METHODS: Nine healthy normotensive subjects participated in this randomized placebo-controlled two-way crossover study examining the effects of 5 days' pretreatment of nafcillin 500 mg or placebo four times daily on the pharmacokinetics of an oral dose of nifedipine 10 mg. Plasma nifedipine concentrations were measured by gas chromatography-mass spectro.
RESULTS: The area under the plasma nifedipine concentration-time curve (AUC0-alpha) in nafcillin-pretreated subjects (80.9 +/- 32.9 micro g l-1 h-1) was significantly decreased compared with subjects who received only nifedipine (216.4 +/- 93.2 micro g l-1 h-1) (P < 0.001). Total plasma clearance of nifedipine (CL/F) was significantly increased with nafcillin pretreatment (138.5 +/- 42.0 l h-1 vs 56.5 +/- 32.0 l h-1) (P < 0.002).
CONCLUSIONS: The results show that nafcillin pretreatment markedly increased the clearance of nifedipine and suggest that nafcillin is a potent inducer of CYP enzyme.
OBJECTIVE: To assess the effects of pharmacist-led interventions within DMTAC on the outcomes of patients with type 2 diabetes mellitus in two distinct hospitals in Kedah, Malaysia.
METHODS: Patients with type 2 diabetes were randomly selected from the two hospitals included in this study. The study population was divided into two equal groups. The control group consisted of 200 patients receiving routine care from the hospitals. On the other hand, the intervention group included those patients with type 2 diabetes (200), who received separate counseling sessions from pharmacists in the DMTAC departments along with the usual treatment. The study lasted 1 year, during which both study groups participated in two distinct visits.
RESULTS: Parametric data were analyzed by a paired t-test and one-way ANOVA, while non-parametric data were analyzed by a Chi-squared test using SPSS v24. A p
METHODS: Detailed phenotyping and next-generation sequencing (panel and exome).
RESULTS: Our analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello-Carey syndrome-like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average.
CONCLUSION: By expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions.
METHOD: We performed an international study of adults (≥ 18 years) who underwent surgery for PPU from 1st January 2022 to 30th June 2022. Patients who were treated conservatively or had an underlying gastric cancer were excluded. Patients were divided into subgroups according to age (≤ 50 and > 50 years) and time from onset of symptoms to hospital presentation (≤ 24 and > 24 h). Univariate and Multivariate analyses were carried out to identify factors associated with higher 30-day morbidity and mortality.
RESULTS: 1874 patients from 159 centres across 52 countries were included. 78.3% (n = 1467) of the patients were males and the median (IQR) age was 49 years (25). Thirty-day morbidity and mortality were 48.5% (n = 910) and 9.3% (n = 174) respectively. Median (IQR) hospital stay was 7 (5) days. Open surgery was performed in 80% (n = 1505) of the cohort. Age > 50 years [(OR = 1.7, 95% CI 1.4-2), (OR = 4.7, 95% CI 3.1-7.6)], female gender [(OR = 1.8, 95% CI 1.4-2.3), (OR = 1.9, 95% CI 1.3-2.9)], shock on admission [(OR = 2.1, 95% CI 1.7-2.7), (OR = 4.8, 95% CI 3.2-7.1)], and acute kidney injury [(OR = 2.5, 95% CI 1.9-3.2), (OR = 3.9), 95% CI 2.7-5.6)] were associated with both 30-day morbidity and mortality. Delayed presentation was associated with 30-day morbidity [OR = 1.3, 95% CI 1.1-1.6], but not mortality.
CONCLUSIONS: This study showed that surgery for PPU was associated with high 30-day morbidity and mortality rate. Age, female gender, and signs of shock at presentation were associated with both 30-day morbidity and mortality.
MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process.
RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit.
CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.
MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations.
RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate.
CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.