Sexual problems in MS: Sex differences and their impact on quality of life.

BACKGROUND: Low sexual function and satisfaction are common problems among people with multiple sclerosis (PwMS), but the literature on which patient variables are associated with these issues is inconsistent. OBJECTIVE: To investigate the associations between sexual function and satisfaction in PwMS with clinical, demographic, and patient-reported quality of life (QOL) measures and determine if sex differences exist. METHODS: This analysis includes PwMS enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB), who completed patient-reported outcome measures: Multiple Sclerosis Quality of Life-54 (MSQOL-54), Modified Fatigue Impact Scale (MFIS), and Center for Epidemiologic Studies Depression Scale (CES-D). Regression models were used to analyze associations between patient variables and function and satisfaction. Results were stratified by sex. Cross-sectional and longitudinal data were used. RESULTS: 702 PwMS (526 females,176 males, mean age 42.2 +/-11.1, median EDSS 1.5) were included in the cross-sectional analysis. Data from 341 PwMS were used in the three-year longitudinal analysis. Increasing age, disease duration, and disability were associated with reduced sexual function and satisfaction to the same degree in males and females. However, sex differences existed in the strength of associations with QOL variables. There was no significant longitudinal change in females or males. CONCLUSIONS: Age and disease duration were associated with reduced sexual function and satisfaction in males and females. In females, function was significantly associated with disability and satisfaction with fatigue. Males had stronger associations with sexual function in domains related to emotional well-being, health perceptions, and overall QOL. Males had stronger associations with satisfaction in emotional and social functioning and physical health domains. These findings can help better understand the multidimensional problems of sexual function and satisfaction in PwMS and better guide patient care.

Impact of long-term daylight deprivation on retinal light sensitivity, circadian rhythms and sleep during the Antarctic winter.

Long-term daylight deprivation such as during the Antarctic winter has been shown to lead to delayed sleep timing and sleep fragmentation. We aimed at testing whether retinal sensitivity, sleep and circadian rest-activity will change during long-term daylight deprivation on two Antarctic bases (Concordia and Halley VI) in a total of 25 healthy crew members (mean age: 34 ± 11y; 7f). The pupil responses to different light stimuli were used to assess retinal sensitivity changes. Rest-activity cycles were continuously monitored by activity watches. Overall, our data showed increased pupil responses under scotopic (mainly rod-dependent), photopic (mainly L-/M-cone dependent) as well as bright-blue light (mainly melanopsin-dependent) conditions during the time without direct sunlight. Circadian rhythm analysis revealed a significant decay of intra-daily stability, indicating more fragmented rest-activity rhythms during the dark period. Sleep and wake times (as assessed from rest-activity recordings) were significantly delayed after the first month without sunlight (p < 0.05). Our results suggest that during long-term daylight deprivation, retinal sensitivity to blue light increases, whereas circadian rhythm stability decreases and sleep-wake timing is delayed.

Standardizing the influenza neuraminidase inhibition assay among United States public health laboratories conducting virological surveillance.

BACKGROUND: Monitoring influenza virus susceptibility to neuraminidase (NA) inhibitors (NAIs) is vital for detecting drug-resistant variants, and is primarily assessed using NA inhibition (NI) assays, supplemented by NA sequence analysis. However, differences in NI testing methodologies between surveillance laboratories results in variability of 50% inhibitory concentration (IC50) values, which impacts data sharing, reporting and interpretation. In 2011, the Centers for Disease Control and Prevention (CDC), in collaboration with the Association for Public Health Laboratories (APHL) spearheaded efforts to standardize fluorescence-based NI assay testing in the United States (U.S.), with the goal of achieving consistency of IC50 data. METHODS: For the standardization process, three participating state public health laboratories (PHLs), designated as National Surveillance Reference Centers for Influenza (NSRC-Is), assessed the NAI susceptibility of the 2011-12 CDC reference virus panel using stepwise procedures, with support from the CDC reference laboratory. Next, the NSRC-Is assessed the NAI susceptibility of season 2011-12 U.S. influenza surveillance isolates (n = 940), with a large subset (n = 742) tested in parallel by CDC. Subsequently, U.S. influenza surveillance isolates (n = 9629) circulating during the next three influenza seasons (2012-15), were independently tested by the three NSRC-Is (n = 7331) and CDC (n = 2298). RESULTS: The NI assay IC50s generated by respective NSRC-Is using viruses and drugs prepared by CDC were similar to those obtained with viruses and drugs prepared in-house, and were uniform between laboratories. IC50s for U.S. surveillance isolates tested during four consecutive influenza seasons (2011-15) were consistent from season to season, within and between laboratories. CONCLUSION: These results show that the NI assay is robust enough to be standardized, marking the first time IC50 data have been normalized across multiple laboratories, and used for U.S. national NAI susceptibility surveillance.

