Neurological factors and Cesarean section in Australian women with epilepsy.

OBJECTIVES: To analyze the records of the pregnancies of 2283 Australian women with epilepsy in the Australian Register of Antiepileptic Drugs in Pregnancy database to identify neurological factors relevant to the Cesarean sections carried out in these pregnancies. RESULTS: The Cesarean section rate in Australian women overall increased by an average of 0.59% annually over 20 years, from 26.0% to its calculated 2020 value of 37.3%. For the operations in women with epilepsy, the corresponding figures were 0.71% annually, and 34.4% and 48.7%. The average annual rate of increase for pre-labor operations was 0.89% to a 2020 value of 39.1%, the annual rate for operations during labor showing no statistically significant change. Multivariate regression analysis identified a number of characteristics of women with epilepsy that were statistically significantly associated with an increased likelihood of Cesarean section, but of these only seizures continuing to occur in the third trimester and having chronic illness, in particular migraine, were neurological ones. In 70 migraine-affected women, the Cesarean section rate was 51.4%, compared with 39% in the remaining pregnancies (P < 0.05). CONCLUSIONS: Having seizures in the final trimester of pregnancy and having chronic neurological illness, especially migraine, favored Cesarean section being carried out in Australian women with epilepsy, but did not adequately account for the increasing rates of occurrence of the operation over the past 20 years.

Antiepileptic drug polytherapy in pregnant women with epilepsy.

OBJECTIVE: To study seizure control and rates of foetal malformation in pregnancies of women with epilepsy treated with antiepileptic drug polytherapy. METHODS: The use of conventional statistical methods to analyse the Australian Pregnancy Register records of 1810 pregnancies in women with epilepsy, 508 treated with antiepileptic drug polytherapy. RESULTS: Polytherapy-treated pregnancies were less often seizure free than monotherapy-treated ones, for both focal (36.0% vs 51.9%: P < .05) and primary generalized epilepsies (41.1% vs 69.3%; P < .05). Drug combinations with dissimilar and similar mechanisms of action achieved similar rates of seizure freedom during pregnancy (36.3% vs 38.3%). The increased rate of malformed foetuses in polytherapy pregnancies depended on valproate or topiramate being in the drug combinations. The combinations of lamotrigine and levetiracetam offered the chance of seizure control and foetal safety. CONCLUSIONS: In pregnancy, the use of antiepileptic drug combinations is not necessarily disadvantageous to mother and foetus if valproate and topiramate are avoided.

Predicting epileptic seizure control during pregnancy.

OBJECTIVE: The objective of the study was to assess whether the type of seizure disorder present in the prospective mother with epilepsy, her use of antiepileptic drugs (AEDs) in early pregnancy, and her seizure control before pregnancy help predict her prospects for seizure freedom throughout pregnancy. METHODS: This paper is based on data accumulated in the Australian Pregnancy Register (APR) between 1998 and late 2016. Information was analyzed concerning epileptic seizure occurrence and AED therapy taken before and during pregnancy, using simple statistical and confidence interval (C.I.) methods, mainly relative risk (R.R.) calculations. RESULTS: After excluding pregnancies lost to follow-up, and those that ended prematurely because of spontaneous abortion or stillbirth, 1939 pregnancies were available for study. Seizures had occurred during pregnancy in 829 (42.8%), and convulsive seizures in 385 (19.9%). Seizures of any type occurred in 78.4% of pregnancies where seizures had occurred in the previous year (active epilepsy) and in 22.3% of those associated with inactive epilepsy. Seizures of any type had occurred in 54.9% of pregnancies initially unexposed to AEDs and in 45.5% of those treated with AEDs throughout. The corresponding figures for convulsive seizures during pregnancy were 31.7% and 22.3%. There was statistically significant evidence that, in women with epilepsy (WWE), having a seizure disorder that was active in the prepregnancy year and one untreated in early pregnancy was associated with decreased prospects of seizure freedom during pregnancy. Decreased chances of seizure-free pregnancies in women with focal epilepsies and those treated with multiple AEDs were probably explained by greater frequencies of active seizure disorders in these patient categories. CONCLUSIONS: Women with epilepsy who experience seizures in the year prior to pregnancy appear 3 or 4 times more likely to continue to have seizures during pregnancy than women whose seizures are fully controlled prior to pregnancy. Not taking AEDs in early pregnancy also increases the hazard for seizure occurrence in pregnancy.

