PLoS One. 2023 Sep 7;18(9):e0289222. doi: 10.1371/journal.pone.0289222. eCollection 2023.

ABSTRACT

BACKGROUND: Loss to follow-up (LTFU) is an unsuccessful treatment outcome for tuberculosis (TB) patients. In Malaysia, LTFU affects around 1 in 20 TB patients. Integration of qualitative research methods and evidence will provide a better understanding of LTFU and its underlying issues. In this study, we qualitatively explored TB patients' experiences in receiving treatment and their reasons for leaving TB care.

METHOD: In-depth interviews of 15 patients with a history of LTFU were conducted from January to September 2020. Interview guides were developed to explore TB patients' experiences while receiving treatment, including challenges faced and reasons for treatment interruption. Data were thematically analysed using the framework method.

RESULTS: We identified 11 emerging themes that occurred at four levels of interaction with TB patients. First, at the patient personal level, TB beliefs referring to patients' perception of illness and wellness, patients' perceived role of traditional and complementary medicine, and substance abuse were important. Second, the healthcare system and treatment factors that were highlighted included the organisation of care and treatment, interaction with healthcare professionals, particularly in communication and counselling, and TB medications' side effects. Third, structural factors including financial burden, logistical and transportation issues and work-related factors were identified to be barriers to treatment continuation. Fourth, the interpersonal level interaction of patients should not be neglected; this includes family relationships and support as well as peer influence.

CONCLUSION: Study findings put forth issues and challenges faced by TB patients while receiving treatment and underscore areas where actions can be taken. This will contribute to informing the development and implementation of future TB control strategies that are responsive to TB patients' needs and concerns, to effectively address LTFU and ensure better treatment completion rates among TB patients in Malaysia.

PMID:37676902 | PMC:PMC10484432 | DOI:10.1371/journal.pone.0289222

Scand J Immunol. 2023 Jul;98(1):e13274. doi: 10.1111/sji.13274. Epub 2023 May 4.

ABSTRACT

Increased levels of neutrophil extracellular traps (NETs) have been detected in individuals with vaccine complications after the ChAdOx1 nCov vaccine with a correlation between the severity of vaccine side effects and the level of NETosis. DNases may disrupt NETs by degrading their content of DNA, and a balance has been reported between NETs and DNases. Because of this and since the inflammatory marker NETs may be used as a confirmatory test in diagnosing VITT, it is of interest to monitor levels of DNase in patients with increased NETs levels. The current novel rapid DNase ELISA was tested in blood samples of patients with known increased levels of NETs with or without VITT after ChAdOx1 nCoV-19 vaccination. DNase levels in VITT patients were significantly increased compared with normal unvaccinated blood donors and compared with patients with post-vaccination symptoms but not VITT. However, since EDTA was found to inhibit DNase, serum and not EDTA-plasma samples should be applied for DNase testing. The novel DNase assay may serve as a supplementary test to the NETs test when analysing samples from patients with suspected increased NETs levels.

PMID:37676118 | DOI:10.1111/sji.13274

Cochrane Database Syst Rev. 2023 Sep 7;9:CD013472. doi: 10.1002/14651858.CD013472.pub2.

ABSTRACT

BACKGROUND: Preterm birth interferes with brain maturation, and subsequent clinical events and interventions may have additional deleterious effects. Music as therapy is offered increasingly in neonatal intensive care units aiming to improve health outcomes and quality of life for both preterm infants and the well-being of their parents. Systematic reviews of mixed methodological quality have demonstrated ambiguous results for the efficacy of various types of auditory stimulation of preterm infants. A more comprehensive and rigorous systematic review is needed to address controversies arising from apparently conflicting studies and reviews.

OBJECTIVES: We assessed the overall efficacy of music and vocal interventions for physiological and neurodevelopmental outcomes in preterm infants (< 37 weeks' gestation) compared to standard care. In addition, we aimed to determine specific effects of various interventions for physiological, anthropometric, social-emotional, neurodevelopmental short- and long-term outcomes in the infants, parental well-being, and bonding.

SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, RILM Abstracts, and ERIC in November 2021; and Proquest Dissertations in February 2019. We searched the reference lists of related systematic reviews, and of studies selected for inclusion and clinical trial registries.

