The effect of incarceration on TB treatment outcomes.

BACKGROUND: TB notifications in Latin American prisons have more than doubled over the past two decades; however, treatment outcomes and their determinants among incarcerated individuals in this region are not well understood.METHODS: Newly diagnosed drug-susceptible TB cases reported to Brazil´s Information System for Notifiable Diseases (Sistema de Informação de Agravos de Notificação, SINAN) between January 2015 and December 2017 were included. Multivariate logistic regression was used to assess socio-economic and clinical factors associated with treatment success among incarcerated individuals.RESULTS: Incarcerated individuals (n = 17,776) had greater treatment success than non-incarcerated individuals (n = 160,728; 82.2% vs. 75.1%; P < 0.0001), including after adjusting for demographic and clinical risk factors (adjusted odds ratio aOR 1.27, 95% CI 1.19-1.34). These differences were partially mediated by increased use of directly observed therapy among incarcerated individuals (DOT) (61% vs. 47%; P < 0.001), which was associated with greater efficacy in the incarcerated population (aOR 2.56 vs. aOR 2.17; P < 0.001). DOT was associated with improved treatment success among incarcerated subpopulations at elevated risk of poor outcomes.CONCLUSION: TB treatment success among incarcerated individuals in Brazil is higher than non-incarcerated individuals, but both fall below WHO targets. Expanding the use of DOT and services for socially and medically vulnerable individuals may improve outcomes in carceral settings.

Congenital high myopia and central macular atrophy: a report of 3 families.

AIMS: To report the clinical phenotype in a series of four children from three families with the rare association of high myopia, central macular atrophy, and normal full-field electroretinography (ERG). METHODS: Four male patients were ascertained with reduced vision, nystagmus, and atrophy of the macula from early childhood. Patients underwent full ophthalmic examination, electrophysiological testing, and retinal imaging. RESULTS: Minimum duration of follow-up was 8 years. At last review, visual acuity ranged from 0.22 to 1.20 logMAR (6/9.5-6/95 Snellen) at a mean age of 10.5 years (median 9.5 years, range 9-14 years). Refractive error ranged from a spherical equivalent of -7.40 D to -24.00 D. Three had convergent squint. Fundus examination and imaging demonstrated bilateral macular atrophy in all patients that varied from mild atrophy of the retinal pigment epithelium (RPE) to well-demarcated, punched-out atrophic lesions of retina, RPE, and choroid. Flash ERG was normal under photopic and scotopic conditions in all patients. Pattern ERG, performed in three patients, was consistent with mild to severe macular dysfunction. Progression of the area of atrophy was evident in one patient and of the myopia in two patients but all patients had stable visual acuity. CONCLUSIONS: Patients with congenital high myopia and macular atrophy present in infancy with reduced visual acuity and nystagmus. The macular atrophic lesions vary in size and severity but electrophysiological testing is consistent with dysfunction confined to the macula. There was no deterioration in visual acuity over 8-10 years of monitoring.

Class II alloantibody and mortality in simultaneous liver-kidney transplantation.

Hyperacute kidney rejection is unusual in crossmatch positive recipients of simultaneous liver-kidney transplants (SLKT). However, recent data suggest that these patients remain at risk for antibody-mediated kidney rejection. To further investigate the risk associated with donor-specific alloantibodies (DSA) in SLKT, we studied 86 consecutive SLKT patients with an available pre-SLKT serum sample. Serum samples were analyzed in a blinded fashion for HLA DSA using single antigen beads (median florescence intensity≥2,000=positive). Post-SLKT samples were analyzed when available (76%). Thirty patients had preformed DSA, and nine developed de novo DSA. Preformed class I DSA did not change the risk of rejection, patient or allograft survival. In contrast, preformed class II DSA was associated with a markedly increased risk of renal antibody mediated rejection (AMR) (p=0.006), liver allograft rejection (p=0.002), patient death (p=0.02), liver allograft loss (p=0.02) and renal allograft loss (p=0.045). Multivariable modeling showed class II DSA (preformed or de novo) to be an independent predictor of patient death (HR=2.2; p=0.043) and liver allograft loss (HR=2.2; p=0.044). These data warrant reconsideration of the approach to DSA in SLKT.

