Prevention and control of neglected tropical diseases: overview of randomized trials,systematic reviews and meta-analyses

Objective

To analyse evidence from randomized controlled trials (RCTs) on the prevention and control of neglected tropical diseases (NTDs) and to identify areas where evidence is lacking.

Methods

The Cochrane Central Register of Controlled Trials and PubMed were searched for RCTs and the Cochrane Database of Systematic Reviews and PubMed were searched for meta-analyses and systematic reviews, both from inception to 31 December 2012.

Findings

Overall, 258 RCTs were found on American trypanosomiasis, Buruli ulcer, dengue, geohelminth infection, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis or trachoma. No RCTs were found on cysticercosis, dracunculiasis, echinococcosis, foodborne trematodes, or human African trypanosomiasis. The most studied diseases were geohelminth infection (51 RCTs) and leishmaniasis (46 RCTs). Vaccines, chemoprophylaxis and interventions targeting insect vectors were evaluated in 113, 99 and 39 RCTs, respectively. Few addressed how best to deliver preventive chemotherapy, such as the choice of dosing interval (10) or target population (4), the population coverage needed to reduce transmission (2) or the method of drug distribution (1). Thirty-one publications containing 32 systematic reviews (16 with and 16 without meta-analyses) were found on American trypanosomiasis, dengue, geohelminths, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis or trachoma. Together, they included only 79 of the 258 published RCTs (30.6%). Of 36 interventions assessed, 8 were judged effective in more than one review.

Conclusion

Few RCTs on the prevention or control of the principal NTDs were found. Trials on how best to deliver preventive chemotherapy were particularly rare.     

The Patient Health Questionnaire-9 for detection of major depressive disorder in primary care: consequences of current thresholds in a crosssectional study

Background

The Charlson comorbidity index is widely used in ICD-9 administrative data, however, there is no translation for Read/OXMIS coded data despite increasing use of the General Practice Research Database (GPRD). Our main objective was to translate the Charlson index for use with Read/OXMIS coded data such as the GPRD and test its association with mortality. We also aimed to provide a version of the comorbidity index for other researchers using similar datasets.

Methods

Two clinicians translated the Charlson index into Read/OXMIS codes. We tested the association between comorbidity score and increased mortality in 146 441 patients from the GPRD using proportional hazards models.

Results

This Read/OXMIS translation of the Charlson index contains 3156 codes. Our validation showed a strong positive association between Charlson score and age. Cox proportional models show a positive increasing association with mortality and Charlson score. The discrimination of the logistic regression model for mortality was good (AUC = 0.853).

Conclusion

We have translated a commonly used comorbidity index into Read/OXMIS for use in UK primary care databases. The translated index showed a good discrimination in our study population. This is the first study to develop a co-morbidity index for use with the Read/OXMIS coding system and the GPRD. A copy of the co-morbidity index is provided for other researchers using similar databases.     

Improvement in Obesity-associated Medical Conditions following Vertical Banded Gastroplasty and Gastrointestinal Bypass

Thirty-nine patients undergoing either Silastictrade mark ring vertical banded gastroplasty (SRVG, n = 23) or Roux-en-Y gastrointestinal bypass (RGB, n = 16) over a 1-year period were analyzed retrospectively. Weight loss averaged 40 kg (89 lb). Clinical diabetes mellitus was markedly improved in seven out of nine patients (p = 0.023). Shortness of breath resolved in all 26 patients who had this condition preoperatively (p < 0.001). Orthopedic problems, high blood pressure, and self-assessment of general health and quality of life were also dramatically improved. We conclude that bariatric surgery serves as an effective method to alleviate a multitude of conditions associated with morbid obesity.     

Physical and mental development in 4-6-year-old triplets

A total of 21 families with complete sets of triplets, born within 200 km of Stockholm, were invited to participate in a follow-up study with the aim of assessing the physical and mental development of their triplets at 4-6 years of age. Four families declined to participate in the study and thus the study group consisted of 17 sets of triplets who were born at 33-36 gestational weeks from 1986 to 1989. Mean birth weight was 2104g (range 1310-2670g) for the boys and 1882g (range 1290-2590g) for the girls. At birth, none of the 51 triplets showed any malformations. No asphyxia or other major complications were noted to have occurred at delivery. The children were examined in their homes with a neurological examination and the Griffiths mental development scales (GMDS). No major physical disabilities were found. In a group of triplets born small for dates, the total GMDS score and most of the subscale scores were significantly lower than for their siblings. In contrast to what has been found in singletons and twins, the differences in mental development between triplet boys and girls were not significant. On the whole, physical and mental development did not differ from what has been found in twins and singletons of the same age and with the same birth weight.     

Plasma cytokine levels in necrotizing enterocolitis

Plasma concentrations of tumour necrosis factor (TNF) and interleukin-6 (IL-6) were measured by ELISA in samples taken from 24 infants with necrotizing enterocolitis (NEC) between 0 and 306 h from diagnosis. TNF was detected (>10pg/ml) in 71% samples with a mean of 48pg/ml (95% CI 42 to 55 pg/ml) and did not vary with either time from diagnosis or severity of disease. IL-6 was raised during the first 48 h with a significant difference between stage II (mean 127 pg/ml, 95% CI 10 to 329 pg/ml) and stage HI (mean 3127 pg/ml, 95% CI 1809 to 4445 pg/ml, p = 0.001). Postoperative plasma IL-6 concentration fell to similar levels seen in stage II (mean 150 pg/ml, 95% CI 37 to 283 pg/ ml, p = 0.79). We conclude that plasma concentration of IL-6 rather than TNF reflects the clinical severity of necrotizing enterocolitis and that the relative level of these cytokines has important implications for the use of anti-cytokine therapy in NEC.     

Necrotizing enterocolitis—multisystem organ failure of the newborn?

Evidence of failure of organ system other than the gastrointestinal tract was reviewed in a series of 46 infants treated for necrotizing enterocolitis (NEC) at a regional combined medical and surgical neonatal unit. Respiratory failure was identified in 42 infants (91%), renal failure in 39 (85%), cardiovascular failure in 15 (33%) and hepatic failure in 7 (15%). The number of systems involved correlated with both severity of disease and outcome. Onset of failure in the above systems was closely related to the diagnosis of NEC and 29 cases predated the clinical onset. We conclude that NEC is part of a syndrome of multisystem failure and that this has important implications for the treatment of NEC.