J Coll Physicians Surg Pak. 2023 Jan;33(1):77-79. doi: 10.29271/jcpspcr.2023.77.

ABSTRACT

Capillary haemangiomas are the most common periocular tumours among children. Most of them resolve spontaneously. The most common indication for intervention is visual impairment. Intralesional bleomycin injections have been used successfully to treat periocular haemangiomas resistant to conventional treatment modalities. In the literature, the most commonly reported side effects of intralesional bleomycin are local skin reactions like erythema, swelling, and pigmentation. Here, we report a highly unusual case of a severe allergic reaction to the fourth dose of intralesional bleomycin injection in a periocular haemangioma in a 7-year child. The clinical features and subsequent management of the patient are also discussed. Key Words: Anaphylaxis, Intralesional bleomycin, Periocular haemangioma.

PMID:37710948 | DOI:10.29271/jcpspcr.2023.77

J Coll Physicians Surg Pak. 2023 Jan;33(1):34-35. doi: 10.29271/jcpspcr.2023.34.

ABSTRACT

Trichobezoar is a rare and potentially dangerous surgical condition in which patients swallow their own hair, often as a result of trichotillomania or trichophagia. This case report focuses on a 12-year female who experienced abdominal pain, anaemia, and gastric perforation due to her mental health conditions. Further examination revealed the presence of hairs, fibers, and bile in her stomach wall - indicative of trichobezoar - which had to be surgically removed. It is important for paediatric surgeons to remain aware and informed about this condition so that prompt treatment can be provided when necessary. The patient in this case was also treated with therapy for underlying mental health issues. With careful diagnosis and treatment plans tailored to each individual's needs, patients suffering from trichobezoar can receive the help they need for successful recovery. Key Words: Bezoars, Gastric rupture, Trichotillomania, Emotional disturbance.

PMID:37710932 | DOI:10.29271/jcpspcr.2023.34

J Coll Physicians Surg Pak. 2023 Jan;33(1):26-28. doi: 10.29271/jcpspcr.2023.26.

ABSTRACT

Patients suffering from multiple sclerosis (MS) often develop neuropathic pain. Trigeminal neuralgia (TN) is the most common type in these patients. The pain is characterised by recurrent, unilateral, brief, electric shock-like episodes, abrupt in onset and termination, and limited to the distribution of one or more divisions of the trigeminal nerve, which is difficult to treat when compared to classical TN. The recommended first line of therapy includes medications like carbamazepine, lamotrigine, baclofen, and gabapentinoids to which most of the patients respond well with mild to moderate side effects. Some patients do not respond to conventional pharmacological therapy and may require a combination of other pain medications. A 30-year female patient presented in the pain clinic with TN due to MS and was treated with carbamazepine. However, due to severe side effects she had to quit its use. The patient was then successfully treated with an intravenous infusion of lidocaine and remained pain-free without any other pain medications. Key Words: Trigeminal neuralgia, Multiple sclerosis, Lidocaine.

PMID:37710929 | DOI:10.29271/jcpspcr.2023.26

Acta Neurol Belg. 2023 Sep 15. doi: 10.1007/s13760-023-02366-z. Online ahead of print.

ABSTRACT

BACKGROUND: Ocrelizumab is a humanized antiCD20, thought to be a highly effective disease-modifying therapy (DMT). Its most frequent adverse effects are infusion-related reactions (IRRs). To reduce these reactions, the first dose of ocrelizumab is administered as two 300 mg infusions separated by two weeks. However, in the phase II trial of ocrelizumab, severe IRRs were not significantly different between two doses of 600 mg dose (two separate 300 mg doses) and 2000 mg dose (two separate 1000 mg doses). We compared the IRRs in undivided full (one 600 mg) and divided (two 300 mg) doses of ocrelizumab which is the standard protocol.

METHODS: MS patients (relapsing or primary progressive MS) who are selected to receive ocrelizumab by neurologist or MS fellowship were enrolled in an open-label randomized controlled trial. Iranian biosimilar of the drug (Xacrel® by Cinnagen, approved by the Iranian Food and Drug Administration in 2021) was used. The participants received the first dose of ocrelizumab as either one 600 mg dose in one session or two 300 mg doses in two weeks apart. IRRs during or in the first 24 h after infusion were recorded.

RESULTS: Of 332 participants, 150 received two 300 mg doses, and 182 received one 600 mg dose (by random selection). Life-threatening adverse effects were not observed in both groups. Overnight admission or permanent drug discontinuation was not needed. Temporary drug discontinuation was significantly higher in the one 600 mg dose group (p-value < 0.001). During the infusions, malaise (p-value: 0.003), skin reactions (p-value: 0.04), throat swelling (p-value: 0.03), and dyspnea (p-value: 0.01) were significantly increased in the intervention group. However, in the first 24 h, there was no significant difference between two different treatment protocols (one 600 mg dose or two 300 mg doses) in the onset of IRRS (p-value: 0.12).