SELECTION CRITERIA: We included parallel, and cluster-randomised controlled trials with preterm infants < 37 weeks` gestation during hospitalisation, and parents when they were involved in the intervention. Interventions were any music or vocal stimulation provided live or via a recording by a music therapist, a parent, or a healthcare professional compared to standard care. The intervention duration was greater than five minutes and needed to occur more than three times.

DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data. We analysed the treatment effects of the individual trials using RevMan Web using a fixed-effects model to combine the data. Where possible, we presented results in meta-analyses using mean differences with 95% CI. We performed heterogeneity tests. When the I2 statistic was higher than 50%, we assessed the source of the heterogeneity by sensitivity and subgroup analyses. We used GRADE to assess the certainty of the evidence.

MAIN RESULTS: We included 25 trials recruiting 1532 infants and 691 parents (21 parallel-group RCTs, four cross-over RCTs). The infants gestational age at birth varied from 23 to 36 weeks, taking place in NICUs (level 1 to 3) around the world. Within the trials, the intervention varied widely in type, delivery, frequency, and duration. Music and voice were mainly characterised by calm, soft, musical parameters in lullaby style, often integrating the sung mother's voice live or recorded, defined as music therapy or music medicine. The general risk of bias in the included studies varied from low to high risk of bias. Music and vocal interventions compared to standard care Music/vocal interventions do not increase oxygen saturation in the infants during the intervention (mean difference (MD) 0.13, 95% CI -0.33 to 0.59; P = 0.59; 958 infants, 10 studies; high-certainty evidence). Music and voice probably do not increase oxygen saturation post-intervention either (MD 0.63, 95% CI -0.01 to 1.26; P = 0.05; 800 infants, 7 studies; moderate-certainty evidence). The intervention may not increase infant development (Bayley Scales of Infant and Toddler Development (BSID)) with the cognitive composition score (MD 0.35, 95% CI -4.85 to 5.55; P = 0.90; 69 infants, 2 studies; low-certainty evidence); the motor composition score (MD -0.17, 95% CI -5.45 to 5.11; P = 0.95; 69 infants, 2 studies; low-certainty evidence); and the language composition score (MD 0.38, 95% CI -5.45 to 6.21; P = 0.90; 69 infants, 2 studies; low-certainty evidence). Music therapy may not reduce parental state-trait anxiety (MD -1.12, 95% CI -3.20 to 0.96; P = 0.29; 97 parents, 4 studies; low-certainty evidence). The intervention probably does not reduce respiratory rate during the intervention (MD 0.42, 95% CI -1.05 to 1.90; P = 0.57; 750 infants; 7 studies; moderate-certainty evidence) and post-intervention (MD 0.51, 95% CI -1.57 to 2.58; P = 0.63; 636 infants, 5 studies; moderate-certainty evidence). However, music/vocal interventions probably reduce heart rates in preterm infants during the intervention (MD -1.38, 95% CI -2.63 to -0.12; P = 0.03; 1014 infants; 11 studies; moderate-certainty evidence). This beneficial effect was even stronger after the intervention. Music/vocal interventions reduce heart rate post-intervention (MD -3.80, 95% CI -5.05 to -2.55; P < 0.00001; 903 infants, 9 studies; high-certainty evidence) with wide CIs ranging from medium to large beneficial effects. Music therapy may not reduce postnatal depression (MD 0.50, 95% CI -1.80 to 2.81; P = 0.67; 67 participants; 2 studies; low-certainty evidence). The evidence is very uncertain about the effect of music therapy on parental state anxiety (MD -0.15, 95% CI -2.72 to 2.41; P = 0.91; 87 parents, 3 studies; very low-certainty evidence). We are uncertain about any further effects regarding all other secondary short- and long-term outcomes on the infants, parental well-being, and bonding/attachment. Two studies evaluated adverse effects as an explicit outcome of interest and reported no adverse effects from music and voice.

