysfunction have been adopted is disproportionate to the amount of data currently available to support their clinical use. Pharmacotherapy for female sexual dysfunction has considerably more research evidence to justify its use. Patients must be empowered to make an informed, autonomous determination as to whether the risk/reward ratio favors the use of pharmacotherapy, energy-based therapy, or some other treatment intervention.

The shoulder is structurally and functionally complex. Shoulder pain may be refractory to conventional treatments, such as physical therapy, pharmacotherapy, and corticosteroid injections. In such cases, radiofrequency ablation may serve as an alternative treatment plan. Current literature has demonstrated 4 target nerves for ablative therapy: the suprascapular nerve, axillary nerve, lateral pectoral nerve, and subscapular nerve. Special caution is needed when targeting these nerves in order to avoid motor denervation. This article summarizes the current evidence for radiofrequency ablation as a useful treatment option for chronic shoulder pain as well as the described techniques for performing this promising procedure.

Purpose Trigeminal neuralgia (TN) refractory to pharmacotherapy requires surgical interventions which vary from percutaneous procedure to microvascular decompression (MVD). The aim of the systematic review is to find evidence for the surgical treatment for TN with high success rate and low complications which improves the quality-of-life (QOL). Methods A systematic literature search was made on published studies from MEDLINE, SCOPUS, Science direct, and Cochrane Library databases that report the available surgical treatment for TN up to March 2020 and studies referred in the selected papers. Relevant studies were selected based on predefined eligibility criteria. The primary outcome measured was success rate, pain relief and secondary outcome measured was QOL, recurrence and complication rate. Results Ten studies with a sum of 11,154 individuals were included in this qualitative analysis. Seven studies compared MVD whereas 4 studies compared Gamma knife radiosurgery with other techniques like percutaneous balloon compression, percutaneous glycerol rhizotomy etc. The result showed that MVD has a considerable higher rate of initial pain-free outcomes (96.6%) followed by Gamma knife radiosurgery (96.2%), cryotherapy (95.4%), percutaneous balloon compression (87%), percutaneous glycerol rhizotomy (85%) and the lowest rate of cohorts who were never pain-free (1.7%).QOL was improved to 100% as a result of pain relief which was evaluated in only 2 studies . Overall the recurrence rate was 0.45 to 52%. MVD has lower rate of long-term recurrence 0.45 and 6.1% for 2 years and 8 years, respectively, and cryotherapy has the highest rate of 52% at 6 months. Conclusion Outcomes of the literature search showed that it lacks the knowledge to generally support 1 or the other treatment. Each type of TN requires individualized protocols to treat based on pain response which ultimately improve the QOL. We also propose there should be more reliable data reporting by using a universally acceptable pain scale for better analysis of treatment outcome.

Background The objective of this study was to investigate whether persistence of antidepressant use differs between refugee youth and Swedish-born youth after a diagnosis of a common mental disorder (CMD), and if clinical and sociodemographic factors are associated with antidepressant discontinuation. Methods Youth aged 16-25 years, with an incident diagnosis of CMD (depression, post-traumatic stress disorder (PTSD), anxiety disorders) accessing specialized healthcare in Sweden 2006-2016 were included. New users were identified with a one-year washout period. Refugees (N=1575) were compared with Swedish-born youth (N=2319). Cox regression models [reported as adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs)] were used to investigate factors associated with discontinuation of antidepressant use. Results Among youth (mean age 20.9 years, SD 2.7, 50% females), the median duration of antidepressant use differed considerably between refugee (101 days, IQR 31-243) and Swedish-born youth (252 days, IQR 101-558). Refugees were more likely to discontinue treatment (HR 1.61, 95% CI 1.47-1.77). Factors associated with an increased risk for discontinuation in refugees included ≤5 years duration of formal residency (HR 1.28, 95% CI 1.12-1.45), antidepressant type, and dispensing lag (time from prescription to dispensing) of >7 days (1.43, 1.25-1.64), whereas PTSD (0.78, 0.64-0.97) and anxiolytic use (0.79, 0.64-0.96) were associated with a lower discontinuation risk. Limitations Only persons treated in specialized healthcare could be included. Conclusion The relatively short treatment durations among refugee youth suggest that antidepressant treatment may not be optimal in CMD, and better monitoring of treatment as well as transcultural education of healthcare personnel are warranted.

