Evaluation of socio-economic factors causing discontinuation of epilepsy treatment resulting in seizure recurrence: a study in an urban epilepsy clinic in India.

BACKGROUND AND PURPOSE: The prevalence rate of epilepsy in India ranges between 4.15 and 7.03 per 1000 population. In the developing countries, the major problems of epilepsy are lying in the treatment gap and discontinuation of treatment due to various adverse socio-economic factors. The objective of this study was to evaluate the rate of discontinuation of epilepsy treatment and its related socio-economic factors responsible for discontinuation. MATERIAL AND METHODS: Among 1450 patients with epilepsy who were recurrently followed up at an intervals of 2 months from 05 January to 06 January; 620 patients discontinued their treatment. Among them 88.7% patient had breakthrough seizures for more than in two occasions. Socio-economic factors in respect to the treatment were evaluated during the follow-up period vis-a-vis income and expenditure, unemployment status, negative attitude towards medical treatment, non-availability of drugs locally, co-morbid psychiatric and other illnesses, polytherapy and socialillusional thoughts about epilepsy. RESULTS: Discontinuation of epilepsy treatment was detected in 42.75% (n = 620) of total patients resulting in recurrence of seizures. Reasons for discontinuation were multiple in most of the cases. The discontinued group had an average annual cost of treatment and income of Rs. 5500 ($110) and Rs. 12,800 ($256), respectively, amounting to 40% of their total income being expended for the cost of the treatment, while in continued group annual cost of treatment and income were Rs. 4500 ($ = 90) and Rs. 24,400 ($ = 580) respectively amounting to only 18% of the total income (p < 0.001) for the cost of treatment. Among the discontinued group, 90% of the patients reported the cost factors, 29.09% due to the unemployment, 20% from the frustration and despair, 20.09% due to non-availability of medicines locally, 17.27% spiritual illusional thoughts about epilepsy, 10% for marital disharmony were the causes for discontinuation of treatment. In the discontinued group, 10% got polytherapy against 9.03% in the continued group (p > 0.01), co-morbid psychiatric illnesses were observed in 4.54% against 3.25% in the continued group (p > 0.10). CONCLUSION: The study showed a significant number of patients (42.75%) discontinued epilepsy treatment within 1 year due to poor knowledge regarding the problem of discontinuation, cost and income disparity, unemployment, spiritual illusional thoughts about epilepsy, frustration and mental impairment, lack of uniform availability of drugs in local market. To tide these shortcomings, uniform availability of cheaper antiepileptic drugs with adequate information and communication regarding the disease and upliftment of socio-economic status are to be ensured.     

Dynamic intraoperative kinking of flexometallic tube.

A 22-year-old male patient had two episodes of oxygen desaturation with concomitant increase in end-tidal carbon dioxide and airway pressure while undergoing transoral odontoidectomy under fluoroscopy. Dynamic kinking of the flexometallic endotracheal tube from compression by a Dingman retractor was responsible. Fluoroscopic imaging was helpful in confirming the etiology of sudden alteration in the monitoring parameters.     

Blindness following pituitary apoplexy: Timing of surgery and neuro-ophthalmic outcome

The aim of this study is to report the neuro-ophthalmic outcome in patients who underwent transsphenoidal decompression for unilateral or bilateral blindness that was due to pituitary apoplexy. Four patients who were rendered blind (with an absence of light perception) unilaterally or bilaterally as a result of pituitary apoplexy were studied. Neuro-ophthalmic evaluation was performed pre- and post-operatively. Patients underwent CT and MRI pre-operatively and CT post-operatively. All four patients underwent transethmoidal decompression of the pituitary adenoma. One patient underwent a second transcranial procedure to remove the remaining suprasellar component of the tumor. Visual acuity, visual fields and extra-ocular movements were documented during the follow-up period. There were three males and one female. Ages ranged from 40 to 68 years. Three patients had unilateral blindness and one was blind in both eyes. Two of the four patients had associated ophthalmoplegia. All the four patients presented within one week of ictus. One patient underwent surgery within the first week, two patients underwent surgery two and three weeks after ictus and the other patient underwent surgery two months after ictus. The patient who was operated on within the first week recovered from bilateral blindness to a visual acuity of 6/9 and 6/12 with superior quadrantic field defects. The two patients who were operated on two and three weeks after ictus improved to 6/60 in the affected eyes and the patient who was operated on after two months improved to 1/60 in the affected eye. Both the patients with ophthalmoplegia improved completely even though the surgery was delayed by two months for one patient. Although blindness following pituitary apoplexy is rare, visual acuity improves in most patients following transsphenoidal surgery. Early surgery within the first week after ictus leads to excellent visual outcome when compared with surgery that is performed at a later stage. In contrast to visual outcome, ophthalmoplegia improves even if surgical decompression is delayed.     