AUTHORS' CONCLUSIONS: Music/vocal interventions do not increase oxygen saturation during and probably not after the intervention compared to standard care. The evidence suggests that music and voice do not increase infant development (BSID) or reduce parental state-trait anxiety. The intervention probably does not reduce respiratory rate in preterm infants. However, music/vocal interventions probably reduce heart rates in preterm infants during the intervention, and this beneficial effect is even stronger after the intervention, demonstrating that music/vocal interventions reduce heart rates in preterm infants post-intervention. We found no reports of adverse effects from music and voice. Due to low-certainty evidence for all other outcomes, we could not draw any further conclusions regarding overall efficacy nor the possible impact of different intervention types, frequencies, or durations. Further research with more power, fewer risks of bias, and more sensitive and clinically relevant outcomes are needed.

PMID:37675934 | DOI:10.1002/14651858.CD013472.pub2

Pulm Pharmacol Ther. 2023 Sep 5:102252. doi: 10.1016/j.pupt.2023.102252. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Chronic refractory cough is a challenging condition that requires a thorough evaluation and management approach. P2X3 receptors that are ATP-dependent play an important part in nerve fiber sensitization and pathological pain pathways. We conducted this systematic review and meta-analysis to determine the long-term safety and efficacy of P2X3 receptor antagonist drugs in chronic cough.

METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase to identify all relevant published studies through January 15, 2023 that assessed P2X3 antagonists in chronic cough. The protocol was registered in the PROSPERO database with ID: CRD42023422408. Efficacy outcomes were awake (daytime) cough frequency, night cough frequency, 24-h cough frequency, Cough Severity Diary, and total Leicester Cough Questionnaire score. We used the random-effect model to pool the data using RStudio and CMA software.

RESULTS: A total of 11 randomized controlled trials comprising 1350 patients receiving a p2x3 antagonist compared to the placebo group were included in this meta-analysis. A significant decrease in 24-h cough frequency (MD = -4.99, 95% CI [-7.15 to 2.82], P < 0.01), awake (daytime) cough frequency (MD = -7.18, 95% CI [-9.98 to 4.37], P > 0.01), and total Leicester Cough Questionnaire score (MD = 1.74, 95% CI [1.02 to 2.46], P < 0.01) exhibited between the P2X3 antagonist and placebo groups. The frequency of the night cough showed an insignificant difference between the two groups. According to the safety, drug-related adverse events, dysgeusia, hypogeusia, and ageusia significantly increased between the P2X3 antagonist and placebo groups.

CONCLUSION: P2X3 receptor antagonists are promising drugs for treating chronic cough by significantly reducing the frequency, severity, and quality. Some potential side effects may include drug-related adverse events such as hypogeusia, ageusia, and dysgeusia.

PMID:37678663 | DOI:10.1016/j.pupt.2023.102252

J Ocul Pharmacol Ther. 2023 Sep 7. doi: 10.1089/jop.2023.0056. Online ahead of print.

ABSTRACT

Purpose: The melanocortin receptor pan-agonist PL9643, a potential therapy for ocular diseases, was investigated in a phase 2, 12-week study in patients with dry eye disease (DED). Methods: This was a placebo-controlled study evaluating efficacy and safety of thrice-daily PL9643. Placebo (vehicle) was similar to tears. Primary endpoints were intra-patient changes in inferior corneal fluorescein staining and ocular discomfort after 12 weeks. Secondary endpoints were changes in additional DED signs or symptoms. Multiple secondary endpoints were not adjusted for multiplicity. Patients with moderate or severe DED were analyzed in addition to the overall intent-to-treat (ITT) population. Results: In the ITT population (n = 160) the PL9643 group did not demonstrate significant treatment difference versus placebo at week 12/day 85 for the primary endpoints (P > 0.05). In patients with moderate or severe DED (n = 53), PL9643 treatment demonstrated either nominally significant (P < 0.05) or trending (P < 0.1) improvement over placebo in mean change from baseline at week 12/day 85 in several sign endpoints, including fluorescein staining in inferior, superior, corneal sum, and total sum regions; lissamine green staining in temporal, nasal, conjunctival sum, and total sum regions; and tear film breakup time. Conjunctival redness also showed (nonsignificant) improvement at week 12/day 85. There were no drug-related adverse events (AEs) and no drug-related discontinuations. Conclusions: PL9643 showed no significant efficacy for the ITT population; however, efficacy results across several signs and symptoms in the subpopulation of moderate to severe DED patients, the low number of ocular AEs, and no tolerability issues suggest that PL9643 shows promise as a therapeutic for DED. Clinical Trial Registration number: NCT04268069.