Background Cardiac contractility modulation (CCM) is an FDA-approved device-based therapy for patients with systolic heart failure and normal QRS width who are symptomatic despite optimal drug therapy. The purpose of this study was to compare the long-term therapeutic effects of CCM therapy in patients with ischemic (ICM) versus non-ischemic cardiomyopathy (NICM). Methods Changes in NYHA class, KDIGO CKD stage, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and NT-proBNP levels were compared as functional parameters. Moreover, observed mortality rates at 1 and 3 years were compared to those predicted by the MAGGIC heart failure risk score, and observed mortality rates were compared between groups for the entire follow-up period. Results One hundred and seventy-four consecutive patients with chronic heart failure and CCM device implantation between 2002 and 2019 were included in this retrospective analysis. LVEF was significantly higher in NICM patients after 3 years of CCM therapy (35 ± 9 vs. 30 ± 9%; p = 0.0211), and after 5 years, also TAPSE of NICM patients was significantly higher (21 ± 5 vs. 18 ± 5%; p = 0.0437). There were no differences in other effectiveness parameters. Over the entire follow-up period, 35% of all patients died (p = 0.81); only in ICM patients, mortality was lower than predicted at 3 years (35 vs. 43%, p = 0.0395). Conclusions Regarding improvement of biventricular systolic function, patients with NICM appear to benefit particularly from CCM therapy.

Background Interstitial pneumonia (IP) is associated with high comorbidity of lung cancer (LC). We aimed to investigate whether concomitant IP affects palliative pharmacotherapy for end-stage symptom relief in patients with LC. Methods We retrospectively examined the clinical records of LC patients who died in our hospital between 2015 and 2017. The patients were divided into the IP-LC (LC with comorbid IP) and LC (LC without IP) groups according to the presence of IP to compare the use of opioid and midazolam in their terminal period. Results In total, 236 patients were enrolled in this study and divided into the IP-LC (n = 70) and LC (n = 166) groups. Among them, 51.2% and 65.7% patients in the LC and IP-LC groups, respectively, required continuous opioid administration to relieve dyspnea and/or pain. There were no significant between-group differences in the median initial and maximum doses and continuous opioid administration duration. The frequency of concomitant use of continuous midazolam and opioids was higher in the IP-LC group than in the LC group (20.5% vs. 7.1%; p = 0.01), primarily because of refractory dyspnea in all patients in both groups. The median survival time after the initiation of continuous opioid administration did not change irrespective of continuous midazolam administration. Conclusions Compared with patients with LC, those with IP-LC are more likely to require continuous midazolam administration because continuously administered opioids alone are not sufficiently effective in relieving end-stage dyspnea among the latter.

Background Real world predictors of relapse following routine treatment for depression remain under-researched. We sought to investigate this in an outpatient clinical sample with depressive disorders receiving stepwise pharmacotherapy based on early clinical decision-making, applying a naturalistic 24-month prospective design. Methods Patients were recruited at a University hospital in South Korea from March 2012 to April 2017. After 3-week antidepressant monotherapy (N = 1262), next treatment steps (1, 2, 3, and 4 or over) with alternative strategies (switching, augmentation, combination, and mixtures of these approaches) were administered based on measurements and patient preference at 3-week points in the acute treatment phase (3, 6, 9, and 12 weeks) (N = 1246). For those who responded [Hamilton Depression Rating Scale (HAMD) score of≤14] (N = 937), relapse (HAMD>14) was identified every 3 months from 6 to 24 months (N = 816). Predictors of relapse were evaluated using multi-variate Cox proportional hazards models. Results Four independent relapse predictors were identified: higher number of previous depressive episodes, higher anxiety at baseline, higher number of treatment steps, and poor medication adherence. In particular, treatment Step 4 was significantly associated with relapse compared to treatment Step 1, 2, and 3 after adjustment for relevant covariates. Limitation Withdrawal syndromes after discontinuing psychotropic drugs, known to confound the determination of relapse, were not evaluated. The study was conducted at a single site, which maximised consistency but may limit generalizability. Conclusions Predictors of relapse reported from more restricted trial or cohort samples were replicated in this long-term naturalistic prospective design.

Medical therapies for dizziness are aimed at vertigo reduction, secondary symptom management, or the root cause of the pathologic process. Acute peripheral vertigo pharmacotherapies include antihistamines, calcium channel blockers, and benzodiazepines. Prophylactic pharmacotherapies vary between causes. For Meniere disease, betahistine and diuretics remain initial first-line oral options, whereas intratympanic steroids and intratympanic gentamicin are reserved for uncontrolled symptoms. For cerebellar dizziness and oculomotor disorders, 4-aminopyridine may provide benefit. For vestibular migraine, persistent postural perceptual dizziness and mal de débarquement, treatment options overlap and include selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants and calcium channel blockers.

