Health technology assessment of varicella vaccine in the Armed Forces.

Background: The Indian Armed Forces, on entry, vaccinates all cadets and recruits with varicella vaccine for the prevention of varicella. This health technology assessment (HTA) report puts forth evidence for HTA of varicella vaccination in the Armed Forces in various domains namely clinical, societal, ethical, economic, and legal. Methods: The policy question under each domain has been developed according to best-practice methods for HTA. The costs included were hospitalization cost due to varicella infection; training lost cost; the varicella vaccine cost; cost of the side effects of vaccine; and the outbreak investigation cost. The incremental cost-effectiveness ratio (ICER) for varicella cases averted and man-days saved, and quality-adjusted life years (QALYs) gained due to varicella vaccination strategy were calculated. Results: Evidence suggests a reduction of 81% in hospitalization rates with 19392 man-days saved per 1 lakh population due to varicella vaccination strategy. The ICER for varicella cases averted is estimated to be Rs 56732/- per case averted and Rs 5687/- per man-day saved. QALYs gained due to two-dose varicella vaccination strategy is estimated to be 1152 per 1 lakh population with cost per QALY gained Rs 95735/-. Conclusion: The study showed a large reduction in hospitalizations and consequently man-days lost after the introduction of the vaccination strategy. The QALYs was another aspect of importance brought out by this study. Thus, a two-dose vaccination strategy for varicella-zoster virus (VZV) for the Armed Forces trainees is a cost-effective policy.

Review article: dyssynergic defaecation and biofeedback therapy in the pathophysiology and management of functional constipation.

BACKGROUND: Functional constipation is a common clinical presentation in primary care. Functional defaecation disorders are defined as the paradoxical contraction or inadequate relaxation of the pelvic floor muscles during attempted defaecation (dyssynergic defaecation) and/or inadequate propulsive forces during attempted defaecation. Prompt diagnosis and management of dyssynergic defaecation is hindered by uncertainty regarding nomenclature, diagnostic criteria, pathophysiology and efficacy of management options such as biofeedback therapy. AIM: To review the evidence pertaining to the pathophysiology of functional defaecation disorders and the efficacy of biofeedback therapy in the management of patients with dyssynergic defaecation and functional constipation. METHODS: Relevant articles addressing functional defaecation disorders and the efficacy of biofeedback therapy in the management of dyssynergic defaecation and functional constipation were identified from a search of Pubmed, MEDLINE Ovid and the Cochrane Library. RESULTS: The prevalence of dyssynergic defaecation in patients investigated for chronic constipation is as many as 40%. Randomised controlled trials have demonstrated major symptom improvement in 70%-80% of patients undergoing biofeedback therapy for chronic constipation resistant to standard medical therapy and have determined it to be superior to polyethylene glycol laxatives, diazepam or sham therapy. Long-term studies have shown 55%-82% of patients maintain symptom improvement. CONCLUSIONS: Dyssynergic defaecation is a common clinical condition in patients with chronic constipation not responding to conservative management. Biofeedback therapy appears to be a safe, successful treatment with sustained results for patients with dyssynergic defaecation. Further studies are required to standardise the diagnosis of dyssynergic defaecation in addition to employing systematic protocols for biofeedback therapy.

State of newborn health in India.

About 0.75 million neonates die every year in India, the highest for any country in the world. The neonatal mortality rate (NMR) declined from 52 per 1000 live births in 1990 to 28 per 1000 live births in 2013, but the rate of decline has been slow and lags behind that of infant and under-five child mortality rates. The slower decline has led to increasing contribution of neonatal mortality to infant and under-five mortality. Among neonatal deaths, the rate of decline in early neonatal mortality rate (ENMR) is much lower than that of late NMR. The high level and slow decline in early NMR are also reflected in a high and stagnant perinatal mortality rate. The rate of decline in NMR, and to an extent ENMR, has accelerated with the introduction of National Rural Health Mission in mid-2005. Almost all states have witnessed this phenomenon, but there is still a huge disparity in NMR between and even within the states. The disparity is further compounded by rural-urban, poor-rich and gender differentials. There is an interplay of different demographic, educational, socioeconomic, biological and care-seeking factors, which are responsible for the differentials and the high burden of neonatal mortality. Addressing inequity in India is an important cross-cutting action that will reduce newborn mortality.

