Host population persistence in the face of introduced vector-borne diseases: Hawaii amakihi and avian malaria

The past quarter century has seen an unprecedented increase in the number of new and emerging infectious diseases throughout the world, with serious implications for human and wildlife populations. We examined host persistence in the face of introduced vector-borne diseases in Hawaii, where introduced avian malaria and introduced vectors have had a negative impact on most populations of Hawaiian forest birds for nearly a century. We studied birds, parasites, and vectors in nine study areas from 0 to 1,800 m on Mauna Loa Volcano, Hawaii from January to October, 2002. Contrary to predictions of prior work, we found that Hawaii amakihi (Hemignathus virens), a native species susceptible to malaria, comprised from 24.5% to 51.9% of the avian community at three low-elevation forests (55-270 m). Amakihi were more abundant at low elevations than at disease-free high elevations, and were resident and breeding there. Infection rates were 24-40% by microscopy and 55-83% by serology, with most infected individuals experiencing low-intensity, chronic infections. Mosquito trapping and diagnostics provided strong evidence for year-round local transmission. Moreover, we present evidence that Hawaii amakihi have increased in low elevation habitats on southeastern Hawaii Island over the past decade. The recent emergent phenomenon of recovering amakihi populations at low elevations, despite extremely high prevalence of avian malaria, suggests that ecological or evolutionary processes acting on hosts or parasites have allowed this species to recolonize low-elevation habitats. A better understanding of the mechanisms allowing coexistence of hosts and parasites may ultimately lead to tools for mitigating disease impacts on wildlife and human populations.     

Cerebrospinal fluid shunt placement for pseudotumor cerebri-associated intractable headache: predictors of treatment response and an analysis of long-term outcomes

OBJECT: Cerebrospinal fluid (CSF) shunts effectively reverse symptoms of pseudotumor cerebri postoperatively, but long-term outcome has not been investigated. Lumboperitoneal (LP) shunts are the mainstay of CSF shunts for pseudotumor cerebri; however, image-guided stereotaxy and neuroendoscopy now allow effective placement of a ventricular catheter without causing ventriculomegaly in these cases. To date it remains unknown if CSF shunts provide long-term relief from pseudotumor cerebri and whether a ventricular shunt is better than an LP shunt. The authors investigated these possibilities. METHODS: The authors reviewed the records of all shunt placement procedures that were performed for intractable headache due to pseudotumor cerebri at one institution between 1973 and 2003. Using proportional hazards regression analysis, predictors of treatment failure (continued headache despite a properly functioning shunt) were assessed, and shunt revision and complication rates were compared between LP and ventricular (ventriculoperitoneal [VP] or ventriculoatrial [VAT]) shunts. Forty-two patients underwent 115 shunt placement procedures: 79 in which an LP shunt was used and 36 in which a VP or VAT shunt was used. Forty patients (95%) experienced a significant improvement in their headaches immediately after the shunt was inserted. Severe headache recurred despite a properly functioning shunt in eight (19%) and 20 (48%) patients by 12 and 36 months, respectively, after the initial shunt placement surgery. Seventeen patients without papilledema and 19 patients in whom preoperative symptoms had occurred for longer than 2 years experienced recurrent headache, making patients with papilledema or long-term symptoms fivefold (relative risk [RR] 5.2, 95% confidence interval [CI] 1.5-17.8; p < 0.01) or 2.5-fold (RR 2.51, 95% CI 1.01-9.39; p = 0.05) more likely to experience headache recurrence, respectively. In contrast to VP or VAT shunts, LP shunts were associated with a 2.5-fold increased risk of shunt revision (RR 2.5, 95% CI 1.5-4.3; p < 0.001) due to a threefold increased risk of shunt obstruction (RR 3, 95% CI 1.5-5.7; p < 0.005), but there were similar risks between the two types of shunts for overdrainage (RR 2.3, 95% CI 0.8-7.9; p = 0.22), distal catheter migration (RR 2.1, 95% CI 0.3-19.3; p = 0.55), and shunt infection (RR 1.3, 95% CI 0.3-13.2; p = 0.75). CONCLUSIONS: Based on their 30-year experience in the treatment of these patients, the authors found that CSF shunts were extremely effective in the acute treatment of pseudotumor cerebri-associated intractable headache, providing long-term relief in the majority of patients. Lack of papilledema and long-standing symptoms were risk factors for treatment failure. The use of ventricular shunts for pseudotumor cerebri was associated with a lower risk of shunt obstruction and revision than the use of LP shunts. Using ventricular shunts in patients with papilledema or symptoms lasting less than 2 years should be considered for those with pseudotumor cerebri-associated intractable headache.     

