Drug Regimens Research Articles

Old and new equations for maximal and anaerobic threshold heart rate prediction in coronary heart disease in Chinese population

BackgroundThe prediction of maximal heart rate (MHR) and anaerobic threshold heart rate (HRAT) in patients with coronary heart disease (CHD), particularly among the Chinese population, remains a significant challenge. Existing equations for MHR prediction are primarily designed for healthy individuals not on medication for optimized β-blocker (BB) therapy, showing limited efficacy for individuals on various drug regimens. Moreover, the prediction of HRAT lacks established formulas. This study aims to develop equations for MHR and HRAT, assess the accuracy of historical MHR formulas, and examine their correlation with HR measurements at the anaerobic threshold (AT).MethodsAmong 2021 to 2023, 170 CHD patients were recruited. Patients were categorized into groups based on BB usage. BB dose was transformed into carvedilol dose. Multiple linear stepwise regression analysis was employed to identify predictors of MHR and HRAT, incorporating key patient variables according to prior studies (age, sex, height, weight, carvedilol dose, HRrest). The mean absolute percentage errors (MAPEs) were calculated and compared among abovementioned MHR and HRAT prediction formulas. Besides, the percentages of MHR in predicting HRAT among different formulas were calculated.ResultsFor the patients with BB medication, the simplified equations derived for MHR and HRAT were 176 − 1.2*age + 0.7*HRrest − 0.4*weight and 98 − 0.6*age + 0.7*HRrest − 0.3*weight, respectively. For those without BB medication, the derived equations for MHR and HRAT were 200 − 1.1*age and 91 − 0.5*age + 0.5*HRrest, respectively. There are significant differences between the results predicted by the new formula and the prior formulas. The new formulas are helpful for predicting the MHR of patients during exercise more accurately and guiding exercise training more scientifically.ConclusionsThe new equations for estimating MHR and HRAT in CHD patients enhance the accuracy of prior formulas. Given the BB impact on sympathetic nerve activity, the predictive formulas for MHR and HRAT were significantly improved.

The Long and Winding Road: Three-year Mortality Following Prescription of Multi-drug Antibiotic Treatment for Mycobacterium avium complex Pulmonary Disease in United States Medicare Beneficiaries with Bronchiectasis

Abstract Background/Aims Although increased mortality has been reported among people with Mycobacterium avium complex pulmonary disease (MAC-PD), data are limited on survival associated with various antibiotic regimens used to treat MAC-PD. We conducted a comparative analysis of 3-year mortality in Medicare beneficiaries with bronchiectasis using various MAC-PD regimens. Methods We included Medicare beneficiaries >65 years with bronchiectasis (01/2006–12/2014). We limited our cohort to new MAC-PD therapy users. MAC-PD therapy was defined as ≥60-day prescriptions for a macrolide plus ≥1 one other MAC-PD antibiotic. Guideline based therapy (GBT) included a macrolide, ethambutol +/- rifamycin. Using Cox proportional hazard models, we calculated adjusted hazard ratios (aHR) for death up to 3 years after therapy start between the following groups: 1) 2007 GBT vs. non-GBT; 2) 2020 GBT vs. non-GBT; and 3) macrolide-ethambutol-rifamycin (3-drug) vs. macrolide-ethambutol (2-drug). Results We identified 4,820 new MAC-PD therapy users, of whom 866 (17.9%) were deceased within 3 years of therapy initiation. Of 3,040 (63.1%) beneficiaries prescribed 2007 GBT, 472 (15.5%) were deceased by 3 years, compared to 394 (22.1%) of 1,780 (36.9%) prescribed non-GBT (aHR 0.82 [95%CI 0.72, 0.94]). We observed a similar trend for 2020 GBT vs non-GBT (aHR 0.81 [95%CI 0.70, 0.94]). Three-year-mortality was similar between those starting 3-drug vs. 2-drug regimens (aHR 0.89 [95%CI 0.74, 1.08]). Conclusions Among Medicare new MAC-PD therapy users, 3-year-mortality was higher in those prescribed non-GBT regimens compared to GBT regimens. Whether this finding suggests improved efficacy of GBT and/or differential characteristic of those using non-GBT regimens deserves further study.

Virtual screening of plant-derived molecules against zinc-dependent imipenemases in class B metallo-β-lactamases of Acinetobacter baumannii.