PMID:37677000 | DOI:10.1089/jop.2023.0056

Malar J. 2023 Sep 6;22(1):260. doi: 10.1186/s12936-023-04690-4.

ABSTRACT

BACKGROUND: While Ghana has a good track record in the Expanded Programme on Immunization, there are substantial challenges with regards to subsequent vaccinations, particularly after the first year of life of the child. Given that the last dose of the RTS, S/AS01E vaccine against malaria is administered at 24 months, there is a high likelihood of default. Hence, it is imperative to understand the dynamics and reasons for the defaults to enable the development of effective implementation strategies. This study explored why caregivers default on the RTS, S/AS01E vaccine from the perspective of health service providers and caregivers.

METHODS: This study employed an exploratory, descriptive approach. Using a purposive sampling technique, caregivers who defaulted and health service providers directly involved in the planning and delivery of the RTS, S/AS01E vaccine at the district level were recruited. A total of five health service providers and 30 mothers (six per FGD) participated in this study. Data analysis was done using NVivo-12 following Collaizi's thematic framework for qualitative analysis. The study relies on the Standards for Reporting Qualitative Research.

RESULTS: Reasons for defaulting included the overlap of timing of the last dose and the child starting school, disrespectful attitudes of some health service providers, concerns about adverse side effects and discomforts, travel out of the implementing district, the perception that the vaccines are too many, and lack of support from partners.

CONCLUSION: To reduce the occurrence of defaulting on the RTS, S/AS01E vaccine programme, stakeholders must reconsider the timing of the last dose of the vaccine. The schedule of the RTS, S/AS01E vaccine should be aligned with the established EPI schedule of Ghana. This will significantly limit the potential of defaults, particularly for the last dose. Also, the findings from this study underscore a need to encourage male partner involvement in the RTS, S/AS01E vaccine programme. Health promotion programmes could be implemented to raise caregivers' awareness of potential adverse reactions and discomforts-this is necessary to prepare the caregiver for the vaccine process psychologically.

PMID:37674197 | PMC:PMC10483715 | DOI:10.1186/s12936-023-04690-4

J Smooth Muscle Res. 2023;59:67-80. doi: 10.1540/jsmr.59.67.

ABSTRACT

In contrast to the long-standing focus on the pathophysiology of skeletal muscles in the hunt for a cure for Duchenne muscular dystrophy (DMD), we opine that the malfunctioning of dystrophin produced by vascular smooth muscle is a major contributor to the pathology of the illness. We believe that a biological response modifier glucan (BRMG), which has been shown in clinical studies of DMD to boost the expression of vascular smooth muscle dystrophin and provide anti-fibrotic and anti-inflammatory effects, may play a key role in reducing the pathogenesis of DMD. According to the evaluation of biomarkers, this BRMG, which is safe and side-effect-free, reduces the pathogenesis of DMD. We describe the possible mechanisms of action by which this BRMG helps in alleviating the symptoms of DMD by targeting smooth muscle dystrophin, in addition to its advantages over other therapeutic modalities, as well as how it can serve as a valuable adjunct to existing therapies. We suggest that using BRMG adjuncts that target smooth muscle dystrophin would be a potential therapeutic approach that prolongs the lifespan and extends the duration of ambulation from the onset of DMD. Further studies are needed to validate this hypothesis.

PMID:37673649 | DOI:10.1540/jsmr.59.67

Elife. 2023 Sep 6;12:e91831. doi: 10.7554/eLife.91831.

ABSTRACT

Blocking a protein known as EPAC1 may prevent the development of heart-related side effects caused by a chemotherapy drug.

PMID:37672034 | PMC:PMC10482425 | DOI:10.7554/eLife.91831

Front Immunol. 2023 Aug 21;14:1203073. doi: 10.3389/fimmu.2023.1203073. eCollection 2023.

