A survey of patients with surgical wounds healing by secondary intention; an assessment of prevalence, aetiology, duration and management.

BACKGROUND: Surgical wounds healing by secondary intention (SWHSI) are often difficult and costly to treat. There is a dearth of clinical and research information regarding SWHSI. The aim of this survey was to estimate the prevalence of SWHSI and to characterise the aetiology, duration and management of these wounds. METHODS: Anonymised data were collected from patients with SWHSI receiving treatment in primary, secondary and community settings. Over a two weeks period, data were collected on the patients, their SWHSI, clinical and treatment details. RESULTS: Data were collected from 187 patients with a median age of 58.0 (95% CI = 55 to 61) years. The prevalence of SWHSI was 0.41 (95% CI = 0.35 to 0.47) per 1000 population. More patients with SWHSI were being treated in community (109/187, 58.3%) than in secondary (56/187, 29.9%) care settings. Most patients (164/187, 87.7%) had one SWHSI and the median duration of wounds was 28.0 (95% CI = 21 to 35) days. The most common surgical specialities associated with SWHSI were colorectal (80/187, 42.8%), plastics (24/187, 12.8%) and vascular (22/187, 11.8%) surgery. Nearly half of SWHSI were planned to heal by secondary intention (90/187, 48.1%) and 77/187 (41.2%) were wounds that had dehisced. Dressings were the most common single treatment for SWHSI, received by 169/181 (93.4%) patients. Eleven (6.1%) patients were receiving negative pressure wound therapy. CONCLUSIONS: This survey provides a previously unknown insight into the occurrence, duration, treatment and types of surgery that lead to SWHSI. This information will be of value to patients, health care providers and researchers.

On reducing information asymmetry in U.S. health care.

Information asymmetry is a significant issue facing the U.S. health care system. In this article, we investigate some methods of reducing this asymmetry. We trace the information asymmetry using the "wicked problem" of the health care distribution system. An information asymmetry reduction method requiring joint responsibilities among health care stakeholders is developed. It is argued that information asymmetry is a contributor to enormous health care inflation. Hence, any reduction in such asymmetry will reduce health care costs. Concepts from both signaling and corrective justice theories are integrated in this article to help reduce the information asymmetry that exists in the U.S. health care system. Getting health care costs in line with other "advanced" nations, is the long-term solution to the wicked problem that currently exists in the U.S. health care system. There is an immediate need for a centralized health care database with adequate provisions for individual privacy. Both processes as well as an outcome-based control system are essential for reducing information asymmetries in the U.S. health care system.

5% dimethyl sulfoxide (DMSO) and pentastarch improves cryopreservation of cord blood cells over 10% DMSO.

BACKGROUND: Cell number and viability are important in cord blood (CB) transplantation. While 10% dimethyl sulfoxide (DMSO) is the standard medium, adding a starch to freezing medium is increasingly utilized as a cytoprotectant for the thawing process. Similar to hetastarch, pentastarch has the advantages of faster renal clearance and less effect on the coagulation system. STUDY DESIGN AND METHODS: We compared a lower DMSO concentration (5%) containing pentastarch with 10% DMSO and performed cell viability assay, colony-forming units (CFUs), and transplantation of CB cells in NOD/SCID IL2Rγ(null) mice. RESULTS: CB cells in 5% DMSO/pentastarch had similar CD34+, CD3+, and CD19+ cell percentages after thawing as fresh CB cells. CB cells in 5% DMSO/pentastarch had higher viability (83.3±9.23%) than those frozen in 10% DMSO (75.3±11.0%, p<0.05). We monitored cell viability postthaw every 30 minutes. The mean loss in the first 30 minutes was less in the 5% DMSO/pentastarch group. At the end of 3 hours, the viability decreased by a mean of 7.75% for the 5% DMSO/pentastarch and 17.5% for the 10% DMSO groups. CFUs were similar between the two cryopreserved groups. Frozen CB cells engrafted equally well in IL2Rγ(null) mice compared to fresh CB cells up to 24 weeks, and CB cells frozen in 5% DMSO/pentastarch engrafted better than those in 10% DMSO. CONCLUSION: Our data indicate that the lower DMSO concentration with pentastarch represents an improvement in the CB cryopreservation process and could have wider clinical application as an alternate freezing medium over 10% DMSO.