BACKGROUND: In pulmonary arterial hypertension (PAH), there are no data comparing initial triple oral therapy with initial double oral therapy. OBJECTIVES: TRITON (The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension; NCT02558231), a multicenter, double-blind, randomized phase 3b study, evaluated initial triple (macitentan, tadalafil, and selexipag) versus initial double (macitentan, tadalafil, and placebo) oral therapy in newly diagnosed, treatment-naive patients with PAH. METHODS: Efficacy was assessed until the last patient randomized completed week 26 (end of main observation period). The primary endpoint was change in pulmonary vascular resistance (PVR) at week26. RESULTS: Patients were assigned to initial triple (n=123) or initial double therapy (n=124). At week 26, both treatment strategies reduced PVR compared with baseline (by 54% and 52%), with no significant difference between groups (ratio of geometric means: 0.96; 95% confidence interval: 0.86-1.07; P=0.42). Six-minute walk distance and N-terminal pro-brain natriuretic peptide improved by week 26, with no difference between groups. Risk for disease progression (to end of main observation period) was reduced with initial triple versus initial double therapy (hazard ratio: 0.59; 95% confidence interval: 0.32-1.09). Most common adverse events with initial triple therapy included headache, diarrhea, and nausea. By the end of the main observation period, 2 patients in the initial triple and 9 in the initial double therapy groups had died. CONCLUSIONS: In patients with newly diagnosed PAH, both treatment strategies markedly reduced PVR by week 26, with no significant difference between groups (primary endpoint not met). Exploratory analyses suggested a possible signal for improved long-term outcomes with initial triple versus initial double oral therapy.

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air-blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment., Graphical abstract Nanomedicine has demonstrated great potential in achieving specific targeting and amplifying therapeutic efficiency. This review focuses on the recent breakthroughs and targeting strategies to provide insights into nanomedicine for acute respiratory distress syndrome treatment.Image 1

Dystonia is a movement disorder characterised by sustained muscle contractions that produce repetitive twisting movements or abnormal postures. It can be classified according to the aetiology as primary (idiopathic and genetic forms), or secondary. The presentation associated with generalised, intense episodes and with exacerbation of severe muscle contractures and usually refractory to traditional pharmacotherapy is known as dystonic status or dystonic storm. In the present article, a case is presented of a 33-year-old patient with a history of congenital deafness, stimulant use disorder and on psychopharmacological treatment with antipsychotics, who presented with a severe dystonic reaction that evolved to a status dystonicus.

Background: Low-grade inflammation (LGI) and endothelial dysfunction (ED) might play a key role in the development of depression. We investigated the associations and mediation of LGI and ED with four-year incidence and course of depressive symptoms (remitted, recurrent or persistent). Design, setting, participants, measurements: In this prospective cohort study (mean age 59.6 +/- 8.2 years, 48.9% women, 26.6% diabetes by design), Cox and multinomial regression analyses, adjusted for age, sex, educational level and diabetes status were used to investigate the associations of LGI and ED with onset and course of depressive symptoms as assessed by the PHQ-9 questionnaire. Results: During 10,847 person-years of follow-up, 264 participants developed incident depression. Higher levels of LGI (OR [95%CI] per SD 1.32[1.16-1.49], p < 0.001) and ED (1.26[1.11-1.43], p < 0.001) were associated with incident depressive symptoms. In mediation analysis, 60% of the total effect of ED with incident depressive symptoms could be attributed to LGI. 76 out of 2637 participants had a persistent course of depressive symptoms. Higher levels of LGI (1.75[1.40-2.19], p < 0.001) and ED (1.33[1.04-1.71], p = 0.021) were associated with a persistent course of depressive symptoms. Higher ED was more strongly associated with persistent depressive symptoms (1.33[1.04-1.71], p = 0.021), while LGI was associated with remission of depression symptoms. Conclusions: LGI and ED were both associated with incident depressive symptoms, where the latter association was substantially mediated by LGI. ED was further associated with a persistent course of depressive symptoms, while LGI was not. These results suggest a temporal, vascular contribution of both LGI and ED to the etiology and chronicity of depressive symptoms.

