Nevin Manimala

Neurol Sci. 2024 Dec 9. doi: 10.1007/s10072-024-07920-y. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: The goal of this study was to assess the clinical profile of myasthenia gravis (MG) in patients diagnosed above 65-years of age (VLOMG) and identify clinical/serological parameters associated with their MG status and prognosis.

METHODS: This was a retrospective assessment of consecutive patients with VLOMG (n = 70) Demographics, clinical characteristics, medical comorbidities, the Myasthenia Gravis Foundation of America (MGFA) severity scale scores, and MGFA Post-Intervention Status (MGFA-PIS) were collected.

RESULTS: The research population was diagnosed with MG at an average age of 73.16 ± 6.33 years, a male/female ratio of 2.3/1 and a mean follow-up time of 53.09 ± 46.37 months. The titer of acetylcholine receptor antibodies (AChR Abs) was positive at 95.71% of patients. The predominant distribution of myasthenic weakness was oculobulbar (63.79%). At the last follow-up, 75.71% of patients reached Pharmacological-Remission (PR) or Minimal-Manifestations (MM), 17% manifested improvement and 7.14% were clinically unchanged, worse or dead, according to MGFA-PIS. Most patients responded to low doses of steroids. Males and patients with generalized muscle involvement upon disease-onset were more likely to reach PR or MM than females or ocular presentation (OR = 3.84 and O.18, respectively). Six patients (8.57%) were treated with at least one cycle of rituximab due to disease severity. Five (83%) reached PR or MM and one improved (mean follow up time: 7.5 months).

INTERPRETATION: We found that patients with VLOMG are usually males, with oculobulbar muscle involvement and positive titer of AChR Abs. The majority had a favorable prognosis and an adequate response to low doses of prednisolone and long-term immunosuppression.

PMID:39648250 | DOI:10.1007/s10072-024-07920-y

Signal Transduct Target Ther. 2024 Dec 9;9(1):345. doi: 10.1038/s41392-024-02047-0.

ABSTRACT

The large population of HER2-low breast cancer patients necessitates further research to provide enhanced clinical guidance. In this study, we retrospectively analyzed 1071 metastatic breast cancer (MBC) patients and the circulating tumor DNA (ctDNA) to investigate clinicopathological and genetic alterations of HER2-low MBC patients. The effect of HER2-low status on different treatment modalities was explored in two prospective clinical trials (NCT03412383, NCT01917279) and a retrospective study. Our findings suggest TP53, PIK3CA, and ESR1 are frequently mutated genes in HER2-low MBC. Compared to the HER2-0 group, mutations observed in the HER2-low group are more closely associated with metabolic pathway alterations. Additionally, among patients with ERBB2 mutations and treated with pyrotinib, the HER2-low group may experience superior prognosis when compared to the HER2-0 group. Notably, we did not find any statistically significant disparity in the response to chemotherapy, endocrine therapy, or CDK4/6 inhibitor therapy between HER2-0 and HER2-low breast cancer patients. Interestingly, within the subgroup of individuals with metabolic pathway-related gene mutations, we found that HER2-low group exhibited a more favorable response to these treatments compared to HER2-0 group. Additionally, dynamic analysis showed the HER2-low MBC patients whose molecular tumor burden index decreased or achieved early clearance of ctDNA after the initial two treatment cycles, exhibited prolonged survival. Moreover, we classified HER2-low MBC into three clusters, providing a reference for subsequent treatment with enhanced precision. Our study offers valuable insights into the biology of HER2-low MBC and may provide reference for personalized treatment strategies.

PMID:39648226 | DOI:10.1038/s41392-024-02047-0

Glob Health Res Policy. 2024 Dec 9;9(1):51. doi: 10.1186/s41256-024-00392-9.