CONCLUSION: These findings suggest one 600 mg dose of ocrelizumab administration for the first dose is relatively safe. With some protocol modifications, it could lead to fewer patient referrals, saving time and cost and improvement the access for patients.

PMID:37715074 | DOI:10.1007/s13760-023-02366-z

Cancer Res Commun. 2023 Sep 14;3(9):1853-1861. doi: 10.1158/2767-9764.CRC-23-0333.

ABSTRACT

PURPOSE: CB-103 selectively inhibits the CSL-NICD (Notch intracellular domain) interaction leading to transcriptional downregulation of oncogenic Notch pathway activation. This dose-escalation/expansion study aimed to determine safety, pharmacokinetics, and preliminary antitumor activity.

EXPERIMENTAL DESIGN: Patients ≥18 years of age with selected advanced solid tumors [namely, adenoid cystic carcinoma (ACC)] and hematologic malignancies were eligible. CB-103 was dosed orally in cycles of 28 days at escalating doses until disease progression. Notch-activating mutations were required in a dose confirmatory cohort. Endpoints included dose-limiting toxicities (DLT), safety, tumor response, pharmacokinetics, and pharmacodynamics. Exploratory analyses focused on correlates of Notch and target gene expression.

RESULTS: Seventy-nine patients (64, 12 dose-escalation cohorts; 15, confirmatory cohort) enrolled with 54% receiving two or more lines of prior therapy. ACC was the dominant tumor type (40, 51%). Two DLTs were observed [elevated gamma-glutamyl transferase (GGT), visual change]; recommended phase II dose was declared as 500 mg twice daily (5 days on, 2 days off weekly). Grade 3-4 treatment-related adverse events occurred in 15 patients (19%), including elevated liver function tests (LFTs), anemia, and visual changes. Five (6%) discontinued drug for toxicity; with no drug-related deaths. There were no objective responses, but 37 (49%) had stable disease; including 23 of 40 (58%) patients with ACC. In the ACC cohort, median progression-free survival was 2.5 months [95% confidence interval (CI), 1.5-3.7] and median overall survival was 18.4 months (95% CI, 6.3-not reached).

CONCLUSIONS: CB-103 had a manageable safety profile and biological activity but limited clinical antitumor activity as monotherapy in this first-in-human study.

SIGNIFICANCE: CB-103 is a novel oral pan-Notch inhibitor that selectively blocks the CSL-NICD interaction leading to transcriptional downregulation of oncogenic Notch pathway activation. This first-in-human dose-escalation and -confirmation study aimed to determine the safety, pharmacokinetics, and preliminary antitumor efficacy of CB-103. We observed a favorable safety profile with good tolerability and biological activity but limited clinical single-agent antitumor activity. Some disease stabilization was observed among an aggressive NOTCH-mutant ACC type-I subgroup where prognosis is poor and therapies are critically needed. Peripheral downregulation of select Notch target gene levels was observed with escalating doses. Future studies exploring CB-103 should enrich for patients with NOTCH-mutant ACC and investigate rational combinatorial approaches in tumors where there is limited success with investigational or approved drugs.

PMID:37712875 | DOI:10.1158/2767-9764.CRC-23-0333

Br J Clin Pharmacol. 2023 Sep 15. doi: 10.1111/bcp.15908. Online ahead of print.

ABSTRACT

AIM: A key reason for the failure of anti-tuberculosis (TB) treatment is missed doses (instances where medication is not taken). Adverse drug reactions (ADRs) are one cause of missed doses, but the global evidence, their relative contribution to missed doses versus other causes, the patterns of missed doses due to ADRs, and the specific ADRs associated with missed doses have not been appraised. We sought to address these questions through a scoping review.

METHODS: MEDLINE, Embase and Web of Science were searched on 3 November 2021 using terms around active TB, missed doses and treatment challenges. Studies reporting both ADR and missed dose data were examined. (PROSPERO: CRD42022295209).

RESULTS: Searches identified 108 eligible studies. 88/108 (81%) studies associated ADRs with an increase in missed doses. 33/61 (54%) studies documenting the reasons for missed doses gave ADRs as a primary reason. No studies examined patterns of missed doses due to ADRs. 41/108 (38%) studies examined associations between 68 types of ADR (across 15 organ systems) and missed doses. Nuance around ADR-missed doses relations regarding drug susceptibility testing profile and whether the missed doses originated from the patient, healthcare professionals, or both were found.

CONCLUSIONS: There is extensive evidence that ADRs are a key driver for missed doses of anti-TB treatment. Some papers examined specific ADRs and none evaluated the patterns of missed doses due to ADRs, demonstrating a knowledge deficit. Knowing why doses both are and are not missed is essential in providing targeted interventions to improve treatment outcomes.

PMID:37712491 | DOI:10.1111/bcp.15908

Front Neurol. 2023 Aug 30;14:1236046. doi: 10.3389/fneur.2023.1236046. eCollection 2023.