Patients with surgical wounds healing by secondary intention: A prospective, cohort study.

BACKGROUND: Surgical wounds healing by secondary intention can be difficult and costly to manage and are profoundly under researched. This prospective inception, cohort study aimed to derive a better understanding of surgical wounds healing by secondary intention and to facilitate the design of future research investigating effective treatments. OBJECTIVES: To investigate the clinical characteristics of patients with surgical wounds healing by secondary intention and the surgeries that preceded their wounds; to clearly delineate the clinical outcomes of these patients, specifically focusing on time to wound healing and its determinants; to explore the types of treatments for surgical wounds healing by secondary intention; and to assess the impact surgical wounds healing by secondary intention have on patients' quality of life. DESIGN: Prospective, inception cohort study. SETTING: Acute and community settings in eight sites across two large centres in the United Kingdom (Hull and Leeds, UK). METHODS: Patients with a surgical wounds healing by secondary intention (an open wound, <3 weeks' duration, resulting from surgery), were recruited and followed up for at least 12 months. Key outcome events included: time to healing; treatment type; infection; hospital re-admission and further procedures; health-related quality of life and pain. RESULTS: In total, 393 patients were recruited. Common co-morbidities were cardiovascular disease (38%), diabetes (26%) and peripheral vascular disease (14.5%). Baseline median SWHSI area was 6 cm2 (range 0.01-1200). Abdominal (n = 132), foot (n = 59), leg (n = 58) and peri-anal (n = 34) wounds were common. The majority of wounds (236, 60.1%) were intentionally left open following surgery; the remainder were mostly dehisced wounds. Healing was observed in 320 (81.4%) wounds with a median time to healing of 86 days (95% CI: 75-130). Factors associated with delayed healing included wound infection at any point and baseline wound area above the median. Health-related quality of life scores were low at baseline but improved with time and healing. CONCLUSIONS: This is the first inception cohort study in patients with surgical wounds healing by secondary intention. Patient characteristics have been clearly defined, with prolonged healing times and adverse events being common impacting on patient's health-related quality of life. Areas for, and factors crucial to the design of, future research have been identified.

Low-dose parenteral busulfan provides an extended window for the infusion of hematopoietic stem cells in murine hosts.

OBJECTIVE: Myeloablative total body irradiation (TBI) in the setting of autologous transplantation of genetically modified hematopoietic stem cells (HSC) is associated with substantial toxicity. Nonmyeloablative doses of TBI are less toxic, but result in low-level engraftment of genetically modified HSCs. As an alternative to TBI, escalating doses of parenteral busulfan were tested for their hematologic toxicity, their ability to promote donor leukocyte engraftment, and the time window for such engraftment. MATERIALS AND METHODS: Hematologic toxicity of busulfan was assessed in C57BL6 mice after single nonmyeloablative doses of intraperitoneal busulfan ranging from 1 to 40 mg/kg by serial complete blood counts monitored up to 40 days. The level of donor engraftment attainable after nonmyeloablative busulfan was determined by infusion of 20 million congenic murine bone marrow nucleated cells (BMNC) following 5 to 40 mg/kg of busulfan. To determine the effects of delayed HSC infusions, BMNCs were infused 1, 10, 15, and 20 days after a single dose of 10 mg/kg of busulfan. RESULTS: Busulfan doses from 1 to 40 mg/kg produced hematologic toxicity that was most pronounced in the 2nd to 3rd week. In transplantation experiments, dose-dependent donor leukocyte engraftment was attained with levels >70% after only 20 mg/kg of busulfan. Similar levels of engraftment were achieved even when infusion of BMNCs was delayed up to 20 days after busulfan injection. CONCLUSION: Nonmyeloablative parenteral busulfan produced transient myelosuppressive effects, clinically relevant levels of engraftment, and an extended time window for HSC infusion in murine hosts.

