Treatment guidelines for rare, early-onset conditions associated with epileptic seizures: a literature review on Rett syndrome and tuberous sclerosis complex.

BACKGROUND: Rett syndrome (RTT) and tuberous sclerosis complex (TSC) are two rare disorders presenting with a range of different epileptic seizures. Seizure management requires careful therapy selection, thereby necessitating development of high-quality treatment guidelines. This targeted literature review (TLR) aimed to characterise country-specific and international treatment guidelines available for pharmacological management of seizures in RTT and TSC. METHODS: A TLR was performed between 25-Jan and 11-Mar 2021. Manual searches of online rare disease and guideline databases, and websites of national heath technology assessment bodies were conducted for the following countries: Australia, Canada, France, Germany, Israel, Italy, Japan, Spain, Switzerland, UK, and US as defined by pre-specified eligibility criteria. Search terms were developed for each condition and translated into local languages where appropriate. Eligible publications were defined as guidelines/guidance reporting pharmacological management of seizures in patients with RTT and TSC. Guideline development methodology, geographical focus, author information and treatment recommendations were extracted from guidelines. An author map was generated using R version 3.5.1 to visualise extent of collaboration between authors. RESULTS: 24 total guidelines were included, of which three and six contained only recommendations for RTT and TSC, respectively (some provided recommendations for ≥ 1 condition). Guideline development processes were poorly described (50% [12 guidelines] had unclear/absent literature review methodologies); reported methodologies were variable, including systematic literature reviews (SLRs)/TLRs and varying levels of expert consultation. Most (83% [20/24]) were country-specific, with guideline authors predominantly publishing in contained national groups; four guidelines were classified as 'International,' linking author groups in the US, UK, Italy and France. High levels of heterogeneity were observed in the availability of treatment recommendations across indications, with 13 and 67 recommendations found for RTT and TSC, respectively. For RTT, all treatment recommendations were positive and sodium valproate had the highest number of positive recommendations (Khwaja, Sahin (2011) Curr Opin Pediatr 23(6):633-9). All TSC treatments (21 medications) received either exclusively negative (National Organization for Rare Disorders (2019)) or positive (Chu-Shore et al. (2010) Epilepsia 51(7):1236-41) recommendations; vigabatrin received the highest number of positive recommendations (Kaur, Christodoulou (2019)). CONCLUSIONS: This review highlights the need for the development of international high-quality and comprehensive consensus-based guidance for the management of seizures with pharmacological therapy in RTT and TSC. TRIAL REGISTRATION: Not applicable.

Short Stature for Age in Children of 5 to 16 Years: The First Research from the Northern Himalayan Region of India.

Introduction: Anthropometric parameters play vital role in monitoring growth in pediatrics. Many etiological factors lead to short stature. So, before assessing the etiological factors short stature needs to be addressed. This study aimed to screen short stature for age in school-going children aged 5 to 16 years in Uttarakhand. Material and Methods: In this cross-sectional observational study, the height (through stadiometer) and weight (through weight machine) of 4189 students of government and private school in Rishikesh (Uttarakhand) aged 5-16 years were measured after the verbal assent of the students and individual's height is in the 3rd percentile for the mean height of a given age, sex, and population group and was considered short stature. The data collection was performed from October 2019 to July 2021. The data were categorized according to different age groups to 5-8 years, 9-12 years, and 13-16 years. The data were recorded in Microsoft (MS) Excel spreadsheet program. Statistical Package for the Social Sciences (SPSS) v23 (IBM Corp.) was used for data analysis. Descriptive statistics were elaborated in the form of means or standard deviations and medians or Interquartile range IQRs for continuous variables and frequencies and percentages for categorical variables. The Chi-square test was used for group comparisons for categorical data. Results: 7.1% of children were short stature (height 143.16 ± 15.09 cm) in the Himalayan belt, and males were more prone to short stature at age of 9-12 years. Conclusion: In the growing phase of children, the etiology of short stature has to be rectified, so the children can achieve such proper growth. Parents and physicians have to assess and monitor the growth of children timely. This study can be a stepping stone for further epidemiological studies.