ABSTRACT

BACKGROUND: No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study on perampanel early add-on therapy in China. This interventional study aimed to assess efficacy and safety of perampanel as an early add-on treatment of focal-onset seizures (FOS) with or without focal-to-bilateral tonic-clonic seizures (FBTCS) in Chinese patients.

METHODS: In this multicenter, open-label, single-arm, phase 4 interventional study, Chinese patients ≥ 12 years old with FOS with or without FBTCS who failed anti-seizure medication (ASM) monotherapy from 15 hospitals in China were enrolled and treated with perampanel add-on therapy (8-week titration followed by 24-week maintenance). The primary endpoint was 50% responder rate. Secondary endpoints included seizure-freedom rate and changes in seizure frequency from baseline. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were recorded.

RESULTS: The full analysis set included 150 patients. The mean maintenance perampanel dose was 5.9 ± 1.5 mg/day and the 8-month retention rate was 72%. The 50% responder rate and seizure-freedom rate for all patients during maintenance were 67.9 and 30.5%, respectively. Patients with FBTCS had higher 50% responder rate (96.0%) and seizure-freedom rate (76.0%) during maintenance. Patients on concomitant sodium valproate had a significantly higher seizure-freedom rate than those on concomitant oxcarbazepine. Eight-six (55.1%) patients experienced treatment-related TEAEs, and the most common TEAEs were dizziness (36.5%), hypersomnia (11.5%), headache (3.9%), somnolence (3.2%), and irritability (3.2%). Withdrawal due to TEAEs occurred to 14.7% of the patients.

CONCLUSION: Perampanel early add-on was effective and safe in treating Chinese patients≥12 years old with FOS with or without FBTCS.Clinical trial registrationwww.chictr.org.cn, Identifier ChiCTR2000039510.

PMID:37712083 | PMC:PMC10499319 | DOI:10.3389/fneur.2023.1236046

BMC Complement Med Ther. 2023 Sep 14;23(1):321. doi: 10.1186/s12906-023-04144-z.

ABSTRACT

BACKGROUND: The use of complementary and alternative medicines (CAM) among cancer patients varies greatly. The available data suggest an increasing use of CAM over time and a higher prevalence in low- and middle-income countries. However, no reliable data are available from Latin America. Accordingly, we examined the prevalence of CAM use among cancer patients from six Colombian regions.

METHODS: We conducted a survey on cancer patients attending comprehensive cancer centres in six capital cities from different regions. The survey was designed based on a literature review and information gathered through focus groups on CAM terminology in Colombia. Independent random samples of patients from two comprehensive cancer centres in every city were obtained. Patients 18 years and older with a histopathological diagnosis of cancer undergoing active treatment were eligible. The prevalence of CAM use is reported as a percentage with the corresponding confidence interval. CAM types are reported by region. The sociodemographic and clinical characteristics of CAM users and non-users were compared using Chi square and t tests.

RESULTS: In total, 3117 patients were recruited. The average age 59.6 years old, and 62.8% were female. The prevalence of CAM use was 51.7%, and compared to non-users, CAM users were younger, more frequently women, affiliated with the health insurance plan for low-income populations and non-Catholic. We found no differences regarding the clinical stage or treatment modality, but CAM users reported more treatment-related side effects. The most frequent types of CAM were herbal products, specific foods and vitamins, and individually, soursop was the most frequently used product. Relevant variability between regions was observed regarding the prevalence and type of CAM used (range: 36.6% to 66.7%). The most frequent reason for using CAM was symptom management (30.5%), followed by curative purposes (19.5%).

CONCLUSIONS: The prevalence of CAM use among cancer patients in Colombia is high in general, and variations between regions might be related to differences in cultural backgrounds and access to comprehensive cancer care. The most frequently used CAM products and practices have little scientific support, suggesting the need to enhance integrative oncology research in the country.

PMID:37710213 | PMC:PMC10500828 | DOI:10.1186/s12906-023-04144-z

BMC Cancer. 2023 Sep 14;23(1):865. doi: 10.1186/s12885-023-11291-6.

ABSTRACT

BACKGROUND: Radiotherapy (RT) following breast-conserving surgery (BCS) is mainly used to decrease the rate of ipsilateral breast tumor recurrence (IBTR) in women with breast ductal carcinoma in situ (DCIS). Recent studies have demonstrated that low-dose tamoxifen significantly reduces IBTR in breast DCIS. Here, we aim to determine whether the administration of low-dose tamoxifen is non-inferior to RT in preventing IBTR in patients with low-risk characteristics of breast DCIS.