Pilot feasibility randomized clinical trial of negative-pressure wound therapy versus usual care in patients with surgical wounds healing by secondary intention.

BACKGROUND: Surgical wounds healing by secondary intention (SWHSI) are increasingly being treated with negative-pressure wound therapy (NPWT) despite a lack of high-quality research evidence regarding its clinical and cost-effectiveness. This pilot feasibility RCT aimed to assess the methods for and feasibility of conducting a future definitive RCT of NPWT for the treatment of SWHSI. METHODS: Eligible consenting adult patients receiving care at the study sites (2 acute and 1 community) and with a SWHSI appropriate for NPWT or wound dressing treatment were randomized 1 : 1 centrally to receive NPWT or usual care (no NPWT). Participants were followed up every 1-2 weeks for 3 months. Feasibility (recruitment rate, time to intervention delivery) and clinical (time to wound healing) outcomes were assessed. RESULTS: A total of 248 participants were screened for eligibility; 40 (16·1 per cent) were randomized, 19 to NPWT and 21 to usual care. Twenty-four of the 40 wounds were located on the foot. Participants received NPWT for a median of 18 (range 0-72) days. Two participants in the NPWT group never received the intervention and 14 received NPWT within 48 h of randomization. Five participants in the usual care group received NPWT during the study. Ten of the 40 wounds were deemed to have healed during the study. CONCLUSION: A full-scale RCT to investigate the clinical and cost-effectiveness of NPWT for SWHSI is feasible. This study identified crucial information on recruitment rates and data collection methods to consider during the design of a definitive RCT. Registration number: ISRCTN12761776 (http://www.iscrtn.com).

Perioperative intraperitoneal chemotherapy for peritoneal surface malignancy.

The treatment of peritoneal surface malignancy mainly focuses on diffuse malignant peritoneal mesothelioma, pseudomyxoma peritonei from appendiceal cancer, and peritoneal dissemination from gastrointestinal and ovarian cancers. Cancer progression causes peritoneal implants to be distributed throughout the abdominopelvic cavity. These nodules plus the ascitic fluid result in abdominal distension. As the disease progresses, these tumors cause intestinal obstruction leading to debilitating symptoms and a greatly impaired quality of life. In the past, the prognosis of patients with peritoneal surface malignancy was regarded dismal and cure was not an option. Recently, cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has shown an improved survival in selected patients with this disease. To date, multiple different treatment regimens of perioperative intraperitoneal chemotherapy have been used. This review focuses on the perioperative intraperitoneal chemotherapy currently in use in conjunction with cytoreductive surgery for the treatment of peritoneal surface malignancy at the Washington Cancer Institute.

Hematopoietic stem cell transplantation prevents diabetes in NOD mice but does not contribute to significant islet cell regeneration once disease is established.

The treatment of type I diabetes by islet cell transplantation, while promising, remains restricted due to the incomplete efficacy and toxicity associated with current immunosuppression, and by limited organ availability. Given reports suggesting bone marrow derived stem cell plasticity, we sought to determine whether such cells could give rise to pancreatic islet cells in vivo. In the context of autoimmune diabetes, we transplanted unfractionated bone marrow from beta-gal trangenic donor mice into NOD mice prior to, at, and two weeks beyond the onset of disease. Successful bone marrow engraftment before diabetes onset prevented disease in all mice and for 1 year after transplant. However, despite obtaining full hematopoietic engraftment in over 50 transplanted mice, only one mouse became insulin independent, and no beta-Gal positive islets were detected in any of the mice. To test whether tolerance to islets was achieved, we injected islets obtained from the same allogeneic donor strain as the hematopoietic cells into 4 transplant recipients, and 2 had a reversion of their diabetes. Thus allogeneic bone marrow transplantation prevents autoimmune diabetes and tolerizes the recipient to donor islet grants, even in diabetic animals, yet the capacity of bone marrow derived cells to differentiate into functional islet cells, at least without additional manipulation, is limited in our model.