Metallo-β-lactamases (MBLs), enzymes of class B, employ zinc ions to degrade β-lactam antibiotics such as penicillins, cephalosporins, carbapenems, and cephamycins. Carbapenem-resistant Acinetobacter baumannii (CRAB) is linked to the existence of carbapenemase enzymes such as oxacillinase and MBL. The most prevalent resistance mechanisms include imipenemases (IMP), verona integron-encoded MBL, and New Delhi MBL-1. The effectiveness of current antibiotics against the MBL enzyme is limited due to the presence of metal ions, underscoring the need for new antimicrobial agents. Recent research has demonstrated that natural compounds can effectively inhibit MBL. This study aims to screen natural phytochemicals against IMP-2 MBL using in silico virtual screening techniques via AutoDock Vina and molecular dynamic simulations with GROMACS for 200ns, followed by molecular mechanics/Poisson‒Boltzmann surface area analysis. This procedure identified new lead molecules against A. baumannii that produce IMP. A total of 588 natural compounds were screened against IMP, along with the imipenem substrate and known inhibitors of L-captopril. The top four compounds, N025-0038 (NC1), N062-0008 (NC2), eupalitin, and Rosmorinic acid, demonstrated binding affinities of ‒8.5, ‒8.4, ‒7.5, and ‒7.2kcal/mol, respectively. The structural stability of these complexes was observed to be maintained throughout the simulation in a dynamic environment, as determined by molecular dynamics trajectory analysis, and all these compounds met the SWISS-ADME (adsorption, distribution, metabolism, and excretion) properties. NC1 and NC2 compounds are considered potential drug molecules against IMP. However, while these selected compounds showed superior binding energy in computational analysis, further in vitro analysis is required to establish an effective drug regimen against A. baumannii that produces IMP.

Effectiveness of pharmacological procedural sedation in children with autism spectrum disorder: A systematic review and meta-analysis.

Management of primary healthcare and routine minor procedures for children with autism spectrum disorder (ASD) can be challenging; therefore, when behavioural strategies fail, sedative medications are often employed. We evaluated the effectiveness of the current pharmacological strategies for managing children with ASD. We performed a systematic review and meta-analysis of the current approaches for procedural sedation in children with ASD. Twenty studies met inclusion criteria. Dexmedetomidine, midazolam, propofol and chloral hydrate were the most efficient agents for successful procedures, while propofol had the highest number of adverse events. The most frequently used agents were dexmedetomidine and midazolam or a combination of the two, and the effectiveness of dexmedetomidine plus midazolam was superior to dexmedetomidine alone. Multiple effective drug regimens exist for procedural sedation in children with ASD. These results could support the development of specific guidelines for procedural sedation in children with ASD.

Valuation of prescription patterns of <i>Helicobacter pylori</i> drugs in outpatient department, Meru Teaching and Referral Hospital

BACKGROUND Helicobacter pylori infects up to half of the world’s population. Infection with Helicobacter pylori is a major contributing factor for gastric ulcers, gastric carcinoma, and extra gastric disease. The main aim of this study was to observe the prescription patterns of Helicobacter pylori drugs at Meru Teaching and Referral Hospital, Meru. This infection is mostly treated by a triple-drug regimen for successful eradication. The available regimens are a combination of proton pump inhibitors, antibiotics, bismuth sulfate, and histamine blockers. METHODOLOGY A cross-sectional retrospective review of the patient files for Helicobacter pylori was done at Meru Teaching and Referral Hospital (MeTRH). Systematic random sampling was used to select 262 medical records for review. Data was collected using the pre-tested abstraction forms and was coded and analyzed for descriptive statistics. RESULTS Out of the 262 medical records that were reviewed, 147 (56.4%) were males prescribed the Helicobacter pylori drug regimen. Among all the young adults (age: 12-39 years) were more likely to get Helicobacter pylori infection. The medication regimens that were highly preferred at MeTRH were 14-day and 7-day clarithromycin triple-based therapy. The 14-day triple therapy accounted for 74.5% of all patient files. The most administered drug class for Helicobacter pylori were proton pump inhibitors at 45.3% followed by antibiotics at 38.8% and the least prescribed drugs were the H2 blockers with 15.9%. CONCLUSION Regarding the most prescribed drug, the proton pump inhibitors while the most preferred regimen was the 14-day clarithromycin triple-based therapy. This data will certainly be important for the pharmaceutical management chain to manage the stock of analyzed drugs and also can spread awareness regards the appropriate handling of drugs which can improve adherence and reduce the rate of treatment failure and the emergence of antibiotic drug resistance.