METHODS/DESIGN: This is a prospective, international, open-label, randomized, non-inferiority trial. Patients with low-risk clinicopathologic features (> 40 years old, low risk of breast cancer susceptibility gene (BRCA) 1 and BRCA2 mutations, mammographically detected unicentric and non-mass lesions, low- or intermediate-grade without comedo or necrosis, measuring < 2.5 cm with margins ≥ 3 mm, and estrogen receptor-positive status) of DCIS who underwent BCS will be randomized at a 1:1 ratio to either receive tamoxifen (5 mg/day) for 5 years or undergo RT with conventional fractions (50 Gy in 25 fractions) or hypofractionations (40.05 Gy in 15 fractions). Randomization will be stratified by the Taiwan Breast Cancer Consortium. As approximately 5% of patients cannot tolerate the side effects of low-dose tamoxifen and will receive RT, we estimate that 405 patients will be randomized to a low-dose tamoxifen arm and 405 patients to the RT arm, according to a non-inferiority margin within 5% of IBTR difference and 90% β-power noticing non-inferiority. The primary endpoints are breast tumor recurrence, including ipsilateral, regional, contralateral, and distant recurrence of breast DCIS or invasive cancer. The secondary endpoints are overall survival and adverse effects of RT and tamoxifen. Translational studies will also be conducted for this trial.

DISCUSSION: This is the first non-inferiority trial on breast DCIS. This study will provide an important recommendation for clinical physicians on whether to use low-dose adjuvant tamoxifen for patients with low-risk breast DCIS who do not want to receive adjuvant RT.

TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT04046159, Registered on April 30, 2019.

PMID:37710198 | PMC:PMC10500726 | DOI:10.1186/s12885-023-11291-6

BMJ Open. 2023 Sep 14;13(9):e071079. doi: 10.1136/bmjopen-2022-071079.

ABSTRACT

OBJECTIVES: The slow progress of pharmacovigilance (PV) in low-income and middle-income countries (LMIC) raises questions about core challenges on the growth of PV, and the appropriateness of strategies used so far to develop PV. Therefore, this scoping review aims to describe strategies and interventions to strengthen PV in LMIC and to propose recommendations for future investments in PV capacity building.

INCLUSION CRITERIA: Publications included were primary studies, articles, policy and guideline papers, describing interventions to strengthen PV in LMIC.

METHODS: The review was conducted following the Joanna Briggs Institute (JBI) guidelines on conducting scoping reviews. Literature searches were performed in MEDLINE, EMBASE, Web of Science, PDQ-evidence, CINAHL and other relevant websites from January 1990 to January 2021. Two reviewers independently screened titles, abstracts and full texts. One reviewer performed data extraction and descriptive analysis, which were reviewed by two other reviewers.

RESULTS: 10 922 unique titles were screened and 152 were eligible for full text review. Of these, 57 and an additional 13 reports from grey literature fulfilled eligibility criteria for inclusion in the review. These were grouped into two categories: (1) Interventions aimed at increasing PV knowledge and adverse drug reactions (ADR) reporting (45 papers), primarily education of healthcare professionals (HCP), alone or in combination with other interventions such as mobile and electronic reporting and (2) Interventions aimed at strengthening various components of the national PV system (25 papers), describing strategies or mixed interventions implemented at the national level, targeting different components of the national PV system.

CONCLUSIONS: Results of this review suggest that educating HCP on ADR reporting is the most common approach to build PV capacity in LMIC. Though important, education alone is insufficient and should ideally be organised within the holistic framework of strengthening national PV systems, with a focus on also building capacity for advanced activities such as signal detection.

PMID:37709326 | PMC:PMC10503375 | DOI:10.1136/bmjopen-2022-071079

Cochrane Database Syst Rev. 2023 Sep 15;9(9):CD011345. doi: 10.1002/14651858.CD011345.pub3.

ABSTRACT

BACKGROUND: Many factors influence fertility, one being the timing of intercourse. The 'fertile window' describes a stage in the cycle when conception can occur and is approximately five days before to several hours after ovulation. 'Timed intercourse' is the practice of prospectively identifying ovulation and, thus, the fertile window to increase the likelihood of conception. Methods of predicting ovulation include urinary hormone measurement (luteinising hormone (LH) and oestrogen), fertility awareness-based methods (FABM) (including tracking basal body temperatures, cervical mucus monitoring, calendar charting/tracking apps), and ultrasonography. However, there are potentially negative aspects associated with ovulation prediction, including stress, time consumption, and cost implications of purchasing ovulation kits and app subscriptions. This review considered the evidence from randomised controlled trials (RCTs) evaluating the use of timed intercourse (using ovulation prediction) on pregnancy outcomes.

OBJECTIVES: To evaluate the benefits and risks of ovulation prediction methods for timing intercourse on conception in couples trying to conceive.

SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group Specialised Register, CENTRAL, MEDLINE, and Embase in January 2023. We also checked the reference lists of relevant studies and searched trial registries for any additional trials.

SELECTION CRITERIA: We included RCTs that compared methods of timed intercourse using ovulation prediction to other forms of ovulation prediction or intercourse without ovulation prediction in couples trying to conceive.

DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane to select and analyse studies in this review. The primary review outcomes were live birth and adverse events (such as depression and stress). Secondary outcomes were clinical pregnancy, pregnancy (clinical or positive urinary pregnancy test not yet confirmed by ultrasound), time to pregnancy, and quality of life. We assessed the overall quality of the evidence for the main comparisons using GRADE methods.