HUS1 regulates in vivo responses to genotoxic chemotherapies.

Cells are under constant attack from genotoxins and rely on a multifaceted DNA damage response (DDR) network to maintain genomic integrity. Central to the DDR are the ATM and ATR kinases, which respond primarily to double-strand DNA breaks (DSBs) and replication stress, respectively. Optimal ATR signaling requires the RAD9A-RAD1-HUS1 (9-1-1) complex, a toroidal clamp that is loaded at damage sites and scaffolds signaling and repair factors. Whereas complete ATR pathway inactivation causes embryonic lethality, partial Hus1 impairment has been accomplished in adult mice using hypomorphic (Hus1(neo)) and null (Hus1(Δ1)) Hus1 alleles, and here we use this system to define the tissue- and cell type-specific actions of the HUS1-mediated DDR in vivo. Hus1(neo/Δ1) mice showed hypersensitivity to agents that cause replication stress, including the crosslinking agent mitomycin C (MMC) and the replication inhibitor hydroxyurea, but not the DSB inducer ionizing radiation. Analysis of tissue morphology, genomic instability, cell proliferation and apoptosis revealed that MMC treatment caused severe damage in highly replicating tissues of mice with partial Hus1 inactivation. The role of the 9-1-1 complex in responding to MMC was partially ATR-independent, as a HUS1 mutant that was proficient for ATR-induced checkpoint kinase 1 phosphorylation nevertheless conferred MMC hypersensitivity. To assess the interplay between the ATM and ATR pathways in responding to replication stress in vivo, we used Hus1/Atm double mutant mice. Whereas Hus1(neo/neo) and Atm(-/-) single mutant mice survived low-dose MMC similar to wild-type controls, Hus1(neo/neo)Atm(-/-) double mutants showed striking MMC hypersensitivity, consistent with a model in which MMC exposure in the context of Hus1 dysfunction results in DSBs to which the ATM pathway normally responds. This improved understanding of the inter-dependency between two major DDR mechanisms during the response to a conventional chemotherapeutic illustrates how inhibition of checkpoint factors such as HUS1 may be effective for the treatment of ATM-deficient and other cancers.

Are anonymous evaluations a better assessment of faculty teaching performance? A comparative analysis of open and anonymous evaluation processes.

OBJECTIVE: We compared teaching performance of medical school faculty using anonymous evaluations and open evaluations (in which the evaluator was not anonymous) and examined barriers to open evaluation. METHODS: Residents and medical students evaluated faculty using an open evaluation instrument in which their identity was indicated in the evaluation. Following this, they completed anonymous evaluation on the same faculty members. Aggregate outcomes using the two evaluation systems were compared. Outcomes by group of evaluators (residents and students) were analyzed. Trainees were also asked to rate the barriers to the open evaluation process. RESULTS: A statistically significant difference between the open and anonymous evaluations was noted across all items, with faculty receiving lower scores on the anonymous evaluations. The mean score for all the items on the open evaluations was 4.45 +/- 0.65, compared to mean score of 4.07 +/- 0.80 on the anonymous evaluations. There was also a statistically significant difference between open and anonymous evaluations in five clinical teaching domains that were evaluated individually. Residents perceived that the three most common barriers to optimal evaluation were an apprehension of possible encounters with the same attending physician in the future, destruction of working relationships with the attending, and a feeling of frustration with the evaluation system. CONCLUSIONS: The evaluation of faculty teaching performance is complex. Most academic medical centers use the open evaluation format. This study supports the case for the use of the anonymous evaluation method as a more accurate reflection of teaching performance.

Longitudinal assessment of occupational exposures to the organophosphorous insecticides chlorpyrifos and profenofos in Egyptian cotton field workers.