Antiepileptic drugs, foetal malformations and spontaneous abortions.

BACKGROUND: Some recent studies have found an association between foetal malformations in earlier antiepileptic drug (AED)-exposed pregnancies and an increased hazard of such malformations in subsequent pregnancies. We investigated this matter further, and also considered the possible role of spontaneous abortions in previous pregnancies, in this situation. METHODS: Analysis of foetal malformation data for current and previous pregnancies in women taking AEDs and women with untreated epilepsy in the Australian Register of Antiepileptic Drugs in Pregnancy (APR) from 1999 to late 2014. RESULTS: Antiepileptic drug-treated women with either a malformed foetus or a spontaneous abortion in their previous pregnancy had a statistically significant twofold to threefold increased risk of foetal malformation in their next pregnancy, compared with similarly treated women with normal offspring in their previous pregnancy. This was not seen in the same circumstances in women with untreated epilepsy. On AED treatment, the women were more likely to have spontaneous abortions than in their previous untreated pregnancies. Possibly some of the increased abortion rate resulted from drug-related malformations that were incompatible with continuing intrauterine survival. CONCLUSIONS: In assessing the hazard of an AED-treated woman having a malformed foetus, it is important to know both the AEDs being taken and, if there had been a previous pregnancy, whether a foetal malformation or a spontaneous abortion occurred in it.

Improving transfusion education for junior doctors; exploring UK experiences.

OBJECTIVES: To provide evidence-based guidance on how transfusion education should be delivered to junior doctors by employing established qualitative research methodology. BACKGROUND: There is a global call for increased transfusion education for doctors to support the delivery of evidence-based practice. Education is reported as an effective measure to improve transfusion practice, although there is a paucity of research evaluating how this should be effectively delivered. METHODS: Serial focus groups with junior doctors and relevant healthcare professionals explored experiences of, and reactions to, education and competency assessments in transfusion, which were audio-recorded and transcribed. Temporal and final analysis, performed by two independent assessors, informed subsequent recruitment, analysis and challenging of emerging theories - until saturation was reached. RESULTS: Eight focus groups were held involving 53 personnel, 77% of whom were junior doctors. Current transfusion education for doctors in the UK is reliant on e-learning and 'cascade training' (on-the-job from senior clinicians/nursing staff). E-learning is viewed as a 'tick box exercise'. There is a call for relevant and practical continuing education delivered face to face by good educators in an environment away from clinical practice. Preferred methods include small group and simulation learning based on real-life cases. In contrast to practical competency, the assessment of clinical competency is deemed unfeasible. CONCLUSION: Current methods of transfusion education employed in the UK are unsatisfactory to ensure safe transfusion practice. Ongoing education is deemed necessary throughout career progression, and suggested improvements include increased emphasis on face-to-face teaching and simulation training. Employed educational methods and decision support tools require appropriate evaluation.

Transfusion e-learning for junior doctors: the educational role of 'LearnBloodTransfusion'.

OBJECTIVES: To critically analyse the educational role of 'LearnBloodTransfusion' (LBT) in enabling junior doctors to be safe transfusion practitioners. BACKGROUND: Computer assisted learning, or e-learning, enables the educational needs of learners to be flexibly met. Education and learning in the health service is necessary to ensure appropriate skills, behaviours and training are provided, to assure excellence in healthcare delivery. LBT is a computer-assisted learning programme that has been designed to meet the needs of practitioners involved in the transfusion process. It is widely adopted across the NHS and within undergraduate medical training. METHOD: Critical analysis of LBT relating to learning outcomes, assessment tools and functionality, as pertaining to the transfusion curriculum for junior doctors. RESULTS: Learning outcomes of LBT adhere to Bloom's taxonomy, addressing cognitive, psycho-motor and affective domains of learning. LBT flexibly meets differing styles, strategies and levels of learning although there is scope to enhance the computer-facilitated flexibility of this learning tool. LBT is unable to address the complex clinical reasoning skills or clinical competency required by doctors in the transfusion process. CONCLUSION: LBT uses effective educational methodology to deliver the transfusion curriculum to junior doctors although LBT must be complemented by additional methods of learning to ensure clinical competency.