Platelet Reactivity with MACE in Acute Coronary Syndrome Patients Post-PCI under Dual Antiplatelet Therapy: A Meta-Analysis.

Aim/Background Acute coronary syndrome (ACS), a condition characterized by acute cardiac ischemia, is among the major causes of death from cardiovascular diseases (CVD). However, whether there is a correlation between platelet reactivity and major adverse cardiovascular events (MACE) remains debatable, and whether platelet function tests should be tailored for ACS patients after percutaneous coronary intervention (PCI) is still under discussion. This study aims to investigate the relationship between platelet reactivity and the occurrence of MACE in ACS patients post-PCI and to discuss the implications of these findings. Methods Clinical studies on 'PCI, ACS, dual antiplatelet therapy (DAPT), platelet reactivity, major adverse cardiovascular events (MACE)' up to 31 October 2023, were systematically collected from Embase, PubMed, and the Cochrane Library. Twelve articles meeting predefined criteria were selected. Meta-analysis was performed using Review Manager 5.4 (Cochrane, London, UK) and Stata 15.0 (StataCorp LLC, College Station, TX, USA) to compute pooled effect sizes, assess heterogeneity, explore sources of heterogeneity, and evaluate publication bias. Results Twelve articles consisting of 9297 patients were included. The meta-analysis showed that ACS patients with high platelet reactivity (HPR) who received PCI and used DAPT for 1-2 years had a greater risk of MACE (risk ratio (RR) = 1.79, 95% confidence interval (CI): 1.30-2.46) compared to those with low platelet reactivity. Moreover, greater platelet reactivity was associated independently with all-cause mortality (RR = 2.26, 95% CI: 1.63-3.12), cardiac mortality (RR = 2.87, 95% CI: 2.16-3.8), myocardial infarction (RR = 1.98, 95% CI: 1.53-2.5), in-stent restenosis (RR = 1.87, 95% CI: 1.22-2.87), as well as stroke (RR = 1.62, 95% CI: 1.02-2.57), but not with coronary revascularization events (RR = 0.99, p = 0.96, 95% CI: 0.80-1.24). On the other hand, meta-regression revealed that region (p = 0.99), type of ACS patient (p = 0.16), drug regimen (p = 0.48), testing method (p = 0.51), sampling time (p = 0.70), follow-up time (p = 0.45), and PCI protocol (p = 0.27) were not sources of heterogeneity in the study. Conclusion The meta-analysis outcomes indicate that in ACS patients receiving PCI and using dual antiplatelet therapy for 1-2 years, HPR was independently positively correlated with major adverse cardiovascular events, all-cause (or cardiac) mortality, recurrent myocardial infarction, in-stent restenosis, and stroke. This suggests that platelet reactivity testing has clinical and translational significance in predicting patients' risk of adverse cardiovascular events.

Virologically suppressed switch to Dolutegravir/Lamivudine 2-Drug regimen versus switch to commonly prescribed 3-Drug regimens in the United States

BackgroundTwo-drug regimens (2DRs) have been introduced in recent years to potentially reduce antiretroviral therapy (ART) toxicities and drug-drug interactions while demonstrating comparable efficacy to three-drug regimens (3DRs) for people with HIV (PWH). The objective of this study was to compare the real-world effectiveness and durability of a single-tablet 2DR of dolutegravir/lamivudine (DTG/3TC) with that of commonly prescribed 3DRs in ART-experienced, virologically suppressed PWH during the first 24 months of DTG/3TC availability in the United States.MethodsVirologically suppressed (viral load [VL] < 200 copies/mL) adult PWH initiating DTG/3TC 2DR, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), or a DTG-based 3DR between 01MAY2019 and 31OCT2020 were identified in the OPERA® cohort and followed through 30APR2021. Univariate Poisson regression (incidence rates) and marginal structural Cox proportional hazards models with inverse probability of treatment weights (hazard ratios) were used to quantify relationships between regimen type and confirmed virologic failure (2 consecutive VLs ≥ 200 copies/mL) or regimen discontinuation. Reasons for discontinuation were examined.ResultsA total of 8,037 ART-experienced, virologically suppressed PWH met the inclusion criteria and switched to DTG/3TC (n = 1,450), BIC/FTC/TAF (n = 5,691), or a DTG-based 3DR (n = 896). Incidence rates of confirmed virologic failure were low for all groups, at 0.66 (DTG/3TC), 0.84 (BIC/FTC/TAF), and 1.78 (DTG 3DR) per 100 person-years (py). Compared to DTG/3TC, only the DTG 3DRs were associated with a statistically significant increased hazard of confirmed virologic failure (hazard ratio: 5.21, 95% confidence interval: 1.85, 14.67). Discontinuation rates per 100 py were highest in the DTG 3DR group (24.90), followed by the DTG/3TC group (17.69) and the BIC/FTC/TAF group (8.30). Regardless of regimen, discontinuations were infrequently attributed to effectiveness (VL ≥ 200 copies/mL; 4%) or tolerability (adverse diagnoses, side effects, or lab abnormalities; 6%).ConclusionsAmong virologically suppressed PWH initiating a new regimen, few individuals experienced virologic failure in real-world clinical care. While rates of regimen discontinuation were high, most discontinuations could not be attributed to a lack of virologic control or poor tolerability. These findings suggest that DTG/3TC is an effective option for ART-experienced, virologically suppressed PWH.