Chlorpyrifos (CPF) and profenofos (PFF) are organophosphorus (OP) insecticides that are applied seasonally in Egypt to cotton fields. Urinary trichloro-2-pyridinol (TCPy), a specific CPF metabolite, and 4-bromo-2-chlorophenol (BCP), a specific PFF metabolite, are biomarkers of exposure, while inhibition of blood butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) activities are effect biomarkers that may be associated with neurotoxicity. Urinary TCPy and BCP and blood BChE and AChE activities were measured in 37 adult Egyptian Ministry of Agriculture workers during and after 9-17 consecutive days of CPF application followed by an application of PFF (9-11 days), and a second CPF application (5 days) in 2008. During the OP applications, urinary TCPy and BCP levels were significantly higher than baseline levels, remained elevated following the application periods, and were associated with an exposure related inhibition of blood BChE and AChE. Analysis of blood AChE levels before and after the PFF application period suggests that individual workers with peak BCP levels greater than 1000 µg/g creatinine exhibited further inhibition of blood AChE with PFF application, demonstrating that PFF exposure had a negative impact on AChE activity in this highly exposed worker population. While large interindividual differences in exposure were observed throughout this longitudinal study (peak urinary BCP and peak TCPy levels for individuals ranging from 13.4 to 8052 and 16.4 to 30,107 µg/g creatinine, respectively), these urinary biomarkers were highly correlated within workers (r=0.75, p<0.001). This suggests that the relative exposures to CPF and PFF were highly correlated for a given worker. The variable exposures between job classification and work site suggest that job title and work location should not be used as the sole basis for categorizing OP exposures when assessing neurobehavioral and other health outcomes in Egyptian cotton field workers. Together, these findings will be important in educating the Egyptian insecticide application workers in order to encourage the development and implementation of work practices and personal protective equipment to reduce their exposure to CPF and PFF.

A comparison of sulpiride, dothiepin, diazepam and placebo in the treatment of depressed out-patients.

The effects of sulpiride, dothiepin, diazepam and placebo were compared in out-patients who were suffering from depressive states of moderate severity. No major differences were found between the regimens after 4 weeks administration. A notable finding was the high recovery rate among those patients who received the placebo. The need for drug treatment in the milder depressive states is discussed.

Practical appraisal of a new rating scale (MRSS) for rehabilitation.

Rating scales are available to assess patients undergoing rehabilitation for chronic psychiatric disorders. Few are universally acceptable because of pitfalls in their structure or administration. This study examines the recently printed Morningside Rehabilitation Status Scale in one rehabilitation network. The MRSS was found to be suitable in discriminating between severely and moderately disabled groups but not between mildly and moderately disabled groups.

[Eclampsia in the late postpartum. Contribution of x-ray computed tomography and magnetic resonance imaging]. / Eclampsie du post-partum tardif. Apport du scanner X et de l'imagerie par résonance magnétique.

A 28-year-old woman developed late post-partum eclampsia. CT scan showed focal cortical hypodensities and diffuse and bilateral hypodensity of the hemispheric white matter. These lesions were hypointense on T1-weighted sequences and hyperintense on T2-weighted sequences. The CT and MRI abnormalities resolved completely within a few weeks. These changes are similar to those which occur with the more common prepartum eclampsia.

[Is measurement of body temperature by infrared tympanic thermometry reproducible?]. / La mesure de la température corporelle par thermomètre tympanique infrarouge est-elle reproductible?

OBJECTIVE: To assess the reliability of body temperature estimated by infrared tympanic thermometry. STUDY DESIGN: Prospective study. PATIENTS AND METHODS: 71 patients in a neurosurgical intensive care unit. 393 triplets of measurements were performed: right ear, left ear and right ear again. RESULTS: Limits of agreements are [-1, +1 degree C] between both ears, and [-0.6, +0.7 degree C] for two consecutive measurements in the right ear. The Bland and Altman diagram show that most of the points responsible for the lack of accuracy are between 36 and 37 degrees C. CONCLUSION: These values give an estimation of the technique's accuracy. In our point of view, such a reproducibility is adequate for daily clinical practice. The accuracy of infrared tympanic thermometry with the First Temp Genius seems reasonable for the clinical practice when the temperature is over 37 degrees C.

