Hypertens Res. 2023 May 12. doi: 10.1038/s41440-023-01292-0. Online ahead of print.

ABSTRACT

There is limited evidence on the blood pressure (BP)-lowering effect of esaxerenone on home BP, including nighttime BP. Using two newly developed nocturnal home BP monitoring devices (brachial and wrist), this multicenter, open-label, prospective study investigated the nighttime home BP-lowering effect of esaxerenone in patients with uncontrolled nocturnal hypertension being treated with an angiotensin receptor blocker (ARB) or calcium-channel blocker (CCB). In total, 101 patients were enrolled. During the 12-week study period, change in nighttime home systolic/diastolic BP from baseline to end of treatment measured by the brachial device was -12.9/-5.4 mmHg in the total population and -16.2/-6.6 and -10.0/-4.4 mmHg in the ARB and CCB subcohorts, respectively (all p < 0.001). For the wrist device, the change was -11.7/-5.4 mmHg in the total population and -14.6/-6.2 and -8.3/-4.5 mmHg in each subcohort, respectively (all p < 0.001). Similar significant reductions were shown for morning and bedtime home BP and office BP. Urinary albumin-to-creatinine ratio, N-terminal pro-brain natriuretic peptide, and cardio-ankle vascular index improved in the total population and each subcohort. Incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 38.6% and 16.8%, respectively; most were mild or moderate. The most frequent drug-related TEAEs were associated with serum potassium elevation (hyperkalemia, 9.9%; blood potassium increased, 3.0%); however, no new safety concerns were raised. Esaxerenone was effective in lowering nighttime home BP as well as morning and bedtime home BP and office BP, safe, and showed organ-protective effects in patients with uncontrolled nocturnal hypertension. Caution is warranted regarding elevated serum potassium levels. This study investigated the effect of esaxerenone on nighttime home BP and organ damage (UACR and NT-proBNP) in patients with uncontrolled nocturnal hypertension despite treatment with an ARB or CCB. Our results show that safe 24-h BP control and organ protection are possible with esaxerenone.

PMID:37173430 | DOI:10.1038/s41440-023-01292-0

PLoS One. 2023 May 11;18(5):e0284365. doi: 10.1371/journal.pone.0284365. eCollection 2023.

ABSTRACT

Chemotherapy, a mainstay in the treatment of cancer, is associated with severe and debilitating side effects. Side effects can be physical (e.g., gastrointestinal distress, anemia, and hair loss) or mental (e.g., fatigue, cognitive dysfunction). Chemotherapy is known to alter the gut microbiota; thus, communication through the gut-brain axis may influence behavioral side effects. Here, we used a clinically-relevant paclitaxel chemotherapy regimen in combination with antibiotics to test the hypothesis that gut microbes contribute to chemotherapy-associated fatigue-like behaviors in female mice. Data presented suggest that chemotherapy-altered gut microbes contribute to fatigue-like behaviors in mice by disrupting energy homeostasis.

PMID:37167214 | PMC:PMC10174578 | DOI:10.1371/journal.pone.0284365

Arch Osteoporos. 2023 May 11;18(1):67. doi: 10.1007/s11657-023-01261-7.

ABSTRACT

PURPOSE: Osteoporosis is a metabolic bone disease that commonly results in middle-aged and elderly people following fractures. Odanacatib (ODN), a potential osteoporosis medication, was stopped in the Long-term Odanacatib Fracture Trial (LOFT) phase III study because it increased the risk of stroke. Herein, we conducted a systematic review and meta-analysis to further assess the efficacy and safety of ODN in osteoporosis treatment.

METHODS: We searched the PubMed, EMBASE, Cochrane Library, and Web of Science, using the core search terms "osteoporosis" and "odanacatib." The primary outcomes were the percentage change in markers of bone turnover and bone formation as well as that in the bone mineral density (BMD) of the lumbar spine, hip, femoral neck, and greater trochanter. The secondary outcome was the risk of adverse events (AEs), used to explore the safety of ODN.