Effects of six antipsychotic drug treatment regimens on short-term heart rate variability in patients with schizophrenia.

Many antipsychotic drugs have cardiac side effects due to their pharmacological actions. Heart rate variability (HRV) analysis can be used as a potential indicator of cardiotoxicity in cases where a decrease in HRV occurs after the administration of antipsychotics such as clozapine. The purpose of this study was to explore the effects of 6 antipsychotic drug regimens on short-term HRV in patients with schizophrenia. Data from 164 patients with schizophrenia between January 2018 and June 2023 were retrospectively analysed. Based on the drug used for treatment, the patients were categorised into clozapine combination (clozapine combined with aripiprazole, risperidone or ziprasidone), clozapine alone, olanzapine, aripiprazole, ziprasidone or risperidone groups. Heart rate variability indices were calculated using time domain analysis, including the standard deviation of the RR intervals (SDNN), the root mean square of successive RR interval differences (RMSSD) and the percentage of successive RR intervals over 50ms (PNN50). Compared with the pretreatment period, the SDNN, RMSSD and PNN50 were significantly lower in the clozapine combination, clozapine, olanzapine and aripiprazole groups at the end of weeks 2 and 4 of treatment (P < 0.05). However, these indicators in ziprasidone and risperidone groups did not show this significant decrease (P > 0.05). The effects of clozapine combination and clozapine on HRV were greater than for olanzapine, aripiprazole, ziprasidone or risperidone. Attention should be paid to controlling the dosage of clozapine combination and clozapine and monitoring the patient's electrocardiogram during administration.

Brief communication: coagulation profiles of HIV positive patients on antiretroviral therapy (ART) at the Mampong Municipal Hospital, Ashanti-Region, Ghana: a case control study

This study aimed to ascertain how the current two ART regimens used in Ghana affected HIV patients’ coagulation profiles. A case-control study was conducted on 102 HIV positive patients at the Mampong Municipal Hospital. Coagulation parameters measured showed APTT was normal in majority of ART-experienced participants but prolonged in majority of ART-naïve participants. The mean platelet count was significantly higher in ART-experienced participants. No significant differences were found between the coagulation profiles of ART-experienced patients on two different drug regimens. In conclusion, current ART can enhance the coagulation profiles in HIV-infected patients, by improving platelet count and APTT.

Adverse drug reactions following treatment of latent tuberculosis infection: a linked national tuberculosis surveillance with claims database.

Few real-world studies explored factors associated with latent tuberculosis infection (LTBI) treatment-related adverse drug reactions (ADRs). This study evaluate ADRs that lead to the discontinuation of LTBI treatment and identify the associated factors, including age groups and drug regimens. Using the Korean national tuberculosis registry and HHC investigation database linked to the National Health Insurance Service claims database, we examined treatment discontinuation due to ADRs among HHCs on LTBI treatment from January 2015 to December 2018. Multivariable logistic regression analysis was conducted to examine factors associated with ADRs, including demographics, LTBI treatment, comorbidities, and steroid use. Among 11,913 participants initiated LTBI treatment, 633 participants (5.3%) discontinued treatment due to ADRs. The primary contributors to discontinuation were adverse skin reactions (2.0%) and abnormal liver function (1.9%). Risk associated with ADRs and abnormal liver function showed age-related increase, except for the age group 66-75 (adjusted odds ratio [AOR] 3.82, 95% confidence interval [CI] 2.31-6.31) which reported lower OR to that of age group 36-65 (AOR 4.38, 95% CI 3.09-6.21). Three months isoniazid/rifampin and 4 months rifampin exhibited a lower odds of ADRs and abnormal liver function when compared to 6-9 months isoniazid. We discovered the real-world prevalence of LTBI treatment discontinuation due to ADRs among HHCs. Our findings suggest a notably increased odds of ADRs resulting in discontinuation with age of 76 years or above, emphasizing careful attention when prescribing LTBI treatment in this population. Further studies are warranted to validate these results.