ABSTRACT

BACKGROUND: Tuberculosis (TB) poses a significant social and economic burden to households of persons with TB (PwTB). Despite free diagnosis and care under the National TB Elimination Programme (NTEP), individuals often experience significant out-of-pocket expenditure and lost productivity, causing financial catastrophe. We estimated the costs incurred by the PwTB during TB care and identified the factors associated with the costs.

METHODS: In our cross-sectional study, we used multi-stage sampling to select PwTB notified under the NTEP, whose treatment outcome was declared between May 2022 and February 2023. Total patient costs were measured through direct medical, non-medical and indirect costs. Catastrophic costs were defined as expenditure on TB care > 20% of the annual household income. We determined the factors influencing the total cost of TB care using median regression. We plotted concentration curves to depict the equity in distribution of catastrophic costs across income quintiles. We used a cluster-adjusted, generalized model to determine the factors associated with catastrophic costs.

RESULTS: The mean (SD) age of the 1407 PwTB interviewed was 40.8 (16.8) years. Among them, 865 (61.5%) were male, and 786 (55.9%) were economically active. Thirty-four (2.4%) had Drug Resistant TB (DRTB), and 258 (18.3%) had been hospitalized for TB. The median (Interquartile range [IQR] and 95% confidence interval [CI]) of total costs of TB care was US$386.1 (130.8, 876.9). Direct costs accounted for 34% of the total costs, with a median of US$78.4 (43.3, 153.6), while indirect costs had a median of US$279.8 (18.9,699.4). PwTB < 60 years of age (US$446.1; 370.4, 521.8), without health insurance (US$464.2; 386.7, 541.6), and those hospitalized(US$900.4; 700.2, 1100.6) for TB experienced higher median costs. Catastrophic costs, experienced by 45% of PwTB, followed a pro-poor distribution. Hospitalized PwTB (adjusted prevalence ratio [aPR] = 1.9; 1.6, 2.2) and those notified from the private sector (aPR = 1.4; 1.1, 1.8) were more likely to incur catastrophic costs.

CONCLUSIONS: PwTB in India incur high costs mainly due to lost productivity and hospitalization. Nearly half of them experience catastrophic costs, especially those from poorer economic quintiles. Enabling early notification of TB, expanding the coverage of health insurance schemes to include PwTB, and implementing TB sensitive strategies to address social determinants of TB may significantly reduce catastrophic costs incurred by PwTB.

PMID:39648213 | DOI:10.1186/s41256-024-00392-9

High Blood Press Cardiovasc Prev. 2024 Dec 9. doi: 10.1007/s40292-024-00694-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Abnormalities in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are each associated with increased cardiovascular risk, after adjusting for non-lipid risk factors. However, whether and to what extent the association for each lipid measure is confounded by other lipid measures is less understood.

AIM: This study aims to investigate the association of each lipid measure with cardiovascular and all-cause mortality while precluding the confounding caused by abnormalities in other lipid measures.

METHODS: The study utilized data from the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) and ten cycles of continuous NHANES (1999-2018). The study cohort included 23,761 participants who were 20 years or older, not pregnant, not receiving lipid-lowering treatment, and had complete data on all four lipid measures and mortality status. Participants were categorized into seven subgroups based on their lipid profiles. Kaplan-Meier survival curves and Cox proportional hazards models were used to examine the association between lipid abnormalities and mortality.

RESULTS: During a median follow-up of 140 months, 5,003 participants (14.1%) died, with 1,665 deaths (4.2%) attributable to cardiovascular causes. Compared with the reference group in which the four lipid measures were all normal, the subgroups with isolated high TC, two to three lipid abnormalities, and four lipid abnormalities were associated with increased risks for both cardiovascular and all-cause mortality in univariate analysis. However, only those with isolated high TC (for cardiovascular mortality, HR 1.52, 95% CI 1.13-2.06) and four lipid abnormalities (for all-cause mortality, HR 1.34, 95% CI 1.04-1.72) remained statistically significant after adjusting for non-lipid risk factors. Of note, compared with the reference group, the profile of non-lipid risk factors was apparently less favorable in the subgroup with two to three lipid abnormalities but similar (and some factors even more favorable) in the subgroup with isolated high TC. When the lipid measures were analyzed as continuous variables, a U-shaped relationship between HDL-C and mortality risk was observed for both cardiovascular and all-cause mortality, and very low LDL-C level was associated with increased mortality risk. No statistically significant association was found between TG levels and mortality risk.