Quality of patient-reported outcome data captured using paper and interactive voice response diaries in an allergic rhinitis study: is electronic data capture really better?

BACKGROUND: Accuracy and reliability of diary data collected in allergic rhinitis trials depends on how and when the information is recorded by the subjects. OBJECTIVE: To compare diary data collected by using paper (optical mark readable) and electronic [telephone, interactive voice response system (IVRS)] tools. METHODS: There was a randomized, 3-week, 3-way, crossover trial, in 87 adults with allergic rhinitis recording diary data at home. Outcome measures were (1) comparison of symptom data during weeks when both or only 1 instrument was used; (2) missing data: and (3) ease of use and participant preference. RESULTS: More than 40,000 symptom data elements were recorded by 72 protocol-correct subjects. Symptoms recorded during the week that both instruments were used and when the 2 instruments were used alone were indistinguishable. Overall, 0.45% of paper and 4.12% of IVRS symptom data were missing. Of 10,080 paired data collected on paper and IVRS diaries during the week in which subjects used both, 94.44% were identical. Using IVRS, 63.2% of protocol-correct data were entered within the designated time and 87.6% within 1 half-day of the time specified; 85% of subjects preferred the paper instrument, 4% preferred IVRS, and 11% had no preference. CONCLUSIONS: A paper-based instrument can capture data indistinguishable from data captured from an electronic product. Processes to collect diary data should be evaluated for each study rather than simply to use the "latest" technology. Another interpretation is that frequency of recording diary data does not have a significant impact on outcomes.     

Does heparin prophylaxis prevent exacerbations of hereditary angioedema?

BACKGROUND: Hereditary angioedema (HAE) is a rare disorder characterized by episodes of angioedema of the skin, mucous membranes, and gastrointestinal tract resulting from a defect in the gene that produces C1 esterase inhibitor. Although in vitro laboratory data and past reports suggested that heparin might be efficacious in preventing HAE attacks, no controlled study has been reported to examine heparin's efficacy in this regard. OBJECTIVES: We sought to determine the safety and efficacy of inhaled and subcutaneous heparin versus that of placebo in the prevention of HAE attacks. METHODS: We performed a double-blind, double-dummy, saline placebo-controlled, randomized, 3-way crossover study with 11 visits. RESULTS: The study was designed to enroll 24 patients. Twenty-two patients were randomized and received the study drug. Patients did not have a significant decrease in average flare intensity after they received injected or inhaled heparin compared with that seen after placebo, the primary endpoint. However, when patients received injected heparin, they had a statistically significant decrease in average flare intensity compared with that seen with inhaled heparin after a normalizing transformation was applied. When the means are back transformed, this translates into median flare intensities of 9.2, 8.0, and 5.1 in the patients treated with inhaled heparin, placebo, and injected heparin, respectively. There were no significant differences when individual symptoms were examined, when total numbers of flares over a 6-week observation period were examined, or when global evaluations by the patients and investigators were evaluated. Adverse event severity was fairly uniform across treatments, with the majority of events classified as moderate and the remainder split between mild and severe. Injected heparin treatment was associated with higher rates of relatedness than other treatments, which was partially explained by 17 adverse events specifically related to the injection process itself (tenderness, bruising, redness, pain, and itching at the injection site). The injection treatment was also associated with a larger overall number of reported adverse events (70 vs 48 in the placebo treatment). Tenderness and bruising at the injection site were entirely confined to the injected heparin treatment. CONCLUSIONS: Injected and inhaled heparin failed to attenuate average flare intensity, the primary endpoint, compared with placebo. Interestingly, after patients injected heparin, they had a significant decrease in average flare intensity compared with that seen after inhalation of heparin. There were no differences among groups in other efficacy parameters. Taken together, these data indicate that commercial heparin was ineffective in preventing exacerbations of HAE.     

Microarrays: spotlight on gene function and pharmacogenomics

The introduction of microarray technology has dramatically changed the way that researchers address many biomedical questions. DNA microarrays can measure expression of thousands of genes simultaneously, providing extensive information on gene interaction and function. Microarray technology is a powerful tool for identifying novel molecular drug targets and for elucidating mechanisms of drug action. Furthermore, microarrays can monitor the global profile of gene expression in response to specific pharmacologic agents, providing information on drug efficacy and toxicity. Over the last several years, dramatic advancements have occurred in array technology. In this review we describe basic aspects of microarray instrumentation and experimentation. Each of the major array formats including oligonucleotides arrays, spotted arrays, and macroarrays are examined, and advantages and options for using each format are presented. Important factors in the design and analysis of microarray experiments are also discussed. Most importantly, we explore recent developments in microarray technology that are relevant to pharmacogenomics and the discovery of gene function.