Mild to moderate increases in activity are associated with increased seizure incidence in dogs with idiopathic epilepsy receiving anti-epileptic drugs.

OBJECTIVE: Epilepsy is a chronic disorder, and approximately 25% to 30% of dogs with epilepsy are refractory to anti-epileptic drugs. As increased activity has been shown to reduce seizure frequency in people with epilepsy, the goal of this study was to evaluate the relationship between deviation from baseline activity and seizure incidence in dogs with epilepsy. MATERIALS AND METHODS: Activity and seizure data were obtained using a canine activity monitoring device and owner observed seizure logs in 53 dogs with idiopathic epilepsy receiving anti-epileptic drugs. Each dog's activity was individually measured, and 14-day baseline averages were calculated. Logistic regression was performed to evaluate how an observed increase in activity, ranging from 0% to 50%, above baseline activity, affects the incidence of a seizure in the following 24 hours. RESULTS: A total of 8540 activity days and 365 seizure days were used in the final analysis with an average of 11 seizures per dog (range 0 to 30 seizures). Seizure incidence was significantly more likely when activity was 10%, 20%, or 30% above baseline activity in the 24 hours before the day of a documented seizure [95% confidence interval (1.02 to 1.60), P=0.033; 95% confidence interval (1.08 to 1.80), P=0.010; 95% confidence interval (1.13 to 2.07), P=0.005, respectively]. However, when activity levels were 40% and 50% above baseline, the effect diminished (95% confidence interval (0.74 to 1.70), P=0.532; or 95% confidence interval (0.56 to 1.66), P=0.988, respectively). CLINICAL SIGNIFICANCE: Differently than in humans, this study demonstrated that a mild to moderate increase in activity resulted in a higher seizure incidence within 24 hours in dogs with epilepsy.

Effect of an intervention of exercise on sleep and seizure frequency in idiopathic epileptic dogs.

OBJECTIVE: The goal of this study was to compare sleep and seizure frequency between epileptic dogs prescribed a 20% activity increase and epileptic dogs not prescribed an activity increase. METHODS: Sixty-nine dogs receiving anti-epileptic drug therapy were enrolled in a 6-month prospective, randomised, placebo-controlled clinical trial with an intention-to-treat analysis. A canine activity monitoring device was used to measure activity levels and sleep scores. RESULTS: Using an intention-to-treat analysis, the treatment group had an average of 0.381 more seizures per month (95% CI: 0.09 to 0.68) compared with the control group, although the difference in seizure days per month was not statistically significant. In a subgroup analysis of dogs whose activity increased by at least 10%, partial compliers had 0.719 more seizures per month (95% CI: 0.22 to 1.22) and 0.581 seizure days per month (95% CI: 0.001 to 1.16) compared with the control group. Sleep scores increased by 1.2% in the treatment compared with the control group (95% CI: 0.2 to 2.3%). CONCLUSIONS: Seizure frequency and sleep score increased slightly, but significantly, in dogs with idiopathic epilepsy prescribed an increase in activity, compared with a control group.

Design, Manufacturing, Characterization and Evaluation of Lipid Nanocapsules to Enhance the Biopharmaceutical Properties of Efavirenz.

Despite their incredible contribution to fighting viral infections, antiviral viral resistance is an increasing concern and often arises due to unfavorable physicochemical and biopharmaceutical properties. To address this kind of issue, lipid nanocapsules (LNC) are developed in this study, using efavirenz (EFV) as a drug model. EFV solubility was assessed in water, Labrafac Lipophile and medium chain triglycerides oil (MCT oil). EFV turned out to be more soluble in the two latter dissolving media (solubility > 250 mg/mL); hence, given its affordability, MCT oil was used for LNC formulation. LNC were prepared using a low-energy method named phase inversion, and following a design of experiments process. This one resulted in polynomial models that predicted LNC particle size, polydispersity index and zeta potential that were, respectively, around 50 nm, below 0.2 and below −33 mV, for the optimized formulations. Once synthesized, we were able to achieve an encapsulation efficacy of 87%. On the other hand, high EFV release from the LNC carrier was obtained in neutral medium as compared to acid milieu (pH 4) with, respectively, 42 and 27% EFV release within 74 h. Other characterization techniques were applied and further supported the successful encapsulation of EFV in LNCs in an amorphous form. Stability studies revealed that the developed LNC were quite stable over the period of 28 days. Ultimately, LNCs have been demonstrated to improve the biopharmaceutical properties of EFV and could therefore be used to fight against antiviral resistance.

