Category: Nevin Manimala

BMJ Open Gastroenterol. 2024 Jun 2;11(1):e001395. doi: 10.1136/bmjgast-2024-001395.

ABSTRACT

OBJECTIVE: Patients with coeliac disease (CD) need to follow a strict gluten-free diet to manage symptoms and prevent complications. Restrictions imposed by the diet can be challenging and affect quality of life (QoL). We explored sources of variation in QoL among patients with CD.

DESIGN: We conducted an online survey of coeliac patients in the UK, including a CD-specific QoL tool (CD-QOL V.1.0), questions on diet adherence and an optional comment box at the end. The survey was disseminated via social media and went live between January and March 2021. We performed multiple linear regression and free text analysis.

RESULTS: We found a median CD-QOL score of 61 (IQR 44-76, range 4-100, n=215) suggesting good QoL (Good >59); however, the individual QoL scores varied significantly. Regression analyses showed that people who found diet adherence difficult and people adhering very strictly had a lower QoL. Free text comments suggested that people who adhered very strictly may do so because they have symptoms with minimal gluten exposure. People who found diet adherence difficult may be people who only recently started the diet and were still adjusting to its impact. Comments also highlighted that individuals with CD often perceive a lack of adequate follow-up care and support after diagnosis.

CONCLUSION: Better support and follow-up care is needed for people with CD to help them adjust to a gluten-free diet and minimise the impact on their QoL. Better education and increased awareness are needed among food businesses regarding cross-contamination to reduce anxiety and accidental gluten exposure.

PMID:38830687 | DOI:10.1136/bmjgast-2024-001395

CMAJ. 2024 Jun 2;196(21):E716-E723. doi: 10.1503/cmaj.231682.

ABSTRACT

BACKGROUND: To eliminate cervical cancer in Canada by 2040, defined as an annual age-standardized incidence rate (ASIR) lower than 4.0 per 100 000 women, the Canadian Partnership Against Cancer (CPAC) identified 3 priorities for action: increasing human papillomavirus (HPV) vaccine coverage, implementing HPV-based screening and increasing screening participation, and improving follow-up after abnormal screen results. Our objective was to explore the impact of these priorities on the projected time to elimination of cervical cancer in British Columbia.

METHODS: We used OncoSim-Cervical, a microsimulation model led and supported by CPAC and developed by Statistics Canada that simulates HPV transmission and the natural history of cervical cancer for the Canadian population. We updated model parameters to reflect BC’s historical participation rates and program design. We simulated the transition to HPV-based screening and developed scenarios to explore the additional impact of achieving 90% vaccination coverage, 95% screening recruitment, 90% ontime screening, and 95% follow-up compliance. We projected cervical cancer incidence, ASIR, and year of elimination for the population of BC for 2023-2050.

RESULTS: HPV-based screening at current vaccination, participation, and follow-up rates can eliminate cervical cancer by 2034. Increasing on-time screening and follow-up compliance could achieve this target by 2031. Increasing vaccination coverage has a small impact over this time horizon.

INTERPRETATION: With the implementation of HPV-based screening, cervical cancer can be eliminated in BC before 2040. Efforts to increase screening participation and follow-up through this transition could potentially accelerate this timeline, but the transition from cytology- to HPV-based screening is fundamental to achieving this goal.

PMID:38830680 | DOI:10.1503/cmaj.231682

Saudi Med J. 2024 Jun;45(6):565-571. doi: 10.15537/smj.2024.45.6.20230878.

ABSTRACT

OBJECTIVES: To study the prevalence of tumor marker (TM) carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), and cancer antigen 15-3 (CA 15-3) levels in the Saudi population, based on gender, age, and demographic region, and whether the patients were referred by a hospital or self-referred.

METHODS: Retrospective analysis was carried out on 7,019 samples gathered from the Western, Northern, Central, Southern, and Eastern regions of Saudi Arabia between 2021-2022. The TMs were categorized into normal and abnormal levels, according to the reference ranges. Statistical analysis was carried out to assess the relations between variants (age groups, gender, and demographic regions) using the Chi-square test, and their correlations were assessed using Spearman’s test.