Community participation patterns among preschool-aged children who have received Part C early intervention services.

BACKGROUND: We examined activity-specific patterns and child, family and environmental correlates of participation restriction in nine community-based activities among preschoolers with disabilities who have received Part C early intervention services. METHODS: Data were gathered from a subsample of 1509 caregivers whose children (mean age = 67.7 months) had enrolled in the National Early Intervention Longitudinal Study (NEILS) and completed a 40-min computerized telephone interview or 12-page mailed survey. Data were analysed on cases with complete data on the variables of interest. Bivariate relationships were examined between variables, including patterns of co-reporting participation difficulties for pairs of community activities. RESULTS: Caregivers were more than twice as likely to report difficulty in one activity (20%) than difficulties in 2-3, 4-5, or 6-9 activities. Co-reporting paired difficulties was strong for activities pertaining to neighbourhood outings but less conclusive for community-sponsored activities and recreation and leisure activities. Our data show strong and positive associations between child functional limitations in mobility, toileting, feeding, speech, safety awareness, and friendships and participation difficulty in 7-9 activities. Lower household income was associated with participation difficulty in 7 out of 9 activities and difficulty managing problematic behaviour was strongly associated with participation difficulty in all 9 activities. Each of the three environmental variables (limited access to social support, transportation and respite) was associated with participation restrictions in all nine activities. CONCLUSION: Results provide practitioners with detailed descriptive knowledge about modifiable factors related to the child, family and environment for promoting young children's community participation, as well information to support development of a comprehensive assessment tool for research and intervention planning to promote community participation for children enrolled in early intervention.

COVID-19 vaccination in pregnancy: How discrepant public health discourses shape responsibility for fetal health.

Early in COVID-19 vaccine rollout, expert recommendations about vaccination while pregnant and breastfeeding changed rapidly. This paper addresses the (re)production of gendered power relations in these expert discourses and recommendations in Canada. We collected texts about COVID-19 vaccine use in pregnancy (N â€‹= â€‹52) that Canadian health organizations (e.g., professional societies, advisory groups, health authorities) and vaccine manufacturers made publicly available online. A discourse analysis was undertaken to investigate intertextuality (relations between texts), social construction (incorporation of assumptions about gender), and contradictions between and within texts. National expert recommendations varied in stating COVID-19 vaccines are recommended, should be offered, or may be offered, while manufacturer texts consistently stated there was no evidence. Provincial and territorial texts reproduced discrepancies between the Society of Obstetricians and Gynaecologists of Canada and National Advisory Committee on Immunization recommendations, including that COVID-19 vaccines should be versus may be offered in pregnancy. Our findings suggest gaps in data and discrepant COVID-19 vaccine recommendations, eligibility, and messaging limit guidance regarding vaccination in pregnancy. We argue that these discrepancies magnified the already common practice of deferring responsibility for the uncertainties of vaccination in pregnancy onto parents and healthcare providers. The deferral of responsibility could be reduced by harmonizing recommendations, regularly updating texts that describe evidence and recommendations, and prioritizing research into disease burden, vaccine safety, and efficacy before vaccine rollout.

Antiepileptic drugs and foetal malformation: analysis of 20 years of data in a pregnancy register.

PURPOSE: This paper reports additional data supplementing earlier publications based on Australian Pregnancy Register (APR) data. METHOD: Over 20 years, the APR has collected Information on pregnancies in Australian women with epilepsy (WWE), untreated WWE and those taking AEDs for other indications. Contact is by telephone, at set intervals. Treatment is not interfered with. Data are analysed using conventional statistical techniques, confidence interval methods, and logistic regression. RESULTS: By 2018, the APR contained details of 2148 pregnancies. AEDs were taken throughout 1972 of the pregnancies (91.8%). The remaining 176 (8.2%) did not receive AEDs, at least early in pregnancy. There were (i) dose-related increased incidences of pregnancies carrying foetal malformations associated with maternal intake of valproate and topiramate when topiramate was a component of AED polytherapy (P < .05), (ii) a similar dose-related trend in relation to carbamazepine intake, (iii) no evidence that levetiracetam and lamotrigine were unsafe from the foetal standpoint, (iv) insufficient data to permit conclusions regarding teratogenicity in relation to other AEDs, and (v) no evidence that pre-conception folate supplementation reduced the hazard of AED-associated foetal malformation. AED polytherapy did not increase foetal hazard unless valproate or topiramate was involved in the AED combination. Genetic factors probably contributed to the malformation hazard. Seizures occurring in earlier pregnancy probably did not contribute to the malformation hazard. CONCLUSIONS: If it were not for the importance of maintaining seizure control, the above findings suggest that it would be better to avoid using certain AEDs, particularly valproate and topiramate, during pregnancy.

