Female urethral stricture disease

Female urethral stricture disease is a rare entity. The most common etiologies are traumatic injury, iatrogenic injury, and inflammatory disease resulting in periurethral fibrosis. Hallmark symptoms are frequency and urgency, and may also be dysuria, hesitancy, slow stream, incontinence, and recurrent urinary tract infections. Female bladder outlet obstruction is a difficult entity to define, and the subset representing stricture disease may also be elusive. The diagnosis of female urethral stricture disease is usually based on symptoms, meatal appearance, and difficult instrumentation of the patient. Other testing, such as urodynamics, voiding urography, or cystoscopy, may be helpful. Treatment options are conservative management with dilatation, endoscopic treatment, or open repair with various tissue flaps or grafts. Considerable controversy surrounds the efficacy of urethral dilatation in women with voiding dysfunction.     

Sedation in the neurologic intensive care unit

Opinion statement Providing adequate sedation in the neurologic intensive care unit (ICU) depends on determination of proper goals for sedation, adequate assessment of the level of sedation, and appropriate choice of drug based on the patient’s physiology. The management of sedation in the ICU will influence long-term outcome. Delirium, anxiety, and pain must be identified and treated separately. The use of protocols can improve compliance with published evidence-based recommendations. Propofol and dexmedetomidine may be used for rapidly titratable sedation, benzodiazepines for anxiolysis, neuroleptics for treatment of delirium, and opiates for analgesia. Unique aspects of patients with acute brain disease, such as elevated intracranial pressure or status epilepticus, require adaptation of sedative regimens. Processed EEG monitoring and volatile anesthetic agents have not yet proven beneficial or practical for use in the ICU.     

Autoimmune myelopathy associated with collapsin response-mediator protein-5 immunoglobulin G

Several autoimmune myelopathies are recognized clinically. We describe 57 patients in whom serological evaluation for myelopathy of uncertain cause demonstrated collapsin response-mediator protein 5 IgG. Most had spinal imaging and cerebrospinal fluid abnormalities and insidiously progressive presentation; some had acute monophasic or relapsing myelopathy. Initial diagnoses included multiple sclerosis, transverse myelitis, and unspecified neurodegenerative myelopathy. Most were smokers; neoplasia was discovered in 68% (most commonly small-cell lung carcinoma and after collapsin response-mediator protein-5 IgG detection). Collapsin response-mediator protein-5 autoimmune myelopathy and occult neoplasia are important considerations in patients with insidiously progressive myelopathy, especially with known cancer risk.     

FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer

On October 11, 2006, the U.S. Food and Drug Administration granted approval for bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA), administered in combination with carboplatin and paclitaxel, for the initial treatment of patients with unresectable, locally advanced, recurrent, or metastatic, nonsquamous, non-small cell lung cancer (NSCLC). Approval is based on a significant improvement in overall survival (OS). A randomized, open label, multicenter clinical trial, conducted by the Eastern Cooperative Oncology Group (ECOG), in chemotherapy-na?ve patients with stage IIIB/IV nonsquamous NSCLC, evaluated bevacizumab plus carboplatin and paclitaxel (BV/CP, n = 434) versus carboplatin and paclitaxel alone (CP, n = 444). Exclusion of patients with squamous or predominantly squamous histology was based on life-threatening or fatal hemoptysis occurring in 4 of 13 patients with squamous histology who received a BV/CP regimen in a phase II study. Among the 878 randomized patients, the median age was 63, 46% were female, 76% had stage IV disease, 12% had stage IIIB disease with malignant pleural effusion, 11% had recurrent disease, and 40% had an ECOG performance status score of 0. OS was significantly longer in patients receiving BV/CP than in those receiving CP alone (median OS, 12.3 versus 10.3 months; hazard ratio [HR], 0.80; p = .013, stratified log rank test). Although a consistent effect was observed across most subgroups, in an exploratory analysis, evidence of a survival benefit was not observed in women (HR, 0.99; 95% confidence interval, 0.79-1.25). Severe and life-threatening adverse events occurring more frequently in patients receiving BV/CP were neutropenia (27% versus 17%), fatigue (16% versus 13%), hypertension (8% versus 0.7%), infection without neutropenia (7% versus 3%), thrombosis/embolism (5% versus 3%), pneumonitis or pulmonary infiltrate (5% versus 3%), infection with grade 3 or 4 neutropenia (5% versus 2%), febrile neutropenia (5% versus 2%), hyponatremia (4% versus 1%), proteinuria (3% versus 0), and headache (3% versus 0.5%). Fatal, treatment-related adverse events in patients receiving bevacizumab were pulmonary hemorrhage (2.3% versus 0.5%), gastrointestinal hemorrhage, central nervous system infarction, gastrointestinal perforation, myocardial infarction, and neutropenic sepsis. The most serious, and sometimes fatal, bevacizumab toxicities are gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, congestive heart failure, and neutropenic sepsis. The most common adverse events in patients receiving bevacizumab are asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis, and proteinuria.     