CONCLUSION: Isolated high TC, very low LDL-C, and concurrent abnormalities in all four lipid measures were associated with increased mortality risk, whereas isolated high TG was not. A U-shaped relationship may exist between HDL-C level and mortality. Overall, these findings underscore the need for integrated management of dyslipidemia that takes all four lipid measures as well as non-lipid cardiovascular risk factors into account, particularly for those with concurrent abnormalities in two or more lipid measures.

PMID:39648198 | DOI:10.1007/s40292-024-00694-6

Front Optoelectron. 2024 Dec 9;17(1):39. doi: 10.1007/s12200-024-00142-2.

ABSTRACT

Achilles tendon injuries, as a widely existing disease, have attracted a lot of research interest. Mueller matrix polarimetry, as a novel label-free quantitative imaging method, has been widely used in various applications of lesion identification and pathological diagnosis. However, focusing on the recovery process of Achilles tendon injuries, current optical imaging methods have not yet achieved the label-free precise identification and quantitative evaluation. In this study, using Mueller matrix polarimetry, various Achilles tendon injury samples were characterized specifically, and the efficacy of different recovery schemes was evaluated accordingly. Experiments indicate that injured Achilles tendons show less phase retardance, larger diattenuation, and relatively disordered orientation. The combination of experiments with Monte Carlo simulation results illustrate the microscopic mechanism of the Achilles tendon recovery process from three aspects, that is, the increased fiber diameter, a more consistent fiber orientation, and greater birefringence induced by more collagen protein. Finally, based on the statistical distribution of polarization measurements, a polarization specific characterization parameter was extracted to construct a label-free image, which cannot only intuitively show the injury and recovery of Achilles tendon samples, but also give a quantitative evaluation of the treatment.

PMID:39648187 | DOI:10.1007/s12200-024-00142-2

Int Orthop. 2024 Dec 9. doi: 10.1007/s00264-024-06384-1. Online ahead of print.

ABSTRACT

PURPOSE: To explore the efficacy and feasibility of arthroscopy combined with bone tunnel technique in treating Berndt and Harty stage III or IV osteochondral lesions of the talus (OLT).

METHODS: A retrospective analysis was conducted on the clinical data of 21 patients with Berndt and Harty stage III or IV OLT who underwent surgical treatment at our institution from September 2017 to September 2022. Under arthroscopy, the displaced talar osteochondral lesion was restored. A 2.0 mm Kirschner wire (K-wire) was used to create a bone tunnel from the medial (or lateral) malleolus to the realigned osteochondral lesion. A 1.5 mm K-wire was then used to drill through this tunnel into the osteochondral fragment, and a 1.5 mm absorbable bone rod was inserted for fixation. Preoperative and final follow-up visual analogue scale (VAS) for pain and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale were recorded and compared.

RESULTS: All 21 patients were followed up for an average of 23.95 ± 6.01 months. All wounds healed by primary intention, with no nerve, blood vessel, or tendon injuries. All osteochondral lesions healed, with an average healing time of 3.71 ± 0.62 months. The VAS score decreased from a preoperative average of 5.38 ± 0.59 to 0.48 ± 0.51 at the final follow-up. The AOFAS ankle-hindfoot scale increased from a preoperative average of 56.29 ± 5.98 to 88.43 ± 2.68 at the final follow-up (P < 0.05), showing statistically significant differences. Two cases experienced medial pain after 12 months, which was tolerable with non-steroidal anti-inflammatory drugs.

