Epidemiological profile,management and outcomes of patients with acute coronary syndrome: Single centre experience from a tertiary care hospital in North India

BackgroundCardiovascular disease is the leading cause of death in India. Our aim is to study the clinical, epidemiological profile and in-hospital outcomes of patients presenting with acute coronary syndrome.MethodsWe did a prospective single center observational study of the 1203 patients presenting with ACS to a tertiary referral center in North India over a period of one year (July 2018–June 2019).ResultsThe mean age of study population was 58.4 ± 12.5 years. STEMI and NSTE-ACS accounted for 69.9% and 31.1% respectively. 62.1% of our patients were from rural background. The median time to hospital admission was 600 min for STEMI patients, thrombolysis was performed in 52% of cases. Cardiogenic shock at presentation was noted in 18%. Coronary angiography and percutaneous coronary intervention were done in 1062 (88.3%) and 733 (60.9%) patients respectively. The overall in-hospital mortality was 7.6%. STEMI patients had higher mortality than NSTE-ACS (8.9% vs 4.5% p < 0.001). Female gender (OR?3.306 C.I. 1.87–5.845), severe MR (OR?4.65, C.I.?1.187–18.18), acute kidney injury (AKI) at admission (OR-5.15, C.I.?2.5–10.63), higher Killip class (class III/IV) (OR?3.378,C.I.?1.292–8.849), AF (OR?3.25, C.I.?1,18–8.92), complete heart block (CHB) (OR?4.44,C.I.?2.09–9.43) and right bundle branch block (RBBB) (OR?2.86, C.I.?1.2–6.8) were significant predictors of in hospital mortality.ConclusionsOur study represents the predominance of STEMI as the initial ACS presentation with a considerable delay in first medical contact and higher prevalence of cardiogenic shock (CS). STEMI patients had higher mortality. Female sex, severe MR, AKI, higher Killips class, AF, CHB, RBBB being predictors of high in-hospital mortality in ACS patients.     

Treatment strategies for central nervous system infections: an update

Introduction: Central nervous system infection continues to be an important cause of mortality and morbidity worldwide. Our incomplete knowledge on the pathogenesis of how meningitis-causing pathogens cause CNS infection and emergence of antimicrobial resistance has contributed to the mortality and morbidity. An early empiric antibiotic treatment is critical for the management of patients with bacterial meningitis, but early recognition of bacterial meningitis continues to be a challenge.

Areas covered: This review gives an overview on current therapeutic strategies for CNS infection with a focus on recent literature since 2010 on bacterial meningitis. Bacterial meningitis is a medical emergency, requiring early recognition and treatment. The selection of appropriate empiric antimicrobial regimen, after incorporating the epidemiology of bacterial meningitis, impact of vaccination, emergence of antimicrobial-resistant bacteria, role of adjunctive therapy and the current knowledge on the pathogenesis of meningitis and associated neuronal injury are covered.

Expert opinion: Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood–brain barrier, with efficacy in cerebrospinal fluid. Emergence of CNS-infecting pathogens with resistance to conventional antibiotics has been increasingly recognized, but development of new antibiotics has been limited. More complete understanding of the microbial and host factors that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.     

Applications of In Vitro–In Vivo Correlations in Generic Drug Development: Case Studies

In vitro–in vivo correlation (IVIVC) is a predictive mathematical model describing the relationship between an in vitro property and a relevant in vivo response. The main objective of an IVIVC is to serve as a surrogate for human bioequivalence (BE) studies, which may reduce the number of BE studies performed during the initial approval process as well as with certain scale-up and postapproval changes. The US Food and Drug Administration (FDA) published a regulatory guidance related to development, evaluation, and applications of IVIVC for extended-release (ER) oral dosage forms in September 1997. Despite the publication of this guidance, the deficiencies related to IVIVC are still identified by the Division of Bioequivalence in the process of Abbreviated New Drug Application (ANDA) review. Thus, the main objective of this article is to present the most commonly occurring deficiencies associated with IVIVCs via selected case studies from the ANDAs for oral ER drug products only. We searched internal FDA databases from January 1996 to December 2014 to identify the ANDAs for proposed generic oral ER drug products containing IVIVC. Only 14 ANDA submissions had IVIVC data, and most were not acceptable. Only one ANDA submission included adequate information related to IVIVC data enabling the completion of BE review within first review cycle. It is hoped that awareness of the deficiencies presented in our article would help the generic drug applicants to submit complete and appropriate information related to IVIVC data, ultimately, resulting in a more timely approval of ANDAs.KEY WORDS: bioequivalence, extended-release drug products, generics, IVIVC, SUPAC     

Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine

Variants in ACTA1, which encodes α-skeletal actin, cause several congenital myopathies, most commonly nemaline myopathy. Autosomal recessive variants comprise approximately 10% of ACTA1 myopathy. All recessive variants reported to date have resulted in loss of skeletal α-actin expression from muscle and severe weakness from birth. Targeted next-generation sequencing in two brothers with congenital muscular dystrophy with rigid spine revealed homozygous missense variants in ACTA1. Skeletal α-actin expression was preserved in these patients. This report expands the clinical and histological phenotype of ACTA1 disease to include congenital muscular dystrophy with rigid spine and dystrophic features on muscle biopsy. This represents a new class of recessive ACTA1 variants, which do not abolish protein expression.     