Do health care providers trust product monograph information regarding use of vaccines in pregnancy? A qualitative study.

BACKGROUND: Influenza immunization is recommended in pregnancy to prevent severe infections in pregnant women and newborns, yet vaccine uptake remains low. Studies suggest that cautionary language in vaccine product monographs regarding safety and use in pregnancy affects health care providers' perceptions of vaccine safety and how they counsel pregnant women. OBJECTIVE: To conduct a qualitative analysis of health care provider perceptions of the safety of inactivated influenza vaccines and their recommendations for use in pregnancy based on product monograph language statements. METHODS: Health care providers were recruited at two international health conferences and from teaching programs in Ethiopia, Ghana, Uganda, and Laos during September and October 2015. After reading the product monograph excerpts for three licensed inactivated influenza vaccines, participants completed a ten-item online survey with quantitative and qualitative components that captured perceptions of vaccine safety. RESULTS: Health care providers identified a lack of trust in manufacturers' and product monograph information. They perceived product monograph language as ambiguous and not "up-to-date" with current evidence. Health care providers wanted product monograph language that clearly conveyed evidence for the risks and benefits of the vaccine in an understandable manner. CONCLUSION: This study suggests that adopting best practices in the wording of product monographs would help to support evidence-based use of vaccines in pregnant women.

Greek adaptation and validation of the Ankylosing Spondylitis Quality of Life (ASQoL) measure.

BACKGROUND: Ankylosing Spondylitis (AS) is a chronic rheumatic disease that has a significant impact on patient's quality of life (QoL). The Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire is a disease-specific patient-reported outcome measure for assessing QoL in AS. While the ASQoL has been adapted for use in 46 countries worldwide, a Greek language version of the measure has not been available and was required for an international clinical trial. AIM: The aim was to develop and assess the psychometric properties of a Greek language version of the ASQoL. METHODS: The adaptation of the ASQoL into Greek involved three procedures: translation, assessment of face and content validity, and formal validation. The measure was translated into Greek using two translation panels. Cognitive debriefing interviews were employed to determine face and content validity. Finally, the translation's psychometric properties were examined by administering it on two occasions, with a 14-day interval. The Nottingham Health Profile (NHP) was used as a comparator measure. RESULTS: The ASQoL proved straightforward to translate into Greek and interviewees found it relevant, comprehensible and easy to complete.  The measure had good internal consistency (α =0.92) and test-retest reliability (r =0.98). Predicted correlations with the NHP provided evidence of the convergent validity of the two measures. Construct validity was confirmed by the measure's ability to distinguish groups of AS patients varying by perceived disease severity and general health. CONCLUSIONS: The Greek ASQoL has been shown to be well-accepted, reliable and valid and can be recommended for use in clinical studies and routine clinical practice in AS. Hippokratia 2015; 19 (2):119-124.

Results of radiotherapeutic management of primary carcinoma of the vagina.

Forty-five previously untreated patients with primary carcinoma of the vagina were treated with curative radiotherapy from 1965 through 1985. All patients were staged according to the FIGO system. One patient was classified as Stage 0, 15 as Stage I, 22 as Stage II, 6 as Stage III, and 1 as Stage IV. Treatment consisted of intracavitary irradiation alone in Stage 0 patients. Stage I patients received intracavitary/interstitial irradiation alone or in combination with external irradiation and an implant when feasible. When treated with an implant only, the total tumor dose delivered was between 65-70 Gy. External irradiation consisted of delivering a dose of 45-50 Gy over a period of 4 1/2-5 weeks to the whole pelvis to treat the regional lymph nodes. An additional dose of 20-25 Gy was delivered to the site of original involvement using an implant when feasible. If not technically feasible, as in advanced stages, the patient was treated with additional external irradiation to a total dose of 65-70 Gy by a shrinking field technique. All patients except one were followed either until death or for a minimum of 2 years. The actuarial 5-year survival rates were 100% for Stage 0, 78% for Stage I, and 71% for Stage II patients. None of the patients with Stage III or IV disease survived. Of the patients who recurred, all but two did so within 16 months after diagnosis. Pelvic recurrence as the first site of recurrence occurred in 86% of the patients who recurred. Distant recurrence as a component occurred in 20% of all failures. Complications as a consequence of therapy occurred in 18% of the patients. Vaginal necrosis that healed with conservative treatment was seen in four patients and the other four patients had rectal complications of varying severity. Thus, curative radiotherapy is an effective method of treatment, with acceptable morbidity, in patients with early stage primary carcinoma of the vagina.

