Front Pharmacol. 2021 Apr 28;12:636352. doi: 10.3389/fphar.2021.636352. eCollection 2021.

ABSTRACT

Adefovir dipivoxil (ADV) is widely used for chronic hepatitis B therapy in China. To explore the clinical features and prognosis of ADV-induced osteomalacia and to analyze the association between osteomalacia and genetic variants in 51 drug transporters genes. Clinical and follow-up data of the ADV-treated patients were collected. Target capture sequencing was used to identify genetic variations of 51 drug transporter genes. A total of 193 hepatitis B patients treated with ADV were enrolled, of whom 140 had osteomalacia. The other 53 without osteomalacia were included in the control group. The median duration of ADV treatment before the onset of osteomalacia was 6.5 years (range:1.5-7 years). We found that most patients with osteomalacia had hypophosphatemia, high serum alkaline phosphatase levels, hypouricemia, nondiabetic glycosuria, proteinuria. Stopping ADV administration, supplementing calcitriol and calcium were effective treatments. During 3-6 months of follow-up, the clinical symptoms and biochemical indicators of patients with osteomalacia have been significantly improved. There was no significant difference in duration of adefovir treatment in patients with or without osteomalacia (p = 0.791). Through regression analysis, we found that age was a risk factor for osteomalacia [per 1 year, odds ratio (OR), 1.053; 95% confidence interval (95% CI), 1.020-1.087; p = 0.015]. 1992 single nucleotide variants were found using target capture sequencing. However, the associations of genetic variants of 51 drug transporter genes and the risk of osteomalacia were negligible. Osteomalacia is prone to occur in patients with chronic hepatitis B treated with long-term ADV at a therapeutic dose. After standard treatment, the prognosis is mostly good. We failed to find genetic variants that can predict the risk of ADV-induced osteomalacia.

PMID:33995038 | PMC:PMC8113870 | DOI:10.3389/fphar.2021.636352

J Clin Exp Hepatol. 2021 May-Jun;11(3):343-353. doi: 10.1016/j.jceh.2020.08.009. Epub 2020 Aug 25.

ABSTRACT

AIMS AND BACKGROUND: There is limited information on comparison of clinical outcomes with carvedilol for secondary prophylaxis following acute variceal bleed (AVB) when compared with propranolol. We report long-term clinical and safety outcomes of a randomised controlled trial comparing carvedilol with propranolol with respect to reduction in hepatic venous pressure gradient (HVPG) in patients after AVB.

METHODS: We conducted a post-hoc analysis of patients recruited in an open-label randomized controlled trial comparing carvedilol and propranolol following AVB, and estimated long-term rates of rebleed, survival, additional decompensation events and safety outcomes. Rebleed and other decompensations were compared using competing risks analysis, taking death as competing event, and survival was compared using Kaplan-Meier analysis.

RESULTS: Forty-eight patients (25 taking carvedilol; 23 propranolol) were followed up for 6 years from randomization. More number of patients on carvedilol had HVPG response when compared with those taking propranolol (72%- carvedilol versus 47.8% propranolol, p = 0.047). Comparable 1-year and 3-year rates of rebleed (16.0% and 24.0% for carvedilol versus 8.9% and 36.7% for propranolol; p = 0.457) and survival (94.7% and 89.0% for carvedilol versus 100.0% and 79.8% for propranolol; p = 0.76) were obtained. New/worsening ascites was more common in those receiving propranolol (69.5% vs 40%; p = 0.04). Other clinical decompensations and complications of liver disease occurred at comparable rates between two groups. Drug-related adverse-events were similar in both groups.

CONCLUSION: Despite higher degree of HVPG response, long-term clinical, survival and safety outcomes in carvedilol are similar to those of propranolol in patients with decompensated cirrhosis after index variceal bleed with the exception of ascites that developed less frequently in patients with carvedilol.