Biochemical comparisons of osteoarthritic human synovial fluid with calf sera used in knee simulator wear testing.

Osteoarthritic human synovial fluid was obtained from the knees of 20 patients and was compared with four different calf sera solutions frequently used as lubricants in knee simulator wear testing. Assuming that the fluid after arthroplasty was the same as the fluid in patients with osteoarthritis, the total protein concentration, protein constituent fractions, osmolality, trace element concentrations, and the thermal stability obtained via differential scanning calorimetry were determined. Human synovial fluid, with an average total protein concentration of 34 g/L, was significantly different from all undiluted calf sera. However, alpha-calf serum and iron-supplemented alpha-calf serum were closest in protein constituent fractions (albumin, alpha-1-globulin, alpha-2-globulin, ss-globulin, and gamma-globulin) to human synovial fluid. Diluting calf sera with low-ion distilled water to a total protein concentration of 17 g/L (as recommended by ISO 14243) produced non-clinically relevant total protein concentration and osmolality levels. Performing the same dilution of iron-supplemented alpha-calf serum with phosphate-buffered saline solution and 1.5 g/L hyaluronic acid produced an artificial lubricant with both a clinically relevant level of osmolality and clinically relevant thermal stability as seen in human synovial fluid from patients with osteoarthritis. The present study suggested that alpha-calf serum, phosphate-buffered saline solution and hyaluronic acid were essential constituents of an artificial lubricant to mimic the major biochemical properties of human synovial fluid for simulator wear testing of total knee replacements.

Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial.

BACKGROUND: Dienogest is a selective progestin that has been investigated in a clinical trial programme for the treatment of endometriosis. The current non-inferiority trial compared the efficacy and safety of dienogest against leuprolide acetate (LA) for treating the pain associated with endometriosis. METHODS: Patients with confirmed endometriosis were randomized to treatment with dienogest (2 mg/day, orally) or LA (3.75 mg, depot i.m. injection, every 4 weeks) for 24 weeks. The primary efficacy variable was absolute change in pelvic pain from baseline to end of treatment, assessed by visual analogue scale (VAS). Safety variables included adverse event profile, laboratory parameters, bone mineral density (BMD), bone markers and bleeding patterns. RESULTS: A total of 252 women were randomized to treatment with dienogest (n = 124) or LA (n = 128); 87.9 and 93.8% of the respective groups completed the trial. Absolute reductions in VAS score from baseline to Week 24 were 47.5 mm with dienogest and 46.0 mm with LA, demonstrating the equivalence of dienogest relative to LA. Hypoestrogenic effects (e.g. hot flushes) were reported less frequently in the dienogest group. As expected, bleeding episodes were suppressed less with dienogest than with LA. Changes in mean lumbar BMD between screening and final visit were +0.25% with dienogest and -4.04% with LA subgroups (P = 0.0003). Markers of bone resorption increased with LA but not dienogest. CONCLUSIONS: Dienogest 2 mg/day orally demonstrated equivalent efficacy to depot LA at standard dose in relieving the pain associated with endometriosis, although offering advantages in safety and tolerability.

Autotrophic nitrogen removal in sequencing batch biofilm reactors at different oxygen supply modes.