Baseline Quality-of-Life of Caregivers of Patients With Heart Failure Prior to Advanced Therapies: Findings From the Sustaining Quality of Life of the Aged: Transplant or Mechanical Support (SUSTAIN-IT) Study.

BACKGROUND: We compared health-related quality of life (HRQOL), depressive symptoms, anxiety, and burden in caregivers of older patients with heart failure based on the intended therapy goal of the patient: awaiting heart transplantation (HT) with or without mechanical circulatory support (MCS) or prior to long-term MCS; and we identified factors associated with HRQOL. METHODS: Caregivers (n = 281) recruited from 13 HT and MCS programs in the United States completed measures of HRQOL (EQ-5D-3L), depressive symptoms (PHQ-8), anxiety (STAI-state), and burden (Oberst Caregiving Burden Scale). Analyses included ANOVA, Kruskal-Wallis tests, χ2 tests, and linear regression. RESULTS: The majority of caregivers were female, white spouses with ≤ 2 comorbidities, median [Q1,Q3] age = 62 [57.8, 67.0] years. Caregivers (HT with MCS = 87, HT without MCS = 98, long-term MCS = 96) reported similarly high baseline HRQOL (EQ-5D-3L visual analog scale median score = 90; P = 0.67 for all groups) and low levels of depressive symptoms. STAI-state median scores were higher in the long-term MCS group vs the HT groups with and without MCS, (38 vs 32 vs 31; P < 0.001), respectively. Burden (task: time spent/difficulty) differed significantly among groups. Caregiver factors (number of comorbidities, diabetes and higher anxiety levels) were significantly associated with worse caregiver HRQOL, R2 = 26%. CONCLUSIONS: Recognizing caregiver-specific factors, including comorbidities and anxiety, associated with the HRQOL of caregivers of these older patients with advanced HF may guide support strategies.

In vivo antimalarial activity of self-nanoemulsifying drug delivery systems containing ethanolic extract of Morinda lucida in combination with other Congolese plants extracts

Abstract Morinda lucida leaves are largely used by Congolese traditional healers for the treatment of uncomplicated malaria. The antimalarial activity of their ethanolic extract has been confirmed both in vitro and in vivo. However, the development of relevant formulations for potential clinical application is hampered since the active ingredients contained in this extract exhibit poor water solubility and low oral bioavailability. Hence, this work aims not only to develop self-nanoemulsifying drug delivery systems (SNEDDSs) for oral delivery of the ethanolic extract of Morinda lucida (ML) but also to evaluate its oral antimalarial activity alone and in combination with other Congolese ethanolic plant extracts (Alstonia congensis, Garcinia kola, Lantana camara, Morinda morindoides or Newbouldia laevis). Based on the solubility of these different extracts in various excipients, SNEDDS preconcentrates were prepared, and 200 mg/g of each plant extract were suspended in these formulations. The 4-day suppressive Peter's test revealed a significant parasite growth inhibiting effect for all the extract-based SNEDDS (from 55.0 to 82.4 %) at 200 mg/kg. These activities were higher than those of their corresponding ethanolic suspensions given orally at the same dose (p<0.05). The combination therapy of MLSNEDDS with other extract-based SNEDDS exhibited remarkable chemosuppression, ranging from 74.3 % to 95.8 % (for 100 + 100 mg/kg) and 86.7 % to 95.5 % (for 200 + 200 mg/kg/day). In regard to these findings, SNEDDS suspension may constitute a promising approach for oral delivery of ML alone or in combination with other antimalarial plants.

Application of Lipid-Based Nanocarriers for Antitubercular Drug Delivery: A Review.

The antimicrobial drugs currently used for the management of tuberculosis (TB) exhibit poor bioavailability that necessitates prolonged treatment regimens and high dosing frequency to achieve optimal therapeutic outcomes. In addition, these agents cause severe adverse effects, as well as having detrimental interactions with other drugs used in the treatment of comorbid conditions such as HIV/AIDS. The challenges associated with the current TB regimens contribute to low levels of patient adherence and, consequently, the development of multidrug-resistant TB strains. This has led to the urgent need to develop newer drug delivery systems to improve the treatment of TB. Targeted drug delivery systems provide higher drug concentrations at the infection site, thus leading to reduced incidences of adverse effects. Lipid-based nanocarriers have proven to be effective in improving the solubility and bioavailability of antimicrobials whilst decreasing the incidence of adverse effects through targeted delivery. The potential application of lipid-based carriers such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, nano and microemulsions, and self-emulsifying drug delivery systems for the treatment of TB is reviewed herein. The composition of the investigated lipid-based carriers, their characteristics, and their influence on bioavailability, toxicity, and sustained drug delivery are also discussed. Overall, lipid-based systems have shown great promise in anti-TB drug delivery applications. The summary of the reviewed data encourages future efforts to boost the translational development of lipid-based nanocarriers to improve TB therapy.