PMID:33994717 | PMC:PMC8103346 | DOI:10.1016/j.jceh.2020.08.009

Reg Anesth Pain Med. 2021 May 14:rapm-2021-102754. doi: 10.1136/rapm-2021-102754. Online ahead of print.

NO ABSTRACT

PMID:33990441 | DOI:10.1136/rapm-2021-102754

J Glob Antimicrob Resist. 2021 May 11:S2213-7165(21)00112-0. doi: 10.1016/j.jgar.2021.04.013. Online ahead of print.

ABSTRACT

OBJECTIVES: In the present work, we aimed to evaluate the efficacy and safety of oritavancin (ORI) versus its comparators for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) based on available clinical studies.

METHODS: PubMed, Cochrane Library, and Embase were searched from database inception to July 28, 2020 to identify clinical studies assessing the efficacy and safety of ORI and its comparators for the treatment of ABSSSIs. Primary efficacy outcome, investigator-assessed clinical cure, lesion size reduction ≥20%, additional post-treatment antibiotics, 30-day emergency room (ER) visits and readmission were assessed as efficacy outcomes, while adverse events (AEs) and mortality were assessed as safety outcomes. I2 statistic was calculated for heterogeneity, and the fixed-effects or random-effects model was used for estimation of risk ratio (RR).

RESULTS: A total of 9,213 patients from two randomized clinical trials (RCTs) and four cohorts were included in the present meta-analysis. ORI was statistically non-inferior to its control agents in all efficacy and safety outcomes. Moreover, ORI significantly reduced the occurrence of 30-day readmission (RR=0.42, P=0.0004) and drug-related AEs (RR=0.78, P=0.002). In the subgroup analysis, ORI also had a lower rate of 30-day ER visits in the outpatient setting (RR=0.34, P<0.00001).

CONCLUSIONS: ORI was not inferior to its comparators for the treatment of ABSSSIs. Meanwhile, it showed advantages in reducing the rate of readmission and drug-related AEs. More high-quality and large-scale RCTs are still required to further confirm the efficacy and safety of ORI.

PMID:33989846 | DOI:10.1016/j.jgar.2021.04.013

Cureus. 2021 Apr 11;13(4):e14414. doi: 10.7759/cureus.14414.

ABSTRACT

Ipilimumab and nivolumab are immune checkpoint inhibitors that have recently been used in the treatment of metastatic melanoma and other cancers. Immune-mediated colitis is one of their adverse events that need to be differentiated from low-grade diarrhea as one of the most common side effects. A 51-year-old woman with relapsed metastatic melanoma presented with intractable diarrhea, nausea, vomiting, and generalized abdominal pain. The patient had been treated with ipilimumab and nivolumab in the past two months. The infectious workup was inconclusive. Colonoscopy demonstrated severe colitis, and biopsies were consistent with colitis. Combination chemotherapy was stopped. The patient was treated with intravenous and oral steroids, and her symptoms improved. A combination of ipilimumab and nivolumab increases the chance of immune-mediated colitis, and steroids should be started promptly to avoid complications such as bowel perforation and toxic megacolon.

PMID:33987063 | PMC:PMC8112207 | DOI:10.7759/cureus.14414

Front Psychiatry. 2021 Apr 27;12:587122. doi: 10.3389/fpsyt.2021.587122. eCollection 2021.

