Classic ketogenic diet versus further antiseizure medicine in infants with drug-resistant epilepsy (KIWE): a UK, multicentre, open-label, randomised clinical trial

BACKGROUND: Many infancy-onset epilepsies have poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in children older than 2 years and adults who are unresponsive to antiseizure medicines. We aimed to establish the efficacy of a classic ketogenic diet at reducing seizure frequency compared with further antiseizure medicine in infants with drug-resistant epilepsy. METHODS: In this phase 4, open-label, multicentre, randomised clinical trial, infants aged 1-24 months with drug-resistant epilepsy (defined as four or more seizures per week and two or more previous antiseizure medications) were recruited from 19 hospitals in the UK. Following a 1-week or 2-week observation period, participants were randomly assigned using a computer-generated schedule, without stratification, to either a classic ketogenic diet or a further antiseizure medication for 8 weeks. Treatment allocation was masked from research nurses involved in patient care, but not from participants. The primary outcome was the median number of seizures per day, recorded during weeks 6-8. All analyses were by modified intention to treat, which included all participants with available data. Participants were followed for up to 12 months. All serious adverse events were recorded. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). The trial was terminated early before all participants had reached 12 months of follow-up because of slow recruitment and end of funding. FINDINGS: Between Jan 1, 2015, and Sept 30, 2021, 155 infants were assessed for eligibility, of whom 136 met inclusion criteria and were randomly assigned; 75 (55%) were male and 61 (45%) were female. 78 infants were assigned to a ketogenic diet and 58 to antiseizure medication, of whom 61 and 47, respectively, had available data and were included in the modifified intention-to-treat analysis at week 8. The median number of seizures per day during weeks 6-8, accounting for baseline rate and randomised group, was similar between the ketogenic diet group (5 [IQR 1-16]) and antiseizure medication group (3 [IQR 2-11]; IRR 1·33, 95% CI 0·84-2·11). A similar number of infants with at least one serious adverse event was reported in both groups (40 [51%] of 78 participants in the ketogenic diet group and 26 [45%] of 58 participants in the antiseizure medication group). The most common serious adverse events were seizures in both groups. Three infants died during the trial, all of whom were randomly assigned a ketogenic diet: one child (who also had dystonic cerebral palsy) was found not breathing at home; one child died suddenly and unexpectedly at home; and one child went into cardiac arrest during routine surgery under anaesthetic. The deaths were judged unrelated to treatment by local principal investigators and confirmed by the data safety monitoring committee. INTERPRETATION: In this phase 4 trial, a ketogenic diet did not differ in efficacy and tolerability to a further antiseizure medication, and it appears to be safe to use in infants with drug-resistant epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite previously trying two antiseizure medications. FUNDING: National Institute for Health and Care Research

Gap acceptance Behaviour and Operational analysis of Bicyclists at Unsignalized Intersections

Models have been created under homogeneous condition with no exertion on show improvement for heterogeneous condition for bicyclists. In this manner, display improvements under heterogeneous condition are the need of great importance as the bicyclists working under the blended activity conditions are inclined street setbacks. Unsignalized crossing points are the contention hotspot in a street approach. Need of development are ignored in these crossing points making it extreme for the bicyclists to make developments with next to zero accessible space.This makes clashes with respect to bike and vehicle development making it an exceptionally disordered circumstance and hotspot for mischances. Be that as it may, as of late exceptional offices for bike client which incorporates bike paths have not been made accessible influencing the bicyclists to confront a few issues in the blended rush hour gridlock conditions. The city experts have absence of access to benefit expectation and defer estimation strategies required for the foundation of bicycle neighbourly offices. Henceforth, in this investigation approaches have been produced for the estimation of postponement and BLOS considering activity parameters and geometric parameters. Datasets have been collected from 58 Indian unsignalised intersection approaches. Pearson correlation analysis was carried out to identify the significant variables of the delay models and Spearman’s correlation for BLOS models. From the correlation analysis it was observed that road width (EMW), volume per lane (MV/L), delay (D) and commercial activity (CA) were the variables affecting the BLOS models. Critical gap (CG), capacity (C), percentage 2-wheelers (P2W) were the variables having significant impact on delay values. Models were developed using these variables that can be used for estimation ofservice quality and delay at urban unsignalized intersections. Step-wise regression method was used to develop the models. Prediction ability of the models have been analysed using several statistical parameters such as: correlation coefficient (R), maximum absolute error (MAE), absolute average error (AAE) and root mean square error (RMSE)

