FHIRing up OpenMRS: Architecture, Implementation and Real-World Use-Cases in Global Health.

HL7 FHIR was created almost a decade ago and is seeing increasingly wide use in high income settings. Although some initial work was carried out in low and middle income (LMIC) settings there has been little impact until recently. The need for reliable and easy to implement interoperability between health information systems in LMICs is growing with large scale deployments of EHRs, national reporting systems and mHealth applications. The OpenMRS open source EHR has been deployed in more than 44 LMIC with increasing needs for interoperability with other HIS. We describe here the development and deployment of a new FHIR module supporting the latest standards and its use in interoperability with laboratory systems, mHealth applications, pharmacy dispensing system and as a tool for supporting advanced user interface designs. We also show how it facilitates date science projects and deployment of machine leaning based CDSS and precision medicine in LMICs.

Public health genomics: the interface with public health intelligence and the role of public health observatories.

BACKGROUND: Public health genomics is a new field that brings the findings of research in genetic and molecular technologies together with public health. The purpose of this paper is to examine the interface between this new emerging field and that of public health intelligence. We describe the possible areas of integration between genomics and public health, suggesting a future potential role for the Public Health Observatories. METHODS: A small group comprising of a public health geneticist and representatives from Public Health Observatories met and discussed the ways in which the public health information and intelligence community might contribute to the developing agenda of public health genomics. RESULTS: The results of the deliberations are presented in this paper, and a combination of short, medium and longer term possibilities are described. Also, necessary changes and additions to routinely collected data are proposed. CONCLUSIONS: The emerging field of public health genomics has implications for the collection, management and analysis of routine data. The benefits of this will accrue over time, but changes need to be made now in order to make the best use of these developments. A possible supporting action plan for the development of public health genomics within Public Health Observatories is proposed.

The future of health intelligence: challenges and opportunities.

Over the last 10 years, the discipline of health intelligence has come into being. This combines analysis, informatics, public health methodology, skills and interpretation. We have come a long way but there remains a long way to go. In particular, a number of challenges for the next 10 years are articulated, namely: the right information at the right time; real-time data; barriers to information access; and knowledge transfer.

Current differences in referral patterns for pulmonary endarterectomy in the UK.

Pulmonary endarterectomy (PEA) surgery is the treatment of choice in surgically accessible chronic thromboembolic pulmonary hypertension and is potentially curative. The UK is served by seven specialist pulmonary hypertension centres and, consequently, there are regions which do not have a specialist unit. Since 2000, Papworth Hospital (Papworth Everard, UK) has been the sole PEA provider for the UK, offering the opportunity to study the national incidence of operable disease and give potential insight into factors that might affect geographical distribution within the UK. All 262 UK residents who underwent PEA surgery between April 2000 and May 2006 were included in the present study. The age-adjusted cumulative referral rates were compared between regions to test for uniformity. Overall, observed rates differed significantly from expected, with evidence of significant nonuniformity across the UK. The highest rates were observed in proximity to the nationally designated specialist centres and in particular in East Anglia and the West Midlands, nearest Papworth. These two regions differed by >2 x SD from the national mean rate. The present study demonstrates wide geographical variation in the number of patients referred for pulmonary endarterectomy surgery. This suggests that there may be patients who are not presently being offered this potentially curative option.

Adaptive evolution of metabolic pathways in Drosophila.