ABSTRACT

Relevance: Understanding patients' informational needs and adapting drug-related information are the prerequisites for a contextualized informed consent. Current information practices might rather harm by inducing nocebo effects. Objective: To investigate whether informing about the nocebo effect using a short information sheet affects patients' need for information about antidepressants. Methods: A total of 97 patients taking recently prescribed antidepressants (≤4 months intake) were recruited over the internet and randomized to receiving either a one-page written information about the nocebo effect or a control text about the history of antidepressants. After experimental manipulation, informational needs about the side effects and mechanisms of antidepressants were assessed with 3 and 7 items on categorical and 5-point Likert scales. Group differences in informational needs were calculated with Chi-square tests and ANOVAs. Results: Patients received antidepressants for depression (84.5%) and/or anxiety disorders (42.3%). Three participants (6.0%) of the nocebo group reported previous knowledge of the nocebo effect. After the experimental manipulation, participants in the nocebo group reported a reduced desire for receiving full side effect information [ X ( 4 , 97 ) 2 = 12.714, Cramer's V = 0.362, p = 0.013] and agreed more frequently to the usefulness of withholding information about possible side effects [ X ( 4 , 97 ) 2 = 14.878, Cramer's V = 0.392, p = 0.005]. Furthermore, they desired more information about the mechanisms of antidepressants (F = 6.373, p = 0.013, partial η2 = 0.063) and, specifically, non-pharmacological mechanisms, such as the role of positive expectations (F = 16.857, p < 0.001, partial η2 = 0.151). Conclusions: Learning about the nocebo effect can alter patients' informational needs toward desiring less information about the potential side effects of antidepressants and more information about general mechanisms, such as expectations. The beneficial effects of including nocebo information into contextualized informed consent should be studied clinically concerning more functional information-seeking behavior, which may ultimately lead to improved treatment outcomes, such as better adherence and reduced side effect burden.

PMID:33986697 | PMC:PMC8112550 | DOI:10.3389/fpsyt.2021.587122

Eur J Hosp Pharm. 2021 May 13:ejhpharm-2020-002571. doi: 10.1136/ejhpharm-2020-002571. Online ahead of print.

ABSTRACT

OBJECTIVES: Chronic kidney disease (CKD) is a common disorder all over the world. Therapeutic goals are early detection of declining renal function and implementation of adequate pharmacological treatments regarding underlying and secondary diseases. As therapy becomes more complex with increasing stages of CKD, a decision-making tool for healthcare professionals could help to ensure safe drug treatment in patients with CKD in the outpatient setting. Therefore, a list of renally relevant drugs as a decision-making tool was developed to improve medicines optimisation for CKD patients in the outpatient setting long term.

METHODS: A renally relevant drug list (RRD-list) with renally relevant drugs, based on data from a study on medicines optimisation in patients with CKD from June 2015 to March 2018, was developed at the nephrological outpatient clinic at the Klinikum Fulda, Germany. The whole study is published elsewhere. A clinical pharmacist reviewed the patients' medications, current drug-related problems and all nephrologists' recommendations, and categorised all detected drugs into renally relevant and non-renally relevant groups. The 10 most frequently detected renally relevant drug groups were summarised in the RRD-list and extended by treatment alternatives and advice.

RESULTS: The medication of 160 patients, who were receiving overall 1376 drugs, was analysed; 831 drugs were defined as renally relevant. Drug-related problems were caused by 543 renally relevant drugs. The nephrologists made 292 recommendations regarding 28 drug classes. Considering the 10 most frequent drug groups, in total 16 renally relevant drug groups with 36 drug classes were added to the RRD-list.

CONCLUSIONS: The RRD-list could be an essential tool for all healthcare professionals in their daily work, such as general practitioners and community pharmacists, for the treatment of patients with renal insufficiency.

PMID:33986026 | DOI:10.1136/ejhpharm-2020-002571

Therapie. 2021 Apr 21:S0040-5957(21)00103-7. doi: 10.1016/j.therap.2021.04.007. Online ahead of print.

NO ABSTRACT

PMID:33985838 | DOI:10.1016/j.therap.2021.04.007

Zhongguo Zhong Yao Za Zhi. 2021 Apr;46(7):1727-1737. doi: 10.19540/j.cnki.cjcmm.20201224.601.