Rare but not Abdicated: Status of Haemophilia in foothills of Himalaya, Uttarakhand: A cross-sectional study.

BACKGROUND: Haemophilia is one of the bleeding disorders, which is inherited, in an xlinked recessive pattern. The diagnosis is by estimation of factor levels of 8 and 9. Timebound treatment for people living with Haemophilia (PWH) is factor replacement during bleeding manifestation. The prevalence of Haemophilia was mostly underestimated, and it is more so in hilly terrains like the state of Uttarakhand. MATERIALS AND METHOD: This is a crosssectional study by compiling the data of PWH visiting the tertiary care centre for Haemophilia in Uttarakhand. We collected data from the patients with bleeding disorder reporting to the Haemophilia centre from July 2017 to December 2018. In this manuscript, we try to describe the pattern of Haemophilia and the degree of severity and incidence of inhibitors among the sample population of PWH who represent the population of Uttarakhand. The magnitude of problems faced by PWH from this hilly terrain to assess basic treatment in case of emergency is also being depicted. RESULT: We reported Haemophilia A contributing about 80% of the PWH in our centre. Average distance a PWH has to travel to obtain treatment was about 131.5 km (SD ± 83.7 km). Incidence of inhibitors was about 5%. CONCLUSION: We infer from our study that Hemophilia A is more common than Hemophilia B. Through this manuscript we hope to spread awareness of the Haemophilia care that is ongoing, the role of prophylaxis therapy and the future role of primary care physicians that may change the care of PWH in future.

Child abuse: A social evil in Indian perspective.

Child abuse is a social evil which has existed in our society since a long time. The awareness regarding the same has been minimal in developing countries. Many a times, punitive measures taken by parents to discipline their children turn out to be painful scars in their childhood resulting in stunting of their mental and social growth. Doctors and other health care workers have a very important role in identifying and reporting such issues. Law has also evolved over the recent past in safeguarding the future of our children. However, awareness regarding this issue has remained to be the same as before. During the current era of COVID, parents and children have been restricted to their homes. Livelihood of many families have been at risk. These issues have burdened the caretakers at home and absence of teachers who were otherwise their guardian angels have impacted the minds of these children adversely. Hence in this article we intend to provide good clarity about this social evil, and the rights of our children. We also wish to stress upon the duties of parents, doctors, teachers in molding these tender minds so as to get the best out of them.

A review on exploring evidence-based approach to harnessing the immune system in times of corona virus pandemic: Best of modern and traditional Indian system of medicine.

Coronavirus (COVID-19) is the most dreaded pandemic of our times, which lead to a state of chaos among the mightiest nations of the world. The immune system plays a great role in response to any foreign organisms be it bacteria or viruses. Virus-based pandemics like SARS, MERS, COVID-19 have time and again been surfacing leading to mortality and morbidity worldwide. These pandemics have also resurfaced the role of public health and its modes which have been fading in the presence of lucrative hi-tech medical industry. Although Chinese system of medicine has been explored, there is still more to be done in exploring solutions from time tested Indian systems of medicine like Ayurved and Yog. Its time to rethink and explore ways to harness our immune system and look for evidence-based solutions providing the best of both medical systems to the patients, i.e., modern medicine as well as Ayurved and Yog. The present review is a narrative review wherein studies were searched from databases like PubMed, Cochrane, Scopus, and web pages. Given a paucity of studies hereby we explored existing pieces of evidence, thereby concluding that more randomized controlled trials need to be done for assessing the role of Ayurved, Yog, and other Indian systems of medicine to enrich the armamentarium in the fight against such viruses in future. Family physicians can play a vital role in not only suggesting treatment but also changes in lifestyle of the patients as well as their family. Evidence based knowledge of ancient Indian system will open a new door of integration for overall well being of patient with a scientific outlook.

Uncommon presentation of scorpion sting at teaching hospital.