RESULTS: Among all patients, CEA, CA 125, and CA 15-3 levels were found to be significantly correlated with age (p=0.0001). The CEA and CA 15-3 levels increased in both males and females with age. The CA 125 was shown to have an abnormally increased level in males with age.

CONCLUSION: Increased levels of CEA, CA 125, and CA 15-3 TMs in the study population were significantly correlated with age. The CEA and CA 15-3 levels were within the normal range, while CA 125 levels were above the normal range in the older male population. These results suggest that the utilization of such TMs is age dependent and would have validity if applied with other parameters.

PMID:38830664 | DOI:10.15537/smj.2024.45.6.20230878

Saudi Med J. 2024 Jun;45(6):606-616. doi: 10.15537/smj.2024.45.6.20240102.

ABSTRACT

OBJECTIVES: To assess the risk variables related to the types of candidemia for each patient, who was admitted into the intensive care unit regardless of the patient with or without complete diagnosis of COVID-19, during the period of March 2019 to December 2022.

METHODS: The evaluation comparison of demographic and clinical data of COVID-19 positive and negative patients with candidemia confirmed in blood, 113 cases were assessed. Variables such as gender, age, age of hospitalization, history of hospitalization, concurrently infection, The acute physiology and chronic health evaluation-II scores, comorbidity checking, intubation, central venous catheter use, parenteral nutrition use, steroid use, antibiotic use, lymphopenia, and laboratory variables were evaluated. Candida species distribution, antifungal susceptibility in blood culture were determined.

RESULTS: Coronavirus disease-19 was present in 62.8% of cases confirmed candidemia, and these cases were significantly different from COVID-19 negative cases. Significance was found in more intubation, central venous catheter use, parenteral nutrition, and steroid therapy in Group 2. There was no significance with species distribution and associated infection. In total, COVID-19 positive had higher hemoglobin, aspartate aminotransferase, alanine transaminase, and white blood cell levels, which may be associated with the possibility of revealing and controlling candidemia.

CONCLUSION: Candida albicans and Candida Parapsilosis (C. parapsilosis) are the species seen in infected COVID-19 patients, while C. parapsilosis and Candida tropicalis are found in non-COVID-19 ones. Risk factors were intubation, parenteral nutrition, central venous catheter, and steroid in the COVID-19 group.

PMID:38830660 | DOI:10.15537/smj.2024.45.6.20240102

Saudi Med J. 2024 Jun;45(6):585-590. doi: 10.15537/smj.2024.45.6.20240167.

ABSTRACT

OBJECTIVES: To assess the prevalence of various frontal sinus fractures (FSF) and examine the relationships between these fractures, types of treatments, and potential complications.

METHODS: A retrospective study was carried out in King Saud Medical City, Riyadh, Saudi Arabia. The study analyzed the records of patients who were diagnosed and treated with FSF from 2011-2021. Files with missing documents or incomplete treatment were excluded. The retrieved data includes: patients age, gender, types, locations, treatment, and complications of FSF. Data was analyzed by the statistical Package for the Social Sciences Statistics, version 23.0 using descriptive statistics and Chi-square test.

RESULTS: A total of 72 cases were included, 94.4% males and 5.6% females. Road traffic accidents were the common cause of trauma (91%). Frontal sinus fractures were unilateral in 59.7% and associated other injuries in 80.6% of cases. Anterior table fractures were the largest proportion (58.3%), followed by anterior and posterior table (37.5%). The carried out surgical procedures were obliteration (23.9%), cranialization and obliteration (23.9%), and fixation only (52.2%). The post-operative complications were categorized into; neurological (22.2%), ophthalmic (15.3%), infection (2.8%), and deformity (16.7%). Anterior and posterior table had the highest percentage among these categories.

CONCLUSION: Frontal sinus fractures were mostly required surgical treatment (63.9%) and post-operative complications occurred especially the neurological and ophthalmic. We recommend studies on the association of complications and different types of obliteration materials.

PMID:38830653 | DOI:10.15537/smj.2024.45.6.20240167

Saudi Med J. 2024 Jun;45(6):617-625. doi: 10.15537/smj.2024.45.6.20240158.