ABSTRACT

Methotrexate(MTX) is a commonly used antimetabolite, which can be used in the treatment of a variety of diseases. However, hepatotoxicity in the use of MTX severely limits its clinical use. Therefore, how to prevent and treat hepatotoxicity of MTX has become an urgent clinical problem. This paper summarizes and analyzes relevant literatures on the prevention and treatment of hepa-totoxicity caused by MTX with traditional Chinese medicines and natural medicines in recent years. MTX-induced hepatotoxicity mechanisms include folate pathway, oxidative stress damage and adenosine pathway, of which oxidative stress theory is the main research direction. A total of 14 kinds of traditional Chinese medicine and natural medicine extracts including white peony root, and 21 kinds of natural monomer compounds, including berberine, play an anti-MTX-induced hepatotoxic effect by resisting oxidative stress, inhibiting inflammation and regulating signal pathways. According to current studies on the prevention and treatment of hepatotoxicity induced by MTX with traditional Chinese medicines and natural medicines, there are insufficiencies, such as partial and superficial mechanism studies, inadequate combination of experimental research and clinical practice, non-standard experimental design and lack of application of advanced technologies and methods. This paper systematically reviewed the effects and mechanisms of traditional Chinese medicines and natural medicines against hepatotoxicity induced by MTX and defined current studies and deficiencies, in the expectation of proposing new study strategies and directions and providing scientific basis for rational clinical use of MTX and development of new drugs against MTX hepatotoxicity.

PMID:33982476 | DOI:10.19540/j.cnki.cjcmm.20201224.601

Ghana Med J. 2020 Dec;54(4 Suppl):62-70. doi: 10.4314/gmj.v54i4s.10.

ABSTRACT

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is limited information on the safety of drugs used for the treatment of COVID-19.

OBJECTIVE: Objective of this study is to describe the pattern of stimulated spontaneous adverse drug reaction (ADR) reports received from healthcare professionals for SARS-CoV-2 positive patients in Ghana and lessons learnt particularly for low- and middle-income countries.

METHODS: This is a study of individual case safety reports (ICSRs) received from healthcare professionals between 1st April 2020 to 31st July 2020 in SARS-CoV-2 positive patients in Ghana. The ICSRs were retrieved from the SafetyWatch System and descriptive statistics used to describe the ADRs by System Organ Classification and Preferred Term.

RESULTS: Information was received from 40 COVID-19 Treatment Centres across the country with 9 centres submitting a total of 53 ICSRs containing 101 ADRs; approximately two ADRs per ICSR. Females accounted for 29(54.7%) of the ICSRs and males 24(45.3%). Newly reported ADRs of interest were one report each of tremor for doxycycline; scrotal pain, dyspnoea, gait disturbances and dysgeusia for chloroquine; and dry throat, hyperhidrosis, restlessness and micturition frequency increased for hydroxychloroquine. A strong spontaneous system with the availability of focal persons at the Treatment Centres played a key role in reporting ADRs during the pandemic.

CONCLUSION: This is the first experience with spontaneous reporting during COVID-19 pandemic in Ghana. The profile of most of the ADRs reported appears consistent with what is expected from the summary of product characteristics. A study with a larger sample size with well-defined denominator in future studies is paramount in determining the relative risk of these medications in SARS-CoV-2 positive patients.

FUNDING: None declared.

PMID:33976443 | PMC:PMC8087363 | DOI:10.4314/gmj.v54i4s.10

Am J Respir Crit Care Med. 2021 May 11. doi: 10.1164/rccm.202009-3537OC. Online ahead of print.

ABSTRACT

Rationale Infants and young children might be particularly susceptible to the potential clinical side effects of inhaled corticosteroids (ICS) on body mass index (BMI), adiposity rebound and body composition, but this has rarely been studied in long-term studies in this age-group. Objective To determine the association between ICS exposure in the first 6 years of life on BMI, adiposity rebound, body composition and blood lipid levels. Methods Children from the two Copenhagen Prospective Studies on Asthma in Childhood mother-child cohorts were included. ICS use was registered prospectively to age 6 and the cumulative dose was calculated. Multiple linear regression models were used for analysis. Measurements and Main Results A total of 932 (84%) of the 1111 children from the COPSAC cohorts had data on BMI, 786 (71%) had DXA scan data at age 6 years, and 815 (73%) had adiposity rebound age calculated. 291 children (31%) received a cumulative ICS dose > 10 weeks of standard treatment before age 6. ICS treatment during 0-6 years of age was associated with an increased BMI z-score; 0.05 SD [95% CI: 0.005 to 0.09] per one-year standard treatment, p=0.03, an earlier age at adiposity rebound; -0.18 year [95% CI: -0.28 to -0.08], p=0.0006, and a 2 % increased geometric mean android fat percentage, p=0.05. ICS exposure and DXA scan data were not associated. Conclusions ICS use in early childhood was associated with increased BMI z-score at age six, an earlier adiposity rebound and a trend of association with increased android body fat percentage.