Replication of genetic associations in the inflammation, complement, and coagulation pathways with intraventricular hemorrhage in LBW preterm neonates

Intraventricular hemorrhage (IVH) is a significant morbidity seen in very LBW infants. Genes related to the inflammation, infection, complement, or coagulation pathways have been implicated as risk factors for IVH. We examined 10 candidate genes for associations with IVH in 271 preterm infants (64 with IVH grades I-IV and 207 without IVH) weighing <1500 g. The heterozygous genotype OR = 8.1, CI = 2.5-26.0, p = 4 × 10(-4)) and the A allele (OR = 7.3, CI = 2.4-22.5, p = 1 × 10(-4)) of the coagulation factor V (FV) Leiden mutation (rs6025) were associated with an increased risk of developing IVH grade I or II but not grade III or IV after correction for multiple testing with Bonferroni. Lack of association in the severe grades of IVH may be a result of lack of power to detect an effect given the small sample size (n = 8). However, this result is consistent with previous research that demonstrates that the heterozygous genotype of the FV mutation is associated with increased risk for the development of IVH but a decreased risk for the progression or extension to more severe grades of IVH.     

Recent trends in breast cancer incidence among 6 Asian groups in the Greater Bay Area of Northern California

Asians and Pacific Islanders are typically aggregated in United States (US) cancer statistics even though the few studies that have considered subgroups separately have found marked differences in cancer incidence. The objective of this study was to evaluate trends in breast cancer incidence rates separately for US Chinese, Japanese, Filipino, Korean, South Asian and Vietnamese women overall and by age at diagnosis, histologic subtype and stage at diagnosis. Age-adjusted incidence rates and annual percent changes (APC) of new, primary breast cancer diagnosed in the Greater Bay Area Cancer Registry of Northern California (1990-2002) were calculated using SEER*Stat. In women under 50 years of age, annual incidence rates decreased for Japanese (APC = -4.1, p = 0.02) and Filipinas (APC = -1.9, p = 0.11), and increased or fluctuated in other subgroups over the study period. In women 50 years or older, rates of invasive breast cancer increased for most subgroups, except Filipinas (APC = -1.3, p = 0.32), and in Japanese until 1998-2000. Rates of breast cancer in situ increased in most subgroups from 1990 to 2002, as did rates of lobular breast cancer for Chinese (APC = +7.46, p < 0.01) women. In Japanese women, rates of lobular breast cancer were highest in 1995-1997 and decreased thereafter. Our data support the notion that the prevalence of established risk factors influence breast cancer incidence, as breast cancer rates increased for more recently immigrated groups and decreased among more established groups, and may suggest leads into other avenues of research, such as genetic differences, that may explain differences in incidence rates among Asian subgroups.     

Coordinated Strategy for a Model-Based Decision Support Tool for Coronavirus Disease,Utah, USA

The coronavirus disease pandemic has highlighted the key role epidemiologic models play in supporting public health decision-making. In particular, these models provide estimates of outbreak potential when data are scarce and decision-making is critical and urgent. We document the integrated modeling response used in the US state of Utah early in the coronavirus disease pandemic, which brought together a diverse set of technical experts and public health and healthcare officials and led to an evidence-based response to the pandemic. We describe how we adapted a standard epidemiologic model; harmonized the outputs across modeling groups; and maintained a constant dialogue with policymakers at multiple levels of government to produce timely, evidence-based, and coordinated public health recommendations and interventions during the first wave of the pandemic. This framework continues to support the state’s response to ongoing outbreaks and can be applied in other settings to address unique public health challenges.     

High technology medicine and the physician-patient relationship

While technologic problems in critical care have become highly refined with precise solutions, ethical problems and solutions have remained fairly primitive. A useful distinction between technology and techniques is made with individual technologies being the parts that make up the therapeutic techniques as a whole. The phenomena of “technical convergence” is discussed wherein we may control each part of the system, but the system itself may be out of control. This is explained in terms of the logical fallacy of composition, noting that a whole may not necessarily have the same characteristics of its parts. Resolution of some of the ethical problems in critical care is suggested through a reexamination of the physician-patient relationship. It is noted that the relationship needs to be personal-technologic rather than sociotechnologic in nature, with the former focusing solely on the best interest of the individual patient and the latter focusing more on the broader concerns of society in the allocation of limited resources. The detrimental effects for the physician as well as the patient of the shift toward the sociotechnologic relationship is explored, especially the dehumanization of the physician. A call for a reaffirmation of the traditional professional model of medicine emphasizing the best interest of patients as opposed to the more popular business model emphasizing materialism and efficiency is given.