Scorpion envenomation is a major public health problem in tropical and sub-tropical countries, especially in Africa, Middle East, Latin America, and India. Even though most of the scorpion envenomation are harmless, it is generally seen with a set of clinical features, such as pain, edema, numbness, and tenderness in the area of the sting but rarely have serious clinical sequelae with involvement of vital organ systems like cardiovascular system and respiratory system leading to fatal manifestations like acute pulmonary edema, acute heart failure, and acute respiratory distress syndrome (ARDS). Here we present a case of a 19-year-old village boy who developed myocarditis and cardiogenic shock following scorpion envenomation, which was successfully treated with vasopressors, non invasive ventilation, and other supportive care.

Performance evaluation of Cerenkov luminescence imaging: a comparison of 68Ga with 18F.

BACKGROUND: Cerenkov Luminescence Imaging (CLI) is an emerging technology for intraoperative margin assessment. Previous research only evaluated radionuclide 18-Fluorine (18F); however, for future applications in prostate cancer, 68-Gallium (68Ga) seems more suitable, given its higher positron energy. Theoretical calculations predict that 68Ga should offer a higher signal-to-noise ratio than 18F; this is the first experimental confirmation. The aim of this study is to investigate the technical performance of CLI by comparing 68Ga to 18F. RESULTS: The linearity of the system, detection limit, spatial resolution, and uniformity were determined with the LightPath imaging system. All experiments were conducted with clinically relevant activity levels in vitro, using dedicated phantoms. For both radionuclides, a linear relationship between the activity concentration and detected light yield was observed (R2 = 0.99). 68Ga showed approximately 22 times more detectable Cerenkov signal compared to 18F. The detectable activity concentration after a 120 s exposure time and 2 × 2 binning of 18F was 23.7 kBq/mL and 1.2 kBq/mL for 68Ga. The spatial resolution was 1.31 mm for 18F and 1.40 mm for 68Ga. The coefficient of variance of the uniformity phantom was 0.07 for the central field of view. CONCLUSION: 68Ga was superior over 18F in terms of light yield and minimal detection limit. However, as could be expected, the resolution was 0.1 mm less for 68Ga. Given the clinical constraints of an acquisition time less than 120 s and a spatial resolution < 2 mm, CLI for intraoperative margin assessment using 68Ga could be feasible.

Hemophagocytic lymphohistiocytosis as a diagnostic consideration of fever of unknown origin with pancytopenia and chronic liver disease.

Hemophagocytic lymphohistiocytosis (HLH) is a severe disorder of systemic immune dysregulation which can be primary or secondary to autoimmune disorders, malignancy, or infections. We hereby describe a case of a 23-year-old male with severe hepatitis along with pancytopenia and prolonged fever of unknown origin that developed HLH triggered by staphylococcal urinary tract infection. This is a discussion of this unusual disease and its presentation and the diagnostic difficulties which may be encountered in general clinical practice.

Comparison of five commercially available immunochromatographic tests for the detection of norovirus in faecal specimens.

Five CE-marked immunochromatography assay kits for the rapid detection of norovirus were compared with the reference method of real-time polymerase chain reaction (PCR) for the detection of acute norovirus infection. The sensitivity of the assays ranged between 23% and 59% with specificity being 75‒100% when compared with real-time PCR. The data suggest that a reactive immunochromatographic assay indicates norovirus infection. However, the sensitivity of the assay would need to be significantly improved to be suitable for routine diagnostic purposes or as an alternative to laboratory analysis for near-patient testing.

Clinician perceptions of pediatric growth chart use and electronic health records in Kentucky.

BACKGROUND: Growth chart recording is a key component of pediatric care. EHR systems could provide several growth charting functionalities compared to paper methods. To our knowledge, there has been no U.S. study exploring clinicians' perceptions and practices related to recording of growth parameters as they adapt to electronic methods. OBJECTIVES: To explore clinician practices regarding recording growth parameters as they adapt to electronic health records (EHR) and to investigate clinician perceptions of electronic growth charting using EHR. METHODS: An online survey of pediatricians and family practitioners in Kentucky inquiring about EHR usage, specifically use of growth charting with EHR, was conducted. RESULTS: Forty-six percent of respondents utilized EHRs, with pediatricians lagging family practitioners, and academic pediatricians lagging non-academicians. There was no consensus on EHR platforms being used. Almost a third of those who used EHR did not utilize electronic growth charting. Clinicians using EHR reported that electronic growth charts would improve clinician satisfaction and clinical efficiency as well as parent satisfaction and parent education. Only 12% of respondents provided copies of growth charts to parents at the end of their visit and discussed growth parameters with parents, with clinicians using EHR more likely to engage in these activities than non-EHR users. CONCLUSION: Although Kentucky clinicians continue to slowly adopt EHRs, clinician perceptions and practices reflect enduring barriers to widespread use of electronic growth charting in pediatric and family practice. However, our results suggest that electronic growth charting has important benefits for both clinicians and patients, and greater adoption is expected as EHRs become standard across health care systems.