ABSTRACT

Cancer is one of the deadliest diseases, causing million of deaths each year globally. Conventional anti-cancer therapies are non-targeted and have systemic toxicities limiting their versatile applications in many cancers. So, there is an unmet need for more specific therapeutic options that will be effective as well as free from toxicities. Antibody-drug conjugates (ADCs) are suitable alternatives with the right potential and improved therapeutic index for cancer therapy. The ADCs are highly precise new class of biopharmaceutical products that covalently linked a monoclonal antibody (mAb) (binds explicitly to a tumor-associated surface antigen) with a customized cytotoxic drug (kills cancer cells) and tied via a chemical linker (releases the drug). Due to its precise design, it brings about the target cell killing sparing the normal counterpart and free from the toxicities of conventional chemotherapy. It has never been so easy to develop potential ADCs for successful therapeutic usage. With relentless efforts, it took almost a century for scientists to advance the formula and design ADCs for its current clinical applications. Until now, several ADCs have passed successfully through preclinical and clinical trials and because of proven efficacy, a few are approved by the FDA to treat various cancer types. Even though ADCs posed some shortcomings like adverse effects and resistance at various stages of development, with continuous efforts most of these limitations are addressed and overcome to improve their efficacy. In this review, the basics of ADCs, physical and chemical properties, the evolution of design, limitations, and future potentials are discussed.

PMID:37671162 | PMC:PMC10475555 | DOI:10.3389/fimmu.2023.1203073

Nihon Yakurigaku Zasshi. 2023;158(5):408-418. doi: 10.1254/fpj.23047.

ABSTRACT

Darinaparsin, an active ingredient of DARVIAS® Injection 135 ‍mg, is a novel organic arsenical compound of dimethylated arsenic conjugated to glutathione. Darinaparsin is thought to induce apoptosis and cell-cycle arrest and suppress tumor growth by disrupting mitochondrial functions and increasing production of intracellular reactive oxygen species. Darinaparsin is processed at the cell surface by γ-glutamyltranspeptidase (γ-GT), leading to formation of dimethylarsino-cysteine, which is imported via a cystine transporter expressed on cell surface membranes. Numerous tumor cells express high levels of γ-GT and cystine transporter, to maintain high levels of glutathione as an intracellular antioxidant. Darinaparsin is a novel antineoplastic agent designed to exploit the characteristics of tumor cells and to be efficiently taken up by tumor cells to inhibit their growth. In a global phase 2 pivotal study of darinaparsin in Asian patients with relapsed or refractory peripheral T-cell lymphoma (r/r PTCL), the overall response rate was 19.3% (90% confidence interval: 11.2-29.9%) and grade ≥3 drug-related adverse events with an incidence rate ≥5% included neutropenia (9.2%, n = 6), anemia (6.2%, n = 4) and thrombocytopenia (6.2%, n = 4) in 65 patients receiving darinaparsin. Based on the results of this phase 2 trial, which demonstrated the anti-tumor activity and acceptable safety profile of darinaparsin in patients with r/r PTCL, Solasia pharma K.K. received approval for darinaparsin for the treatment of r/r PTCL in June 2022, and Nippon Kayaku Co., Ltd. launched this drug in August 2022. Darinaparsin is expected to contribute to the clinical practice of PTCL as a new treatment option for this disease.

PMID:37673618 | DOI:10.1254/fpj.23047

Ann Oncol. 2023 Sep 4:S0923-7534(23)00828-1. doi: 10.1016/j.annonc.2023.08.013. Online ahead of print.

ABSTRACT

BACKGROUND: Relapsed or refractory peripheral T cell lymphomas (r/r PTCLs) are a group of rare and aggressive diseases, which lack effective therapies. Constitutive activation of Janus kinase (JAK)/signal transducer and activation of transcription (STAT) pathway are reported to be associated with PTCLs. Golidocitinib is an oral, potent JAK1 selective inhibitor evaluated in a phase 1/2 multinational study in r/r PTCLs.

PATIENTS AND METHODS: Patients with r/r PTCLs were eligible. The primary objectives were to assess safety and tolerability of golidocitinib and to define its recommended phase 2 dose (RP2D). The secondary objectives were to evaluate its antitumor activity and pharmacokinetics (PK).