HIV-Risk Behavior Among Adults with Opioid Use Disorder During 12 Months Following Pre-trial Detention: Results from a Randomized Trial of Methadone Treatment.

This was a three group randomized clinical trial of interim methadone and patient navigation involving 225 pre-trial detainees with opioid use disorder in Baltimore. The HIV Risk Assessment Battery (RAB) was administered at baseline (in jail), and at 6 and 12 months post-release. Generalized linear mixed model analyses indicated the condition × time interaction effect failed to reach significance (ps > .05) for both the drug risk and sex risk subscale scores. Therefore, findings suggest that there were no intervention effects on drug or sex risk behaviors. However, increased use of cocaine at baseline was associated with increases in drug- (b = .04, SE = .02) and sex-risk (b = .01, SE = .003) behaviors. These results suggest that interventions targeting cocaine use among pre-trial detainees may serve as a means of reducing HIV risk associated with drug- and sex-risk behaviors.Clinical Trials Registration: Clinicaltrials.gov NCT02334215.

People with Type Diabetes Mellitus (T1DM) self-reported views on their own condition management reveal links to potentially improved outcomes and potential areas for service improvement.

BACKGROUND: The self-management of type 1 diabetes (T1DM) has moved forward in many areas over the last 40 years. Our study asked people with T1DM what is their experience of blood glucose (BG) monitoring day to day and how this influences decisions about insulin dosing. METHODS: An on-line self-reported questionnaire containing 44 questions prepared after consultation with clinicians and patients was circulated to people with T1DM 116 responders provided completed responses. Fixed responses were allocated specific values (e.g. not confident = 0 fairly confident = 1). Multivariate regression analysis was carried out. Only those 5 factors with p-value <0.05 were retained. RESULTS: 59% of respondents were >50 years old and 66% had diabetes for >20 years, with 63% of patients reporting HbA1c results ≤8% or 64 mmol/mol. Findings included; 75% used only 1 m; 56% had used the same meter for ≥3 years; 10% had tried flash monitors; 47% were concerned about current BG level; 85% were concerned about long-term impact of higher BG. 72% of respondents keep BG level high to avoid hypoglycaemia; 25% used ≥7 mmol/L as pre-meal BG target to calculate dose; 65% were concerned they might be over/under-dosing; 83% did not discuss accuracy when choosing meter. However 85% were confident in their meter's performance. The factors that linked to LOWER HbA1c included LESS units of basal insulin (p < 0.001), HIGHER number of daily BG tests (p = 0.008), LOWER bedtime blood glucose (p = 0.009), HIGHER patient's concern over long-term impact of high BG (BG) (p < 0.009 but LOWER patient's concern over current BG values (p = 0.009). The final statistical model could explain 41% of the observed variation in HbA1c. CONCLUSION: Many people still run their BG high to avoid hypoglycaemia. Concern about the longer-term consequences of suboptimal glycaemic control was associated with a lower HbA1c and is an area to explore in the future when considering how to help people with T1DM.

Methadone treatment of arrestees: A randomized clinical trial.

BACKGROUND: Opioid use disorder is common among detainees in US jails, yet methadone treatment is rarely initiated. METHODS: This is a three-group randomized controlled trial in which 225 detainees in Baltimore treated for opioid withdrawal were assigned to: (1) interim methadone (IM) with patient navigation (IM + PN); (2) IM; or (3) enhanced treatment-as-usual (ETAU). Participants in both IM groups were able to enter standard methadone treatment upon release, while ETAU participants received an assessment/referral number. Follow-up assessments at 1, 3, 6, and 12 months post-release determined treatment enrollment, urine drug testing results, self-reported days of drug use, criminal activity, and overdose events. Generalized linear mixed modelling examined two planned contrasts: (1) IM groups combined vs. ETAU; and (2) IM + PN vs. IM. RESULTS: On an intention-to-treat basis, compared to ETAU, significantly more participants in the combined IM groups were in treatment 30 days post-release, while the IM + PN vs. IM groups did not significantly differ. By month 12, there were no significant differences in the estimated marginal means of enrollment in any kind of drug treatment (0.40 and 0.27 for IM + PN and IM groups, respectively, compared to 0.29 for ETAU). There were no significant differences for either contrast in opioid-positive tests, although all groups reported a sharp decrease in heroin use from baseline to follow-up. There were five fatal overdoses, but none occurred during methadone treatment. CONCLUSION: Initiating methadone treatment in jail was effective in promoting entry into community-based drug abuse treatment but subsequent treatment discontinuation attenuated any potential impact of such treatment.

