Pharmacologic Treatment Reduces Pressure Times Time Dose and Relative Duration of Intracranial Hypertension.

INTRODUCTION: Past work has shown the importance of the "pressure times time dose" (PTD) of intracranial hypertension (intracranial pressure [ICP] > 19 mm Hg) in predicting outcome after severe traumatic brain injury. We used automated data collection to measure the effect of common medications on the duration and dose of intracranial hypertension. METHODS: Patients >17 years old, admitted and requiring ICP monitoring between 2008 and 2010 at a single, large urban tertiary care facility, were retrospectively enrolled. Timing and dose of ICP-directed therapy were recorded from paper and electronic medical records. The ICP data were collected automatically at 6-second intervals and averaged over 5 minutes. The percentage of time of intracranial hypertension (PTI) and PTD (mm Hg h) were calculated. RESULTS: A total of 98 patients with 664 treatment instances were identified. Baseline PTD ranged from 27 (before administration of propofol and fentanyl) to 150 mm Hg h (before mannitol). A "small" dose of hypertonic saline (HTS; ≤250 mL 3%) reduced PTD by 38% in the first hour and 37% in the second hour and reduced the time with ICP >19 by 38% and 39% after 1 and 2 hours, respectively. A "large" dose of HTS reduced PTD by 40% in the first hour and 63% in the second (PTI reduction of 36% and 50%, respectively). An increased dose of propofol or fentanyl infusion failed to decrease PTD but reduced PTI between 14% (propofol alone) and 30% (combined increase in propofol and fentanyl, after 2 hours). Barbiturates failed to decrease PTD but decreased PTI by 30% up to 2 hours after administration. All reductions reported are significantly changed from baseline, P < .05. CONCLUSION: Baseline PTD values before drug administration reflects varied patient criticality, with much higher values seen before the use of mannitol or barbiturates. Treatment with HTS reduced PTD and PTI burden significantly more than escalation of sedation or pain management, and this effect remained significant at 2 hours after administration.

Molecular Adsorbent Recirculating System Support Followed by Liver Transplantation for Multiorgan Failure From Heatstroke.

BACKGROUND: Exertional heatstroke is an extremely rare cause of fulminant hepatic failure. Maximal supportive care has failed to provide adequate survival in earlier studies. This is particularly true in cases accompanied by multiorgan failure. METHODS AND MATERIALS: Our prospectively collected transplant database was retrospectively reviewed to identify patients undergoing liver transplantation for heatstroke between January 1, 2012, and December 31, 2016. We report 3 consecutive cases of male patients with fulminant hepatic failure from exertional heatstroke. RESULTS: All patients developed multiorgan failure and required intubation, vasopressor support, and renal replacement therapy. All patients were listed urgently for liver transplantation and were supported with the molecular adsorbent recirculating system while awaiting transplantation. All patients underwent liver transplantation alone and are alive and well, with recovered renal function, normal liver allograft function, and no chronic sequelae of their multiorgan failure at more than one year. CONCLUSION: Extreme heatstroke leading to whole-body organ dysfunction and fulminant liver failure is a complex entity that may benefit from therapy using the Molecular Adsorbent Recirculating System while waiting for liver transplantation as a component of a multidisciplinary, multiorgan system approach.

Multidisciplinary approach for patients with pelvic fractures and hemodynamic instability.

The hemodynamically unstable patient with a pelvic fracture presents a diagnostic and therapeutic challenge. The care of these patients requires a unique multidisciplinary approach with input and expertise from many different specialists. An understanding of pelvic anatomy and fracture patterns can help guide the diagnostic evaluation and treatment plan. The initial management of these patients must focus on rapid airway and hemorrhage control while preparing for ongoing blood loss. Rapid temporary fracture stabilization with simple bedside modalities is crucial in limiting additional blood loss. An exhaustive search must also be performed to evaluate for concomitant injuries that commonly accompany major pelvic fractures and the treatment of these other injuries must be appropriately prioritized. For patients who are unresponsive to standard resuscitation and bedside attempts at limiting hemorrhage, angiographic embolization is often utilized as the next step to attain hemodynamic stability. The key to successful management of these patients lies in the careful coordination of different specialists and the expertise that each brings to the clinical care of the patient.

A new quality assessment parameter for optical coherence tomography.