MAIN RESULTS: This review update included seven RCTs involving 2464 women or couples. Four of the five studies from the previous review were included in this update, and three new studies were added. We assessed the quality of the evidence as moderate to very low, the main limitations being imprecision, indirectness, and risk of bias. Urinary ovulation tests versus intercourse without ovulation prediction Compared to intercourse without ovulation prediction, urinary ovulation detection probably increases the chance of live birth in couples trying to conceive (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.02 to 1.81, 1 RCT, n = 844, moderate-quality evidence). This suggests that if the chance of a live birth without urine ovulation prediction is 16%, the chance of a live birth with urine ovulation prediction is 16% to 28%. However, we are uncertain whether timed intercourse using urinary ovulation detection resulted in a difference in stress (mean difference (MD) 1.98, 95% CI -0.87 to 4.83, I² = 0%, P = 0.17, 1 RCT, n = 77, very low-quality evidence) or clinical pregnancy (RR 1.09, 95% CI 0.51 to 2.31, I² = 0%, 1 RCT, n = 148, low-quality evidence). Similar to the live birth result, timed intercourse using urinary ovulation detection probably increases the chances of clinical pregnancy or positive urine pregnancy test (RR 1.28, 95% CI 1.09 to 1.50, I² = 0, 4 RCTs, n = 2202, moderate-quality evidence). This suggests that if the chance of a clinical pregnancy or positive urine pregnancy test without ovulation prediction is assumed to be 18%, the chance following timed intercourse with urinary ovulation detection would be 20% to 28%. Evidence was insufficient to determine the effect of urine ovulation tests on time to pregnancy or quality of life. Fertility awareness-based methods (FABM) versus intercourse without ovulation prediction Due to insufficient evidence, we are uncertain whether timed intercourse using FABM resulted in a difference in live birth rate compared to intercourse without ovulation prediction (RR 0.95, 95% CI 0.76 to 1.20, I² = 0%, 2 RCTs, n = 157, low-quality evidence). We are also uncertain whether FABM affects stress (MD -1.10, 95% CI -3.88 to 1.68, 1 RCT, n = 183, very low-quality evidence). Similarly, we are uncertain of the effect of timed intercourse using FABM on anxiety (MD 0.5, 95% CI -0.52 to 1.52, P = 0.33, 1 RCT, n = 183, very low-quality evidence); depression (MD 0.4, 95% CI -0.28 to 1.08, P = 0.25, 1 RCT, n = 183, very low-quality evidence); or erectile dysfunction (MD 1.2, 95% CI -0.38 to 2.78, P = 0.14, 1 RCT, n = 183, very low-quality evidence). Evidence was insufficient to detect a benefit of timed intercourse using FABM on clinical pregnancy (RR 1.13, 95% CI 0.31 to 4.07, 1 RCT, n = 17, very low-quality evidence) or clinical or positive pregnancy test rates (RR 1.08, 95% CI 0.89 to 1.30, 3 RCTs, n = 262, very low-quality evidence). Finally, we are uncertain whether timed intercourse using FABM affects the time to pregnancy (hazard ratio 0.86, 95% CI 0.53 to 1.38, 1 RCT, n = 140, low-quality evidence) or quality of life. No studies assessed the use of timed intercourse with pelvic ultrasonography.

AUTHORS' CONCLUSIONS: The new evidence presented in this review update shows that timed intercourse using urine ovulation tests probably improves live birth and pregnancy rates (clinical or positive urine pregnancy tests but not yet confirmed by ultrasound) in women under 40, trying to conceive for less than 12 months, compared to intercourse without ovulation prediction. However, there are insufficient data to determine the effects of urine ovulation tests on adverse events, clinical pregnancy, time to pregnancy, and quality of life. Similarly, due to limited data, we are uncertain of the effect of FABM on pregnancy outcomes, adverse effects, and quality of life. Further research is therefore required to fully understand the safety and effectiveness of timed intercourse for couples trying to conceive. This research should include studies reporting clinically relevant outcomes such as live birth and adverse effects in fertile and infertile couples and utilise various methods to determine ovulation. Only with a comprehensive understanding of the risks and benefits of timed intercourse can recommendations be made for all couples trying to conceive.

PMID:37709293 | PMC:PMC10501857 | DOI:10.1002/14651858.CD011345.pub3

Ann Med. 2023;55(2):2255215. doi: 10.1080/07853890.2023.2255215.

ABSTRACT

BACKGROUND: Chronic migraine (CM) causes great disability and affects an individual's quality of life. OnabotulinumtoxinA (OBT-A, Botox®) was the first prophylactic treatment specifically indicated for CM. The aim of this study was to describe the experiences of women with CM treated with OBT-A.

MATERIALS AND METHODS: The study design is a qualitative descriptive study. A purposeful sampling of 30 women (mean age, 42.7; standard deviation, 10.6) who had received at least two administrations of OBT-A for CM (PREEMPT protocol) was performed. Data collection included in-depth interviews and researchers' field notes. A thematic analysis was carried out according to qualitative research guidelines.