RESULTS: Ten articles-all double-blinded, randomized, placebo-controlled trials-were included. All trials were considered to be of high quality if they met the inclusion and exclusion criteria. We found that ODN increases BMD in the lumbar spine, total hip, and femoral neck, whereas it decreases the concentration of serum C-telopeptides of type I collagen (sCTx) and urinary N-telopeptide/creatinine ratio (uNTx/Cr). We found no significant differences in total, drug-related, serious, or skin AEs between the ODN and control groups. However, significant differences in fracture and stroke AEs were found between the ODN and control groups.

CONCLUSION: ODN is an appealing long-term osteoporosis treatment method; however, further research should focus on the potential increased risk of fracture and stroke.

PMID:37169994 | DOI:10.1007/s11657-023-01261-7

Drug Ther Bull. 2023 May 11:dtb-2023-000023. doi: 10.1136/dtb.2023.000023. Online ahead of print.

ABSTRACT

Overview of: Barker AL, Morello R, Thao LTP, et al Daily low-dose aspirin and risk of serious falls and fractures in healthy older people: a substudy of the ASPREE randomized clinical trial. JAMA Intern Med 2022;182:1289-97.

PMID:37169520 | DOI:10.1136/dtb.2023.000023

Drug Ther Bull. 2023 May 11:dtb-2023-000024. doi: 10.1136/dtb.2023.000024. Online ahead of print.

ABSTRACT

Overview of: Ray KK, Raal FJ, Kallend DG, et al Inclisiran and cardiovascular events: a patient-level analysis of phase III trials. Eur Heart J 2023;44:129-38.

PMID:37169519 | DOI:10.1136/dtb.2023.000024

Curr Drug Metab. 2023 May 9. doi: 10.2174/1389200224666230509104404. Online ahead of print.

ABSTRACT

Drug-related adverse events are higher in older patients than in non-older patients, increasing the risk of medication and reducing compliance. Aging is accompanied by a decline in physiological functions and metabolic weakening. Most tissues and organs undergo anatomical and physiological changes that may affect the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of drugs. Clinical trials are the gold standard for selecting appropriate dosing regimens. However, older patients are generally underrepresented in clinical trials, resulting in a lack of evidence for establishing an optimal dosing regimen for older adults. The physiologically based pharmacokinetic (PBPK) model is an effective approach to quantitatively describe the absorption, distribution, metabolism, and excretion of drugs in older adults by integrating physiological parameters, drug physicochemical properties, and preclinical or clinical PK data. The PBPK model can simulate the PK/PD characteristics of clinical drugs in different scenarios, ultimately compensating for inadequate clinical trial data in older adults, and is recommended by the Food and Drug Administration for clinical pharmacology studies in older adults. This review describes the effects of physiological changes on the PK/PD process in older adults and summarises the research progress of PBPK models. Future developments of PBPK models are also discussed, together with the application of PBPK models in older adults, aiming to assist the development of clinical study strategies in older adults.

PMID:37165496 | DOI:10.2174/1389200224666230509104404

Cancer Chemother Pharmacol. 2023 Jun;91(6):507-521. doi: 10.1007/s00280-023-04538-3. Epub 2023 May 10.

ABSTRACT

PURPOSE: Adverse effects following fluoropyrimidine-based chemotherapy regimens are common. However, there are no current accepted diagnostic markers for prediction prior to treatment, and the underlying mechanisms remain unclear. This study aimed to determine genetic and non-genetic predictors of adverse effects.

METHODS: Genomic DNA was analyzed for 25 single nucleotide polymorphisms (SNPs). Demographics, comorbidities, cancer and fluoropyrimidine-based chemotherapy regimen types, and adverse effect data were obtained from clinical records for 155 Australian White participants. Associations were determined by bivariate analysis, logistic regression modeling and Bayesian network analysis.

RESULTS: Twelve different adverse effects were observed in the participants, the most common severe adverse effect was diarrhea (12.9%). Bivariate analysis revealed associations between all adverse effects except neutropenia, between genetic and non-genetic predictors, and between 8 genetic and 12 non-genetic predictors with more than 1 adverse effect. Logistic regression modeling of adverse effects revealed a greater/sole role for six genetic predictors in overall gastrointestinal toxicity, nausea and/or vomiting, constipation, and neutropenia, and for nine non-genetic predictors in diarrhea, mucositis, neuropathy, generalized pain, hand-foot syndrome, skin toxicity, cardiotoxicity and fatigue. The Bayesian network analysis revealed less directly associated predictors (one genetic and six non-genetic) with adverse effects and confirmed associations between six adverse effects, eight genetic predictors and nine non-genetic predictors.