CONCLUSION: Arthroscopy combined with bone tunnel technique for treating Berndt and Harty stage III or IV OLT has the advantages of minimal injury, visualization of fracture reduction, and fewer complications.

PMID:39648185 | DOI:10.1007/s00264-024-06384-1

Int Orthop. 2024 Dec 9. doi: 10.1007/s00264-024-06378-z. Online ahead of print.

ABSTRACT

PURPOSE: While surgical intervention of scoliosis in cerebral palsy (CP) patients has shown notable improvements in quality of life, the high risk of post-operative complications in CP patients necessitates careful preoperative optimization. A preoperative multidisciplinary (Multi-D) pathway at our tertiary pediatric hospital in effect since 2014 led to a significant reduction in mortality at one year. However, such a strategy delays surgery, potentially increasing the risk of curve progression. This study aims to elucidate the impact of the Multi-D screening process on curve progression in neuromuscular scoliosis among complex CP patients.

METHODS: A retrospective review of all CP patients with scoliosis at a tertiary care center from 2012 to 2020 was conducted. This assessment focused on the progression of the major Cobb angle from the time of the indications conference to surgery of patients who went through Multi-D screening. Patient demographics and perioperative variables were obtained from the electronic medical record (EPIC, Systems Verona, WI).

RESULTS: After exclusion criteria were met, there were 85 patients who went through Multi-D, 78 of whom had surgery, and seven who did not. Surgery was delayed an average of 202 days for Multi-D optimization. We found a trend in increasing Cobb angle over time, but this correlation did not reach statistical significance (p = 0.079). 45 Multi-D surgery participants had a decrease or no change in Cobb angle and had surgery an average of 5.6 months after indications. 33 Multi-D surgery participants had an increase in Cobb angle and had surgery an average of 8.5 months after indications. Cobb angle progressed an average of 13.4° in the increased group, and – 0.4° in the decrease or no change group. There were no associations with change in Cobb angle and GMFCS, starting major curve angle, number of referrals, or intrathecal baclofen pump use according to this analysis.

CONCLUSIONS: Multi-D optimization resulted in an average delay in surgery of 6.7 months. Patients that did not have a change in Cobb angle had surgery within 5.6 months vs. patients that had an increase in Cobb angle had surgery on average 8.5 months after indicated for surgery, with an average increase of Cobb angle of 13.4°.

LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID:39648184 | DOI:10.1007/s00264-024-06378-z

J Pak Med Assoc. 2024 Nov;74(11 (Supple-12)):S19-S23. doi: 10.47391/JPMA.AKU-EPP-05.

ABSTRACT

OBJECTIVE: To examine the perceived impact of incentive-linked prescribing (ILP) on the everyday lives of patients in Pakistan.

METHODS: Adopting a qualitative approach, in-depth interviews were conducted with 26 patients in Karachi. A convenient sampling method was used to recruit patients from different pharmacies located in all six districts of Karachi namely East, West, South, Central, Korangi, and Malir. The interviews were thematically analyzed using the software NVivo Version.12.

RESULTS: ILP was perceived to affect patients in three interrelated ways: financial difficulty, mental distress, and difficulty in adhering to medical treatments. Most of the participants reported experiencing financial difficulties and were unable to afford everyday household needs. ILP was believed to make physicians prescribe expensive brands, which in turn, added to patients’ financial difficulties. Due to expensive medications, some patients stopped seeking healthcare from physicians and instead relied on home remedies. ILP-related financial burden on patients was also perceived to be a contributor to their mental distress.

CONCLUSIONS: Patients are increasingly becoming aware of physicians’ engagement in ILP, and believe it harms them in different ways. It has important implications for physicians’ reputations in society. Physicians must adhere to the principles of patient-centred care by avoiding ILP.