Conventional nitrification-denitrification treatment is a common way to treat nitrogen in wastewater, but this process is costly for low COD/N wastewaters due to the addition of air and external carbon-source. However, ammonia may alternatively be converted to dinitrogen gas by autotrophic bacteria utilizing aerobically autotrophically produced nitrite as an electron acceptor under anoxic conditions. Lab-scale sequencing batch biofilm reactors (SBBRs) inoculated with normal nitrifying sludge were employed to study the potential of an oxygen-limited autotrophic nitrification-denitrification process initiated with typical nitrifying sludge for treating a synthetic ammonia wastewater devoid of organic carbon in one step. The ring-laced fibrous carrier (length 0.32 m, surface area 3.4 m2/m) was fixed vertically in a 3 L reactor. Two different air supply modes were applied:continuous aeration to control dissolved oxygen at 1.5 mg/L and intermittent aeration. High nitrogen removals of more than 50% were obtained in both SBBRs. At an ammonia loading of 0.882 gm N/m2-day [hydraulic retention time (HRT) of 24 hr], the SBBR continuously aerated to 1.5 mg DO/L had slightly higher nitrogen removal (64%) than the intermittently alternated SBBR (55%). The main form of residual nitrogen in the effluent was ammonia, at concentrations of 25 mg/L and 37 mg N/L in continuous and intermittent aeration SBBRs, respectively. Ammonia was completely consumed when ammonia loading was reduced to 0.441 gm N/m2-day [HRT extended to 48 hr]. The competitive use of nitrite by aerobic nitrite oxidizing bacteria (ANOB) with anaerobic ammonia-oxidizing bacteria (anammox bacteria) during the expanded aeration period under low remaining ammonia concentration resulted in higher nitrate production and lower nitrogen loss in the continuous aeration SBBR than in the intermittent aeration SBBR. The nitrogen removal efficiencies in SBBRs with continuous and alternating aerated were 80% and 86% respectively. Specific microorganisms in the biofilm were characterized using fluorescence in situ hybridization. Aerobic ammonia-oxidizing bacteria (AAOB) occurred side by side with putative anammox bacteria (cells hybridizing with probe AMX820) throughout the biofilm, though ANOB were rarely detected.

The clinical effectiveness and cost-effectiveness of screening programmes for amblyopia and strabismus in children up to the age of 4-5 years: a systematic review and economic evaluation.

OBJECTIVES: To estimate the cost-effectiveness of screening for amblyopia and strabismus in children aged up to 4-5 years, also identifying the major areas of uncertainty and so inform future research priorities in this disease area. DATA SOURCES: Major electronic databases were searched in January 2006. REVIEW METHODS: Systematic literature reviews were undertaken to determine the prevalence and natural history, the screening methods, the effectiveness of treatment options and health-related quality of life issues relating to amblyopia and strabismus. The review of treatment interventions was restricted to high-quality reviews, meta-analyses and guidelines. The data derived from the review informed the structure and implementation of the decision-analytic model. RESULTS: The amblyopia screening model was analysed in detail to estimate the cost and effects of six alternative screening options comprising screening at different ages (3, 4 and 5 years) and using alternative sets of tests (visual acuity testing and the cover tests, with and without autorefraction). The reference case results showed that screening programmes that included autorefraction dominated screening programmes without autorefraction. Analyses based on the cost per case of amblyopia prevented showed screening at either 3 or 4 years prevented additional cases at a low absolute cost (3000-6000 pounds sterling). However, when these results were extrapolated to estimate the cost per quality-adjusted life-year (QALY) gained, the reference case analysis found that no form of screening is likely to be cost-effective at currently accepted values of a QALY. The wide-ranging sensitivity analyses found that the results were robust to most parameter changes. The only parameter that radically affected the results was the utility effect of loss of vision in one eye. No direct evidence of a utility effect was identified and the reference case assumed no effect. When a small effect is assumed (a reduction in utility of 2%), the incremental cost per QALY gained becomes extremely attractive for screening at both 3 and at 4 years. The expected value of perfect information was shown to be large when the unilateral vision loss utility parameter was allowed to vary, but not when it was kept constant at zero. CONCLUSIONS: The results show that the cost-effectiveness of screening for amblyopia is dependent on the long-term utility effects of unilateral vision loss. There is limited evidence on any such effect, although our subjective interpretation of the available literature is that the utility effects are likely to be minimal. Any utility study investigating such effects would need to be careful to avoid introducing bias. The reference case model did not represent potential treatment-related utility effects, primarily due to an increased probability of treated children being bullied at school. The evidence indicates that this may be a problem, and additional sensitivity analyses show that small utility decrements from bullying would improve the cost-effectiveness of early screening significantly. A prospective study of the utility effects of bullying would usefully inform the analysis, although such a study would need to be carefully planned in order to distinguish whether the overall incidence of bullying decreases with reduced school-age treatment, or whether it is displaced to other children.