RESULTS: Five themes were identified: (a) A long way to go before Botox®, (b) First time hearing about the treatment and its expectations, (c) The administration of Botox®, (d) Treatment effects, and (e) Follow-up. Patients described a long history of treatment failures prior to the start of OBT-A treatment. Information about this migraine treatment came from the neurologist; following the information, patients had high expectations, including unrealistic expectations regarding the onset and duration of effect. They acknowledged fear of the injections and some discomfort due to the procedure. With treatment, participants reported better migraine control and an improvement in their quality of life. Follow-up had some barriers, such as delayed appointments for subsequent doses, but also strengths, such as effectiveness and few side effects.

CONCLUSIONS: Qualitative research offers insight into how patients with CM experience treatment with OBT-A. Our results highlight some relevant aspects that should be considered when providing OBT-A treatment.

PMID:37708876 | DOI:10.1080/07853890.2023.2255215

PLoS One. 2023 Sep 14;18(9):e0291601. doi: 10.1371/journal.pone.0291601. eCollection 2023.

ABSTRACT

There is an increasing interest in alternatives to peat in growing media due to environmental constraints. However, plants grown in peat substitutes often show impaired growth compared to plants grown in peat-based media. Hence, it would be interesting to know whether these deficiencies can be compensated by supplementing other growth factors, e.g. light. The present study aims to investigate the interactive nature between growing media and supplemental lighting on plant growth and morphology, and to examine whether supplemental light emitting diode (LED) lighting may compensate adverse growing media effects. Basil (Ocimum basilicum L.) and Chinese cabbage (Brassica rapa subsp. pekinensis) were grown in different growing media consisting of peat, green compost, coconut pulp, wood fibre, perlite and sphagnum moss under blue, red and far-red supplemental LED lighting. We found significant interactions between growing media and supplemental photosynthetically active radiation (PAR) on plant growth, morphology and development. At low light intensities, peat-based and substituted growing media performed similarly, whereas with increasing light intensities the peat-based growing media significantly outperformed their alternatives. The substrate choice determines the required amount of supplemental light to compensate for adverse growing media effects and the amount varies depending on plant species and season. Thereby, it was indicated that red light alleviates adverse growing media effects best. We also found that far-red light is not effective when background PAR is low and becomes more effective under high background PAR. The implications and prospects of the results are discussed.

PMID:37708207 | PMC:PMC10501627 | DOI:10.1371/journal.pone.0291601

PLoS Negl Trop Dis. 2023 Sep 14;17(9):e0011590. doi: 10.1371/journal.pntd.0011590. eCollection 2023 Sep.

ABSTRACT

BACKGROUND: The treatment of brucellosis suffers from a high recurrence rate and drug resistance. Our study researched the differences in efficacy and side effects between triple antibiotics therapy and dual antibiotics therapy in the treatment of brucellosis through a systematic review and meta-analysis.

METHODS: We searched 4 English electronic databases and 2 Chinese electronic databases for randomized controlled trials and cohort studies published through September 2022 on the use of triple antibiotics versus dual antibiotics in the treatment of brucellosis. Overall outcome indicators were therapeutic failure rate, relapse rate, overall therapeutic failure rate, and side effect rate. Relative risk (RR) and 95% confidence intervals (95% CIs) were used as summary statistics. A fixed-effects model was used to combine the overall effect sizes.

RESULTS: The meta-analysis included 15 studies consisting of 11 randomized controlled trials and 4 cohort studies. Triple antibiotics showed better efficacy than dual antibiotics in a comparison of 3 overall outcome indicators (therapeutic failure rate (RR 0.42; 95% CI 0.30 to 0.59 heterogeneity P = 0.29, I2 = 15%), relapse rate (RR 0.29; 95% CI 0.18 to 0.45 heterogeneity P = 0.88, I2 = 0%), and overall therapeutic failure rate (RR 0.37; 95% CI 0.28 to 0.48 heterogeneity P = 0.35, I2 = 9%)). The incidence of side effects in patients with brucellosis treated with triple antibiotics was not significantly different from that in brucellosis patients treated with dual antibiotics (RR 0.85; 95% CI 0.67 to 1.06 heterogeneity P = 0.1, I2 = 35%). Sensitivity analyses showed robust results and Peter's test showed no publication bias. The results of subgroup analyses for the research type, drugs, and type of brucellosis were largely consistent with the overall outcome indicators, indicating the reliability and robustness of the overall results.

CONCLUSIONS: In the treatment of brucellosis, triple antibiotics have better efficacy than dual antibiotics and do not increase the incidence of side effects.

PMID:37708094 | PMC:PMC10501551 | DOI:10.1371/journal.pntd.0011590

Post Reprod Health. 2023 Sep;29(3):135-142. doi: 10.1177/20533691231199803.