Prevalence of lameness in sheep transported to meat processing plants in New Zealand and associated risk factors.

Aims: To estimate the prevalence of lameness in sheep transported to meat processing plants in New Zealand, and to identify factors associated with the prevalence of lameness. Methods: The survey was conducted over the main meat processing season, running from October 2012 to the end of May 2013, at 10 sheep processing premises (five North Island and five South Island). A sample of 50 sheep selected from approximately six sheep consignments per week from each of the processing plants were scored for lameness, using a scale from Grade 1 (mild) to 3 (severe, non-weight-bearing). For each consignment the breed, age class and mean carcass weight were recorded. A multivariable regression model was fitted to identify the risk factors for prevalence of lame sheep (Grade 1-3) within a consignment. Results: In total, 1,854/78,833 (2.4 (95% CI = 2.2-2.5)%) sheep were diagnosed with lameness. Of the 1,854 lame sheep, lameness severity was Grade 1 in 1,349 (72.8%), Grade 2 in 450 (24.3%) and Grade 3 in 55 (3.0%) sheep. Within consignments ≥1 lame sheep was observed in 600/1,682 (35.7 (95% CI = 33.4-38.0)%) consignments. In Merino lambs and ewes the prevalence of lameness was greater than that of other breeds (p < 0.001), but in rams/wethers, the prevalence of lameness was lower in Merino than other breeds (p < 0.05). In sheep originating from the North Island, increasing mean carcass weight was associated with an increase in the prevalence of lameness (p < 0.001), but in the South Island prevalence was similar for different carcass weights (p = 0.5). In the North Island increasing yarding time was associated with an increase in the lameness prevalence (p < 0.01), but not in the South Island (p = 0.7). Sheep from the South Island generally had a higher prevalence of lameness than the North Island and the prevalence of lameness was lower over summer and autumn relative to the previous spring (p < 0.01). Conclusion: The results from this survey provided a measure of the prevalence of lameness in a section of the New Zealand sheep population, namely those animals sent for slaughter; as well as identification of several risk factors associated with lameness.

Risk factors for oral health in young, urban, Aboriginal and Torres Strait Islander children.

BACKGROUND: The caries process follows a strong social gradient which can commence in the first years of life. Yet data on young children remain limited. This study reports the potential risk factors and indicators in urban, Aboriginal and Torres Strait Islander children aged less than 5 and estimates the prevalence of caries. METHODS: Demographic and risk factor and risk indicator data were collected at baseline in a cohort study of children attending a health clinic in north Brisbane. Dentulous children received a basic oral examination to explore the presence of decayed, missing and filled teeth (dmft). Descriptive analyses were performed. A backwards stepwise logistic regression model was performed to identify potential associations with dmft status. RESULTS: In this study, 180 children enrolled: 111 children received the oral examination, of whom 14 (12.6%) (mean age 35 months) were estimated to have dmft >0. There was a high prevalence of socio-economic, dietary and behavioural risk factors/indicators present for children. Due to the small sample size, planned regression was not performed. CONCLUSIONS: Overall, the prevalence of risk factors and risk indicators for caries in the study population is high. More culturally appropriate resources that support preventive care need to be invested before children are school aged.

Identifying substance misuse in primary care: TAPS Tool compared to the WHO ASSIST.