PMID:39648171 | DOI:10.47391/JPMA.AKU-EPP-05

J Pak Med Assoc. 2024 Nov;74(11 (Supple-12)):S6-S10. doi: 10.47391/JPMA.AKU-EPP-03.

ABSTRACT

OBJECTIVE: To investigate private General Practitioners’ (GPs) interest in continuous professional development (CPD), with a focus on ethical practices.

METHOD: A mixed method study design conducted a cross-sectional survey of registered private GPs (n=419) in Karachi was conducted in the year 2022 on their professional and ethical practices with perspectives on engagement in training in the year 2022. Qualitative interviews were conducted with 28 GPs to get a deeper understanding of their views on professional development.

RESULTS: The median age of participants was 55 years (IQR 48-63 years) and 361 (86.2%) were males. The median number of years of professional experience was 31.0 years (IQR 24-37 years). It was observed that 116 (27.6%) of GPs saw more than 50 patients per day, and 377 (90%) met with pharmaceutical sales representative (PSR) regularly. Reported awareness of guidelines on ethical practices was 325 (77.6.0%), and willingness to sign a pledge committing to a code of ethics and to be part of a professional network of ethical doctors was high, 389 (~93.0%). However, both qualitative and quantitative data indicated that GPs had limited time for training, despite the interest in filling gaps in knowledge about ethical practice.

CONCLUSIONS: Most GPs were willing to engage in CPD activities with a focus on ethics. Many GPs met regularly with PSRs, and CPD may reduce the pharmaceutical industry influence on their prescribing practices.

PMID:39648169 | DOI:10.47391/JPMA.AKU-EPP-03

J Int AIDS Soc. 2024 Dec;27(12):e26395. doi: 10.1002/jia2.26395.

ABSTRACT

INTRODUCTION: Disengagement and re-engagement with antiretroviral therapy (ART) are common in South Africa, but routine monitoring is insufficient to inform policy development. To address this gap, Anova implemented the 2020 National Adherence Guidelines’ re-engagement standard operating procedure (re-engagement SOP) and collected additional data to describe the characteristics of re-engagement visits to inform HIV programmes.

METHODS: Between July and December 2022, we conducted a study at nine primary healthcare facilities in Johannesburg. Staff were trained on the re-engagement SOP and provided with job aides to support implementation. Administration clerks categorized visits based on the time elapsed since the missed appointment: ≤14days and >14 days, with the latter identified as re-engaging. For these clients, clinicians filled out “re-engagement clinical assessment forms” that included visit dates, both clinician-assessed and self-reported treatment interruptions, and clinical details. Data on missed appointments and previous viral loads were extracted from medical records. The information was entered into REDCap. We present data from three out of the nine facilities, selected for their comprehensive data collection and high coverage of all re-engaging clients.

RESULTS: A total of 2342 clients returned following a missed scheduled appointment. The majority, 1523 (65%), missed their appointments by ≤ 14 days, while 819 (35%) were >14 days late (re-engaging). Among those re-engaging, 635 (78%) re-engagement clinical assessment forms were completed. A missed appointment date was available for 623 with 25% (n = 161) returning 2-4 weeks late, 47% (n = 298) 4-12 weeks and 26% (n = 164) >12 weeks late. Self-reported ART interruption, available for 89% (567/635), indicated the majority (54%, n = 304) experienced no interruption. Clinical concerns were identified in 65 (10%) cases. A majority (79%, 504/635) had prior viral load results, with 73% (370/504) below 50 copies/ml.

CONCLUSIONS: Clients frequently return to care shortly after missed appointments. Despite missing scheduled ART refill dates, many report not interrupting treatment, either having treatment on hand or sourcing ART elsewhere. Most re-engaging clients were adherent prior to disengagement, and clinical concerns are rare. A differentiated service delivery approach, prioritizing flexibility and reduced healthcare burden, is required to support client’s needs and preferences at re-engagement.

PMID:39648158 | DOI:10.1002/jia2.26395