Background It is not clear which method is more cost-effective: To initially provide all depressed patients with combination therapy (COMB; i.e. cognitive behavioural therapy plus pharmacotherapy), followed by antidepressant treatment (AD) for those still in depression; or, to first provide AD for all patients, followed by COMB for non-remission patients. The aim is to investigate whether a COMB-first strategy would be more cost-effective than an AD-first strategy, in treating depression. Methods A Markov model was developed to perform the analysis. The primary outcome was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) at 104 weeks. Probabilistic sensitivity analysis and scenario analysis were performed, to investigate the uncertainty associated with the clinical parameters and the impact of CBT's cost on the results, respectively. Results The ICER per QALY at 104 week, was JPY 591,822 (USD 5,725) for moderate depression and JPY 499,487 (USD 4,832) for severe one. The scenario analysis revealed the ICER became JPY 1,147,518 (USD 11,101) for moderate and JPY 968,484 (USD 9,369) for severe when the CBT cost was set as JPY 14,400 (USD 139)(i.e. GBP 96: the unit cost of CBT in UK), which is well below the threshold recommended by NICE (i.e. GBP 20,000–30,000). Limitations This is a model-based analysis which was conducted from the health insurance perspective. Then, the analysis from the societal perspective would generate different results. Conclusions The results suggest that a COMB-first strategy would be more cost effective than an AD-first strategy.

One of the most common dysfunction is overactive bladder. The clinical symptoms are associated with an involuntary contraction of the detrusor muscle of the urethra. Drugs are the basis of overactive bladder therapy. However, the duration of drug therapy is limited due to the frequent development of side effects. The study aimed to examine the efficacy of using botulinum toxin type A (BTX-A) in patients with overactive bladder. A total of 90 patients with overactive bladder (mean age 39.86 ± 3.47 years; 59 (65.6%) women and 31 (34.4%) men) divided into two groups (45 patients each) were examined: Group 1 included patients without imperative urinary incontinence, and Group 2 included patients with imperative urinary incontinence. Patients in both groups underwent intravesical injection of 200 units of botulinum toxin type A (Xeomin). The BTX- A for treating patients with overactive bladder reduces clinical symptoms, increases the functional volume of the bladder, and facilitates an improvement in the life quality of patients. The use of BTX-A in patients suffering from overactive bladder and not responding to drug therapy with m-cholinolytics is effective and safe, which allows recommending this treatment method to correct the studied bladder dysfunction in such patients.

Background Not all pharmacies stock and dispense buprenorphine, potentially complicating continuous access to care for patients with opioid use disorder (OUD). This may become problematic if a patient’s primary pharmacy can no longer provide buprenorphine, and the patient cannot locate a new pharmacy. Objectives To identify how often patients treated with buprenorphine for OUD switch pharmacies and to estimate the association between switching pharmacies and a clinically significant gap in therapy of 7 days or longer. Methods A retrospective repeated measures longitudinal cohort design was used. Patients initiating treatment with a buprenorphine product indicated for OUD were identified from the 2016-2018 Texas Prescription Monitoring Program. The predictor of interest—switching pharmacies—was defined by comparing the dispensaries used between subsequent prescriptions. The outcome of interest was defined as a gap in medication possession of 7 days or longer on the basis of the National Quality Forum’s definition of continuity of pharmacotherapy for OUD. A generalized estimating equation approach was used to estimate a repeated measures logistic regression measuring the association between switching pharmacies and a gap in therapy. Results Of 13,375 eligible patients, 29.6% switched pharmacies at least once during treatment, and 51.6% of these did so more than once. The median time to initial switch was 30 days (interquartile range: 13-66 days). When patients switched pharmacies, they were significantly more likely to have a gap in therapy of between 7 and 29 days (adjusted odds ratio 1.67 [95% CI 1.57–1.78]). Conclusion Patients receiving buprenorphine switch pharmacies early and frequently in treatment, which leads to clinically significant gaps in therapy. Although qualitative explanatory work is needed to understand why patients switch pharmacies so often, pharmacists and prescribers must ensure that patients have reliable access to a convenient source of buprenorphine to prevent gaps in therapy.

Cryptococcal meningoencephalitis was first described over a century ago. This fungal infection is preventable and treatable yet continues to be associated with excessive morbidity and mortality. The largest burden of disease resides in people living with HIV in low-income and middle-income countries. In this group, mortality with the best antifungal induction regimen (7 days of amphotericin B deoxycholate [1·0 mg/kg per day] and flucytosine [100·0 mg/kg per day]) in a clinical trial setting was 24% at 10 weeks. The world is now at an inflection point in terms of recognition, research, and action to address the burden of morbidity and mortality from cryptococcal meningoencephalitis. However, the scope of interventional programmes needs to increase, with particular attention to implementation science that is specific to individual countries. This Review summarises causes of excessive mortality, interventions with proven survival benefit, and gaps in knowledge and practice that contribute to the ongoing high death toll from cryptococcal meningoencephalitis. TRANSLATIONS: For the Vietnamese and Chichewa translations of the abstract see Supplementary Materials section.