Aviation, tourism and dreaming in 1960s Bombay cinema

In the history of Bombay cinema, the 1960s is a peculiar world marked by a reworking of nationalist anxieties, sovereignty, the place of the woman, and the world of location and mobility. India’s defeat in the border war against China in 1962 jolted the Nehruvian consensus of the 1950s. This was followed by food shortages, currency crisis, and the eventual turn to the United States (US) for grants to purchase food grain. It was as if the vast control regime set up in the 1950s, whose most visible signs were the Five-Year Plans, national sovereignty, and self-sustainability, started to crack. The wild abandonment of the 1960s seemed to lift this mood for the middle class, acknowledging their dreams of travel. This article returns to the cinema of the 1960s to track both the opening of the global and a fascination with urban infrastructure, tourism, fashion, and consumption. The arrival of color, the widespread circulation of travel imagery, the promotion of railway tourism, and the explosion in aviation congealed in creating a kind of cinematic tourism that was unique in the history of Bombay cinema. Many of these films traveled to spectacular global cities like Paris, Tokyo, London, Rome, and Beirut (An Evening in Paris, Sangam, Love in Tokyo, Around the World). Through this mobility the films encountered the global currents of the 1960s and also played out anxieties around questions of love, marriage, and erotic desire

Classic ketogenic diet versus further antiseizure medicine in infants with drug-resistant epilepsy (KIWE):a UK, multicentre, open-label, randomised clinical trial

BACKGROUND: Many infancy-onset epilepsies have poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in children older than 2 years and adults who are unresponsive to antiseizure medicines. We aimed to establish the efficacy of a classic ketogenic diet at reducing seizure frequency compared with further antiseizure medicine in infants with drug-resistant epilepsy.METHODS: In this phase 4, open-label, multicentre, randomised clinical trial, infants aged 1-24 months with drug-resistant epilepsy (defined as four or more seizures per week and two or more previous antiseizure medications) were recruited from 19 hospitals in the UK. Following a 1-week or 2-week observation period, participants were randomly assigned using a computer-generated schedule, without stratification, to either a classic ketogenic diet or a further antiseizure medication for 8 weeks. Treatment allocation was masked from research nurses involved in patient care, but not from participants. The primary outcome was the median number of seizures per day, recorded during weeks 6-8. All analyses were by modified intention to treat, which included all participants with available data. Participants were followed for up to 12 months. All serious adverse events were recorded. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). The trial was terminated early before all participants had reached 12 months of follow-up because of slow recruitment and end of funding.FINDINGS: Between Jan 1, 2015, and Sept 30, 2021, 155 infants were assessed for eligibility, of whom 136 met inclusion criteria and were randomly assigned; 75 (55%) were male and 61 (45%) were female. 78 infants were assigned to a ketogenic diet and 58 to antiseizure medication, of whom 61 and 47, respectively, had available data and were included in the modifified intention-to-treat analysis at week 8. The median number of seizures per day during weeks 6-8, accounting for baseline rate and randomised group, was similar between the ketogenic diet group (5 [IQR 1-16]) and antiseizure medication group (3 [IQR 2-11]; IRR 1·33, 95% CI 0·84-2·11). A similar number of infants with at least one serious adverse event was reported in both groups (40 [51%] of 78 participants in the ketogenic diet group and 26 [45%] of 58 participants in the antiseizure medication group). The most common serious adverse events were seizures in both groups. Three infants died during the trial, all of whom were randomly assigned a ketogenic diet: one child (who also had dystonic cerebral palsy) was found not breathing at home; one child died suddenly and unexpectedly at home; and one child went into cardiac arrest during routine surgery under anaesthetic. The deaths were judged unrelated to treatment by local principal investigators and confirmed by the data safety monitoring committee.INTERPRETATION: In this phase 4 trial, a ketogenic diet did not differ in efficacy and tolerability to a further antiseizure medication, and it appears to be safe to use in infants with drug-resistant epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite previously trying two antiseizure medications.FUNDING: National Institute for Health and Care Research.</p