Isolation and characterisation of degradant impurities in dipyridamole formulation.

Dipyridamole is an antithrombotic drug. In the stability study of drug product of Dipyridamole, two unknown impurities (referred as DP-I and DP-II) were detected at levels of 0.25% and 0.54% by gradient reverse phase HPLC method. The drug product was subjected to stress to enhance the level of these impurities. An elegant isocratic preparative method was employed using a Reprosil CN column with a short run time of 14 min to isolate these impurities. The DP-I and DP-II were isolated with purities of 99.1% and 99.8% respectively. Structural studies of these impurities were undertaken using spectroscopic techniques such as IR, NMR and Mass. Based on the spectral data, the structures of DP-I and DP-II have been characterised to be 2,2',2″,2'″-(4-hydroxy-8-(piperidin-1-yl) pyrimido [5,4-d]pyrimidine-2,6 diyl) bis(azanetriyl) tetraethanol, 4-(2-((6-(bis (2-hydroxyethyl) amino)-4, 8-di (piperidin-1-yl) pyrimido [5,4-d] pyrimidin-2-yl) (2-hydroxyethyl) amino) ethoxy)-2, 3-dihydroxy-4-oxobutanoic acid, respectively. A detailed elucidation of the structure is presented in this article.

Detection of endogenous magnetic nanoparticles with a tunnelling magneto resistance sensor.

The magnetotactic bacterium Magnetospirillum sp. has been cultured and the properties of its endogenous magnetic nanoparticles characterized. Electron-microscopic analyses indicate that the endogenous magnetite nanoparticles in Magnetospirillum sp. are coated with a 3-4 nm thick transparent shell, forming a magnetosome. These magnetite nanoparticles had diameters of 50.9+/-13.3 nm, in good agreement with the diameter of 40.6+/-1.2 nm extracted from magnetometry. Each Magnetospirillum sp. bacterium contained chains of 5-25 magnetosomes. Superconducting quantum interference device magnetometry results indicate that the extrinsic superparamagnetic response of the bacterial solution at room temperature can be attributed to the reversal of the magnetization by physical rotation of the nanoparticles. The intrinsic blocking temperature of a sample of freeze-dried bacteria was estimated to be 282+/-13 K. A tunnelling magneto resistance sensor was used to detect the stray fields of endogenous magnetic nanoparticles in static and quasi-dynamic modes. Based on the tunnelling magneto resistance sensor results, the magnetic moment per bacterium was estimated to be approximately 2.6 x 10(-13) emu. The feasibility of this detection method either as a mass-coverage device or as part of an integrated microfluidic circuit for detection and sorting of magnetosome-containing cells was demonstrated.

Identification of degradation products in stressed tablets of Rabeprazole sodium by HPLC-hyphenated techniques.

Three unknown impurities of Rabeprazole, a proton pump inhibitor, were formed in the formulated drug under the stress conditions, [40 degrees C/75% relative humidity (RH) for 6 months] with relative retention times (RRTs) 0.17, 0.22 and 0.28. The Impurity-I (0.17 RRT) was isolated using preparative HPLC and characterized by NMR and MS. The other two impurities, Impurity-II (RRT 0.22) and Impurity-III (RRT 0.28) could not be isolated, hence they are characterized by HPLC-hyphenated techniques, LC-NMR and high-resolution LC-MS. On the basis of the spectral data, the Impurity-I, Impurity-II and Impurity-III were characterized as 1-(1H-benzo[d]imidazol-2-yl)-3-methyl-4-oxo-1,4-dihydropyridine-2-carboxylic acid, 1H-benzo [d] imidazole-2-sulfonic acid and 4-(3-methoxy propoxy)-3-methyl-2-pyridine carboxylic acid, respectively.