CONCLUSION: This study is the first to link both genetic and non-genetic predictors with adverse effects following fluoropyrimidine-based chemotherapy. Collectively, we report a wealth of information that warrants further investigation to elucidate the clinical significance, especially associations with genetic predictors and adverse effects.

PMID:37162533 | PMC:PMC10191967 | DOI:10.1007/s00280-023-04538-3

Ned Tijdschr Geneeskd. 2023 May 10;167:D7477.

ABSTRACT

Despite advances in the prevention and management of chemotherapy-induced nausea and vomiting (CINV), these side effects remain among the most distressing for patients. We discuss the systematic review and meta-analysis by Patel et al (2022) evaluating effective and safe interventions to prevent acute phase CINV in adult and pediatric patients. With the advent of newer antiemetics during the last few decades, the incidence of CINV has improved especially for patients receiving highly emetogenic chemotherapy. Control of nausea remains an unmet need. Data on antiemetic safety are lacking. Future research should focus on patients receiving multiple-day chemotherapy, moderately emetogenic chemotherapy, but also on patients treated with low or minimally emetogenic chemotherapy. The identification of patients at high risk for CINV based on key patient-related risk factors prior to the initiation of a chemotherapy regimen is imperative, but in our view, these factors are not adequately taken into account.

PMID:37163378

Integr Cancer Ther. 2023 Jan-Dec;22:15347354231172940. doi: 10.1177/15347354231172940.

ABSTRACT

BACKGROUND AND AIM: Fatigue is a common side effect of radiotherapy. While warm footbath and foot reflexology can both reduce fatigue, it is still unclear which method is more effective in reducing fatigue. This study aimed to compare the effects of warm footbath and foot reflexology on the fatigue of patients undergoing radiotherapy.

METHOD: A randomized clinical trial study was conducted on 62 patients undergoing radiotherapy. Eligible patients were randomly assigned to the 2 groups. Patients in the footbath group immersed their feet in 41°C water for 20 minutes every night for 2 weeks starting from the seventh day of radiotherapy. Patients in the reflexology group received 20 minutes of foot reflexology every night for 2 weeks starting from the seventh day of radiotherapy. Fatigue was measured by the Multidimensional Fatigue Inventory (MFI) once on the seventh day of radiotherapy and 3 more times on days 7, 14, and 28 after the start of the intervention. Data were analyzed by SPSS20 and descriptive/inferential statistics.

RESULTS: The total MFI score of both groups declined significantly over time (P < .001). The reflexology group indicated a significant reduction from 90.9 ± 3.2 in the pre-test to 56.0 ± 3.7 on the 28th day in, while the footbath group indicated it from 90 ± 2.6 in the pre-test to 71.4 ± 2.8 on the 28th day.

CONCLUSION: Our results showed that foot reflexology and warm footbath reduced the fatigue of patients undergoing radiotherapy. However, foot reflexology was more effective in reducing the fatigue of patients undergoing radiotherapy than warm footbath. It is recommended that simple and low cost non-pharmacological interventions such as foot reflexology to decrease of side effect of radiotherapy among cancer patients should be widely performed.Trial registration: Iranian Registry of Clinical Trials (IRCT20190625044009N1).

PMID:37162156 | DOI:10.1177/15347354231172940

An Acad Bras Cienc. 2023 May 8;95(1):e20220033. doi: 10.1590/0001-3765202320220033. eCollection 2023.