ABSTRACT

BACKGROUND: Urogenital atrophy is caused by lack of estrogen, most commonly due to the menopause. Symptoms frequently experienced include vaginal dryness, itching, burning, sexual difficulties and urinary problems, all of which can have a significant adverse effect on quality of life. Effective treatments are available for women with a confirmed diagnosis. The aim of this review is to determine whether a consistent diagnostic intervention exists, to support an accurate indication of prevalence.

MATERIALS AND METHODS: This study is a review of the literature.

RESULTS: A total of 1469 papers were identified on an initial search, including randomised controlled trials, cross sectional and cohort studies. By adoption of a systematic process, the number of papers in the final review was eight.There is inconsistent use of available assessment methods to diagnose urogenital atrophy in symptomatic women. There are no validated clinical assessment tools.

CONCLUSION: Absence of a defined intervention with which to confirm a diagnosis of urogenital atrophy, based on symptoms, influences research outcomes, but more importantly affects access to an accurate diagnosis and treatment, for affected women. This would ideally take place in a primary care setting.

PMID:37707431 | DOI:10.1177/20533691231199803

JMIR Mhealth Uhealth. 2023 Sep 13;11:e45091. doi: 10.2196/45091.

ABSTRACT

BACKGROUND: There is a tendency for older adults to become more physically inactive, especially older women. Physical inactivity has been exacerbated since the COVID-19 pandemic. Lockdowns and information-based preventive measures for COVID-19 increased the number of short-form video app users and short-form video exposure, including content exposure and the duration of exposure, which has demonstrated important effects on youths' health and health-related behaviors. Despite more older adults viewing short-form videos, less is known about the status of their short-form video exposure or the impacts of the exposure on their physical activity.

OBJECTIVE: This study aims to describe physical activity-related content exposure among older adults and to quantify its impacts along with the duration of short-form video exposure on step counts, low-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA).

METHODS: We analyzed a subsample (N=476) of older women who used smartphones and installed short-form video apps, using the baseline data collected from an ongoing cohort study named the Physical Activity and Health in Older Women Study (PAHIOWS) launched from March to June 2021 in Yantai, Shandong Province, China. The information on short-form video exposure was collected by unstructured questions; physical activity-related content exposure was finalized by professionals using the Q-methodology, and the duration of exposure was transformed into hours per day. Step counts, LPA, and MVPA were assessed with ActiGraph wGT3X-BT accelerometers. Multiple subjective and objective covariates were assessed. Linear regression models were used to test the effects of short-form video exposure on step counts, LPA, and MVPA. MVPA was dichotomized into less than 150 minutes per week and 150 minutes or more per week, and the binary logistic regression model was run to test the effects of short-form video exposure on the achievement of spending 150 minutes or more on MVPA.

RESULTS: Of 476 older women (mean age 64.63, SD 2.90 years), 23.7% (113/476) were exposed to physical activity-related short-form videos, and their daily exposure to short-form videos was 1.5 hours. Physical activity-related content exposure increased the minutes spent on MVPA by older women (B=4.14, 95% CI 0.13-8.15); the longer duration of short-form video exposure was associated with a reduced step count (B=-322.58, 95% CI -500.24 to -144.92) and minutes engaged in LPA (B=-6.95, 95% CI -12.19 to -1.71) and MVPA (B=-1.56, 95% CI -2.82 to -0.29). Neither content exposure nor the duration of exposure significantly increased or decreased the odds of older women engaging in MVPA for 150 minutes or more per week.

CONCLUSIONS: Short-form video exposure has both positive and negative impacts on the physical activity of older adults. Efforts are needed to develop strategies to leverage the benefits while avoiding the harms of short-form videos.

PMID:37707321 | DOI:10.2196/45091

Front Endocrinol (Lausanne). 2023 Aug 29;14:1235040. doi: 10.3389/fendo.2023.1235040. eCollection 2023.

ABSTRACT

Primary hypertrophic osteoarthropathy (PHO) is a genetic disorder mainly characterized by clubbing fingers, pachydermia and periostosis. Mutations in the HPGD or SLCO2A1 gene lead to impaired prostaglandin E2 (PGE2) degradation, thus elevating PGE2 levels. The identification of the causative genes has provided a better understanding of the underlying mechanisms. PHO can be divided into three subtypes according to its pathogenic gene and inheritance patterns. The onset age, sex ratio and clinical features differ among subtypes. The synthesis and signaling pathways of PGE2 are outlined in this review. Cyclooxygenase-2 (COX-2) is the key enzyme that acts as the rate-limiting step for prostaglandin production, thus COX-2 inhibitors have been used to treat this disease. Although this treatment showed effective results, it has side effects that restrain its use. Here, we reviewed the genetics, clinical features, differential diagnosis and current treatment options of PHO according to our many years of clinical research on the disease. We also discussed probable treatment that may be an option in the future.

PMID:37705574 | PMC:PMC10497106 | DOI:10.3389/fendo.2023.1235040

Cancer Res Commun. 2023 Sep 12;3(9):1830-1839. doi: 10.1158/2767-9764.CRC-23-0157. eCollection 2023 Sep.