Evaluation of a point-of-care blood test for identification of Ebola virus disease at Ebola holding units, Western Area, Sierra Leone, January to February 2015.

Current Ebola virus disease (EVD) diagnosis relies on reverse transcription-PCR (RT-PCR) technology, requiring skilled laboratory personnel and technical infrastructure. Lack of laboratory diagnostic capacity has led to diagnostic delays in the current West African EVD outbreak of 2014 and 2015, compromising outbreak control. We evaluated the diagnostic accuracy of the EVD bedside rapid diagnostic antigen test (RDT) developed by the United Kingdom's Defence Science and Technology Laboratory, compared with Ebola virus RT-PCR, in an operational setting for EVD diagnosis of suspected cases admitted to Ebola holding units in the Western Area of Sierra Leone. From 22 January to 16 February 2015, 138 participants were enrolled. EVD prevalence was 11.5%. All EVD cases were identified by a positive RDT with a test line score of 6 or more, giving a sensitivity of 100% (95% confidence interval (CI): 78.2-100). The corresponding specificity was high (96.6%, 95% CI: 91.3-99.1). The positive and negative predictive values for the population prevalence were 79.0% (95% CI: 54.4-93.8) and 100% (95% CI: 96.7-100), respectively. These results, if confirmed in a larger study, suggest that this RDT could be used as a 'rule-out' screening test for EVD to improve rapid case identification and resource allocation.

Advanced airway management is necessary in prehospital trauma patients.

BACKGROUND: Treatment of airway compromise in trauma patients is a priority. Basic airway management is provided by all emergency personnel, but the requirement for on-scene advanced airway management is controversial. We attempted to establish the demand for on-scene advanced airway interventions. Trauma patients managed with standard UK paramedic airway interventions were assessed to determine whether airway compromise had been effectively treated or whether more advanced airway management was required. METHODS: A prospective observational study was conducted to identify trauma patients requiring prehospital advanced airway management attended by a doctor-paramedic team. The team assessed and documented airway compromise on arrival, interventions performed before and after their arrival, and their impact on airway compromise. RESULTS: Four hundred and seventy-two patients required advanced airway intervention and received 925 airway interventions by ground-based paramedics. Two hundred and sixty-nine patients (57%) still had airway compromise on arrival of the enhanced care team; no oxygen had been administered to 52 patients (11%). There were 45 attempted intubations by ground paramedics with a 64% success rate and 11% unrecognized oesophageal intubation rate. Doctor-paramedic teams delivering prehospital anaesthesia achieved definitive airway management for all patients. CONCLUSIONS: A significant proportion of severely injured trauma patients required advanced airway interventions to effectively treat airway compromise. Standard ambulance service interventions were only effective for a proportion of patients, but might not have always been applied appropriately. Complications of advanced airway management occurred in both provider groups, but failed intubation and unrecognized oesophageal intubation were a particular problem in the paramedic intubation group.

The effectiveness of a hospital diabetes outreach service in supporting care for acutely admitted patients with diabetes.