ABSTRACT

OBJECTIVES: To analyze the relationship between chronically ill patients’ behaviors in acquiring and verifying health information from a digital environment with health literacy and patient empowerment using a structural equation modeling approach.

METHODS: This study was carried out in a public hospital in Turkey between February and May 2023. The study consisted of 365 participants and used descriptive and correlation-based designs for statistical analyses. It also executed computations for descriptive statistics and correlations to carry out a path analysis to assess model fitness and to identify direct and indirect effects.

RESULTS: This study identified that Web 1.0 and health information acquisition and digital verification variables statistically and significantly affected access to information, understanding information, appraisal (valuing)/evaluation, and application/use variables. The study also found that access to information variables was statistically significant on identity/identicalness, self-control, decision-making, and recognition and comprehension. The tested model fit the data well and adequately explained the direct effects of the variables.

CONCLUSION: The study concluded by suggestively improving the chronically ill patients’ media or digital literacy levels through special training to stimulate their internet use effectively.

PMID:38830649 | DOI:10.15537/smj.2024.45.6.20240158

Int J Gynecol Cancer. 2024 Jun 2:ijgc-2024-005402. doi: 10.1136/ijgc-2024-005402. Online ahead of print.

ABSTRACT

OBJECTIVES: External beam radiation with sensitizing platinum is the recommended therapy for locally advanced vulvar cancers not amenable to curative surgery and is associated with considerable acute and chronic side effects. Radical vulvectomy post-radiation for persistent disease is often compromised with poor wound healing. We describe clinical outcomes for patients who received neoadjuvant chemotherapy plus bevacizumab followed by radical vulvectomy for locally advanced vulvar cancer.

METHODS: We performed retrospective analyses of all patients at our institution who underwent radical vulvectomy from January 2015 to November 2023. Of 113 patients, 13 patients underwent neoadjuvant chemotherapy. Demographics and clinicopathologic data were extracted, and descriptive statistical analyses were performed. Cases with neoadjuvant chemotherapy plus bevacizumab were further evaluated for response, adverse effects, and survival.

RESULTS: Neoadjuvant chemotherapy was administered to 13 patients with stage II-IV disease that involved the urethra, vagina, or anus. Lesion sizes ranged from 4 to 20 cm (median 7 cm). Patients received 2-6 cycles of carboplatin or cisplatin, paclitaxel, and bevacizumab. Nine (69.2%) patients had partial pathologic responses, and four patients had complete responses. All patients had negative surgical margins. Ten (76.9%) patients had radiographic evidence of inguinal lymph node metastasis prior to neoadjuvant chemotherapy, and four had residual nodal disease. Only one patient developed a superficial groin seroma. Three patients developed recurrence, two locally and one distant, and there was one death. The median follow-up was 23 months (range 6-84 months).

CONCLUSIONS: Neoadjuvant chemotherapy using combination platinum/paclitaxel/bevacizumab was efficacious for locally advanced vulvar cancer, resulting in complete resections, negative margins, and excellent wound healing. A multi-institutional phase II trial is warranted to validate these findings.

PMID:38830645 | DOI:10.1136/ijgc-2024-005402

Nephrology (Carlton). 2024 Jun 3. doi: 10.1111/nep.14331. Online ahead of print.

ABSTRACT

BACKGROUND: As an initial treatment for primary membranous nephropathy (PMN), there remains a significant proportion of patients for whom rituximab is not fully effective. Here, we aimed to assess the effectiveness and safety of obinutuzumab as initial treatment in patients with PMN.

METHODS: In this observational case series, patients diagnosed with PMN and treated with obinutuzumab as initial treatment were included. Treatment response was assessed by 24-h urine total protein (24 h UTP) and serum albumin, and immunologic remission was assessed by phospholipase A2 receptor (PLA2R) antibodies.

RESULTS: Twelve patients with PMN receiving obinutuzumab as initial treatment were included. Over 6 months, a statistically significant reduction in 24 h UTP levels (p = 0.003) and an increase in serum albumin levels were observed (p < 0.001). By the 6-month follow-up, two patients (16.7%) achieved complete remission, eight (66.6%) reached partial remission, and two (16.7%) showed no remission. Immunological remission was observed in 44.4% of evaluable patients (n = 9) after 3 months, increasing to 100% (6/6) at 6 months. Except for cases 1, 2, and 3, the total B cell counts in the remaining patients fell to less than 5 cells/μL before the administration of the second dose of obinutuzumab, including seven patients with counts as low as 0 cells/μL. Mild to moderate treatment-related adverse events (TRAEs) were reported in 58.3% (7/12) of the patients. No serious TRAEs were reported.