Egocenter location in children with strabismus: in the median plane and unchanged by surgery.

PURPOSE: Previous studies have shown that there are spatial localization shifts after horizontal strabismus surgery when a patient performs an open-loop pointing task. After monocular enucleation, an adult will also show a shift in the pointing response. Other studies have shown that in children who underwent enucleation, the egocenter location shifts toward the remaining eye. Is the pointing shift after surgery in children with strabismus the result of a shift in egocenter location? METHODS: Using a modified Roelofs' method for measuring the egocenter, eight children were tested before and after horizontal strabismus surgery to see if there were any shifts in egocenter location. One control group consisted of six children undergoing surgery for correction of vertical strabismus in which the horizontal muscles would be unaltered. RESULTS: Presurgery measurements of egocenter location in the people with strabismus were the same as those found in the other control group of 12 normal children. Postsurgical measurements of eye position showed horizontal rotations of 14.5 degrees for the horizontal group and 2.4 degrees for the vertical group. Egocenter measurements showed no postoperative shift for either strabismus group. CONCLUSIONS: Thus, the pointing shift seen in the previous studies is not from a shifting egocenter location but from a change in the registered position of the eye in the orbit.

Adenylate cyclase from term human placenta and its regulation.

The activation of placental AC by either Mg2+ or Mn2+, in the presence and absence of NaF, followed sigmoidal saturation kinetics. Mn2+ enhanced maximally the NaF-stimulated Mg2+-dependent AC activity. The apparent Km of Mg2+-dependent AC for ATP was 0.4 mM, with and without NaF addition. GTP and GMP-P(NH)P stimulated the Mg2+-dependent AC in a dose-dependent manner with half-maximal stimulation taking place at concentrations of approximately 2 microM. In the presence of GMP-P(NH)P (10 microM) the kinetics of the AC dependence on Mg2+ ion concentration changed from sigmoidal to hyperbolic. Most of the AC activity (greater than 83 per cent) was associated with the particulate fractions of placental homogenate. For better reproducibility, the AC assay was performed using sonicated particulate fraction preparations; sonication did not alter the response of AC to stimuli to a variety of agents used in these experiments; freezing and thawing, however, obliterated the stimulation by beta-adrenergic agonists. Placental AC activity was inhibited by p-hydroxymercuriphenyl sodium sulphonate in a dose-dependent fashion, and the inhibition was reversed by dithiothreitol. Mg2+-dependent AC was inhibited by 0.5 mM phenylhydrazine (95 per cent). Mg2+-dependent AC activity was responsive to stimulation by epinephrine, without and with GTP addition, with half-maximal stimulation taking place at a concentration of 2 microM. The stimulatory effect of epinephrine was blocked by propranolol in a dose-dependent manner but was not blocked by phentolamine. Oestrone, oestradiol-17 beta, 2-hydroxyoestreone, 2-hydroxyoestradiol-17 beta, dehydroepiandrosterone sulphate, and progesterone, as well as oxytocin, did not alter either the basal or GMP-P(NH)P-stimulated Mg2+-dependent AC activities. Preincubation of 20 000 g particulate fraction with either NaF or GMP-P(NH)P, followed by washing, resulted in preparations that remained stimulated without the requirement of any further additions.

Significant improvement in flow through a potential internal mammary graft after partial approximation of the sternum.

A large internal mammary artery provided inadequate flow on testing, but its use was fortunately not abandoned until after partial closure of the sternal retractor. Reassessment following this maneuver identified ample flow.

Coronary revascularization in patients with bilateral internal carotid occlusions.