Investigation of immunosuppressive treatment compliance, dyspnea, anxiety, and depression levels in lung transplant recipients: online interview.

Following lung transplantation (LTx), it is important for recipients to comply with immunosuppressive treatment and cope with related problems. In the post-LTx period, the course of dyspnea and psychological problems it causes in case of progression are not known. Depression and anxiety may develop in recipients after LTx. However, the relationship between this situation and treatment compliance and dyspnea is uncertain. The aim of this study was to investigate dyspnea, anxiety, and depression levels of recipients following LTx and their immunosuppressive treatment compliance. The study was planned as a descriptive, correlational, and cross-sectional study. Data were collected on various social media platforms via an online interview, and 65 LTx recipients were included in the sample (n = 65). A Participant Information Form, the Modified Borg Scale, the Beck Anxiety Inventory, the Beck Depression Inventory, and the Immunosuppressive Drug Compliance Scale were employed to collect data. The collected data were analyzed using descriptive statistics, the Mann-Whitney U test, and the Kruskal-Wallis test. The mean age of the participants was found to be 52.60 ± 9.44 years, and 56.9% were male. Forty percent of the participants were dependent on oxygen support, and 32.2% had hypertension. Their dyspnea levels were mild, anxiety levels were moderate, depression levels were high, and immunosuppressive treatment compliance levels were slightly above-average. According to the correlation analysis results, dyspnea was associated with anxiety and depression (p < 0.05). As depression increased, immunosuppressive treatment compliance decreased, and the correlation between the two variables was statistically significant (p < 0.05). In this study, as the severity of dyspnea experienced by LTRs increased, the severity of their anxiety and depression also increased. Additionally, there was an inverse correlation between depression and immunosuppressive treatment compliance. LTRs demonstrated insufficient adherence to their immunosuppressive drug regimens, which is very significant in terms of graft survivability. These results suggest that LTRs should be closely monitored at home.

A systematic review on the epidemiology and treatment options of multiple Myeloma in Asia

Multiple myeloma (MM) accounts for almost 15 % of all neoplastic malignancies around the globe. This systematic review intends to analyse data on the treatment and management of MM in selected regions in Asia to identify and prioritize areas that need attention. A comprehensive review of original articles, published in English from 2005 to 2022, derived from the PubMed/MEDLINE database was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. There were 98 studies from select regions of Asia (China, India, Taiwan, Hong Kong, and Singapore) on newly diagnosed MM and relapsed/refractory MM. This review evaluated the trends in disease outcomes with the gradual shift in treatment regimens from doublet to triplet. Additionally, this review also explored autologous stem cell transplant outcome and anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy in MM patients. This is the first systematic review attempting to collect data on the utility and comparison of innovative agents and modifications in treatment regimens in the context of the Asian population. This review established that the body of evidence for the management of MM was generally of poor quality and there is a need for more versatile studies in the region. Novel and innovative drug regimens may help in combating the illness but consorted efforts by researchers, industry partners, policymakers, and the government are key factors in the long-term survival of MM patients. In the current systematic review, the authors have tried to give a comprehensive account of the available treatments, trends in MM management and prognosis for MM in Asia.

Real-world analysis of safety, tolerability, and adherence to nirmatrelvir-ritonavir (paxlovid) in primary care COVID-19 outpatients.