Inpatient care of small and sick newborns in healthcare facilities.

Neonatal units in teaching and non-teaching hospitals both in public and private hospitals have been increasing in number in the country since the sixties. In 1994, a District Newborn Care Programme was introduced as a part of the Child Survival and Safe Motherhood Programme (CSSM) in 26 districts. Inpatient care of small and sick newborns in the public health system got a boost under National Rural Health Mission with the launch of the national programme on facility-based newborn care (FBNC). This has led to a nationwide creation of Newborn Care Corners (NBCC) at every point of child birth, newborn stabilization units (NBSUs) at First Referral Units (FRUs) and special newborn care units (SNCUs) at district hospitals. Guidelines and toolkits for standardized infrastructure, human resources and services at each level have been developed and a system of reporting data on FBNC created. Till March 2015, there were 565 SNCUs, 1904 NBSUs and 14 163 NBCCs operating in the country. There has been considerable progress in operationalizing SNCUs at the district hospitals; however establishing a network of SNCUs, NBSUs and NBCCs as a composite functional unit of newborn care continuum at the district level has lagged behind. NBSUs, the first point of referral for the sick newborn, have not received the desired attention and have remained a weak link in most districts. Other challenges include shortage of physicians, and hospital beds and absence of mechanisms for timely repair of equipment. With admission protocols not being adequately followed and a weak NBSU system, SNCUs are faced with the problem of admission overload and poor quality of care. Applying best practices of care at SNCUs, creating more NBSU linkages and strengthening NBCCs are important steps toward improving quality of FBNC. This can be further improved with regular monitoring and mentoring from experienced pediatricians, and nurses drawn from medical colleges and the private sector. In addition there is a need to further increase such units to address the unmet need of facility-based care.

Care of newborn in the community and at home.

India has contributed immensely toward generating evidence on two key domains of newborn care: Home Based Newborn Care (HBNC) and community mobilization. In a model developed in Gadchiroli (Maharashtra) in the 1990s, a package of Interventions delivered by community health workers during home visits led to a marked decline in neonatal deaths. On the basis of this experience, the national HBNC program centered around Accredited Social Health Activists (ASHAs) was introduced in 2011, and is now the main community-level program in newborn health. Earlier in 2004, the Integrated Management of Neonatal and Childhood Illnesses (IMNCI) program was rolled out with inclusion of home visits by Anganwadi Worker as an integral component. IMNCI has been implemented in 505 districts in 27 states and 4 union territories. A mix of Anganwadi Workers, ASHAs, auxiliary nursing midwives (ANMs) was trained. The rapid roll out of IMNCI program resulted in improving quality of newborn care at the ground field. However, since 2012 the Ministry of Health and Family Welfare decided to limit the IMNCI program to ANMs only and leaving the Anganwadi component to the stewardship of the Integrated Child Development Services. ASHAs, the frontline workers for HBNC, receive four rounds of training using two modules. There are a total of over 900 000 ASHAs per link workers in the country, out of which, only 14% have completed the fourth round of training. The pace of uptake of the HBNC program has been slow. Of the annual rural birth cohort of over 17 million, about 4 million newborns have been visited by ASHA during the financial year 2013-2014 and out of this 120 000 neonates have been identified as sick and referred to health facilities for higher level of neonatal care. Supportive supervision remains a challenge, the role of ANMs in supervision needs more clarity and there are issues surrounding quality of training and the supply of HBNC kits. The program has low visibility in many states. Now is the time to tap the missed opportunity of miniscule coverage of HBNC; that at least half of the country's birth cohort should be covered by this program by 2016, coupled with rapid scale up of the community-based treatment of neonates with pneumonia or sepsis, where referral is not possible.