ABSTRACT

Invasive Candida infections threaten human health due to the increasing incidence of resistance to the currently available antifungal agents. Amphotericin B (AMB) is the gold standard therapy to treat these infections. Nevertheless, the use of such substance in the clinic is aggravated by its toxicity. Since AMB binds to membrane sterols, it forms pores on human plasma membranes, mainly in kidney cells, leading to nephrotoxicity. The combination of this drug to a second substance could allow for the use of smaller concentrations of AMB, consequently lowering the probability of adverse effects. This mini-review summarizes information regarding an array of substances that enhance AMB antifungal activity. It may be noticed that several of these compounds target plasma membrane. Interestingly, substances approved for human use also presented combinatory anti-Candida activity with AMB. These data reinforce the potential of associating AMB to another drug as a promising therapeutical alternative to treat Candida infections. Further studies, regarding mechanism of action, pharmacokinetics and toxicity parameters must be conducted to confirm the role of these substances as adjuvant agents in candidiasis therapy.

PMID:37162085 | DOI:10.1590/0001-3765202320220033

Trials. 2023 May 9;24(1):320. doi: 10.1186/s13063-023-07257-5.

ABSTRACT

BACKGROUND: Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks' gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short-term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD.

METHODS: An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks' postmenstrual age (PMA; primary outcome). Extremely preterm infants aged < 48 h after birth are eligible if: (1) they are mechanically ventilated, or (2) they are receiving non-invasive respiratory support and there is a clinical decision to treat with surfactant. The intervention is budesonide (0.25 mg/kg) mixed with poractant alfa (200 mg/kg first intervention, 100 mg/kg if second intervention), administered intratracheally via an endotracheal tube or thin catheter. The comparator is poractant alfa alone (at the same doses). Secondary outcomes include the components of the primary outcome (death, BPD prior to or at 36 weeks' PMA), potential systemic side effects of corticosteroids, cost-effectiveness, early childhood health until 2 years of age, and neurodevelopmental outcomes at 2 years of age (corrected for prematurity).

DISCUSSION: Combining budesonide with surfactant for intratracheal administration is a simple intervention that may reduce BPD in extremely preterm infants and translate into health benefits in later childhood. The PLUSS trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants regardless of their initial mode of respiratory support. Should intratracheal budesonide mixed with surfactant increase survival free of BPD, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( https://www.anzctr.org.au ), ACTRN12617000322336. First registered on 28th February 2017.

PMID:37161488 | DOI:10.1186/s13063-023-07257-5

BMC Pregnancy Childbirth. 2023 May 9;23(1):332. doi: 10.1186/s12884-023-05669-4.

ABSTRACT

BACKGROUND: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women.

METHODS: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively.

RESULTS: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination.

CONCLUSIONS: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines.

PMID:37161480 | DOI:10.1186/s12884-023-05669-4

BMC Womens Health. 2023 May 9;23(1):241. doi: 10.1186/s12905-023-02303-5.

ABSTRACT

BACKGROUND: Bacterial vaginosis is a common and distressing condition for women. Short-term antibiotic treatment is usually clinically effective, but recurrence is common. We assessed the effectiveness of intravaginal lactic acid gel versus oral metronidazole for treating recurrent bacterial vaginosis.

METHODS: We undertook an open-label, multicentre, parallel group, randomised controlled trial in nineteen UK sexual health clinics and a university health centre. Women aged ≥ 16 years, with current bacterial vaginosis symptoms and a preceding history of bacterial vaginosis, were randomised in a 1:1 ratio using a web-based minimisation algorithm, to 400 mg twice daily oral metronidazole tablets or 5 ml once daily intravaginal lactic acid gel, for 7 days. Masking of participants was not possible. The primary outcome was participant-reported resolution of symptoms within 2 weeks. Secondary outcomes included time to first recurrence of symptoms, number of recurrences and repeat treatments over 6 months and side effects.

RESULTS: Five hundred and eighteen participants were randomised before the trial was advised to stop recruiting by the Data Monitoring Committee. Primary outcome data were available for 79% (204/259) allocated to metronidazole and 79% (205/259) allocated to lactic acid gel. Resolution of bacterial vaginosis symptoms within 2 weeks was reported in 70% (143/204) receiving metronidazole versus 47% (97/205) receiving lactic acid gel (adjusted risk difference -23·2%; 95% confidence interval -32.3 to -14·0%). In those participants who had initial resolution and for whom 6 month data were available, 51 of 72 (71%) women in the metronidazole group and 32 of 46 women (70%) in the lactic acid gel group had recurrence of symptoms, with median times to first recurrence of 92 and 126 days, respectively. Reported side effects were more common following metronidazole than lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively).