RESULTS: A total of 51 patients were enrolled and received golidocitinib treatment at 150 mg or 250 mg once daily (QD). The median prior lines of therapies were 2 (range: 1 - 8). Golidocitinib was tolerated at both doses tested while a higher incidence of serious adverse events (SAEs) and dose modifications at 250 mg were observed. The most common ≥ grade 3 drug-related treatment-emergent adverse events (TEAEs) included neutropenia (27.5%) and thrombocytopenia (11.8%). An objective response rate of 39.2% and a complete response rate of 21.6%were observed. With median follow-up time of 14.7 months and 15.9 months, respectively. The median duration of response (DoR) and progression-free survival (PFS) were 8.0 and 3.3 months, respectively. Based on the above data, 150 mg QD was defined as the RP2D. Golidocitinib demonstrated a favorite PK profile as an oral agent. Biomarker analysis suggested a potential correlation between JAK/STAT pathway aberrations and clinical activity of golidocitinib.

CONCLUSIONS: In this phase 1 study, golidocitinib demonstrated an acceptable safety profile and encouraging antitumor efficacy in heavily pre-treated patients with r/r PTCLs. These results support the initiation of the multinational pivotal study in patients with r/r PTCLs.

PMID:37673210 | DOI:10.1016/j.annonc.2023.08.013

BMC Geriatr. 2023 Sep 5;23(1):537. doi: 10.1186/s12877-023-04151-2.

ABSTRACT

BACKGROUND: Numerous studies have shown that the dietary inflammatory index (DII) is associated with adverse health effects. However, the relationship between DII and prostate cancer (PCa) remains controversial. Although alcohol is included in DII as a dietary factor, the various adverse health effects of alcohol consumption are not only related to inflammation. On the other hand, it has been a long-standing debate whether alcohol consumption is linked to the risk of PCa. Therefore, to clarify whether drinking affects the relationship between DII and PCa, we evaluated the correlation between DII and prostate-specific antigen (PSA) based on the National Health and Nutrition Examination Survey (NHANES) database.

METHODS: We used data from the NHANES spanning from 2005 to 2010 to analyze the relationship between PCa and DII. Out of the 31,034 NHANES participants, we enrolled 4,120 individuals in our study, utilizing dietary intake data from a twenty-four-hour period to determine DII scores. Demographic data, physical and laboratory test results were collected to compare between low PSA and high PSA groups, and to calculate the odds ratio between both groups, we employed a logistic regression analysis.

RESULTS: In this cross-sectional investigation of PCa, drinkers and non-drinkers had different relationships between DII and PSA levels (OR: 1.2, 95% Cl: 1-1.44 vs. OR: 0.98, 95% Cl: 0.9-1.07), and DII and abstaining from alcohol were effective in reducing the incidence of PSA (p-value for significant interaction = 0.037).

CONCLUSION: The results of our study suggest that drinking may influence the relationship between DII and PSA levels. DII is likely to be a reliable indicator for estimating PSA levels among non-drinkers, who may limit their intake of pro-inflammatory ingredients to lower the incidence and death of PCa.

PMID:37670257 | PMC:PMC10478225 | DOI:10.1186/s12877-023-04151-2

PLoS One. 2023 Sep 5;18(9):e0291018. doi: 10.1371/journal.pone.0291018. eCollection 2023.

ABSTRACT

Deployment of solar photovoltaic panels are significantly rising to tackle adverse effects of climate change however, factors affecting output need to be categorized in addition to latitude angle and space. It is important to consider the atmospheric impact which can drastically change output power of solar panels. This study covers dust accumulation of soil, sand and ash at variable weights to foresee its effects on panel power output. Mixtures of these particles at multiple constituents were also analyzed. Experimental results indicated that clean panel gives maximum power output of 21.37W and exergy efficiency of 7.96% whereas ash accumulation showed worst results of 2.88W power output and 1.07% exergy efficiency at 700W/m2 and 50g dust accumulation. Other parameters like energy destruction, exergy losses and sustainability index were also analyzed. Trends have been illustrated in graphs along with the change in solar intensity and dust accumulations.