This retrospective cross-sectional study aims to evaluate the safety, tolerability, and adherence of patients prescribed Nirmatrelvir-ritonavir (Paxlovid) in outpatient settings, focusing on its use in managing category 2 COVID-19 patients across three primary healthcare clinics in Selangor, Malaysia. Data were collected from the Paxlovid pharmacy registry and medical records at Klinik Kesihatan Seksyen 7, Klinik Kesihatan Seksyen 19, and Klinik Kesihatan Kelana Jaya between April 1, 2022, and November 30, 2022. This study analysed data from 415 category 2 COVID-19 patients aged ≥ 18years. The primary and secondary outcomes included the assessment of patient demographics, Paxlovid dosing, current medication, changes in drug regimen, adherence, and adverse drug reactions (ADR). Pharmacists follow-ups were conducted on days 3 and 5 post-medication initiation. The majority (79.5%) of the cohort experienced ADR, predominantly dysgeusia, diarrhoea, body ache, vomiting, and nausea. Despite this, the ADRs were generally well-tolerated, with no severe impacts reported. High adherence was observed, with 96.9% of patients completing the 5-day regimen. The primary reasons for non-adherence included adverse effect intolerability, dosing ambiguity, forgetfulness, concerns about ADR, and perceived health improvement. Notable medications interacting with Paxlovid were simvastatin, amlodipine, and atorvastatin, and 21.7% of 23 concurrent medications were found not to comply with the recommended interventions by the University of Liverpool COVID-19 Drug Interaction database. Paxlovid demonstrates a high level of safety and tolerability in outpatient COVID-19 patients, with optimal adherence observed. This study underscores the vital role of healthcare professionals in managing Paxlovid within primary healthcare and highlights the need for broader research and direct patient involvement to enhance treatment strategies against COVID-19.

Pattern of Adverse Drug Reactions and Performed Monitoring Laboratory-Tests in Patients Receiving Anti Tuberculosis Treatment in an Endemic Region, Zabol

Background: Efficient anti TB treatment considered crucial globally. Anti TB drugs can cause various adverse drug reactions (ADRs). Clinical and laboratory monitoring will decrease rate of these ADRs, improve patient safety as well as drug adherence and treatment outcome. Methods: In this cross-sectional study total of 136 newly diagnosed TB patients were included. All patients received standard anti-TB 4 drug regimen. Predesigned data collection forms were used to gather patient’s lab data as well as clinical symptoms they experienced during treatment course. Monthly follow up visits or phone calls were also performed by investigators and all health issues were recorded. Results: The majority of our patients aged over 70-year-old. About 54% of them were female. We recorded at least one ADR in 80.8% of patients, and hepatic-gastrointestinal (GI) ADRs ranked first (64.7%). Although ADRs were more common in women and patients over 70-year-old, but there was no statistically significant relationship between sex or age and rate of ADRs (P&gt; 0.05). We also observed that recommended baseline laboratory tests for monitoring anti TB treatment was not performed in any of our patients, except complete blood count (CBC) that was performed in 11 cases. This led to diagnoses of anemia and thrombocytopenia in one case. Conclusion: The majority of our patients experienced ADR. Recommended drug monitoring tests that could guarantee safe and effective treatment were not performed routinely in our TB management centres. These facts highlighted the importance of improving surveillance system for TB management based on national standards.

Patient and provider costs of the new BPaL regimen for drug-resistant tuberculosis treatment in South Africa: A cost-effectiveness analysis.

Drug-resistant (DR) tuberculosis (TB) is typically characterized by resistance to a single or combination of first- and/or second-line anti-TB agents and commonly includes rifampicin-resistant (RR)-TB, multidrug-resistant (MDR)-TB, pre-extensively drug-resistant (pre-XDR)-TB and XDR-TB. Historically, all variations of DR-TB required treatment with second-line drugs which are less effective and more toxic than first-line options, have a longer treatment duration and are more expensive to both patients and providers. The World Health Organization (WHO) now recommends a new second-line 3-drug 6-month all-oral regimen consisting of bedaquiline, pretomanid, and linezolid referred to as BPaL. We estimate patient and provider costs of DR-TB treatment with BPaL compared to the current standard of care in South Africa. In coordination with South Africa's BPaL clinical access programme (CAP) we conducted an economic evaluation of A) patient costs through a cross-sectional patient cost survey and B) provider costs through a bottom-up costing analysis consisting of a retrospective medical record review (patient resource-use) and top-down financial record review (fixed/shared costs such as overhead). Across both costing perspectives, we compare costs of 1) BPaL, to current standard of care options including the 2) 9-11-month standard short oral regimen (SSOR) and 3) 18-21-month standard long oral regimen (SLOR). Eligible patients included those ≥14 years old with confirmed sputum pulmonary RR/MDR-TB, pre-XDR or XDR-TB. All costs are reported in 2022 United States Dollar (US$). A total of 72 patients were enrolled and completed the patient cost survey (41.7% on BPaL, 16.7% on the SSOR and 41.7% on the SLOR). Mean on-treatment patient costs were lowest among those on BPaL ($56.6) and increased four-fold among those on the SSOR ($228.1) and SLOR ($224.7). Direct medical patient costs were negligible across all treatment regimens, while direct non-medical patient and guardian costs for travel, food and nutritional supplementation accounted for the largest proportion of total costs ($54.6, $227.8 and $224.3 for BPaL, the SSOR and SLOR respectively). In assessing provider costs, a total of 112 medical records were reviewed (37.5%, 41.1% and 21.4% on BPaL, the SSOR and SLOR respectively). Total provider costs for producing a favorable treatment outcome (cured/completed treatment) were similar among those on BPaL ($4,948.7 per patient) and the SSOR ($4,905.6 per patient) with costs increasing substantially among those on the SLOR ($8,919.9 per patient). Based on incremental cost-effectiveness ratios (ICERs), at even the lowest willingness to pay (WTP) threshold, treatment with the new BPaL regimen was more cost-effective than current standard of care treatment options (ICER: $311.4 < WTP: $3,341). When using the newly recommended BPaL regimen, cost to patients decreased by 75% compared to current standard of care treatment options in South Africa. Due in part to higher resource-use within the BPaL CAP offsetting the shorter treatment duration, cost of treatment provision through BPaL and the 9-11-month SSOR were similar. However, when considering cost and treatment outcomes, BPaL was more cost-effective than other standard of care regimens currently available for DR-TB in South Africa.