BACKGROUND: Patients with diabetes have increased frequency of hospital admissions and longer lengths of stay compared to patients without diabetes. Our specialist diabetes inpatient service was reconfigured to deliver a proactive diabetes outreach service to improve the overall care of this population. AIMS: To ascertain the effect of a structured diabetes outreach service to acutely admitted patients with diabetes on avoidable admissions, delayed discharges and appropriate diabetes related follow-up plans. METHODS: Audits were carried out before and 4 months after the introduction of a diabetes outreach service. The proportion of patients under care of the diabetes team, avoidable admissions, delayed discharges and existence of effective follow-up plans were compared pre- and post-implementation of this outreach service. RESULTS: The number of inpatients with diabetes fell by 35% (83 on a typical day pre-outreach vs. 53 post-outreach) despite a similar number of total medical admissions in that month (1449 vs.1459). This was due to a reduction in those admitted with diabetes related (13 vs. 5) and general medical (29 vs. 10) problems whilst numbers requiring other specialist care (41 vs. 39) remained unchanged. The proportion of patients under the care of diabetes team rose (23% vs. 73%) while those with avoidable admissions (18% vs. 7%), delayed discharges (17% vs. 2%) and inappropriate discharge plans (65% vs. 11%) all fell. CONCLUSION: This reformatted service was associated with a marked improvement in a number of parameters relevant to inpatient care.

King's College's Graduate Program in Health Care Administration helps to achieve community wellness: a case study.

Graduate programs in health care administration can become catalysts in the community wellness initiatives that the Institute of Medicine and the Centers for Disease Control and Prevention have identified as being critical to the improvement of public health among the U.S population. This paper examines the results of such a program at King's College, Wilkes-Barre, Pennsylvania, which developed community wellness programs through the establishment of a center for health promotion, assisted in the establishment of a city health department, developed a peer leader tobacco education program for elementary school students, and produced a 30-minute video on adolescent high-risk behavior. The program's goal is to facilitate coalition building among health agencies and to produce graduates equipped with administrative skills and a thorough knowledge of the value of well-developed community wellness programs. Healthy communities will require the emergence of leaders who can gather information about high-risk health behaviors and work with communities to implement solutions. Health care administration programs have a tremendous opportunity to become catalysts in the development and implementation of educational programs that may improve a community's overall health and reduce health care costs.

The use of prevalence data to unite the community in prevention programs.

This study examined the prevalence of cigarette smoking in a three-county area of northeastern Pennsylvania. More than 14,000 questionnaires have been returned, and results reveal that 5,411 children have experimented with cigarettes and 2,962 of those children continue smoking today. Cigarette experimentation begins as early as age 5 in northeastern Pennsylvania, with the highest number of children (19.8%) experimenting by age 12. This experimentation occurs less frequently among females in the lower grades and more frequently among females in the later years of high school. The results of this study were used to unite the health community of northeastern Pennsylvania in a number of prevention initiatives.

Fiberoptic DNA sensor array capable of detecting point mutations.

The first integrated fiberoptic DNA sensor array capable of simultaneously monitoring multiple hybridization events has been prepared. In this study, 5'-amino-terminal DNA probes were covalently immobilized by reaction with succinimidyl ester residues in acrylamide-based polymer matrices. DNA sensor arrays of three different oligonucleotide probes, p(dA)(18-mer), H-ras wild-type (10-mer), and H-ras mutant (11-mer) were fabricated, and real-time hybridization of 5'-fluorescein isothiocyanate (FITC)-labeled target oligonucleotides to the array was monitored. H-ras wild-type and Eta-ras mutant differ by a one-base substitution (point mutation) and were used to demonstrate the sensor's ability to distinguish point mutations. Thermal studies indicated a 13 degrees C decrease in the Tm of a duplex with a single-base mismatch. The fiberoptic DNA sensor array was used to discriminate a point mutation by monitoring the real-time hybridization of FITC-labeled target oligonucleotides at 54 degrees C and detected labeled-target oligonucleotides in the range 0.2-196 nM. The lower detection limit is approximately an order of magnitude lower than previously reported DNA biosensors. The DNA sensor array was used to positively identify a point mutation of a biotin-primer-labeled (109 bp) PCR product of the H-ras oncogene. The unitary fiberoptic sensor array is highly sensitive, has the ability to determine point mutations, and has the potential to sample submicroliter volumes due to the small volumes of the individual array elements (20 pL).

Fast temporal response fiber-optic chemical sensors based on the photodeposition of micrometer-scale polymer arrays.