The adaptive significance of enzyme variation has been of central interest in population genetics. Yet, how natural selection operates on enzymes in the larger context of biochemical pathways has not been broadly explored. A basic expectation is that natural selection on metabolic phenotypes will target enzymes that control metabolic flux, but how adaptive variation is distributed among enzymes in metabolic networks is poorly understood. Here, we use population genetic methods to identify enzymes responding to adaptive selection in the pathways of central metabolism in Drosophila melanogaster and Drosophila simulans. We report polymorphism and divergence data for 17 genes that encode enzymes of 5 metabolic pathways that converge at glucose-6-phosphate (G6P). Deviations from neutral expectations were observed at five loci. Of the 10 genes that encode the enzymes of glycolysis, only aldolase (Ald) deviated from neutrality. The other 4 genes that were inconsistent with neutral evolution (glucose-6-phosphate dehydrogenase [G6pd]), phosphoglucomutase [Pgm], trehalose-6-phosphate synthetase [Tps1], and glucose-6phosphatase [G6pase] encode G6P branch point enzymes that catalyze reactions at the entry point to the pentose-phosphate, glycogenic, trehalose synthesis, and gluconeogenic pathways. We reconcile these results with population genetics theory and existing arguments on metabolic regulation and propose that the incidence of adaptive selection in this system is related to the distribution of flux control. The data suggest that adaptive evolution of G6P branch point enzymes may have special significance in metabolic adaptation.

Sick individuals and sick populations: 20 years later.

Twenty years after Geoffrey Rose published his classic paper, the central messages remain highly relevant to modern public health policy and practice. The individual and population approaches are fundamentally different but both are needed. Recent examples of powerful population approaches prove Rose's point that norms can change benefiting the most deprived. Individual approaches have also succeeded but their protection of the most deprived communities is limited. Consumerism in health and over-reliance on individual approaches risk widening health inequalities.

Morphologic, Pathologic, and Genetic Investigations of Bolbophorus Species Affecting Cultured Channel Catfish in the Mississippi Delta.

Trematodes belonging to the genus Bolbophorus have recently been reported as the cause of substantial morbidity and mortality in cultured channel catfish Ictalurus punctatus in Mississippi and Louisiana. Previous investigators identified only a single species, B. confusus. In this investigation, genetic techniques were used to identify all stages of the parasite in all of its hosts. The 18s rRNA genes from specimens collected in Mississippi were sequenced and compared; this analysis revealed that there are two distinct species, B. damnificus (previously identified as B. confusus) and another, undescribed species. (Phylogenetic analysis indicated that a third species, B. levantinus, is also closely related to the Mississippi species.) Species-specific polymerase chain reaction assays capable of identifying and differentiating between these two parasites were developed. Both species were found to infect the first intermediate host (the ram's horn snail Planorbella trivolvis) in commercial channel catfish ponds, but only B. damnificus was recovered from the fish themselves. The new, unidentified Bolbophorus species was determined to be highly pathogenic to a number of fish species. The contribution of B. damnificus to disease in cultured channel catfish remains undetermined. Future investigations of these parasites must now take into account the presence of two distinct species.

Unusual structure of ribosomal DNA in the copepod Tigriopus californicus: intergenic spacer sequences lack internal subrepeats.

Eukaryotic nuclear ribosomal DNA (rDNA) is typically arranged as a series of tandem repeats coding for 18S, 5.8S, and 28S ribosomal RNAs. Transcription of rDNA repeats is initiated in the intergenic spacer (IGS) region upstream of the 18S gene. The IGS region itself typically consists of a set of subrepeats that function as transcriptional enhancers. Two important evolutionary forces have been proposed to act on the IGS region: first, selection may favor changes in the number of subrepeats that adaptively adjust rates of rDNA transcription, and second, coevolution of IGS sequence with RNA polymerase I transcription factors may lead to species specificity of the rDNA transcription machinery. To investigate the potential role of these forces on population differentiation and hybrid breakdown in the intertidal copepod Tigriopus californicus, we have characterized the rDNA of five T. californicus populations from the Pacific Coast of North America and one sample of T. brevicornicus from Scotland. Major findings are as follows: (1) the structural genes for 18S and 28S are highly conserved across T. californicus populations, in contrast to other nuclear and mitochondrial DNA (mtDNA) genes previously studied in these populations. (2) There is extensive differentiation among populations in the IGS region; in the extreme, no homology is observed across the IGS sequences (>2 kb) from the two Tigriopus species. (3) None of the Tigriopus IGS sequences have the subrepeat structure common to other eukaryotic IGS regions. (4) Segregation of rDNA in laboratory crosses indicates that rDNA is located on at least two separate chromosomes in T. californicus. These data suggest that although IGS length polymorphism does not appear to play the adaptive role hypothesized in some other eukaryotic systems, sequence divergence in the rDNA promoter region within the IGS could lead to population specificity of transcription in hybrids.