AIM: To create a new, automated method of evaluating the quality of optical coherence tomography (OCT) images and to compare its image quality discriminating ability with the quality assessment parameters signal to noise ratio (SNR) and signal strength (SS). METHODS: A new OCT image quality assessment parameter, quality index (QI), was created. OCT images (linear macular scan, peripapillary circular scan, and optic nerve head scan) were analysed using the latest StratusOCT system. SNR and SS were collected for each image. QI was calculated based on image histogram information using a software program of our own design. To evaluate the performance of these parameters, the results were compared with subjective three level grading (excellent, acceptable, and poor) performed by three OCT experts. RESULTS: 63 images of 21 subjects (seven each for normal, early/moderate, and advanced glaucoma) were enrolled in this study. Subjects were selected in a consecutive and retrospective fashion from our OCT imaging database. There were significant differences in SNR, SS, and QI between excellent and poor images (p = 0.04, p = 0.002, and p<0.001, respectively, Wilcoxon test) and between acceptable and poor images (p = 0.02, p<0.001, and p<0.001, respectively). Only QI showed significant difference between excellent and acceptable images (p = 0.001). Areas under the receiver operating characteristics (ROC) curve for discrimination of poor from excellent/acceptable images were 0.68 (SNR), 0.89 (IQP), and 0.99 (QI). CONCLUSION: A quality index such as QI may permit automated objective and quantitative assessment of OCT image quality that performs similarly to an expert human observer.

Adherence to antiretroviral therapy in HIV-infected adults in Soweto, South Africa.

Little is known about achievable levels of antiretroviral treatment (ART) adherence in resource-limited settings. We conducted a cross-sectional study of adherence among patients at Chris Hani Baragwanath Hospital's Adult HIV Clinic in Soweto, South Africa. Adherence was assessed using a 1-month, self-report questionnaire and was calculated as a ratio of doses taken to doses prescribed. The 66 patients studied had a mean age of 36.1 years, a median duration of ART use of 18 months, and an overall baseline median CD4(+) cell count of 200/mm(3) (IQR: 114-364). The adherence reported by these patients for the previous month was >95% for 58 patients (88%), 90-95% for 6 (9%) and, < 90% for 2 (3%). The main reasons given for missing doses were being away from home (30%), difficulty with the dosing schedules (23%), and running out of pills (12%). Adherence decreased considerably with fear of being stigmatized by the sexual partner (OR = 0.13 95%, CI 0.02-0.70). Plasma HIV RNA levels were <400 copies/ml in the majority of patients (73% of those with adherence >95% and 88% of patients with < or =95% adherence) and the overall median CD4(+) cell count rose to 324/mm(3) (IQR: 193-510). High adherence and viral suppression are achievable for a significant proportion of HIV-infected patients taking ART in a resource-limited area such as Soweto, South Africa. Strategies to maximize adherence in this setting should emphasize ready access to affordable and simple ART regimens, as well as HIV education programs to help increase awareness and decrease disease stigmatization.

Graduate training in psychotherapy: are therapy outcomes enhanced?

Several sources of indirect evidence supporting the value of graduate training in psychotherapy are reviewed here. Training protocols that are known to enhance trainees' skills are briefly discussed, as are conclusions of meta-analytic reviews examining relationships between therapist experience and training, and therapy outcome. An updated meta-analysis of therapy outcome studies involving within-study comparisons of psychotherapists of different levels of training and experience is summarized. It is concluded that a variety of outcome sources are associated with modest effect sizes favoring more trained therapists. In many outpatient settings, therapists with more training tend to suffer fewer therapy dropouts than less trained therapists. Shortcomings of available research and speculations about possible variables influencing outcomes are discussed.

Laparoscopic enucleation of an insulinoma: advantages of using the curved laparoscopic coagulating shears.

Laparoscopic excision is a widely accepted and well-described approach to islet cell tumors of the pancreas. We report the case of a patient with biochemically proven insulinoma who underwent successful enucleation using the curved laparoscopic coagulating shears. We discuss the advantages of using laparoscopy to manage these tumors and the increased benefit of using the curved instrument for this type of procedure.

Gynecologic concerns in the treatment of teenagers with cloaca.

BACKGROUND/PURPOSE: Gynecologic anomalies are common in patients with persistent cloaca, but, except for hydrocolpos, these patients remain asymptomatic in the neonatal period. Anatomic abnormalities may become manifest in puberty when menses occurs. The authors sought to describe the sequelae of these anatomic defects in the teenage cloaca patient and to determine recommendations for prevention and treatment in the neonatal period. METHODS: From a series of 198 patients operated on for persistent cloaca, the authors report a group of 22 patients who have reached puberty. RESULTS: Seven patients are menstruating normally. Six patients have primary amenorrhea because of absent or atretic uteri. Nine patients presented with abdominal pain and cystic abdominal masses and required surgical resection of inflamed collections of old blood in uteri, hemiuteri, tubes, blind vaginas, hemivaginas, or in the peritoneum. The common denominator of this last group was an obstruction of one or more Mullerian structure that interfered with the drainage of menstrual blood. Asymmetric gynecologic anatomy or a vaginal atresia in the neonatal period seemed to correlate with future obstruction to menstrual flow. CONCLUSIONS: To prevent future problems, the management of the neonatal cloaca must include the early clarification of the gynecologic anatomy, specifically the patency of Mullerian structures. Unilateral atretic structures and tubes connected to atretic uteri should be resected. Also, clinicians must be suspicious of menstrual problems in teenagers operated on early in life for persistent cloaca.