Ab initio structure determination of anhydrous sodium alendronate from laboratory powder X-ray diffraction data.

Sodium alendronate, a member of bisphosphonate class of compounds commonly used for treatment of generalized bone disorders, exists in various hydrated forms. Dehydration of sodium alendronate trihydrate has been studied using variable temperature X-ray powder diffraction technique. The crystal structure of anhydrous sodium alendronate, prepared by heating the trihydrate sodium alendronate at 150 degrees C, has been determined from X-ray powder data using direct space global optimization technique for structure solution, followed by the Rietveld refinement. The structure of the anhydrous form of sodium alendronate is compared with that of the trihydrate form, which was determined previously from single crystal X-ray diffraction data. Both anhydrous and trihydrate sodium alendronate crystallize in monoclinic system with space group P2(1)/n. The crystal structure of the anhydrous sodium alendronate is built by edge-sharing of NaO(6) octahedra into a two-dimensional molecular sheet in the (011) plane, whereas in the trihydrate compound, one-dimensional chain along the (010) direction is generated by corner sharing of NaO(6) octahedra.

A remarkable accelerating effect of Ag-salt on intramolecular cyclization of o-(1-alkynyl)benzenesulfonamides.

Herein, we report transition metal-catalyzed intramolecular cyclization of o-(1-alkynyl)benzenesulfonamides to afford 3-substituted benzothiazines regioselectively via a C-N bond forming reaction and Cu-catalyzed sequential C-N and C-C bond formation leading to the corresponding 3,4-disubstituted derivatives.

Supramolecular synthon polymorphism in 2 : 1 co-crystal of 4-hydroxybenzoic acid and 2,3,5,6-tetramethylpyrazine.

Co-crystals of 4-hydroxybenzoic acid and 2,3,5,6-tetramethylpyrazine (2 : 1) exhibit the first supramolecular synthon polymorphism in a co-crystal; metastable anti-hierarchic polymorph I converts to stable hierarchic form II.

Tandem C-C coupling--intramolecular acetylenic Schmidt reaction under Pd/C-Cu catalysis.

A new one-pot reaction for the regioselective construction of a six-membered fused N-heterocyclic ring leading to isoquinolones under Pd/C-Cu catalysis is described.

Structural identification and characterization of potential impurities of pantoprazole sodium.

Six impurities in pantoprazole sodium bulk drug substance were detected by a simple high performance liquid chromatographic method (HPLC) whose area percentage ranged from approximately 0.05 to 0.34%. Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the molecular weight of the impurities. A thorough study was undertaken to characterize these impurities. These impurities were synthesized, subsequently characterized and were co-injected with the sample containing impurities and found the retention time match of the spiked impurities. Based on their spectral data (IR, NMR and MS), these impurities were characterized as; 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]thio]-1H-benzimidazole (Impurity-I); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfonyl]-1H-benzimidazole (Impurity-II); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-1-oxide-2-pyridinyl)methyl]sulfonyl]-1H-benzimidazole (Impurity-III); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]thio]-1-((3,4-dimethoxy-2-pyridinyl)methyl)-1H-benzimidazole (Impurity-IV); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfinyl]-1-((3,4-dimethoxy-2-pyridinyl)methyl)-1H-benzimidazole (Impurity-V); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-1-oxide-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole (Impurity-VI). The formation of these impurities was proposed. The structure of the Impurity-II was unambiguously confirmed by single crystal X-ray diffraction (XRD) studies.

Pharmacophoric 2-hydroxyalkyl benzenesulfonamide: a single-step synthesis from benzenesulfonamide via hemiaminal.

ortho-Acylation attempt of benzenesulfonamide afforded the corresponding hemiaminal as major product. The in situ reduction of the reaction mixture, reported herein, directly provided 2-hydroxyalkyl benzenesulfonamide, an important pharmacophoric element for designing drug-like scaffolds. Its application is demonstrated through designing a novel series of 1,5-diarylpyrazoles for cyclooxygenase-2 (COX-2) inhibition.