PMID:37669283 | PMC:PMC10479914 | DOI:10.1371/journal.pone.0291018

Investig Clin Urol. 2023 Sep;64(5):466-473. doi: 10.4111/icu.20230128.

ABSTRACT

PURPOSE: The proper treatment sequence for administering abiraterone acetate plus prednisolone (AAP) and chemotherapeutic agents has not yet been elucidated for metastatic castration-resistant prostate cancer (mCRPC). Hence, this study evaluated the effectiveness and safety of AAP in pre- and post-chemotherapy settings using real-world data.

MATERIALS AND METHODS: This prospective, multicenter, open-label, observational study included 506 patients with mCRPC. Patients were classified according to the timing of chemotherapy into pre- and post-chemotherapy groups. The effectiveness and safety of AAP were compared between the groups; the prostate-specific antigen (PSA) response, PSA progression-free survival, and radiologic progression-free survival were assessed; and adverse drug reactions were recorded.

RESULTS: Among the included patients, 319 and 187 belonged to the pre- and post-chemotherapy groups, respectively. Risk classification was similar between the two groups. The PSA response was 61.8% in the pre-chemotherapy group and 39.0% in the post-chemotherapy group (p<0.001). The median time to PSA progression (5.00 vs. 2.93 mo, p=0.001) and radiologic progression-free survival (11.84 vs. 9.17 mo, p=0.002) were significantly longer in the pre-chemotherapy group. Chemotherapy status was associated with PSA (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.09-1.77) and radiologic progression (HR 1.66, 95% CI 1.18-2.33) during AAP treatment. Adverse drug reactions were reported at similar frequencies in both groups.

CONCLUSIONS: In this postmarketing surveillance, AAP benefited patients with mCRPC, especially in settings before chemotherapy was administered, resulting in a high PSA response and longer PSA and radiologic progression-free survival with tolerable adverse drug reactions.

PMID:37668202 | DOI:10.4111/icu.20230128

Tidsskr Nor Laegeforen. 2023 Aug 24;143(12). doi: 10.4045/tidsskr.23.0093. Print 2023 Sep 5.

ABSTRACT

This case history describes a case of rhabdomyolysis resulting from treatment with escitalopram as monotherapy at the recommended dose. This is a rare and little-known side effect of selective serotonin reuptake inhibitors.

PMID:37668131 | DOI:10.4045/tidsskr.23.0093

Eur Rev Med Pharmacol Sci. 2023 Aug;27(16):7768-7780. doi: 10.26355/eurrev_202308_33431.

ABSTRACT

OBJECTIVE: The aim of this study was to systematically assess the effects of different targeted therapies associated with adjuvant chemotherapy on clinical remission, survival and safety of patients with triple-negative breast cancer (TNBC).

MATERIALS AND METHODS: This study searched for case-control trials of TNBC patients from January 2010 to May 2022. Two researchers independently extracted data. RevMan 5.3 statistical software was used for analysis.

RESULTS: This study included a total of 7 clinical controlled studies, containing 620 samples. The results showed that compared with the control group, the study group showed significant differences in objective response rate [OR = 2.44, 95% CI (1.69, 3.5), p < 0.00001], 1-year survival rate [OR = 3.59, 95% CI (2.01, 6.39), p < 0.0001], progression-free survival (PFS) [MD = 2.04, 95% CI (1.68, 2.41), p < 0.00001], with statistical significance (p < 0.05), while there are no significant differences in overall survival [MD = 6.33, 95% CI (-1.65, 14.30), p = 0.12] and incidence of adverse events [OR = 0.73, 95% CI (0.52, 1.02), p = 0.006] (p > 0.05).

CONCLUSIONS: Targeted therapy associated with adjuvant chemotherapy can remarkably enhance the outcome of patients with advanced TNBC, prolonging their progression-free survival (PFS) and overall survival (OS) without increasing adverse effects. The validity of this research, however, will require higher quality studies and longer follow-ups.

PMID:37667955 | DOI:10.26355/eurrev_202308_33431

Ned Tijdschr Tandheelkd. 2023 Sep;130(9):373-375. doi: 10.5177/ntvt.2023.09.23034.