CONCLUSIONS: Metronidazole was more effective than lactic acid gel for short-term resolution of bacterial vaginosis symptoms, but recurrence is common following both treatments. Lactic acid gel was associated with fewer reported side effects.

TRIAL REGISTRATION: ISRCTN14161293 , prospectively registered on 18th September 2017.

PMID:37161454 | DOI:10.1186/s12905-023-02303-5

Drugs R D. 2023 May 10. doi: 10.1007/s40268-023-00420-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Despite rasburicase's proven efficiency in Caucasians, Japanese, and Koreans, studies evaluating the safety and effectiveness of rasburicase in Chinese pediatric patients with non-Hodgkin's lymphoma (NHL) and acute leukemia (AL) in particular are lacking.

OBJECTIVE: The aim was to evaluate the safety and effectiveness of rasburicase in Chinese pediatric patients with NHL and AL.

METHODS: In this phase IV, open-label, non-randomized, single-arm, multi-center, interventional study (NCT04349306), children newly diagnosed with NHL or AL who received 0.20 mg/kg/day of rasburicase were included. The primary objective was to assess the safety of rasburicase by the incidence of adverse events (AEs). The secondary objective was to determine the effectiveness of rasburicase in the control of hyperuricemia.

RESULTS: Out of 50 patients, 25 reported a total of 76 treatment-emergent adverse events (TEAEs), including eight TEAEs of grade ≥ 3 in 12 patients. A drug-related serious AE was reported in one patient, and there was no incidence of death. The response rate in the intent-to-treat population was 100.0% (95% confidence interval 82.4-100.0) in patients (n = 19) with baseline uric acid level of > 8.0 mg/dL. Similarly, the response rate was 86.2% (n = 25) among 29 patients (60.4%) with baseline uric acid levels of ≤ 8.0 mg/dL. The maximum mean percentage decrease of plasma uric acid level in the overall patients was 96.9%.

CONCLUSION: Rasburicase was well tolerated and effective in controlling hyperuricemia in Chinese pediatric patients with NHL and AL.

PMID:37165291 | DOI:10.1007/s40268-023-00420-y

Cureus. 2023 Apr 7;15(4):e37269. doi: 10.7759/cureus.37269. eCollection 2023 Apr.

ABSTRACT

Introduction Those who practice self-care using over-the-counter (OTC) products believe that these medications are relatively safe. They can be used to treat mild illnesses that do not require medical consultation. However, improper self-medication using OTC medicines because of inadequate knowledge of their side effects and interactions can result in drug-related issues and even death. The current study was performed using the foundation year students of Princess Nourah Bint Abdul Rahman University (PNU) as subjects, to examine the use of OTC medicines during examination times. Methods This cross-sectional study was done on 213 (response rates 87.7%) foundation-year female students in the Health Colleges at PNU in Riyadh. Using a 26-item, self-administered, online questionnaire, data were collected. Results It was found that more than 50% of the students used OTC medicines habitually during exam periods. A majority (90.6%; p< 0.0001) of the students mentioned that the overuse of Panadol Extra was very safe while 67.6% (p< 0.0001) of them declared that nonsteroidal anti-inflammatory drugs (NSAIDs) would not induce stomach ulcer formation. A higher percentage (67.6%; p<0.0001) of the students confirmed using OTC medicines during exam time for headache relief. A higher percentage (72.8%; p< 0.0001) of the students indicated that because the OTC medications were readily available and they believed these drugs were safe, they used sizable quantities during the time of the examinations. Furthermore, 69% (p< 0.0001) of the students confessed that because of a friend's recommendations, they started trying OTC medicine. Above 67% (p< 0.0001) stated that OTC medications are inexpensive and easily available in Saudi Arabia. Conclusion To conclude, the findings of this study reiterated the high usage of OTC medicines by female students during the time of examination, and the highest used were painkillers.