Fiber-optic chemical sensor microarrays for the detection of pH and O2 have been developed with subsecond response times. Sensor microarrays are fabricated by the covalent immobilization (pH sensor arrays) or the physical entrapment (O2 sensor arrays) of fluorescent indicators in photodeposited polymer matrices on optical imaging fibers. Polymer microarrays are comprised of thousands of individual elements photodeposited as hemispheres such that each element of the sensor array is coupled directly to a discrete optical element of the imaging fiber and is not in contact with other neighboring elements. Because of the hemispherical shape and the individuality of the array elements, diffusion of analyte to the sensor elements is dominated by radial diffusion, resulting in a rapid response time. pH-sensitive arrays based on fluorescein respond to a 1.5-unit pH change within 300 ms, while the O2-sensitive arrays respond to O2 changes within 200 ms (90% of steady state response).

Multianalyte biosensors on optical imaging bundles.

We present an optical biosensor design that expands the utility of enzyme biosensors. These biosensors are fabricated by site-selective photodeposition of analyte-sensitive polymer matrices on optical imaging fibres. These dual-analyte arrays allow for the simultaneous, independent measurement of the analyte of interest and the transducing analyte. The first integrated optical-biosensors using this design have been prepared that allow both the dependent and independent analytes to be measured simultaneously, for example penicillin and pH (Healey & Walt, 1995) or glucose and O2 (Li & Walt, 1995). Independent measurement of the transducing analyte allows penicillin or glucose to be quantitated in the presence of a concurrent pH or O2 change, respectively. Penicillin can be measured in the range 0.25-10.0 mM in the pH range 6.2-7.5. Glucose can be measured in the range 0.6-20.0 mM in the O2 range 20-100%. The utility of the sensor design was demonstrated by using the penicillin-dual-analyte biosensor to quantitate penicillin produced during a Penicillium chrysogenum fermentation.

Concurrent 72-hour continuous infusion of etoposide and cisplatin in metastatic breast cancer.

We conducted a multiinstitutional phase II clinical trial to determine the toxicity, response, and survival rate of concurrent 72-h continuous infusion of etoposide and cisplatin in patients with metastatic breast cancer. A total of 26 women were enrolled, 4 of whom received no prior chemotherapy for metastatic disease. All patients were evaluated for toxicity, response, and survival employing the National Cancer Institute (NCI) Common Toxicity Criteria and the Eastern Cooperative Oncology Group (ECOG) response criteria. A total of 84 cycles of therapy were administered, median 3 (range 1 to 6). Severe grade 3 and grade 4 neutropenia occurred in 22 cycles (26%), and there were only 11 episodes (11%) of similar grade thrombocytopenia. Nausea and vomiting were seen in one third of cycles. A single patient (4%) had a complete remission, and seven patients (27%) had partial remissions for an overall objective response rate of 31% (95% confidence interval, 13 to 49%). Three of four patients (75%) without prior therapy for metastatic disease had objective responses. Median survival was 7 months. This combination regimen is active in extensively treated patients with metastatic breast cancer. It is responsible to further investigate the role of etoposide-cisplatin combination chemotherapy as firstline therapy for patients with metastatic breast cancer.

Improved fiber-optic chemical sensor for penicillin.

An optical penicillin biosensor is described, based on the enzyme penicillinase. The sensor is fabricated by selective photodeposition of analyte-sensitive polymer matrices on optical imaging fibers. The penicillin-sensitive matrices are fabricated by immobilizing the enzyme as micrometer-sized particles in a polymer hydrogel with a covalently bound pH indicator. An array of penicillin-sensitive and pH-sensitive matrices are fabricated on the same fiber. This array allows for the simultaneous, independent measurement of pH and penicillin. Independent measurement of the two analytes allows penicillin to be quantitated in the presence of a concurrent pH change. An analysis was conducted of enzyme kinetic parameters in order to model the penicillin response of the sensor at all pH values. This analysis accounts for the varying activity of the immobilized penicillinase at different pH values. The sensor detects penicillin in the range 0.25-10.0 mM in the pH range 6.2-7.5. The sensor was used to quantify penicillin concentration produced during a Penicillium chrysogenum fermentation.