Coronary revascularization that is neurologically uneventful in patients with bilateral totally occluded internal carotid arteries has not been previously reported. We performed saphenous vein coronary artery bypass grafting on three such patients and observed them for 6 to 23 months. Preoperatively two of our patients had chronic stable symptoms of cerebrovascular insufficiency, and one had received cerebral revascularization via a superficial temporal-to-middle cerebral artery bypass. Controversy exists regarding proper cerebral protective maneuvers during coronary revascularization for patients with advanced cerebrovascular disease. Cerebral protection for our patients during cardiopulmonary bypass included hypothermia and high perfusion flows and pressures. Two patients also received prophylactic sodium thiopental. None of these three patients had a stroke perioperatively or during the follow-up period. We believe that these case histories strongly suggest that the functional state of the cerebral collateral circulation, as judged by preoperative neurological symptoms, predicts neurological outcome after coronary revascularization better than the specific occlusive anatomy of the extracranial carotid arteries.

Clinicopathologic case reports: Optic nerve head metastasis.

A case of tumor metastasis from carcinoma of the lung directly to the cribriform plate is described. Retina and optic nerve were involved, but there was no evidence of tumor invasion of the choroid. It is postulated that the original tumor embolus lodged in a cribriform branch of the arterial circle of Zinn or in the central retinal vessels.

The rate of decline in function in Alzheimer's disease and other dementias.

BACKGROUND: Functional impairment over time is a necessary condition for the diagnosis of dementia. Increasingly, it is recognized that rates of decline may not follow a linear progression. This variability may indicate that dementia in Alzheimer's disease represents disease rather than inevitable aging. In order to investigate decline in function in dementia, we developed a model of the rate of decline in functions in Alzheimer's disease and in other dementias in comparison with normal aging. METHODS: Secondary analysis of a cross-sectional, representative sample of Canadians aged 65 and older (N = 2,914) was performed. We calculated a measure identified as an impairment index, defined as the probability of the occurrences of an impairment or disability in a structured clinical examination. RESULTS: The rate of functional decline varies for different diagnostic groups and increases with severity of the disease. The distribution for the rate of decline in dementia is distinct from that in aging without cognitive impairment. In those without cognitive impairment, the distribution is exponential. Elderly persons with dementia of any type showed a log-normal distribution. CONCLUSIONS: The difference in the distributions between aging with and without dementia likely reflects fundamental differences in the processes of decline in functions in the two groups. This suggests that the declines seen in persons with dementia are distinct from normal aging. It also has implications for the testing of antidementia medications, in that modeling treatment effects based on an assumption of linear decline is likely to be flawed.

Hemodynamic effects of intraaortic administration of protamine.

Seventy-nine consecutive patients were given protamine rapidly into the ascending aorta during neutralization of heparin at the end of cardiopulmonary bypass. Simultaneously left atrial, diastolic pulmonary arterial, or right atrial pressures were maintained constant by appropriate infusion of oxygenated blood into the aorta. The systemic and pulmonary vascular resistances did not change, mean arterial blood pressure increased slightly, and cardiac output increased significantly (p less than 0.001). It seems that this method of heparin neutralization is safe provided that the intravascular volume can be maintained constant.

Infectious morbidity in gynecologic oncology.

Infectious complications are the most frequent cause of death in cancer patients. Broad-spectrum antibacterial therapy is dictated by the polymicrobial nature of infections encountered in gynecologic oncology and is imperative in the empiric therapy of febrile granulocytopenic patients. In addition, the potential for infectious complications after radical pelvic surgery to remove malignancies has influenced most gynecologic oncologists to recommend prophylactic antibiotics. However, the choice of appropriate antibacterial therapy in gynecologic oncology patients is complicated frequently by impaired renal function secondary to cancer chemotherapy or associated with age in this generally elderly population. In addition, the potential cost- and time-saving advantages of simplified antibacterial regimens have resulted in a reexamination of the standard aminoglycoside-containing multiple-drug regimens. The efficacy and safety of monotherapy with broad-spectrum beta-lactam antibiotics or beta-lactam-antibiotic/beta-lactamase-inhibitor combinations, such as ticarcillin/clavulanate, remain to be confirmed in gynecologic oncology patients. The broad spectrum of ticarcillin/clavulanate, including gram-negative and -positive aerobic and anaerobic bacteria, seems plausible for the treatment of these potentially devastating infections.