Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing

The bubble point test is the de facto standard for postproduction filter membrane integrity test in the radiopharmaceutical community. However, the bubble point test depends on a subjective visual assessment of bubbling rate that can be obscured by significant diffusive gas flows below the manufacturer's prescribed bubble point. To provide a more objective means to assess filter membrane integrity, this study evaluates the pressure-hold test as an alternative to the bubble point test. In our application of the pressure-hold test, the nonsterile side of the sterilizing filter is pressurized to 85% of the predetermined bubble point with nitrogen, the filter system is closed off from the pressurizing gas and the pressure is monitored over a prescribed time interval. The drop in pressure, which has a known relationship with diffusive gas flow, is used as a quantitative measure of membrane integrity. Characterization of the gas flow vs. pressure relationship of each filter/solution combination provides an objective and quantitative means for defining a critical value of pressure drop over which the membrane is indicated to be nonintegral. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, [¹⁸F]FDG and [¹¹C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells).     

Are hospitals prepared to support newborn survival? – an evaluation of eight first‐referral level hospitals in Kenya*

Objective To assess the availability of resources that support the provision of basic neonatal care in eight first‐referral level (district) hospitals in Kenya. Methods We selected two hospitals each from four of Kenya’s eight provinces with the aim of representing the diversity of this part of the health system in Kenya. We created a checklist of 53 indicator items necessary for providing essential basic care to newborns and assessed their availability at each of the eight hospitals by direct observation, and then compared our observations with the opinions of health workers providing care to newborns on recent availability for some items, using a self‐administered structured questionnaire. Results The hospitals surveyed were often unable to maintain a safe hygienic environment for patients and health care workers; staffing was insufficient and sometimes poorly organised to support the provision of care; some key equipment, laboratory tests, drugs and consumables were not available while patient management guidelines were missing in all sites. Conclusion Hospitals appear relatively poorly prepared to fill their proposed role in ensuring newborn survival. More effective interventions are needed to improve them to meet the special needs of this at‐risk group.     

West Nile virus preferentially transports along motor neuron axons after sciatic nerve injection of hamsters

Prior findings led us to hypothesize that West Nile virus (WNV) preferentially transports along motor axons instead of sensory axons. WNV is known to undergo axonal transport in cell culture and in infected hamsters to infect motor neurons in the spinal cord. To investigate this hypothesis, WNV was injected directly into the left sciatic nerve of hamsters. WNV envelope-staining in these hamsters was only observed in motor neurons of the ipsilateral ventral horn of the spinal cord, but not in the dorsal root ganglion (DRG). To evaluate the consequence of motor neuron infection by WNV, the authors inoculated wheat germ agglutinin—horseradish peroxidase (WGA-HRP) 9 days after WNV sciatic nerve injection, and stained the spinal cord and the DRG for HRP activity 3 days later. The degree of HRP-staining in DRG was the same in WNV- and sham-infected animals, but the HRP-staining in the motor neuron in the ventral horn was considerably less for WNV-infected hamsters. To investigate the mechanism of WNV transport, hamsters were treated with colchicine, an inhibitor of membranous microtubule-mediated transport. The intensity of the WNV-stained area in the spinal cord of colchicine-treated hamsters at 6 days after WNV infection were significantly reduced (P≤.05) compared to the placebo-treated hamsters. These data suggest that WNV is preferentially transported through the motor axons, but not the sensory axons, to subsequently infect motor neurons and cause motor weakness and paralysis.     

Remission and Recovery in the Treatment for Adolescents With Depression Study (TADS): Acute and Long-Term Outcomes

ObjectiveWe examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS).MethodThe TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive–behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined whether residual symptoms at the end of 12 weeks of acute treatment predicted later remission.ResultsAt week 36, the estimated remission rates for intention-to-treat cases were as follows: combination, 60%; fluoxetine, 55%; cognitive–behavioral therapy, 64%; and overall, 60%. Paired comparisons reveal that, at week 24, all active treatments converge on remission outcomes. The recovery rate at week 36 was 65% for acute phase remitters and 71% for continuation phase remitters, with no significant between-treatment differences in recovery rates. Residual symptoms at the end of acute treatment predicted failure to achieve remission at weeks 18 and 36.ConclusionsMost depressed adolescents in all three treatment modalities achieved remission at the end of 9 months of treatment.