PMID:33975528 | DOI:10.1164/rccm.202009-3537OC

Lakartidningen. 2021 May 11;118:20176.

ABSTRACT

Serious adverse drug reactions, drug intolerance, and lack of effect are major problems in healthcare. Pharmacogenomics is the part of precision medicine that aims to develop predictive risk markers in this respect and establish such testing in clinical practice. The nation-wide project Genomic Medicine Sweden (GMS) is undertaking large-scale sequencing to predict risk of drug toxicity and lack of efficacy in malignant diseases. The aim is to facilitate an improved, individualized treatment with increased patient safety. In addition to accurate genotyping, other technical or infrastructure-related aspects need to be considered for a successful implementation in healthcare, for example electronic accessibility and visibility of pharmacogenomic data of long-standing relevance for an individual's ongoing and future drug treatment.

PMID:33973222

MEDICC Rev. 2021 Apr;23(2):21. doi: 10.37757/MR2021.V23.N2.7. Epub 2021 Apr 30.

ABSTRACT

INTRODUCTION: Disease and deaths from HIV/AIDS have decreased since antiretroviral treatment was introduced in 1996. Since 2005, as treatment availability has increased worldwide, deaths from HIV/AIDS have declined 48%. As of November 2019, 26,952 cases have been reported in Cuba, of which 5159 (19.1%) are deceased. The country has experienced a reduction in mortality rates since 2002, when antiretroviral treatment became available. Although there are clearly benefits to treatment, it is important to understand antiretroviral safety profiles as their toxicity may lower treatment adherence.

OBJECTIVE: Describe adverse reactions attributable to antiretrovirals used in Cuban patients living with HIV/AIDS.

METHODS: I studied notifications of adverse reactions to antiretrovirals used in Cuban patients with HIV/AIDS from January 2003 to December 2017. The sample consisted of 352 notifications in the National Pharmacovigilance Database regarding adverse reactions attributed to antiretrovirals. The variables considered were sex, notification year, antiretroviral drug, and number, type, frequency and severity of adverse reactions, whether or not they were preventable, and the reasons for categorizing them as they were.

RESULTS: Antiretrovirals reported an average adverse reaction rate of 2.1 per million population per year, representing 24.2% of adverse reactions produced by the antiviral drug group in that period. Adult males represented 75% (264/352) of patients who had adverse reactions to antiretrovirals. Most adverse reactions were in response to nevirapine (29.0%; 102/352) and zidovudine (26.7%; 94/352). The most frequent reactions were hypersensitivity (24.4%; 86/352), digestive disorders (15.9%; 56/352) and anemia (15.6%; 55/352). Reactions were common (62.5%; 220/352) and moderate in severity (70.4%; 248/352). Preventable reactions made up 52.6% (185/352) of adverse reactions. Of preventable reactions, 68.1% (126/185) were associated with drug interactions and 16.2% (30/185) with improper dosage or prescription errors.

CONCLUSIONS: Adverse reactions to antiretrovirals in Cuban patients are common and moderate in severity. The drug with the most notifications was nevirapine, and the most common adverse reaction was hypersensitivity. More than half of adverse reactions are considered preventable, and their main causes are prescription errors.