[Functional neurosurgery for epilepsy]. / La chirurgie fonctionnelle de l'épilepsie.

Introduced at the end of the last century, epilepsy surgery is indicated in patients with intractable partial seizures and based on the resection of the epileptogenic cerebral tissue from which ictal discharges originate. Palliative procedures include seizure spread pathways interruption (callosotomy, multiple subpial transections) and chronic stimulation of the vagus nerve. Complete preoperative investigations including seizure observation, clinical tests, video-EEG, MRI and functional MRI, and PET-scan are performed in order to identify the epileptogenic zone. In difficult cases, invasive seizure monitoring through depth electrode implantation (SEEG) is performed. Resections for temporal lobe seizures are associated with favorable outcome: 60 to 90% of patients will be seizure-free after surgery. A less favorable outcome is observed after extra-temporal resections: 40 to 60% seizure-free patients. A better outcome is observed after surgery for epilepsy associated with an image-defined lesion, most often a tumor, rather than for cryptogenic epilepsy. Tumors associated with chronic partial epilepsy are indolent, most of them are dysembryoplastic neuroepithelial tumors (DNET). Outcome after palliative procedures are more variable, depending on the etiology of epilepsy.

[Neurosurgery with a CO2 laser. Evaluation of 61 operations]. / Neurochirurgie au laser CO2. Bilan de 61 interventions.

The authors present the results of their over two years experience with CO2 Laser neurosurgical unit. They explicit the indications and the technical data followed during intra-cranial (N = 44), intra-spinal (N = 12) and intra-orbital (N = 5) procedures. Meningiomas, neurinomas and adenomas are the best indications for tumoral CO2 Laser neurosurgery. In other respects sterilization and cranialization of aeric sinuses are simplified by the use of CO2 Laser: it assures vaporization of the mucosa and carbonization of the walls more easily than an electric coagulator. At last the use of CO2 Laser for dissection and removal of intra-orbital tumors is quite demonstrative. Thus owing to its physical and thermical qualities CO2 Laser is often a very useful, sometimes irreplaceable, apparatus: provided that its indications are precise and rigorous.

[Terson's syndrome and intraocular complications in meningeal hemorrhages (26 cases)]. / Syndrome de Terson et complications intra-oculaires dans les hémorragies méningées (26 cas).

The Terson syndrome was described in the early 1900's as the association of an intra-vitreous humor bleeding and a subarachnoidal hemorrhage (SAH). The high jeopardy of blindness of such a syndrome emphasizes the importance of evaluating as soon as possible the presence of blood in the posterior chamber of patients presenting with a SAH. 250 patients admitted in the Neurosurgical Department of Ste Anne Hospital with a SAH were evaluated between January 1984 and February 1990. 26 had an intra-ocular hemorrhage (10.5%). In those cases the mortality rate was not increased (15.4%) but the morbidity rate was higher (42%). Concerning the intra-ocular bleeding, 4 patients underwent a vitrectomy (2 had a complementary photocoagulation). Only one patient had a visual sequela (partial decrease of visual acuity). These data emphasize the visual risk which has to be considered; a specific treatment (vitrectomy and/or photocoagulation) must be performed as quickly as possible so as to save the vision. In some particular instances, the ophthalmological treatment might even be necessary before the intracranial procedure itself.

[A man with spontaneous pain in shoulders and hips]. / Een man met spontane pijnklachten van heupen en schouders.

A 19-year-old man presented with spontaneous pain in both hips and shoulders. X-ray of the pelvis showed osteopenia throughout the pelvis and a late stadium of coxarthrosis. MRI showed osteonecrosis on both sides in the femur head and acetabulum as well as both humerus heads. Glucocorticoids may induce osteonecrosis.