The progress of Mycobacterium tuberculosis drug targets.

Tuberculosis (TB) has been troubling humans for hundreds of years, is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, Mtb can infect almost all organs of the body and is one of the deadly infectious diseases in the world. At present, the first-line treatment regimen has a long treatment cycle and is prone to multiple drug resistance. Anti-tuberculosis drugs and latent tuberculosis infection (LTBI) resistance are increasing year by year, and new targets and new bioactive compounds are urgently needed to treat this disease. This review focuses on the latest reported anti-TB drug targets and related compounds in recent years, reviews the current TB drug regimen and major defects, outlines the key drug targets developed to date in Mtb, and the current situation of newly discovered anti-TB resistant forms of drugs. To provide a reference for the research and development of new anti-TB drugs and bring new treatment strategies for TB patients.

General practitioners’ views on inappropriate prescribing for older patients: a qualitative study through focus groups

BackgroundInappropriate prescribing (IP) is a common problem in the older population. Despite numerous attempts to tackle this issue, it remains a public health concern. In most European countries, general practitioners (GPs) are responsible for global primary care and are thus gatekeepers for the adequacy of medicines, specifically for older people. An in-depth analysis of the situation is necessary to understand why this phenomenon is still prevalent and to identify solutions that could help avoid IP in primary practice.MethodA qualitative study based on five focus groups (FG) comprising nine to thirteen general practitioners was conducted in the French-speaking part of Belgium. Participants were recruited among the Local Medical Evaluation Groups (LMEG) and selected to guarantee heterogeneity in working organisations, years of professional experience, gender and age. All interviews were recorded with prior agreement and transcribed in verbatims. The transcripts were coded and analysed to highlight the primary themes, considering dominant and marginal discourses.ResultsFifty four GPs participated in the study, with an average experience of 30 years. IPs are perceived as a significant problem in the older population, leading to dangerous health situations. The issue is associated with polypharmacy and multimorbidity, and GPs stated to manage IP using their clinical experience. Most of the study participants faced difficulties managing IP, mostly due to the specificity and complexity of elderly care. Indeed, managing an older patient is challenging due to medical complexity, poor adherence to drug regimes, or low medical literacy. In addition, the medical environment of general practice is challenging, with multiple providers, lack of time, prescribing routine and the absence of effective communication with specialists or other care providers. Additionally, the tools and support available to help medication management in primary care are inadequate. Enhancing collaboration with pharmacists is perceived as a strong potential facilitator.ConclusionThis article addresses the complex management of IP in the old age, from the point of view of GPs. Interesting clues were highlighted, like the need to clarify roles of healthcare providers, the better fit of tools to facilitate medication’s review with particularities of GPs needs and the empowerment of pharmacist collaboration.

Assessing the Risk of QT Prolongation in a Psychiatric Inpatient Cohort: A Retrospective Cross-Sectional Study.