'Empty sella' on routine MRI studies: An incidental finding or otherwise?

BACKGROUND: Empty sella (ES) has been regarded as an incidental finding. Recently, there have been studies documenting association of ES with hormonal and non-hormonal abnormalities. To detect the prevalence of empty sella in routine MRI brain study and to find associations with other diseases. METHODS: A retrospective study was carried out for patients undergoing MRI brain studies in the radiology department of a teaching institution. Patients with ES formed the study group. The rest formed the baseline population. Presence of nine select variables, viz. hormonal disturbances, headache, sensorineural hearing loss, seizures, vertigo, psychiatric disorders, visual disturbances, ataxia and raised intracranial tension, was analyzed amongst the study group, as well as the baseline population. Association of ES and the select variables was analyzed by determining means and proportions and using Chi-square test. RESULTS: During the study period, a total of 12,414 patients underwent MRI brain studies at our centre. ES was found in 241 (1.94%) patients. The proportion of patients in the ES and non-empty sella groups for each of the variables were as follows: hormonal disturbances (3.31% vs 0.56%, P = .000), headache (8.3% vs 7.4%, P = .596), SNHL (3.7% vs 1.3%, P = .0010), seizure (6.2% vs 13%, P = .002), vertigo (4.6% vs 1.6%, P = .000), psychiatric disorders (4.6% vs 1.3%, P = .000), visual disturbances (2% vs 1.1%, P = .166), ataxia (1.7% vs 1.2%, P = .519) and raised ICT (2% vs 0.5%, P = .002). CONCLUSION: Hormonal disturbances, psychiatric disorders, raised ICT and SNHL have been found to be more often associated with ES as compared to general population.

Outcome of behavioural treatment for idiopathic chronic constipation.

BACKGROUND/AIM: Behavioural therapy is effective in patients with chronic intractable constipation despite standard treatment, but long-term results in unselected patients are unclear. This study investigates the effects of behavioural therapy on symptoms, subjective well-being, and the physical and mental quality of life. METHODS: Patients who had failed standard care for idiopathic chronic constipation underwent behavioural therapy in a specialist clinic. Symptom severity and quality of life were assessed before and after therapy using the 'Constipation Scoring System' and the Short-Form 36 questionnaire. The primary outcome was subjective perception of improvement. Secondary outcomes were symptoms of constipation and quality of life scores. RESULTS: Of 233 consecutive patients with self-reported constipation (median symptom duration 5-10 years, median age 44 years, females 86%), 180 (77%) completed treatment in a median of three (range 1-7) sessions. One hundred and sixty-five patients (71% of all referrals or 92% of those completing treatment) reported subjective improvement. Median bowel frequency improved from once every 2-7 days to 1-3 per day (P = 0.05). Pain and bloating improved in more than 80% of patients. The Short-Form 36 physical (P < 0.05) and mental (P < 0.05) composite scores improved significantly. Patients with a longer duration of symptoms were less likely to complete treatment. Digital evacuation prior to treatment was a predictor of poor outcome. CONCLUSION: Behavioural therapy is associated with significant improvement in symptoms of chronic constipation and quality of life. Non-drug therapies that successfully treat patients with functional gut disorders resistant to standard treatment are needed in the mainstream provision of care.

Surveillance during an era of rapidly changing poliovirus epidemiology in India: the role of one vs. two stool specimens in poliovirus detection, 2000-2010.