ABSTRACT

Financial hardship (FH), defined as adverse patient effects due to cancer costs, is experienced by approximately half of individuals diagnosed with cancer. Many individuals diagnosed with cancer also experience disruptions with their employment. This study examines associations of employment disruptions and FH among a nationally representative sample of individuals diagnosed with cancer in the United States. We utilized 2016/2017 Medical Expenditure Panel Survey Experiences with Cancer data from individuals who worked for pay following cancer diagnosis. Employment disruption included taking extended paid time off work; switching to part-time/less demanding jobs; and/or retiring early due to cancer diagnosis/treatment. FH domains included: material (e.g., borrowing money/financial sacrifices); psychologic (e.g., worrying about medical bills/income); and behavioral (delaying/forgoing healthcare services because of cost). Multivariable logistic regression analyses determined associations of employment disruption and FH. Among 732 individuals with a cancer history, 47.4% experienced employment disruptions; 55.9% experienced any FH. Any FH was significantly more common among individuals with versus without employment disruptions across multiple measures and domains (68.7% vs. 44.5%; P value of difference <0.0001). Individuals with employment disruptions were more likely to have any FH [OR, 2.38; 95% confidence interval (CI), 1.62-3.52] and more FHs (OR, 2.76; 95% CI, 1.96-3.89]. This study highlights that employment disruptions are common and significantly associated with multiple domains of FH among individuals with a cancer history. Employer workplace accommodation, physician discussions regarding potential impacts of cancer care on employment, and other policies to minimize employment disruptions among individuals diagnosed with cancer may reduce FH in this vulnerable population.

SIGNIFICANCE: Individuals diagnosed with cancer may have employment disruptions; they may also develop FHs. People with cancer who have employment changes are more likely to also have FHs. Physicians and employers can help individuals with cancer through advancing planning, workplace assistance, and improved medical leave and insurance policies.

PMID:37705562 | PMC:PMC10496757 | DOI:10.1158/2767-9764.CRC-23-0157

Leuk Lymphoma. 2023 Sep 14:1-10. doi: 10.1080/10428194.2023.2254430. Online ahead of print.

ABSTRACT

Chimeric antigen receptor (CAR) T-cell therapy presents a promising treatment for hematologic malignancies, displaying high efficacy but not being exempt from toxicity. In this observational study, we assessed adverse events (AEs) reported to the Food and Drug Adverse Event Reporting System (FAERS) including any of the six approved CAR T-cell therapies. A total of 5249 reports mentioning a CAR T-cell as a suspect product were retrieved from the FAERS database, containing a total of 24333 AEs, of which 3236 (13.3%) were cytopenias. The highest number of AEs mentioned by the report was observed for tisagenlecleucel (mean = 6.7), with the lowest for ciltacabtagene (mean = 1.3). Among all reports, hematopoietic leukopenia was the most frequently reported AEs (n = 1386, 5.7%), with hematopoietic erytropenia the least reported (n = 291, 1.2%). Tisagenlecleucel showed a high reporting odds ratio for hematopoietic erythropenia (27.28, 95%CI 14.04-53.00), leukopenia (4.04, 95%CI 3.52-4.64), and thrombocytopenia (4.01, 95%CI 3.19-5.03). Cytopenias represent one of the most frequently reported AEs in FAERS, a CAR T-cell therapy is indicated, with haematopoetic leukopenia being the most common. When comparing different CAR-T cell therapies, the cytopenias' reporting odds ratio was particularly high for tisagenlecleucel, especially in relation to hematopoietic erythropenia.

PMID:37708442 | DOI:10.1080/10428194.2023.2254430

Adv Cancer Res. 2023;160:253-315. doi: 10.1016/bs.acr.2023.03.005. Epub 2023 Apr 20.

ABSTRACT

Current treatment of solid tumors with standard of care chemotherapies, radiation therapy and/or immunotherapies are often limited by severe adverse toxic effects, resulting in a narrow therapeutic index. Cancer gene therapy represents a targeted approach that in principle could significantly reduce undesirable side effects in normal tissues while significantly inhibiting tumor growth and progression. To be effective, this strategy requires a clear understanding of the molecular biology of cancer development and evolution and developing biological vectors that can serve as vehicles to target cancer cells. The advent and fine tuning of omics technologies that permit the collective and spatial recognition of genes (genomics), mRNAs (transcriptomics), proteins (proteomics), metabolites (metabolomics), epiomics (epigenomics, epitranscriptomics, and epiproteomics), and their interactomics in defined complex biological samples provide a roadmap for identifying crucial targets of relevance to the cancer paradigm. Combining these strategies with identified genetic elements that control target gene expression uncovers significant opportunities for developing guided gene-based therapeutics for cancer. The purpose of this review is to overview the current state and potential limitations in developing gene promoter-directed targeted expression of key genes and highlights their potential applications in cancer gene therapy.

PMID:37704290 | DOI:10.1016/bs.acr.2023.03.005