Use of rDNA polymorphism for identification of Heterophyidae infecting freshwater fishes.

Infections by trematodes are among the most common fish-borne zoonoses. Metacercariae of the Family Heterophyidae in marine and freshwater fishes are nonfastidious in their choice of definitive hosts, and therefore, cause infections in human and domestic animals. In the present study, species-specific polymerase chain reaction (PCR) assays were developed for identifying and differentiating the various species examined. Sequencing and aligning the 18S (SSU) rDNA revealed interspecific variation for which species-specific DNA oligonucleotides were designed and used for the identification of 6 heterophyid species recovered from piscivorous birds. The oligonucleotides were further used to evaluate the various stages (cercariae recovered from snails, metacercariae recovered from fish and adult trematodes) of the digeneans. By applying this method we elucidated for the first time the life cycle of Pygidiopsis genata. The phylogenetic interrelationship among the newly sequenced species of Heterophyidae is outlined.

Clinostomum complanatum and Clinostomum marginatum (Rudolphi, 1819) (Digenea: Clinostomidae) are separate species based on differences in ribosomal DNA.

Infections by metacercariae of Clinostomum (Leidy, 1856) species adversely affect aquacultured fish and are potentially transmissible to humans. Molecular methodologies are efficient tools, which enable diagnosis of all life-history stages of trematodes in their diverse hosts. The small subunit of ribosomal DNA genes of adults of the Old World Clinostomum complanatum (Rudolphi, 1819) and the New World Clinostomum marginatum (Rudolphi, 1819), obtained from a little egret Egretta garzetta (Linnaeus, 1766) and the great blue heron Ardea herodias (Linnaeus, 1758), respectively, were amplified, sequenced, and aligned. The resulting alignment was used to develop a genetic assay to differentiate between these species.

Environmental benefits and economic costs of manure incorporation on dairy waste application fields.

Model simulations performed representing dairies in a 93000 ha watershed in north central Texas suggest that manure incorporation results in reduced phosphorus (P) losses at relatively small to moderate cost to producers. Simulated manure incorporation with a tandem disk on fields double-cropped with sorghum/winter wheat resulted in up to 33, 45, and 37% reductions in per hectare sediment-bound, soluble, and total P losses in edge-of-field runoff, relative to simulated surface manure applications. The effects of incorporation were evaluated at three different manure application rates. On aggregate across all three manure application rates, significant declines in P losses were obtained with incorporation except for sediment-bound P losses under the N-based manure application rate scenario. We found that the practice of incorporating manure shortly after it has been broadcast on the soil surface could help reduce P losses in such situations where P-based rates alone prove inadequate. The cost the producer incurs when manure is incorporated is on average about 1% of net returns when manure is applied at the N rate and 2-3% when it is applied at alternative P-based rates. In practice the costs could be lower because producers may substitute the manure incorporation operation for a tandem disk operation performed prior to manure application. As more and more dairy producers switch to the use of sorghum and corn silage in dairy rations and consequent on-farm production of these forages, the practice of manure incorporation may help to reduce phosphorus losses resulting from dairy manure applications to fields with these forage crops.

Management of drug-resistant cyathostominosis on a breeding farm in central North Carolina.