Efficacy and safety of a low-dose 21-day combined oral contraceptive containing ethinylestradiol 20microg and drospirenone 3mg.

OBJECTIVE: The purpose of this study was to assess the efficacy and safety of a new low-dose oral contraceptive containing ethinylestradiol 20microg and drospirenone 3mg (EE 20microg/drsp 3mg). METHODS: This was an open-label, non-comparative, multicentre study conducted at 33 centres in Germany and Switzerland. The combined contraceptive was administered over 26 cycles of treatment, with each cycle consisting of once-daily treatment for 21 consecutive days followed by a 7-day hormone-free interval. RESULTS: A total of 527 women were randomised, of whom 516 (97.9%) started treatment and had at least one study observation. Two pregnancies occurred during 11 165 cycles of treatment, giving a Pearl Index of 0.23 (upper limit of 97.5% CI 0.84). The corresponding 2-year cumulative pregnancy rate was 0.44% (95% CIs 0, 1.05). One of the two pregnancies was attributed to non-compliance with treatment, giving an adjusted Pearl Index of 0.12 (upper limit of 97.5% CI 0.67) over 10 827 compliant cycles. Only three (0.6%) women discontinued treatment because of bleeding problems in this long-term study, suggesting an acceptable bleeding profile. Overall, the study drug was well tolerated and adverse events experienced were typical of hormonal contraceptive use. The majority of women who responded (435 of 501; 86.8%) were satisfied or very satisfied with the study treatment and most (367 of 501; 73.3%) would continue with it if given the choice. CONCLUSION: The EE 20microg/drsp 3 mg combined oral contraceptive is an effective and well tolerated contraceptive with an acceptable bleeding pattern.

Computer modelling study of the mechanism of optic nerve injury in blunt trauma.

AIM: The potential causes of the optic nerve injury as a result of blunt object trauma, were investigated using a computer model. METHODS: A finite element model of the eye, the optic nerve, and the orbit with its content was constructed to simulate blunt object trauma. We used a model of the first phalanx of the index finger to represent the blunt body. The trauma was simulated by impacting the blunt body at the surface between the globe and the orbital wall at velocities between 2-5 m/s, and allowing it to penetrate 4-10 mm below the orbital rim. RESULTS: The impact caused rotations of the globe of up to 5000 degrees /s, lateral velocities of up to 1 m/s, and intraocular pressures (IOP) of over 300 mm Hg. The main stress concentration was observed at the insertion of the nerve into the sclera, at the side opposite to the impact. CONCLUSIONS: The results suggest that the most likely mechanisms of injury are rapid rotation and lateral translation of the globe, as well as a dramatic rise in the IOP. The strains calculated in the study should be sufficiently high to cause axonal damage and even the avulsion of the nerve. Finite element computer modelling has therefore provided important insights into a clinical scenario that cannot be replicated in human or animal experiments.

Hurricane Isabel-related mortality--virginia, 2003.