BACKGROUND: There is a need for screening and brief assessment instruments to identify primary care patients with substance use problems. This study's aim was to examine the performance of a two-step screening and brief assessment instrument, the TAPS Tool, compared to the WHO ASSIST. METHODS: Two thousand adult primary care patients recruited from five primary care clinics in four Eastern US states completed the TAPS Tool followed by the ASSIST. The ability of the TAPS Tool to identify moderate- and high-risk use scores on the ASSIST was examined using sensitivity and specificity analyses. RESULTS: The interviewer and self-administered computer tablet versions of the TAPS Tool generated similar results. The interviewer-administered version (at cut-off of 2), had acceptable sensitivity and specificity for high-risk tobacco (0.90 and 0.77) and alcohol (0.87 and 0.80) use. For illicit drugs, sensitivities were >0.82 and specificities >0.92. The TAPS (at a cut-off of 1) had good sensitivity and specificity for moderate-risk tobacco use (0.83 and 0.97) and alcohol (0.83 and 0.74). Among illicit drugs, sensitivity was acceptable for moderate-risk of marijuana (0.71), while it was low for all other illicit drugs and non-medical use of prescription medications. Specificities were 0.97 or higher for all illicit drugs and prescription medications. CONCLUSIONS: The TAPS Tool identified adult primary care patients with high-risk ASSIST scores for all substances as well moderate-risk users of tobacco, alcohol, and marijuana, although it did not perform well in identifying patients with moderate-risk use of other drugs or non-medical use of prescription medications. The advantages of the TAPS Tool over the ASSIST are its more limited number of items and focus solely on substance use in the past 3months.

Prevalence, codetection and seasonal distribution of upper airway viruses and bacteria in children with acute respiratory illnesses with cough as a symptom.

Most studies exploring the role of upper airway viruses and bacteria in paediatric acute respiratory infections (ARI) focus on specific clinical diagnoses and/or do not account for virus-bacteria interactions. We aimed to describe the frequency and predictors of virus and bacteria codetection in children with ARI and cough, irrespective of clinical diagnosis. Bilateral nasal swabs, demographic, clinical and risk factor data were collected at enrollment in children aged <15 years presenting to an emergency department with an ARI and where cough was a symptom. Swabs were tested by polymerase chain reaction for 17 respiratory viruses and seven respiratory bacteria. Logistic regression was used to investigate associations between child characteristics and codetection of the organisms of interest. Between December 2011 and August 2014, swabs were collected from 817 (93.3%) of 876 enrolled children, median age 27.7 months (interquartile range 13.9-60.3 months). Overall, 740 (90.6%) of 817 specimens were positive for any organism. Both viruses and bacteria were detected in 423 specimens (51.8%). Factors associated with codetection were age (adjusted odds ratio (aOR) for age <12 months = 4.9, 95% confidence interval (CI) 3.0, 7.9; age 12 to <24 months = 6.0, 95% CI 3.7, 9.8; age 24 to <60 months = 2.4, 95% CI 1.5, 3.9), male gender (aOR 1.46; 95% CI 1.1, 2.0), child care attendance (aOR 2.0; 95% CI 1.4, 2.8) and winter enrollment (aOR 2.0; 95% CI 1.3, 3.0). Haemophilus influenzae dominated the virus-bacteria pairs. Virus-H. influenzae interactions in ARI should be investigated further, especially as the contribution of nontypeable H. influenzae to acute and chronic respiratory diseases is being increasingly recognized.

Relationship Between Hyperglycemia and Heart Transplant Rejection.

PURPOSE: Hyperglycemia increases risks of kidney and liver transplant rejection. To determine whether perioperative and subsequent glycemic control was associated with increased risk of heart transplant rejection over the year after transplantation, we performed a retrospective analysis of glycemic control and rejection rates in heart transplantation patients. METHODS: Perioperative glucose levels were analyzed in 157 patients undergoing transplantation at Northwestern Memorial Hospital from June 2005 to December 2012 and compared in patients with and without rejection found on routine follow-up biopsy specimens. RESULTS: Grade ≤1R rejection on biopsy was observed in 116 patients and grade ≥2R rejection (grade requiring increased anti-rejection treatment) in 41 patients. Although no significant differences in the preoperative fasting or inpatient mean glucose levels were found, the mean glucose levels from discharge to 1 year trended higher in those with grade ≥2R compared to grade ≤1R (128.8 ± 40.9 versus 142.2 ± 46.6 mg/dL, P = .084). In a multivariable logistic regression model, neither the lowest nor highest quartile of glucose levels had significantly different odds ratios (ORs) for the development of ≥2R compared to the middle 50% glucose levels. Older age (OR 0.96, P = .020) and higher body mass index levels (OR 0.86, P = .004) were significantly associated with lower odds of developing grade ≥2R. CONCLUSIONS: Although the glucose trend regarding rejection was not statistically significant, we cannot exclude the possibility that much higher glucose levels would influence rejection rates.

Longitudinal predictors of past-year non-suicidal self-injury and motives among college students.