PMID:33974612 | DOI:10.37757/MR2021.V23.N2.7

J Biochem Mol Toxicol. 2021 May 11:e22795. doi: 10.1002/jbt.22795. Online ahead of print.

ABSTRACT

The world is currently facing an unprecedented pandemic caused by a newly recognized and highly pathogenic coronavirus disease 2019 (COVID-19; induced by SARS-CoV-2 virus), which is a severe and ongoing threat to global public health. Since COVID-19 was officially declared a pandemic by the World Health Organization in March 2020, several drug regimens have rapidly undergone clinical trials for the management of COVID-19. However, one of the major issues is drug-induced organ injury, which is a prominent clinical challenge. Unfortunately, most drugs used against COVID-19 are associated with adverse effects in different organs, such as the kidney, heart, and liver. These side effects are dangerous and, in some cases, they can be lethal. More importantly, organ injury is also a clinical manifestation of COVID-19 infection. These adverse reactions are increasingly recognized as outcomes of COVID-19 infection. Therefore, the differential diagnosis of drug-induced adverse effects from COVID-19-induced organ injury is a clinical complication. This review highlights the importance of drug-induced organ injury, its known mechanisms, and the potential therapeutic strategies in COVID-19 pharmacotherapy. We review the potential strategies for the differential diagnosis of drug-induced organ injury. This information can facilitate the development of therapeutic strategies, not only against COVID-19 but also for future outbreaks of other emerging infectious diseases.

PMID:33973313 | DOI:10.1002/jbt.22795

Antimicrob Agents Chemother. 2021 May 10:AAC.00350-21. doi: 10.1128/AAC.00350-21. Online ahead of print.

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479 or LY-CoV016), in healthy adults. This paper involves a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or a placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose increased from 2.5 to 50 mg/kg. The elimination half-life (t1/2) value did not differ among different dose cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.).

PMID:33972256 | DOI:10.1128/AAC.00350-21

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2021 Apr 28;46(4):404-413. doi: 10.11817/j.issn.1672-7347.2021.200256.

ABSTRACT

The human leukocyte antigen (HLA) molecules encoded within the human major histocompatibility complex are a group of highly conserved cell surface proteins, which are related to antigen recognition. HLA genes display a high degree of genetic polymorphism, which is the basis of individual differences in immunity. Specific HLA genotypes have been highly associated with typical adverse drug reactions. HLA-A*31:01 and HLA-B*15:02 are associated with carbamazepine-induced severe cutaneous adverse reactions, HLA-B*57:01 is related to abacavir-induced drug-induced hypersensitivity syndrome and flucloxacillin/pazopanib-induced drug-induced liver injury, while HLA-B*35:01 is a potential biomarker for predicting polygonum multiflorum-induced liver injury. It is not clear how small drug molecules to interact with HLA molecules and T cell receptors (TCR). There are four mechanistic hypotheses, including the hapten/prohapten theory, the pharmacological interaction concept, the altered peptide repertoire model, and the altered TCR repertoire model.

PMID:33967088 | DOI:10.11817/j.issn.1672-7347.2021.200256

Respiration. 2021 May 10:1-13. doi: 10.1159/000515133. Online ahead of print.

ABSTRACT

BACKGROUND: Various combinations of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta-agonist (LABA) have been used as triple therapy for stable chronic obstructive pulmonary disease (COPD).

OBJECTIVE: Our study was conducted to answer whether there were significant differences among various combinations in efficacy, for reducing exacerbation or mortality, and in safety, for increasing cardiovascular events or pneumonia.

METHOD: We searched parallel-group randomized controlled trials (RCTs) comparing ICS/LAMA/LABA with other inhaled drugs in patients with stable COPD for at least 12 weeks in PubMed, EMBASE, the Cochrane Library, and clinical trial registries from inception to December 31, 2019. We conducted a network meta-analysis with Bayesian statistics using a random-effects model with heterogeneous variance structure (PROSPERO, CRD42019126757).