BACKGROUND: Hurricane Isabel had a massive negative environmental, public health, and economic impact; Virginia bore the highest death toll (32) among nine states affected by this storm. A descriptive mortality analysis was conducted to identify modifiable risk factors and corresponding injury prevention measures that might mitigate future natural disaster-related morbidity and mortality in Virginia. METHODS: Information for the decedents, including demographic data, health status, and injury circumstances, was collected from the records of the Virginia Office of the Chief Medical Examiner and Office of Vital Records/Health Statistics. Criteria from the National Hurricane Center were used to classify deaths as direct or indirect. Storm assessments and emergency-response reports were also reviewed. RESULTS: A total of 32 deaths associated with Hurricane Isabel occurred in several densely populated localities in southeastern and central Virginia. The median age of decedents was 48 years (range: 7-85 years). A disproportionately higher mortality (21 [66%] of 32) occurred among persons older than 45 years (Virginia 2000 Census data). Twelve deaths were directly caused by environmental factors related to the storm (eg, seven drowning deaths and five traumatic head injuries from falling trees). Twenty deaths were indirectly associated with the storm and its effects: six fatal motor vehicle crashes, five related to clean-up operations, seven associated with power outages, and two stress-related (ie, myocardial infarction and suicide). The presence of alcohol or drugs was observed in 9 (28%) of 32 deaths. CONCLUSIONS: Classifying deaths as direct or indirect facilitates better target interventions on the basis of the identification of modifiable risk factors underlying hurricane-associated fatal injuries. Public education messages that reinforce avoidance of use of alcohol and drugs during natural disaster situations might reduce risk for injury.

Neurodevelopmental implications of ocular motor apraxia.

Ocular motor apraxia (OMA), a disorder of saccadic initiation, may be congenital or acquired. While the acquired form is frequently associated with significant neuropathology, the congenital form is often regarded as relatively benign. Many children with congenital OMA who were observed clinically have shown neurodevelopmental disturbance over time. A retrospective review was taken of 34 consecutive patients (22 males and 12 females), seen over a 20-year period, to evaluate the frequency and type of associated neurodevelopmental problems. Age at presentation ranged from 8 weeks to 14 years, with a mean age of 10 years. Of 29 children with congenital OMA, 15 had imaging evidence of structural central nervous system abnormalities (with cerebellar hypoplasia the most frequent abnormality detected). Eleven of the 14 patients with no structural abnormality showed abnormal neurodevelopment. This study suggests that congenital OMA is not a benign diagnosis, even in the absence of overt neurological disturbance at the time of presentation.

Management of childhood epiphora.

AIMS: To examine the effectiveness of a management protocol for childhood epiphora using a joint ophthalmological and otolaryngological team approach. METHOD: A temporally defined retrospective study of 70 children (92 eyes) undergoing surgery for persistent epiphora, despite two previous technically successful probing procedures. All the operations involved a joint approach involving a paediatric ophthalmologist and a paediatric otolaryngologist. RESULTS: In children with congenital nasolacrimal obstruction this joint approach yielded a 73% (89%) success rate, while in children with acquired nasolacrimal obstruction the success rate was 57%. CONCLUSIONS: Endonasal nasolacrimal intubation and endonasal DCR are safe and effective procedures for the management of persistent epiphora in children. They avoid the need for overnight admission and carry a minimal complication rate.

Nitrite oxidation inhibition by hydroxylamine: experimental and model evaluation.

A proposed approach for biological nitrogen removal significantly reduces cost by reducing biomass production and carbon requirements via inhibition of nitrite oxidation (NO2- to NO3-). Batch experiments were conducted to examine the effect of hydroxylamine (HM) on nitrite oxidizers, ammonia oxidizers, and nitrite reducers. Hydroxylamine effect experiments were done at initial pH values of 7.4-8.4, nitrogen concentrations of 100 mg N/L, biomass concentrations of 100-400 mg VSS/L and HM dosages up to 43 mg/L. Nitrite oxidizer activity was completely inhibited by HM at dosages of 7.0 and 8.9 mg/L for pH values of 8.4 and 7.6, respectively. Relatively low HM concentrations (0.35-5.5 mg/L) can be used to completely inhibit nitrite oxidation, but do not significantly affect ammonia oxidizers and nitrite reducers. A model developed to describe the effect of pH on nitrite oxidation rate fits the data well (R2 = 0.89) with values for Vmax of 0.372 (mg N/mg VSS-hr), pH* of 7.72, and the inhibition constant Kh of 0.154. Incorporation of HM inhibition into the model provided a good fit to relative nitrite oxidation rate as a function of undissociated HM concentration (R2 = 0.80, Vmax = 0.028 mg N/mg VSS-hr, pH = 7.89, Kh = 0.302, a = 0.195, and Ki= 0.277 mg/L).