PMID:37162782 | PMC:PMC10164448 | DOI:10.7759/cureus.37269

Ophthalmologie. 2023 May;120(5):559-573. doi: 10.1007/s00347-023-01852-2. Epub 2023 May 9.

ABSTRACT

In recent years, checkpoint inhibitors have revolutionized the treatment of previously untreatable malignant tumors, significantly improving the life expectancy as well as quality of life in many cases. Checkpoint inhibitors comprise a group of drugs with different mechanisms of action. These include immunological checkpoint inhibitors (iCPI) and intracellular signal transduction inhibitors; however, both substance classes can cause inflammatory or toxic ocular side effects. The frequency of intraocular inflammation (uveitis) is reported to be ca. 1-2%, toxic side effects were observed in up to more than 50% of the patients treated with signal transduction inhibitors. In the following article the main mechanisms of these forms of treatment are characterized. Furthermore, this article presents the currently most frequently used therapeutic agents and their typical ophthalmological side effects to increase awareness and to draw attention to these still rare but increasingly more frequent findings.

PMID:37160621 | DOI:10.1007/s00347-023-01852-2

Cochrane Database Syst Rev. 2023 May 9;5(5):CD003781. doi: 10.1002/14651858.CD003781.pub3.

ABSTRACT

BACKGROUND: Around 16% of adults have symptoms of overactive bladder (OAB; urgency with frequency and/or urge incontinence), with prevalence increasing with age. Anticholinergic drugs are commonly used to treat this condition. This is an update of a Cochrane Review first published in 2002 and last updated in 2006.

OBJECTIVES: To assess the effects of anticholinergic drugs compared with placebo or no treatment for treating overactive bladder syndrome in adults.

SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 14 January 2020), and the reference lists of relevant articles. We updated this search on 3 May 2022, but these results have not yet been fully incorporated.

SELECTION CRITERIA: We included randomised or quasi-randomised trials in adults with overactive bladder syndrome that compared an anticholinergic drug alone with placebo treatment.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and extracted data from the included studies, including an assessment of the risk of bias. We assessed the certainty of the body of evidence using the GRADE approach. We processed data as described in the Cochrane Handbook for Systematic Reviews of Interventions.

MAIN RESULTS: We included 104 studies, 71 of which were new or updated for this version of the review. Although 12 studies did not report the number of participants, there were 47,106 people in the remainder of the included studies. The majority of the studies had insufficient information to allow judgement of risk of bias and we judged them to be unclear for all domains. Nine anticholinergic drugs were included in these studies: darifenacin; fesoterodine; imidafenacin; oxybutynin; propantheline; propiverine; solifenacin; tolterodine and trospium. No studies were found that compared anticholinergic drugs to no treatment. At the end of the treatment period, anticholinergics may slightly increase condition-specific quality of life (mean difference (MD) 4.41 lower, 95% confidence interval (CI) 5.28 lower to 3.54 lower (scale range -100 to 0); 12 studies, 6804 participants; low-certainty evidence). Anticholinergics are probably better than placebo in terms of patient perception of cure or improvement (risk ratio (RR) 1.38, 95% CI 1.15 to 1.66; 9 studies, 8457 participants; moderate-certainty evidence), and the mean number of urgency episodes per 24-hour period (MD 0.85 lower, 95% CI 1.03 lower to 0.67 lower; 23 studies, 16,875 participants; moderate-certainty evidence). Compared to placebo, anticholinergics may result in an increase in dry mouth adverse events (RR 3.50, 95% CI 3.26 to 3.75; 66 studies, 38,368 participants; low-certainty evidence), and may result in an increased risk of urinary retention (RR 3.52, 95% CI 2.04 to 6.08; 17 studies, 7862 participants; low-certainty evidence). Taking anticholinergics may be more likely to lead to participants withdrawing from the studies due to adverse events (RR 1.37, 95% CI 1.21 to 1.56; 61 studies, 36,943 participants; low-certainty evidence). However, taking anticholinergics probably reduces the mean number of micturitions per 24-hour period compared to placebo (MD 0.85 lower, 95% CI 0.98 lower to 0.73 lower; 30 studies, 19,395 participants; moderate-certainty evidence).