Rectovestibular fistula with absent vagina: a unique anorectal malformation.

BACKGROUND/PURPOSE: A very unusual anorectal defect consisting of a vestibular fistula and absent vagina is presented. Only two previous isolated reports were found in the literature describing a repair that included both abdominal and perineal approach. The authors present another technical alternative that allows the repair via posterior sagittal. METHODS: Of 1,007 patients with anorectal malformations analyzed, eight female cases shared the common anatomic features of a vestibular fistula and absent vagina. What appeared to be the vagina was actually the rectal orifice ending in the vestibule, and the vagina was absent. With the posterior sagittal approach, the distal rectum was used to create the neovagina. The proximal rectum was mobilized and placed within the limits of the sphincter mechanism. Two of the eight patients were born with a patent upper third remnant of the vagina. In one case, the remnant was anastomosed to the neovagina at the time of colostomy closure; in the second one, the anastomosis was performed during the main repair. RESULTS: Four patients are continent of urine and have voluntary bowel movements. One patient is younger than 3 years and therefore has not been evaluated. One patient has a very poor sacrum and therefore is incontinent. One patient had a primary repair elsewhere and therefore is excluded, and another patient is lost to follow-up. One patient is already sexually active. CONCLUSIONS: It is mandatory to perform a meticulous inspection of the perineum in female patients with anorectal malformations to detect unusual defects. Also, a high index of suspicion is necessary to establish the diagnosis of this defect and avoid an inadequate treatment. The posterior sagittal approach represents another alternative to treat these defects without the need for a laparotomy.

Responsiveness to therapy for increased intracranial pressure in traumatic brain injury is associated with neurological outcome.

In patients with severe traumatic brain injury, increased intracranial pressure (ICP) is associated with poor functional outcome or death. Hypertonic saline (HTS) is a hyperosmolar therapy commonly used to treat increased ICP; this study aimed to measure initial patient response to HTS and look for association with patient outcome. Patients >17 years old, admitted and requiring ICP monitoring between 2008 and 2010 at a large urban tertiary care facility were retrospectively enrolled. The first dose of hypertonic saline administered after admission for ICP >19mmHg was recorded and correlated with vital signs recorded at the bedside. The absolute and relative change in ICP at 1 and 2h after HTS administration was calculated. Patients were stratified by mortality and long-term (≥6 months) functional neurological outcome. We identified 46 patients who received at least 1 dose of HTS for ICP>19, of whom 80% were male, mean age 34.4, with a median post-resuscitation GCS score of 6. All patients showed a significant decrease in ICP 1h after HTS administration. Two hours post-administration, survivors showed a further decrease in ICP (43% reduction from baseline), while ICP began to rebound in non-survivors (17% reduction from baseline). When patients were stratified for long-term neurological outcome, results were similar, with a significant difference in groups by 2h after HTS administration. In patients treated with HTS for intracranial hypertension, those who survived or had good neurological outcome, when compared to those who died or had poor outcomes, showed a significantly larger sustained decrease in ICP 2h after administration. This suggests that even early in a patient's treatment, treatment responsiveness is associated with mortality or poor functional outcome. While this work is preliminary, it suggests that early failure to obtain a sustainable response to hyperosmolar therapy may warrant greater treatment intensity or therapy escalation.

From bad to worse: comorbidity severity and quality of life after treatment for early-stage prostate cancer.

Commonly used measures of comorbidity assess comorbidity number and type but not severity. We sought to evaluate the impact of comorbidity severity on longitudinal health-related quality of life (HRQOL) in men treated with radical prostatectomy (RP) or radiation therapy (RT) using the Total Illness Burden Index for prostate cancer (TIBI-CaP). We sampled 738 men with non-metastatic prostate cancer treated with RP or RT from the Cancer of the Prostate Strategic Urologic Research Endeavor registry. We examined the impact of comorbidity severity on generic and disease-specific HRQOL at baseline and at 6, 12, 18 and 24 months post-treatment. Men with worse TIBI-CaP comorbidity had significantly lower baseline and post-treatment HRQOL in all domains at all time points. In a multivariate model, men with moderate or severe TIBI-CaP comorbidity had significantly worse HRQOL scores at 12 and 24 months after treatment in all domains except sexual and urinary function (P<0.05); in these domains, severe comorbidity was predictive of lower HRQOL (P<0.05). Comorbidity groups had similar absolute declines in HRQOL from baseline to 6 and 24 months after treatment. Although comorbidity groups experienced similar long-term declines from baseline HRQOL after treatment, men with more severe comorbidity had significantly lower baseline scores and therefore poorer long-term HRQOL.