Since 2004, efforts to improve poliovirus detection have significantly increased the volume of specimen testing from acute flaccid paralysis (AFP) patients in India. One option to decrease collection and testing burden would be collecting only a single stool specimen instead of two. We investigated stool specimen sensitivity for poliovirus detection in India to estimate the contribution of the second specimen. We reviewed poliovirus isolation data for 303984 children aged <15 years with AFP during 2000-2010. Using maximum-likelihood estimation, we determined specimen sensitivity of each stool specimen, combined sensitivity of both specimens, and sensitivity added by the second specimen. Of 5184 AFP patients with poliovirus isolates, 382 (7.4%) were identified only by the second specimen. Sensitivity was 91.4% for the first specimen and 84.5% for the second specimen; the second specimen added 7.3% sensitivity, giving a combined sensitivity of 98.7%. Combined sensitivity declined, and added sensitivity increased, as the time from paralysis onset to stool collection increased (P = 0.032). The sensitivity added by the second specimen is important to detect the last chains of poliovirus transmission and to achieve certification of polio eradication. For sensitive surveillance, two stool specimens should continue to be collected from each AFP patient in India.

Selenium supplementation protects trophoblast cells from mitochondrial oxidative stress.

INTRODUCTION: Oxidative stress plays an important role in the pathogenesis of preeclampsia, a placental disorder affecting approximately 7% of pregnancies. Trophoblast cells are susceptible to oxidative stress which causes increased cell death and placental turnover. In this study, inhibitors of the mitochondrial respiratory chain were utilised to induce oxidative stress and the effect that selenium supplementation had on trophoblast viability was investigated. METHODS: Trophoblast cells (BeWo, JEG-3 and Swan-71) were treated with Na Selenite (100 nM) or Selenomethionine (500 nM) to increase the biological activity of antioxidants Glutathione Peroxidase and Thioredoxin Reductase. The cells were then oxidatively stressed with the addition of increasing doses of Antimycin C and Rotenone and the Resazurin end point assay was used to assess cellular activity. RESULTS: There was a significant dose dependent decrease in the cellular activity in BeWo, JEG-3 and Swan-71 when treated for 4 h with increasing concentrations of Antimycin (40-320 µM) and Rotenone (100-800 nM). Prior incubation with Na Selenite and Selenomethionine was able to protect trophoblast cells from oxidative stress at Rotenone concentrations of 200 and 400 nM (P < 0.001) and Antimycin concentrations of 80-240 µM (P < 0.001). DISCUSSION: These data suggest that selenoproteins such as Glutathione Peroxidase and Thioredoxin Reductase have an important role in protecting trophoblast mitochondria from oxidative stress. CONCLUSIONS: This study emphasises the importance of maintaining an adequate selenium supply during pregnancy and especially in pregnancies complicated by conditions such as preeclampsia.

Adipose tissue mass and location affect circulating adiponectin levels.

AIMS/HYPOTHESIS: Plasma levels of adiponectin are inversely associated with body mass. We hypothesised that adipose tissue distribution and body composition influences adiponectin levels. METHODS: We assessed plasma adiponectin concentrations and dual-energy X-ray absorptiometry (DEXA) measurements of body composition among 2,820 participants from the Dallas Heart Study. RESULTS: Among both women and men, adiponectin levels were higher in whites than in either Hispanics or African-Americans (for women: median 9.99 µg/ml [25th,75th percentile 7.11, 13.77] vs 7.56 µg/ml [5.05, 9.98] vs 6.39 µg/ml [4.37, 9.41], respectively, p < 0.0001; for men: 6.43 µg/ml [4.66, 9.19] vs 5.55 µg/ml [3.64, 7.50] vs 5.03 µg/ml [3.39, 7.28], p < 0.0001). In univariate analysis, each individual component of body mass was inversely associated with adiponectin. After multivariate analysis, adiponectin levels were found to be positively associated with lower extremity fat, whether expressed in absolute mass (for women: ß = 0.055, p < 0.0001; for men: ß = 0.061, p < 0.0001), or as a relative proportion (for women: ß = 0.035, p < 0.0001; for men: ß = 0.034, p < 0.0001). This association was consistent across ethnicities. Conversely, adiponectin was negatively correlated with truncal fat, both in absolute (for women: ß = -0.039, p < 0.0001; for men: ß = -0.044, p < 0.0001) and relative terms (for women: ß = -0.027, p < 0.0001; for men ß = -0.033, p < 0.0001). At the extreme of body mass, higher degrees of lower extremity and truncal adiposity were associated with higher levels of adiponectin. CONCLUSIONS/INTERPRETATION: These data suggest that the location of adipose depots differentially influences circulating adiponectin concentrations-a finding observed across ethnicity and sex. Gross measures of body mass alone do not adequately account for adiponectin levels. This supports a role of adiponectin as a mediator of the positive effects of lower extremity adiposity on improvements in insulin sensitivity.