REASONS FOR PERFORMING STUDY: Possible anthelmintic resistance on a breeding farm where a rapid rotation anthelmintic programme had been implemented for 9 years was investigated. Cyathostomins resistant to fenbendazole and pyrantel were documented by faecal worm egg count reduction test (FWECRT). OBJECTIVES: To 1) manage small strongyle transmission in a herd of horses in which resistance to both pyrantel pamoate and fenbendazole was identified and thereby reduce the risk of clinical disease in the individual animal, 2) monitor the change in resistance patterns over time and 3) monitor the efficacy of ivermectin over the study period. METHODS: Targeted ivermectin treatment of horses on the farm was instituted for mature horses with faecal worm egg counts (FWEC) > 200 eggs/g (epg) and for horses < age 2 years with FWEC > 100 epg. RESULTS: Over a 30 month period, targeted ivermectin treatment achieved acceptable control in mares, as judged by FWEC, and improved control of patent cyathostome infection in consecutive foal crops. Egg reappearance time (ERT) after treatment with ivermectin was < 8 weeks in mares and foals more frequently in the second year of the study than in the first year. Numbers of anthelmintic treatments were reduced by 77.6 and 533% in the mare and foal group, respectively. CONCLUSIONS: Targeted ivermectin treatment may be an economically viable method of managing multiple drug resistant cyathostominosis. POTENTIAL RELEVANCE: Use of ivermectin should be monitored closely for development of resistance.

Warm ischemia time does not correlate with recipient graft function in laparoscopic donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) has been shown to be a safe and effective option for renal procurement. Studies comparing open nephrectomy and hand-assisted laparoscopy have emphasized decreased warm ischemia time when compared with "pure" laparoscopic retrieval. However, no data exist that define exactly what constitutes a prolonged warm ischemia time in terms of recipient graft function. The aim of this study was to use a large, single-institution experience with LDN to determine if warm ischemia time correlates with recipient graft function as measured by serum creatinine levels. METHODS: A total of 640 LDNs were performed from March 1996 to August 2001. Warm ischemia times were prospectively collected and were defined as the time from renal artery occlusion to immersion in iced saline. Serial recipient creatinine levels were measured at 1 week and 1, 3, 6, and 12 months (when possible) from the transplant. Data were analyzed using Pearson correlation analysis at a confidence interval of 95%. RESULTS: Mean warm ischemia time was 151 s with a standard error of 3.4 s and ranged from 35 to 720 s. Recipient creatinine mean at 1 week was 1.94 mg/dl with a standard error of 0.06 mg/dl and ranged from 0.5 to 10.5 mg/dl. Recipient creatinine mean at 1 month was 1.68 mg/dl with a standard error of 0.06 mg/dl and ranged from 0.6 to 8.5 mg/dl. Recipient creatinine mean at 3 months was 1.60 mg/dl with a standard error of 0.04 mg/dl and ranged from 0.6 to 8.8 mg/dl. Recipient creatinine mean at 6 months was 1.63 mg/dl with a standard error of 0.06 mg/dl and ranged from 0.7 to 13.5 mg/dl. Recipient creatinine mean at 12 months was 1.70 mg/dl with a standard error of 0.07 mg/dl and ranged from 0.5 to 14.5 mg/dl. No correlation was found between warm ischemia time and recipient creatinine levels at 1 week (p = 0.4737), 1 month (p = 0.9180), 3 months (p = 0.6227), 6 months (p = 0.8349), or 12 months (p = 0.2835). CONCLUSIONS: Warm ischemia time does not correlate with recipient graft function in LDN within the range of times studied. Shorter warm ischemia time associated with open donor nephrectomy and hand-assisted LDN does not necessarily offer a measurable advantage in recipient graft function. During extraction of the kidney, expediency to minimize warm ischemia time should not supersede controlled and safe maneuvers in renal vessel division and extraction of the kidney.

Small bowel obstruction after laparoscopic donor nephrectomy.