QT prolongation is a potential serious adverse drug reaction, and assessing the risk of QT-prolonging drugs is routinely included in psychotropic medication reviews. However, the actual clinical benefits of such assessments are unknown. We investigate whether QT prolongation (QTc value > 480 ms) manifests in psychiatric inpatients at risk of QT prolongation as identified by assessing drug regimens. Secondly, we test the predictive value of well-known risk factors for QT prolongation. The median patient age was 49 years (IQR 34-64) for patients treated with a median of nine drugs (IQR 6-12) and a median QT-prolonging drug sum of three daily defined dosages (IQR 1.88-4.76). We extracted 290 ECGs for patients where pharmacist-led-medication reviews (PMRs) identified an increased risk of QT prolongation and 190 ECGs for patients with no such risk, identifying 33 cases of verified QT prolongation equally distributed between groups. Unadjusted regression analysis revealed that advanced age (OR 3.27 CI 95% 1.60-6.84) and cardiovascular comorbidity (OR 3.53 CI 95% 1.71-7.29) were associated with manifest QT prolongation, while the QT-prolonging drug load was not. We reviewed electronic health records (EHRs) of 799 psychiatric inpatients exposed to PMRs made from 1 September 2016 to 31 December 2018 in Region Zealand Denmark. Patients at risk of QT prolongation as identified by drug reviews rarely manifests with actual QT prolongation. Non-pharmacological risk factors seem to be better predictors for identifying patients with QT prolongation.

Novel combined pharmacological strategy to alleviate acute phase response following zoledronic acid treatment.

Osteoporosis is a common condition associated with high morbidity rates, often requiring treatment with bisphosphonates such as zoledronic acid. However, the persistence to zoledronic acid infusion is commonly limited by acute phase response (APR). This retrospective study aimed to evaluate the efficacy of a novel combination therapy in preventing APR symptoms. A retrospective case-control study was conducted on 931 patients who received their first zoledronic acid infusion between 2011 and 2021. We evaluated the efficacy of combination therapy comprising a single dose of hydrocortisone prior to the infusion and a 3-d oral regimen of non-steroidal anti-inflammatory drugs, acetaminophen, and prednisolone following the infusion. Patients were divided into protocol (receiving combination therapy) and control groups (without treatment). Baseline characteristics, APR incidence, and the efficacy of symptom control were compared between groups using Fisher's exact test and Student's t-test. There was no difference in APR incidence between the protocol (n = 507) and control group (n = 407; p = 0.1442). However, the protocol group exhibited lower intolerable APR levels (3.72% vs. 16.71%; p < 0.0001) and complete symptom relief in 96.28% of cases. The combination therapy protocol effectively reduced intolerable APR and relieved symptoms in most patients following zoledronic acid infusion. This study highlights the importance of proactive management strategies for APR and emphasizes the potential of combination therapy in alleviating APR symptoms and reducing the occurrence of severe APR in patients undergoing osteoporosis management.

Berberine-Loaded Bovine Serum Albumin Nanoparticles: Fabrication, Characterization, and Drug Release Evaluation

Abstract Introduction/Objective Introduction: Numerous studies have highlighted the diverse biochemical and pharmacological properties of berberine (BER), including its anti-inflammatory, antioxidant, anticancer, and hypolipidemic effects. Nanoparticles play a crucial role in enhancing drug delivery by providing a larger surface area, facilitating quicker dissolution in the bloodstream. Methods/Case Report Methods: Blank bovine serum albumin nanoparticles (BSA NPs) were prepared using a desolvation process, followed by the fabrication of berberine-loaded BSA nanoparticles (BER-NP). Physicochemical characterization, including particle size and zeta potential, was conducted using a Malvern Zetasizer. The mean particle size and distribution were determined using photon correlation spectroscopy (PCS), and transmission electron microscope (TEM) images were obtained for visualization. Fourier transform infrared (FTIR) spectra and differential scanning calorimetry (DSC) thermograms were recorded to assess drug encapsulation efficiency (EE). Berberine release from BER-NPs was evaluated using dialysis membranes. Results (if a Case Study enter NA) Results: FTIR spectra and DSC thermograms confirmed successful drug loading into the nanoparticles. Encapsulation efficiency was determined by UV absorption spectroscopy, revealing high efficiency in the encapsulation process. Dialysis membranes demonstrated controlled release kinetics of berberine from BER-NPs, indicating their potential for targeted drug delivery. Conclusion Conclusion: Berberine-loaded bovine serum albumin nanoparticles exhibit favorable characteristics for drug delivery applications, including enhanced permeation across biological barriers. These nanoparticles hold promise for targeted therapy and combination drug regimens, offering potential benefits for various medical interventions.