In vitro fertilization of hamster eggs as a test system for drug effect on spermatozoa--lack of clomipramine effect.

Clomipramine may affect reproduction in male rats and dogs, while other psychotropic drugs can affect sperm motility in vitro. This study investigates the motility of hamster sperm and the fertilization of hamster eggs in vitro with epididymal sperm from alpha-chlorohydrin-pretreated males, and after preincubation with clomipramine. Alpha-chlorohydrin, a compound with a predicted antifertility action, decreased sperm motility and prevented in vitro fertilization. In contrast, clomipramine had no effect on sperm motility, including activated motility, on the acrosome reaction, or on egg penetration in vitro. Clomipramine can, however, influence prolactin levels in man, and follicle-stimulating and luteinizing hormone levels in male rats.

A comparison of infant-adult male relations in a one-male group with those in a multi-male group for yellow baboons (Papio cynocephalus).

We compared interactions between an infant and adult male in a one-male group with those between infants and adult males in a multi-male group in the same area. Proximity interactions in the one-male group were common, like those for dyads in the multi-male group in which the adult male was high-ranking or a likely father of the infant. Contact interactions in the one-male group were rare, like those for dyads in the multi-male group in which the adult male was low-ranking or unlikely to have sired the infant. This suggests that proximity to an adult male is important in coping with the physical environment (similar for both groups), and more contiguous interactions are important in coping with the social environment (more complex in a larger multi-male group).

Effect of antidepressant drugs on the in-vitro egg-penetrating ability of golden hamster epididymal spermatozoa.

Tricyclic antidepressants appeared to be without effect, except for desipramine which significantly decreased whiplash motility after spermatozoa were added to eggs, and clomipramine which decreased motility and whiplash motility in epididymal sperm suspensions after pretreatment of males. Mianserin and viloxazine were also without effect, but nomifensine significantly decreased sperm motility and whiplash motility and inhibited egg penetration almost completely. After 3 h preincubation with 0.75 mmol nomifensine hydrogen maleate/l, 2/181 and 0/256 eggs were penetrated in two separate series of experiments. Control groups in these series gave medians of 90-100% penetration by 4.5-5.5 h after spermatozoa and eggs were mixed. Maleic acid had a similar effect (1/253 eggs penetrated) whilst nomifensine hydrochloride was inactive, suggesting that the effect was due to the maleate moiety of the original nomifensine hydrogen maleate salt used.

Telephone counseling and crisis intervention: a review.

The empirical research pertaining to the effectiveness of telephone counseling and referral systems personnel was critically reviewed. The assessment was organized according to several evaluation strategies that researchers have utilized to evaluate effectiveness. These strategies included, for example, client self-reports, client "shows" versus "no-shows" following referral, data pertaining to suicide rates, counselor ratings of personal effectiveness, and phone workers' ability to offer empathy to clients. It was concluded that discussions of effectiveness should be constrained by a careful consideration of the specific index of efficacy chosen by investigators as well as methodological issues associated with current research in this area. There is reason to believe that the availability of telephone crisis services may be related to reduced suicide rates among young white females. Also, there is a significant need to empirically associate counseling technique and indices of effectiveness with substantive measures of client outcome in future research. Additional topics reviewed include the probable differential effectiveness of lay workers with various presenting problems of clients, and the role that training and maturity seem to play in successful interventions. Guidelines for the use of evaluation techniques which coincide with service goals are also offered.

Adenylate cyclase activity of mouse sperm during capacitation in vitro: effect of calcium and a GTP analogue.

Earlier studies have shown increased adenylate cyclase (AC) activity in epididymal mouse sperm incubated under capacitating conditions in vitro. The present study investigated the effect on AC activity of excluding calcium and/or glucose from the sperm incubation medium, which would modulate expression of fertilizing potential. AC activity was higher in sperm incubated for 120 than 30 min, and was higher in sperm incubated in calcium-containing than calcium-free media for all except acrosome-reacted populations. Calcium added at the time of assay stimulated AC activity, the degree of this response being independent of the functional state of the sperm population. The guanine nucleotide analogue Gpp(NH)p slightly enhanced AC activity, but did not alter the stimulatory effect of calcium. Since calcium can increase AC activity, possibly by interaction with a divalent cation allosteric site on the catalytic subunit of the enzyme, a rise in intracellular calcium levels during capacitation may mediate the increased activity of AC, allowing expression of cAMP dependent events which are a prerequisite for fertilization.