BACKGROUND: Non-suicidal self-injury (NSSI) is the deliberate and direct injuring of body tissue without suicidal intent for purposes not socially sanctioned. Few studies have examined the correlates of NSSI among young adults. This study aimed to identify predictors of lifetime and past-year NSSI, and describe motives for NSSI and disclosure of NSSI to others. METHOD: Interviews were conducted annually with 1081 students enrolled in the College Life Study, a prospective longitudinal study conducted at a large public mid-Atlantic university. NSSI characteristics were assessed at Year 4. Demographic and predictor variables were assessed during Years 1 to 4. Multivariate logistic regression models were used to identify correlates of lifetime NSSI and predictors of past-year NSSI. RESULTS: The prevalence of past-year and lifetime NSSI was 2% and 7% respectively (>70% were female for both lifetime and past-year NSSI). Seven percent of NSSI cases self-injured once, whereas almost half self-injured six or more times. Independent predictors of past-year NSSI were maternal depression, non-heterosexual orientation, affective dysregulation and depression. Independent predictors of lifetime NSSI were depression, non-heterosexual orientation, paternal depression and female sex. One in six participants with NSSI had attempted suicide by young adulthood. The three most commonly reported motives for NSSI were mental distress, coping and situational stressors. Most (89%) told someone about their NSSI, most commonly a friend (68%). CONCLUSIONS: This study identified unique predictors of NSSI, which should help to elucidate its etiology and has implications for early identification and interventions.

Bulk and interfacial effects in Co-Cr2O3 nanocomposites.

The exchange bias field has been measured in a set of Co-Cr2O3 nanocomposites in order to distinguish between the bulk and interfacial contributions to H(ex). The studies were carried out on a set of samples prepared by the sol gel technique in which the Co concentration was varied between 30 and 80 wt%. The particle sizes in all samples were carefully controlled so as to enable a comparison of their magnetic properties. Using thermal activation measurements we are able to distinguish between contributions to H(ex) arising from the thermal stability of the antiferromagnetic particles (bulk behaviour) and that due to changing interface density with increasing Co concentration. We have interpreted our results in terms of the independent particle volume model.

Improving essential obstetric and newborn care in resource-poor countries.

Skilled birth attendance (SBA) and essential obstetric care (EOC) are key strategies for reducing maternal and newborn mortality and morbidity globally. Lack of adequately trained competent staff is a key barrier to achieving this. We assessed the effectiveness of a new package of 'Life Saving Skills - Essential Obstetric and Newborn Care Training' (LSS-EOC and NC) designed specifically around the UN signal functions in seven countries in sub-Saharan Africa. Among 600 healthcare providers (nurse-midwives, doctors, clinical officers and specialists), knowledge about the diagnosis and management of complications of pregnancy and childbirth as well as newborn care significantly increased (p < 0.001). There was measurable improvement in skills (p < 0.001), and participants expressed a high level of satisfaction with the training. The training package was found to meet the needs of healthcare providers, increased awareness of the need for evidence-based care and encouraged teamwork.

Effectiveness of 7-valent pneumococcal conjugate vaccine against radiologically diagnosed pneumonia in indigenous infants in Australia.

OBJECTIVE: To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) in preventing pneumonia, diagnosed radiologically according to World Health Organization (WHO) criteria, among indigenous infants in the Northern Territory of Australia. METHODS: We conducted a historical cohort study of consecutive indigenous birth cohorts between 1 April 1998 and 28 February 2005. Children were followed up to 18 months of age. The PCV7 programme commenced on 1 June 2001. All chest X-rays taken within 3 days of any hospitalization were assessed. The primary endpoint was a first episode of WHO-defined pneumonia requiring hospitalization. Cox proportional hazards models were used to compare disease incidence. FINDINGS: There were 526 pneumonia events among 10,600 children - an incidence of 3.3 per 1000 child-months; 183 episodes (34.8%) occurred before 5 months of age and 247 (47.0%) by 7 months. Of the children studied, 27% had received 3 doses of vaccine by 7 months of age. Hazard ratios for endpoint pneumonia were 1.01 for 1 versus 0 doses; 1.03 for 2 versus 0 doses; and 0.84 for 3 versus 0 doses. CONCLUSION: There was limited evidence that PCV7 reduced the incidence of radiologically confirmed pneumonia among Northern Territory indigenous infants, although there was a non-significant trend towards an effect after receipt of the third dose. These findings might be explained by lack of timely vaccination and/or occurrence of disease at an early age. Additionally, the relative contribution of vaccine-type pneumococcus to severe pneumonia in a setting where multiple other pathogens are prevalent may differ with respect to other settings where vaccine efficacy has been clearly established.