National estimate of HIV seroprevalence among tuberculosis patients in India.

The national estimate for human immunodeficiency virus (HIV) prevalence among tuberculosis (TB) patients in India has previously been estimated indirectly from global data. To derive an improved national estimate from local data, we correlated district-level HIV surveillance data from antenatal clinics and TB diagnostic centres, and applied this correlation to state-level HIV prevalence estimates for the antenatal population. We estimate that among the 1.96 million incident TB cases in 2007, 4.85% (95%CI 4.12-5.73) or 95 240 (95%CI 80 730-112 478) were HIV-infected. With these estimates from local data, the national programme can better plan TB-HIV collaborative activities and monitor efforts to detect HIV infection in this large population.

Non-traditional risk factors predict coronary calcification in chronic kidney disease in a population-based cohort.

The increased burden of cardiovascular disease in chronic kidney disease cannot be explained by traditional risk factors alone. Here, we evaluated the impact of non-traditional factors on the association of chronic kidney disease with coronary artery calcification using logistic regression among 2672 Dallas Heart Study patients of whom 220 had chronic kidney disease. The prevalence of coronary calcification significantly increased across all chronic kidney disease stages and this remained independently associated with coronary calcification after adjusting for traditional factors. The calcium x phosphorus product, homocysteine, and osteoprotegerin each diminished the magnitude of association between kidney disease and coronary calcification. After adjustment for these, the association between kidney disease and coronary calcification was no longer significant with the effects most prominent in the stages 3-5 subgroup. Our study has identified three non-traditional independent predictors of coronary calcification that diminished the association between chronic kidney disease and coronary calcification. These factors may represent novel mechanistic links warranting further investigation.

Increased expression of Mycobacterium tuberculosis 19 kDa lipoprotein obliterates the protective efficacy of BCG by polarizing host immune responses to the Th2 subtype.

Mycobacterium tuberculosis can not only neutralize immune effector functions, but also has the ability to modulate host-signalling cascades involved in the development of these responses. The 19 kDa antigen (Rv3763), a lipoprotein of M. tuberculosis, elicits high levels of interleukin (IL)-12 from macrophages in addition to its powerful immunomodulatory properties, leading to suppression of antigen-presentation signalling cascades. The present study was aimed at analysing the effect of overexpression of this antigen on the immunostimulatory properties of M. bovis Bacille Calmette-Guerin (BCG). We have constructed a recombinant BCG strain (rBCG19N) producing higher levels of the 19 kDa antigen in both the cytoplasmic (approximately eightfold) and extracellular (approximately fivefold) fractions as compared to the wildtype BCG. Immunization of mice with rBCG19N elicited high levels of interferon-gamma (IFN-gamma) and relatively low levels of IL-10 against the purified 19 kDa antigen. However, in response to total BCG sonicate, mice immunized with rBCG19N produced significantly high levels of IL-10 with relatively very low levels of IFN-gamma. This polarization of the host immune responses towards T-helper 2 subtype resulted in complete abrogation of the protective efficacy of BCG, when rBCG19N was used as a live vaccine against M. tuberculosis challenge in guinea pigs.

Effect of lead with vitamin E, C, or Spirulina on malondialdehyde, conjugated dienes and hydroperoxides in rats.