BACKGROUND: Laparoscopic live donor nephrectomy has become the procedure of choice for kidney procurement at many centers worldwide. A decrease in postoperative pain and length of stay, a faster return to work, and no difference in morbidity and mortality compared to open nephrectomy have all been reported. However, few data exist regarding the complication of postoperative internal hernia and small bowel obstruction, which is unique to a laparoscopic/transperitoneal approach. METHODS: We present three case reports of patients who developed small bowel obstruction from an internal hernia and mesenteric defect after laparoscopic donor nephrectomy. RESULTS: A total of 635 patients underwent laparoscopic donor nephrectomy between March 1996 and August 2001 at our institution. Small bowel obstruction developed in three patients (0.47%) within 1 week postoperatively. Each case involved an internal hernia through a left colon mesenteric defect at the site of nephrectomy. Reoperation was necessary in each case and was associated with a prolonged hospital stay (mean, 22.3 days; range, 6-37). Two patients were managed with laparotomy; one patient underwent a laparoscopically assisted exploration. One patient required an additional open exploration for intraabdominal sepsis and cholecystectomy. CONCLUSIONS: Small bowel obstruction from internal hernia following laparoscopic donor nephrectomy is a rare event, but it can lead to significant morbidity in an otherwise healthy patient. These patients may be at higher risk for bowel obstruction given the soft tissue defect remaining after nephrectomy. Vigilance is required when mobilizing the colon to ensure that mesenteric defects are recognized and repaired.

Detection of Latent Sphaeropsis sapinea Infections in Austrian Pine Tissues Using Nested-Polymerase Chain Reaction.

ABSTRACT Sphaeropsis sapinea is the causal agent of Sphaeropsis tip blight disease of pines. Past surveys of diseased and symptomless Austrian and Scots pines revealed that latent infections of symptomless shoots by S. sapinea are common. The role of these latent infections in the tip blight disease is unknown. A sampling technique and nested-polymerase chain reaction (PCR) protocol were developed to detect latent S. sapinea in symptomless pine shoots. The sampling protocol was designed to be minimally destructive to the shoot so it could be preserved for further studies. The primers that were developed were specific for S. sapinea DNA and did not amplify DNA from any of 13 other endophytic fungal species that were commonly isolated from symptomless pine shoots. The PCR primers also amplified DNA of Botryosphaeria obtusa, which was, however, rare in symptomless Austrian pine tissues. The protocol detected as little as 0.93 pg of S. sapinea DNA in terminal bud samples and 10.4 pg of DNA in bark samples. Correlation (chi-square) analyses indicated that the nested-PCR protocol detected latent S. sapinea infections in both bud and bark samples with an efficiency that was statistically equivalent to isolating the fungus from the tissue. The nested-PCR protocol will make it possible to more quickly identify latent S. sapinea infections in symptomless pine shoots and should be useful in future studies of the latency phenomenon.

Genetic and morphologic differentiation of Bolbophorus confusus and B. levantinus (Digenea: Diplostomatidae), based on rDNA SSU polymorphism and SEM.

Metacercariae of Bolbophorus species are serious pathogens of farmed fish. Molecular diagnostic tools, capable of identifying and differentiating these parasites, may assist in the development of rationale control strategies. The rDNA 18S (small sub-unit: SSU) genes of adult B. confusus and B. levantinus obtained from a pelican, Pelecanus onocrotalus, and a night heron, Nycticorax nycticorax, respectively, were amplified, sequenced, and aligned. Based on this alignment, we developed a genetic differentiation assay between B. confusus and B. levantinus. These 2 species were compared genetically with the North American species B. damnificus and Bolbophorus sp. ('Type 2'). The relationship between species is outlined and discussed. In addition to the molecular study, specimens of B. confusus and B. levantinus were compared morphologically, using scanning electron microscopy. Morphologic analysis revealed interspecific differences in details of the holdfast organ and the position of the acetabulum.

Impact of upper endoscopic survey during percutaneous endoscopic gastrostomy tube placement.