Genotoxicity of sludges, wastewater and effluents from three different industries

Many surface waters in Europe, Asia and South America have been reported to be contaminated with genotoxic substances. Therefore, it is important to establish strategies for identification of the most critical sources. In this study, we used a battery of four genotoxicity assays namely chromosomal aberration, DNA strand break, DNA laddering and P53 accumulation tests in mononuclear blood cells. Before cleaning of wastewater high levels of genotoxic contamination could be observed. For instance, we observed an increase in chromosomal aberrations from 2.6 ± 1.1 (aberrant cells in %; control), to 33.6 ± 6.6 in a petrochemical plant, 29.4 ± 3.3 in a petroleum refinery and 14.4 ± 1.8 in a coke plant of steel industry. A good correlation between the four assays was found. The most sensitive and reproducible results were obtained with the chromosomal aberration assay. Interestingly, clear differences in the efficiency of wastewater cleaning in three different treatment plants were observed. The first and second treatment plants in petrochemical industry and coke plant of steel industry completely eliminated genotoxicity of the wastewater. However, the third plant in petroleum refinery could achieve a reduction in genotoxicity but significant genotoxic contaminations were still present. In conclusion, our battery of genotoxicity tests allows the identification of critical sources contributing to contamination of surface waters. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Malignant Otitis Externa

Malignant Otitis Externa, though a misnomer, definitely alarms the surgeon, the idea that it behaves and spreads like a malignancy, in elderly diabetics, and if not treated deligently, can be fatal. Though the main line of treatment is medical, surgical intervention should not be deferred if indicated. We are presenting one such case where we have not only saved the patient's life but also controlled the pain adequately.     

Larotrectinib efficacy and safety in adult patients with tropomyosin receptor kinase fusion sarcomas

Background

Larotrectinib, a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor, has demonstrated efficacy in adult and pediatric patients with various solid tumors harboring NTRK gene fusions. This subset analysis focuses on the efficacy and safety of larotrectinib in an expanded cohort of adult patients with TRK fusion sarcomas.

Methods

Patients (≥18 years old) with sarcomas harboring NTRK gene fusions were identified from three clinical trials. Patients received larotrectinib 100 mg orally twice daily. Response was investigator-assessed per RECIST v1.1. Data cutoff was July 20, 2021.

Results

At the data cutoff, 36 adult patients with TRK fusion sarcomas had initiated larotrectinib therapy: two (6%) patients had bone sarcomas, four (11%) had gastrointestinal stromal tumors, and 30 (83%) had soft tissue sarcomas. All patients were evaluable for response and demonstrated an objective response rate of 58% (95% confidence interval, 41–74). Patients responded well to larotrectinib regardless of number of prior lines of therapy. Adverse events (AEs) were mostly grade 1/2. Grade 3 treatment-emergent AEs (TEAEs) occurred in 15 (42%) patients. There were no grade 4 TEAEs. Two grade 5 TEAEs were reported, neither of which were considered related to larotrectinib. Four (11%) patients permanently discontinued treatment due to TEAEs.

Conclusions

Larotrectinib demonstrated robust and durable responses, extended survival benefit, and a favorable safety profile in adult patients with TRK fusion sarcomas with longer follow-up. These results continue to demonstrate that testing for NTRK gene fusions should be incorporated into the clinical management of adult patients with various types of sarcomas.

Plain Language Summary

• Tropomyosin receptor kinase (TRK) fusion proteins result from translocations involving the NTRK gene and cause cancer in a range of tumor types.
• Larotrectinib is an agent that specifically targets TRK fusion proteins and is approved for the treatment of patients with TRK fusion cancer.
• This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins.
• Over half of patients had a durable response to larotrectinib, with no unexpected side effects.
• These results show that larotrectinib is safe and effective in adult patients with TRK fusion sarcomas.