Lead (100 ppm) was given in doubly deionised water for 30 days to one group of rats. The other groups received lead along with exogenous antioxidants like vitamin E (50 IU/kg), vitamin C (800 mg/kg) or Spirulina (1500 mg/kg) in food for a similar period. Levels of lipid peroxidation products such as malondialdehyde, conjugated diene and hydroperoxide were measured in liver, lung and kidney of treated rats. In lead treated animals there was a significant increase in the levels of these lipid peroxidative products. Administration of exogenous antioxidants in the lead treated animals reduced the levels of malondialdehyde, conjugated diene and hydroperoxide. It indicated that vitamin E, vitamin C and Spirulina had significant (P < 0.001) antioxidant activity thereby protecting the animals from lead induced toxicity.

Endoscopic transvaginal approach to the rabbit uterine cervix: improvement in the technique of selective tubal catheterization.

RATIONALE AND OBJECTIVES: The authors compared two methods of selective fallopian tube catheterization in female rabbits. METHODS: Technical success rates and procedure times in two groups of animals were compared. Group 1 consisted of 20 female rabbits catheterized with a fluoroscopic technique. Group 2 consisted of 55 rabbits catheterized with a combination of endoscopic and fluoroscopic guidance. RESULTS: The technique used in group 2 allowed a statistically significant reduction in the time required for cervical catheterization and the total procedural time (P < .01). There was a parallel statistically significant reduction in fluoroscopy time (P < .01). Technical success rates and adverse effects were similar for the two techniques. CONCLUSION: The combined endoscopic-fluoroscopic technique requires a shorter time than the established fluoroscopic technique and should be considered for future selective tubal catheterization experiments in rabbits.

Profile of epidemic emergencies in India during 1991-95.

Epidemic emergencies have shown increasing trend in India and most parts of the country appear to be vulnerable to these emergencies. In this paper we present a profile of epidemic emergencies attended by the National Institute of Communicable Diseases in the last five years, to delineate aspects that will promote better preparedness and management. Water borne and water related disease epidemics constituted more than 70% of the epidemic emergencies in India. Non 01 cholera epidemics constituted one fourth of total cholera epidemics during 1991-95. Most of the hepatitis outbreaks were attributed to Non A Non B. The source of infection in majority of the cholera and jaundice epidemics was contaminated water. Dengue and resistant typhoid fever were among other emergencies reported during last five years. Some of these epidemic were reported to local health authorities as mysterious diseases due to lack of public health laboratory facilities. Encephalitis and encephalitis like epidemics in the form of Liquor poisoning and chronic Heat syndrome encephalopathy were also observed. The re-emerging disease epidemics like plague in Beed, Pneumonic plague in Surat and malaria in Rajasthan were also investigated during 1994. These observations indicate the weakness in the epidemiological and laboratory surveillance besides inadequacy in water management practices and other socio environmental reasons.

New focus of cutaneous leishmaniasis in India : Preliminary report.

An epidemiological investigation was carried out in hilly areas of western ghats of Kerala state, India during 1993, to verify a focus of cutaneous leishmaniasis. Out of 406 surveyed population, 11 cases were detected, among which two were positive for LD bodies in slit skin scraping examination. The disease was indigenously transmitted. Further investigation is advocated to identify leishmania species, vector and the reservoir.

A comparative study on the optimum time and method of collection of Phlebotomus argentipes and other sandflies. (Diptera: Psychodidae).

A uniform method of collection is imperative for generating comparable entomological data in connection with studies on efficacy of vector control measures against sandflies. Two commonly employed methods for sandfly collections i.e. hand collection by aspirator and sticky paper traps were compared under similar ecological conditions to determine the optimum time and method for generating data on relevant indices. Only two P. argentipes male specimens were collected at dusk time from 12 cattle sheds and 40 human dwelling by aspirator method. By sticky traps placed in the same resting shelters, 243 P. argentipes and 58 specimens of 5 other species were collected. However, the collection by sticky traps comprised only males and unfed females. In the morning collection by aspirators 268 sandflies of 8 species in all stages of gonotropic cycle were collected. It is concluded that morning collections by aspirator method can provide objective assessment of control measures. Sticky traps may be useful as additional method for confirming presence of P. argentipes in sprayed areas.