RESULTS: Nine different combinations of ICS/LAMA/LABA were identified in 21 RCTs containing 29,892 patients with moderate to very severe COPD. We could not find any significant evidence suggesting a better treatment for reducing total exacerbations or all-cause mortality among ICS/LAMA/LABA combinations. There were also no significant differences in moderate to severe exacerbation, COPD-related mortality, or cardiovascular disease-related mortality among ICS/LAMA/LABA combinations, and the risk of major adverse cardiovascular events was not different. A significantly lower risk of pneumonia was found in fluticasone propionate (FP)/glycopyrrolate/salmeterol (SAL) than FP/tiotropium/SAL {median odds ratio [OR] (95% credible interval [CrI]) = 0 [0-0.72]} and FP/umeclidinium/SAL {median OR (95% Crl) = 0 [0-0.97]}.

CONCLUSION: There were no significant differences in clinical outcomes, including acute exacerbation and all-cause mortality among various ICS/LAMA/LABA combinations in patients with moderate to very severe COPD.

PMID:33971649 | DOI:10.1159/000515133

Expert Rev Respir Med. 2021 May 8. doi: 10.1080/17476348.2021.1927718. Online ahead of print.

ABSTRACT

Introduction: Tuberculosis (TB) is a major cause of morbidity and mortality globally. Extrapulmonary TB (EPTB) constitutes about 15%-20% of all TB patients but accounts for 50% among HIV-coinfected. Confirmation of microbial diagnosis of EPTB is usually challenging.Areas covered: Availability of newer imaging modalities like 18FDG-PET-CT, PET-MRI, has facilitated precise anatomical localization of the lesions and mapping the extent of EPTB. The use of image-, endoscopy-guided invasive diagnostic methods has made procurement of tissue/body fluids for diagnostic testing possible. With the advent of universal drug-susceptibility testing, a rapid diagnosis of drug-resistance is now possible in EPTB. Drug-susceptible EPTB usually responds well to first-line anti-TB treatment; TB meningitis, bone and joint TB and lymph node TB often require longer duration of treatment.Expert opinion: Adjunctive use of corticosteroids in the initial period is recommended in central nervous system and pericardial TB. Surgical intervention is helpful to obtain tissue samples for diagnosis. Adjunctive surgical treatment along with medical treatment is useful in treating complications like hydrocephalus, Pott's spine. Follow-up of EPTB patients is crucial as treatment is usually longer, requires recognition of development of immune reconstitution and inflammatory syndrome (IRIS), monitoring of adverse events, serious adverse events like anti-TB drug-induced hepatotoxicity, organ-related complications and treatment adherence.

PMID:33966561 | DOI:10.1080/17476348.2021.1927718

Reg Anesth Pain Med. 2021 May 6:rapm-2021-102656. doi: 10.1136/rapm-2021-102656. Online ahead of print.

NO ABSTRACT

PMID:33963083 | DOI:10.1136/rapm-2021-102656

BMJ Case Rep. 2021 May 7;14(5):e241786. doi: 10.1136/bcr-2021-241786.

ABSTRACT

We report on a male subject with a diagnosis of Niemann-Pick type C (NPC). He received an experimental medicinal product intrathecally initially via lumbar puncture (LP) and eventually via intrathecal drug delivery device. Shortly after implantation, the device catheter migrated outside of the intrathecal space and coiled subcutaneously. The treatment continued via LP after removal of the device. A subdural haematoma developed after repeated LPs. It was surgically evacuated and the patient recovered with sequelae. Surgically implanted drug delivery devices are designed to bypass the blood-brain barrier and deliver a medicinal product directly into the cerebrospinal fluid circulation. Their use has extended into the field of neurodegenerative disorders. Significant adverse events can occur at any given time after implantation including neurological injury, dislodgement or displacement of any of its components, infection and drug-related complications; all can significantly affect the quality of life of patients. Repeated LPs also carry significant risk.

PMID:33962928 | DOI:10.1136/bcr-2021-241786