Photodeposition of micrometer-scale polymer patterns on optical imaging fibers.

Microstructures were fabricated on optical imaging fibers with a photopolymerization technique. Monodisperse polymeric microarrays were produced containing spots of 2.5 micrometers in diameter spaced 4.5 micrometers apart. Polymer microarrays were also deposited on other substrates by using imaging fibers for light delivery. The technique allows micrometer-scale photopatterning with masks larger than the desired dimensions.

Primary lymphoma of the penis with rationale of treatment.

Appropriate care of a patient with primary lymphoma of the penis requires consideration of the diagnoses, thorough evaluation, and knowledge of the various therapeutic approaches. A patient is presented with brief review of similar cases together with the rationale for the use of radiation therapy and chemotherapy rather than surgery.

"Eight-drugs-in-one-day" chemotherapy administered before and after radiotherapy to adult patients with malignant gliomas.

Thirty-one adult patients with malignant glioma (23 with glioblastoma multiforme, six with anaplastic astrocytoma, and two with brainstem glioma) were treated with up to ten cycles of "eight-drugs-in-one-day" chemotherapy (methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 [maximum of 2 mg/cycle], CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2). Chemotherapy was planned as two cycles before and eight cycles after 60 Gy of involved brain irradiation. A total of 117 cycles of chemotherapy was administered. There was one treatment-related death. Myelosuppression was the most frequent toxic effect (leucopenia was less than 1000/mm3 in 9% of cycles and 1000-2500/mm3 in 25%; thrombocytopenia was less than 100,000/mm3 in 33% of cycles). Sixteen patients developed infections requiring treatment, two of which were life-threatening. Five patients suffered ototoxicity. Nausea and vomiting were observed in 35% of patients. A reversible rise in creatinine was observed in five patients. One patient developed a severe motor neuropathy, and three patients developed mild peripheral neuropathies. Three patients had episodes of atrial fibrillation. One new bundle branch block with supraventricular tachycardia was observed in a patient with pulmonary embolus. Five patients developed thrombophlebitis, three of whom had pulmonary emboli. Two patients suffered strokes in areas anatomically separate from their tumor. Eleven patients declined to continue therapy after receiving an average of three cycles. Two had complete, and five had partial responses. The median survival time was 47 weeks. The responses and survival times observed are comparable to less toxic treatment protocols for adults with malignant gliomas.

Eight-drugs-in-one-day chemotherapy in postirradiated adult patients with malignant gliomas.

Fifteen patients, 12 with glioblastoma multiforme and 3 with anaplastic astrocytoma, were treated with "eight-drugs-in-one-day" chemotherapy [methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 (maximum of 2 mg/cycle), CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3,000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2]. All patients had prior brain irradiation but none had previous chemotherapy. The population included 10 patients with progressive disease after irradiation and 5 who presented within 2 months of completing radiation. Patients received an average of 5 monthly cycles of chemotherapy. Three patients achieved a complete and 2 a partial response (CR + PRrate was 33%). The median survival time was 46 weeks. Myelosuppression was the dose-limiting toxicity. Leucocyte counts between 2.0-4.5 x 10(3)/mm3 were observed in 40% of patients, between 1.0- less than 2.0 x 10(3)/mm3 in 33%, and less than 1.0 x 10(3)/mm3 in 7%. Platelet counts between 50-130 x 10(3)/mm3 were observed in 27% of patients, and less than 50 x 10(3)/mm3 in 33%. Six patients suffered infections, 4 had reversible renal toxicity, 2 developed paresthesias, and one a debilitating myopathy related to treatment with dexamethasone. Ototoxicity was seen in 3 patients. Two patients developed pulmonary emboli. Nine patients had nausea and vomiting, in one case associated with Candida esophagitis. One long-term survivor developed necrosis of the corpus callosum and dementia. Four patients discontinued treatment after an average of 3.5 cycles because of toxicity. Although extremely toxic, this regimen has modest activity in previously irradiated adult patients with malignant glioma.