BACKGROUND: No consensus exists concerning the utility of a full diagnostic upper endoscopy during percutaneous endoscopic gastrostomy (PEG) tube placement. We evaluate the effect of a complete survey on identifying and treating unsuspected gastrointestinal pathology. METHODS: During a 10-year period (1990-2000), 1,706 patients underwent attempted PEG tube placement by five different surgical endoscopists at one institution. A complete survey of the esophagus, stomach, and proximal duodenum was attempted in all cases. Endoscopic findings and recommendations were recorded in a computerized log and patient charts. Pathology results were obtained from a computerized pathology database and patient charts. RESULTS: Placement of a PEG tube was successful in 97%, and a full survey was possible in 99% of the cases. Pathologic findings were found in 38% of the surveyed patients (esophagus, 7%; stomach, 24%; duodenum, 7%). One group with gastrointestinal polyps or gastric ulcers (5.7%) was identified as possible candidates for endoscopic intervention. In 30% of this group (1.8% of the total) a biopsy was performed, or bleeding was treated endoscopically. In a second group pathology was identified in the duodenum (6.4%) that would not have been recognized without a full survey. These duodenal findings resulted in a recommendation for treatment change in 38% of this group (2.4% of the total). CONCLUSIONS: Upper endoscopic survey before PEG tube placement showed a significant amount of unsuspected gastrointestinal pathology. Findings requiring biopsy, immediate treatment, or a change in medical treatment occurred in 4.2% of the cases, and these findings did not prevent PEG tube placement in any patient.

Development of an ultrasonically activated trocar system.

BACKGROUND: Although rare, visceral and vascular injuries related to the insertion of conventional laparoscopic trocars may have disastrous consequences. Most of these injuries are due to the high puncture force applied to the trocar. We present the results of an animal laboratory evaluation of a newly developed ultrasonically activated trocar. METHODS: A total of 40 punctures were made in four pigs with an average weight of 53 kg. An 11-mmHg pneumoperitoneum was created through a Veress needle. A 10-mm diameter trocar was inserted in the midline for a laparoscope. A series of five trocars were then inserted on each lateral wall under laparoscopic control. Twenty punctures were made with a conventional reusable 11-mm trocar (CT) whose tip was sharp and conical. Twenty punctures were made with an 11-mm ultrasonically activated trocar (UT), whose fequency was 23.5 KHz and amplitude 150 mm. The cutaneous incision was made large enough so that the skin did not interfere with the trocar insertion. The force applied to the trocar was measured with a push-pull gauge connected to a computer. The following data were recorded: maximal force applied to the trocar to obtain insertion of the tip through the abdominal wall, maximum abdominal pressure increase during trocar insertion, and time for abdominal penetration. RESULTS: The average time needed for trocar penetration was 12.8 s with CT and 4.5 s with UT (p < 0.001). The average maximal force was 6.8 kgF with CT and 0.4 kgF with UT (p < 0.001). The average abdominal pressure increase was 7.6 mmHg with CT and 0.8 mmHg with UT (p < 0.001). At 30 days, no necrosis was found. Pathological findings were similar in both groups. CONCLUSION: Ultrasonically activated trocars required less time and much less force to be inserted. This may be a breakthrough in the safety of trocar insertion.

Morphologic, Pathologic, and Genetic Investigations of Bolbophorus Species Affecting Cultured Channel Catfish in the Mississippi Delta.

Trematodes belonging to the genus Bolbophorus have recently been reported as the cause of substantial morbidity and mortality in cultured channel catfish Ictalurus punctatus in Mississippi and Louisiana. Previous investigators identified only a single species, B. confusus. In this investigation, genetic techniques were used to identify all stages of the parasite in all of its hosts. The 18s rRNA genes from specimens collected in Mississippi were sequenced and compared; this analysis revealed that there are two distinct species, B. damnificus (previously identified as B. confusus) and another, undescribed species. (Phylogenetic analysis indicated that a third species, B. levantinus, is also closely related to the Mississippi species.) Species-specific polymerase chain reaction assays capable of identifying and differentiating between these two parasites were developed. Both species were found to infect the first intermediate host (the ram's horn snail Planorbella trivolvis) in commercial channel catfish ponds, but only B. damnificus was recovered from the fish themselves. The new, unidentified Bolbophorus species was determined to be highly pathogenic to a number of fish species. The contribution of B. damnificus to disease in cultured channel catfish remains undetermined. Future investigations of these parasites must now take into account the presence of two distinct species.