CONCLUSIONS: Obinutuzumab demonstrates promising potential as an initial treatment for PMN, with good effectiveness and a manageable safety profile. Further large-scale prospective studies are needed to confirm these findings.

PMID:38830643 | DOI:10.1111/nep.14331

Asian J Endosc Surg. 2024 Jul;17(3):e13334. doi: 10.1111/ases.13334.

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of an educational stepwise robot-assisted radical prostatectomy (RARP) procedure for urology residents.

METHODS: We performed a detailed evaluation of 42 RARP procedures performed by a single urology resident from July 2019 to February 2022. The RARP procedures were divided into the following nine steps: (1) bladder dissection, (2) endopelvic fascia dissection, (3) bladder neck dissection, (4) seminal vesicle dissection, (5) Denonvilliers’ fascia dissection, (6) dorsal vascular complex ligation, (7) dissection of the prostatic apex, (8) posterior anastomosis, and (9) urethro-vesical anastomosis. The procedures were further subcategorized as anatomical understanding, spatial recognition, and technical skills for evaluation of resident training. The surgeries were divided into first and second halves, and patient characteristics and operative outcomes were statistically analyzed. The operative time of each of the nine steps and the reasons for proctor intervention were compared.

RESULTS: Among 42 patients, there were no significant differences in operative outcomes between the two groups. The median operative time was 169 min (164 vs. 179 min, p = .12), and the median console time was 128 min (127 vs. 130 min, p = .74). Although there were no significant differences in the time of the nine steps, the resident significantly overcame (7) dissection of the prostatic apex and (8) posterior anastomosis based on the evaluation of the proctored reasons for intervention.

CONCLUSIONS: Urology residents can safely perform and efficiently learn RARP with this stepwise educational system. This educational stepwise RARP procedure can effectively help residents to develop their skills.

PMID:38830638 | DOI:10.1111/ases.13334

Br J Clin Pharmacol. 2024 Jun 3. doi: 10.1111/bcp.16131. Online ahead of print.

ABSTRACT

AIMS: Early clinical studies have indicated that the pharmacokinetics of Atuliflapon (AZD5718) are time and dose dependent. The reason(s) for these findings is(are) not fully understood, but pre-clinical profiling suggests that time-dependent CYP3A4 inhibition cannot be excluded. In clinical practice, Atuliflapon will be co-administered with CYP3A4 substrates; thus, it is important to determine the impact of Atuliflapon on the pharmacokinetics (PK) of CYP3A4 substrates. The aim of this study was to evaluate the effect of Atuliflapon on the pharmacokinetics of a sensitive CYP3A4 substrate, midazolam, and to explore if the time-/dose-dependent effect seen after repeated dosing could be an effect of change in CYP3A4 activity.

METHODS: Open-label, fixed-sequence study in healthy volunteers to assess the PK of midazolam alone and in combination with Atuliflapon. Fourteen healthy male subjects received single oral dose of midazolam 2 mg on days 1 and 7 and single oral doses of Atuliflapon (125 mg) from days 2 to 7. A physiologically based pharmacokinetic (PBPK) model was developed to assess this drug-drug interaction.

RESULTS: Mean midazolam values of maximum plasma concentration (C_max) and area under the curve (AUC) to infinity were increased by 39% and 56%, respectively, when co-administered with Atuliflapon vs. midazolam alone. The PBPK model predicted a 27% and 44% increase in AUC and a 23% and 35% increase in C_max of midazolam following its co-administrations with two predicted therapeutically relevant doses of Atuliflapon.

CONCLUSIONS: Atuliflapon is a weak inhibitor of CYP3A4; this was confirmed by the validated PBPK model. This weak inhibition is predicted to have a minor PK effect on CYP3A4 metabolized drugs.

PMID:38830622 | DOI:10.1111/bcp.16131