ABSTRACT

Dry mouth has a complex aetiology which makes proper diagnosis complicated. Until now, dry mouth diagnosis has mainly focused on the overall oral dryness, without taking into account regional differences within the mouth. This research showed, among other things, that there are unique patterns of oral dryness, each with its own cause. For example, patients suffering from Sjogren's syndrome mainly experienced dryness of the posterior of the palate. Patients with dry mouth due to the side effects of medication, in contrast, experienced the front part of the tongue as the driest. These findings suggest that mapping of intraoral dryness may be a useful diagnostic tool to differentiate between possible causes of dry mouth.

PMID:37667634 | DOI:10.5177/ntvt.2023.09.23034

Expert Opin Emerg Drugs. 2023 Sep 5. doi: 10.1080/14728214.2023.2254686. Online ahead of print.

ABSTRACT

INTRODUCTION: Despite the availability of a variety of therapeutic compounds and improved management strategies, one-third of UC patients with moderate-to-severe disease do not benefit from the existing treatments or experience drug-related side effects. This has boosted intensive research focusing on the development of new drugs for UC therapy. This article aims to summarize the available evidence on oral drugs, which are now being explored in clinical trials or are ready to enter the clinics.

AREAS COVERED: From 15 May to 11 June, we searched on PubMed using the keywords 'oral drugs ulcerative colitis,' 'ulcerative colitis clinical trials,' 'UC phase 2 and 3 trials' excluding case reports, case series, phase 1 and 4 studies, and studies about approved therapies.

EXPERT OPINION: The findings discussed in this article suggest that the future treatment of UC patients will be probably characterized by the possibility of using various small-molecule drugs. All these new compounds, even those belonging to the same class, differ in terms of efficacy and safety. Identification of predictors of response could help optimize the efficacy and safety of these treatments, thus improving resource allocation through a pre-treatment stratification of patients.

PMID:37668153 | DOI:10.1080/14728214.2023.2254686

J Clin Hypertens (Greenwich). 2023 Sep 4. doi: 10.1111/jch.14700. Online ahead of print.

ABSTRACT

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

PMID:37667532 | DOI:10.1111/jch.14700

BMC Infect Dis. 2023 Sep 4;23(1):578. doi: 10.1186/s12879-023-08544-x.

ABSTRACT

HIV post- exposure prophylaxis (PEP) is a prevention tool for individuals with a recent potential exposure to HIV. Doravirine has been available since 2019 in combination with tenofovir disoproxil fumarate and lamivudine and has not been evaluated as a PEP. DOR/3TC/TDF is our department's most commonly prescribed PEP treatment since 2021. This study evaluates the completion rate of the DOR/3TC/TDF as compared to EVG/c/FTC/TAF for PEP, which was the regimen prescribed until 2020 in our hospital.This retrospective observational study was conducted between January 2020 and September 2021. The subjects included consecutively were adults who consulted for an HIV sexual exposure accident and for whom DOR/3TC/TDF in 2021 or EVG/c/FTC/TAF in 2020 was prescribed. The outcomes were the completion rate to the end of treatment (28 days), the seroconversion rate, and the description of side effects.During the study period, 311 people were included: 140 treated with DOR/3TC/TDF and 171 treated with EVGc/FTC/TAF. Considering subjects with a follow-up visit, the completion rate was 96.8% (90/93) in the DOR/3TC/TDF group, and 94.6% (123/130) in the EVG/c/FTC/TAF group (p-value: 0.53). The number of people lost to follow-up was nearly equivalent in both groups: 27.1% (38/140) in the DOR/3TC/TDF group and 23.4% (40/171) in the EVG/c/FTC/TAF group (p-value: 0.45). A side effect was described for 38% (36/94) in the DOR/3TC/TDF group, and 29.7% (38/128) in the EVG/c/FTC/TAF group. No cases of seroconversion were observed.DOR/3TC/TDF appears to have a similar safety profile to EVG/c/FTC/TAF. Due to its lower cost, it seems to be a treatment option for consideration in the context of HIV-exposure accidents.

PMID:37667182 | PMC:PMC10478445 | DOI:10.1186/s12879-023-08544-x