Pure neuritic leprosy in India: an appraisal

BACKGROUND: Pure neuritic leprosy (PNL) constitutes a significant proportion of all cases in India, however, this form of disease has not been fully recognized and investigated and there is little information in the existing literature. OBJECTIVE: To study the epidemiological characteristics of PNL in India. MATERIALS AND METHODS: A retrospective analysis of leprosy clinic records for the period 1993 to 2003 was undertaken. Detailed demographic profiles and clinical findings were noted from the predesigned clinic proforma. A slit-skin smear for acid-fast baclli (AFB) was done in all cases from the area of sensory loss. A skin biopsy was done from the area of sensory impairment to study histopathological changes. Further investigations such as nerve conduction velocity studies (NCV), fine needle aspiration cytology (FNAC), or nerve biopsy (superficial nerve twigs) were done if indicated in patients whenever there was difficulty in clinical diagnosis. RESULTS: Of the total 1542 leprosy patients seen over this period, 65 (4.2%) had PNL. Males were more commonly affected than females (2.6:1.). The majority of patients 40/65(61.5%) were aged between 15 and 35 yrs. Predominant presenting symptoms were paresthesia, pain, sensory/motor deficit, and trophic changes. A majority of the patients 39/65 (60.0%) presented with involvement of 2 or more nerves in the same extremity. Mononeuritis was seen in 26 (40%) patients. The nerves most often involved were the right ulnar nerve in the upper extremity, and the right common peroneal nerve in the lower limb. In general, the nerves of the upper extremity were more commonly involved than in the lower limbs (67 vs. 55). Motor deformities such as claw hand and foot drop were present in 13/75 (20%) and 7/65 (10.8%) patients, respectively. Slit-skin smears were negative in all patients, and skin histopathology from the area of sensory loss revealed non-specific inflammation in the dermis in a majority of patients, with perineural inflammation in a few. All patients were treated with multi-drug therapy (MDT); patients with >/=2 peripheral nerve trunk involvements were treated with WHO MDT MB regimen, while others were administered WHO MDT PB regimen. Follow-up for up to 2 yrs was available in only 32/65 (49.2%) patients, none of whom developed any skin lesions during this period. CONCLUSION: PNL is a distinct subset of disease frequently seen in India. There is need to pay more attention to this form of leprosy and diagnose and treat patients earlier to prevent deformities and sequelae of nerve damage.     

Facility-based active management of the third stage of labour: assessment of quality in six countries in sub-Saharan Africa

Objective

To assess the quality of facility-based active management of the third stage of labour in Ethiopia, Kenya, Madagascar, Mozambique, Rwanda and the United Republic of Tanzania.

Methods

Between 2009 and 2012, using a cross-sectional design, 2317 women in 390 health facilities were directly observed during the third stage of labour. Observers recorded the use of uterotonic medicines, controlled cord traction and uterine massage. Facility infrastructure and supplies needed for active management were audited and relevant guidelines reviewed.

Findings

Most (94%; 2173) of the women observed were given oxytocin (2043) or another uterotonic (130). The frequencies of controlled cord traction and uterine massage and the timing of uterotonic administration showed considerable between-country variation. Of the women given a uterotonic, 1640 (76%) received it within three minutes of the birth. Uterotonics and related supplies were generally available onsite. Although all of the study countries had national policies and/or guidelines that supported the active management of the third stage of labour, the presence of guidelines in facilities varied across countries and only 377 (36%) of 1037 investigated providers had received relevant training in the previous three years.

Conclusion

In the study countries, quality and coverage of the active management of the third stage of labour were high. However, to improve active management, there needs to be more research on optimizing the timing of uterotonic administration. Training on the use of new clinical guidelines and implementation research on the best methods to update such training are also needed.     

Evaluation of the Universal Immunization Program and Challenges in Coverage of Migrant Children in Haridwar,Uttarakhand, India

Background:

Studies show that immunization among migrant children is poor. India has a dropout rate of 17.7% between Bacillus Calmette-Guιrin (BCG) and measles (District Level Household Survey (DLHS)-3). Haridwar district had the highest dropout rate of 27.4% from BCG to diphtheria, pertussis, and tetanus (DPT) 3 (DLHS-3) in Uttarakhand. We evaluated the Universal Immunization Programme (UIP) among migrants in Haridwar in two blocks.

Materials and Methods:

We developed input, process, and output indicators on infrastructure, human resources, and service delivery. A facility, session site and cross-sectional survey of 180 children were done and proportions for various indicators were estimated. We determined factors associated with not taking vaccination using multivariate analysis.

Results:

We surveyed 11 cold chain centers, 25 subcenters, 14 sessions, and interviewed 180 mothers. Dropouts were supposed to be tracked using vaccination card counterfoils and tracking registers. The dropout rate from BCG to DPT3 was 30%. Lack of knowledge (adjusted odds ratio (AOR) 6.6,95% confidence interval (CI) 2.6–16.7), mother not being decision maker (AOR 4.0,95%CI 1.7–9.2), lack of contact by Accredited Social Health Activist (ASHA; AOR 3.0,95%CI 1.1–7.7), not being given four post-vaccination messages (AOR 7.7, 95% CI 2.9–20.2), and longer duration of stay in Haridwar (AOR 3.0 95% 1.9–7.6) were risk factors for nonimmunization. The reasons stated by mothers included lack of awareness of session site location (67%) and belief that child should only be vaccinated in their resident district (43%).

Conclusions:

There was low immunization coverage among migrants within adequate supervision, poor cold chain maintenance, and improper tracking of dropouts. Mobile immunization teams, prelisting of migrant children, and change in incentives of ASHAs for child tracking were needed. A monitoring plan for sessions and cold chain needed enforcement.