AUTHORS' CONCLUSIONS: The use of anticholinergic drugs by people with overactive bladder syndrome results in important but modest improvements in symptoms compared with placebo treatment. In addition, recent studies suggest that this is generally associated with only modest improvement in quality of life. Adverse effects were higher with all anticholinergics compared with placebo. Withdrawals due to adverse effects were also higher for all anticholinergics except tolterodine. It is not known whether any benefits of anticholinergics are sustained during long-term treatment or after treatment stops.

PMID:37160401 | PMC:PMC10167789 | DOI:10.1002/14651858.CD003781.pub3

Cell Rep Methods. 2023 Apr 17;3(4):100452. doi: 10.1016/j.crmeth.2023.100452. eCollection 2023 Apr 24.

ABSTRACT

Drug-induced phenotypes result from biomolecular interactions across various levels of a biological system. Characterization of pharmacological actions therefore requires integration of multi-omics data. Proteomics profiles, which may more directly reflect disease mechanisms and biomarkers than transcriptomics, have not been widely exploited due to data scarcity and frequent missing values. A computational method for inferring drug-induced proteome patterns would therefore enable progress in systems pharmacology. To predict the proteome profiles and corresponding phenotypes of an uncharacterized cell or tissue type that has been disturbed by an uncharacterized chemical, we developed an end-to-end deep learning framework: TransPro. TransPro hierarchically integrated multi-omics data, in line with the central dogma of molecular biology. Our in-depth assessments of TransPro's predictions of anti-cancer drug sensitivity and drug adverse reactions reveal that TransPro's accuracy is on par with that of experimental data. Hence, TransPro may facilitate the imputation of proteomics data and compound screening in systems pharmacology.

PMID:37159671 | PMC:PMC10163019 | DOI:10.1016/j.crmeth.2023.100452

Pediatr Ann. 2023 May;52(5):e181-e186. doi: 10.3928/19382359-20230307-04. Epub 2023 May 1.

ABSTRACT

The legalization of recreational and medical cannabis has increased the availability and potency of cannabis products in homes and communities. Although state laws regarding legalization and commercial sale often encompass adult use only, pediatric toxicity from unintentional exposures to cannabis edibles and adolescent harm from chronic use are increasing in states and countries that have relaxed laws on use. Unintentional edible ingestions are shown to increase in regions that legalize and commercialize cannabis products at the retail level. Long-term effects on teenagers regarding psychiatric changes as well as acute gastrointestinal effects from hyperemesis syndrome are well documented in the medical literature. This article provides clinical information on the presentation, evaluation, and management of adverse effects from pediatric and adolescent teen exposures to cannabis seen in acute care and emergent settings. [Pediatr Ann. 2023;52(5):e181-e186.].

PMID:37159059 | DOI:10.3928/19382359-20230307-04

BMC Infect Dis. 2023 May 8;23(1):304. doi: 10.1186/s12879-023-08267-z.

ABSTRACT

BACKGROUND: Candidemia is the fourth most common nosocomial bloodstream infection. Endocarditis from candidemia is a rare but possibly fatal complication. The efficacy of amphotericin and echinocandins for induction and azoles for suppression has been well studied. Source control of infection, including removal of foreign bodies, remains the cornerstone for the success of any antifungal therapy.

CASE PRESENTATION: We are describing a case of a 63-years old patient with multiple comorbidities who developed candidemia secondary to Candida albicans. The prospect of curing the fungemia was made difficult by prosthetic devices, including prosthetic heart valves, intracardiac defibrillator, and inferior vena filter, which could not be extracted due to poor cardiovascular status and higher postoperative mortality risk. Combination therapy with amphotericin and 5-Flucytosine (5FC) was used with the first recurrence. Suppression with fluconazole was contraindicated due to prolonged corrected QT (QTc) interval. Isavuconazole was employed for chronic lifelong suppression.

CONCLUSION: Retaining prosthetics in higher surgical risk patients presents us with unique clinical and pharmacological challenges regarding breakthrough infections, drug interaction, and side effects from prolonged suppressive therapies.

PMID:37158828 | PMC:PMC10165830 | DOI:10.1186/s12879-023-08267-z