Developing a clinical model to predict the need for relaparotomy in severe intra-abdominal sepsis secondary to complicated appendicitis.

BACKGROUND: Complex intra-abdominal sepsis secondary to acute appendicitis is common in South Africa, and management frequently involves relaparotomy. The decision to perform relaparotomy is often difficult, and this study aimed to develop a clinical model to aid the decision-making process. METHOD: The study was conducted from January 2008 to December 2012 at Edendale Hospital, Pietermaritzburg. All patients with intraoperatively confirmed acute appendicitis and all patients in this group who subsequently underwent relaparotomy were included. The clinical course, intraoperative findings and outcome of all patients were recorded until discharge (or death). Using a combination of preoperative and intraoperative parameters, a clinical model was developed to predict the need for relaparotomy. RESULTS: Of the total of 1 000 patients identified, 54.1% were males. The median age for all patients was 21 years. Of 406 relaparotomies, 227 (55.9%) were planned and 179 (44.1%) on demand (expectant treatment). In the relaparotomy group, 367 patients (90.4%) had positive findings. Logistic regression analysis showed that the following four factors accurately predicted the need for subsequent relaparotomy: patients referred from any rural centre, duration of illness >5 days, heart rate >120 bpm, and perforation associated with generalised intraabdominal sepsis. Th is model had a predictive value of >90%. CONCLUSION: We have constructed a model that uses clinical data available at initial laparotomy to predict the need for subsequent relaparotomy in patients with complicated acute appendicitis. It is hoped that this model can be integrated into routine clinical practice, but further study is first needed to validate this model.

A Randomised Phase II Trial of Hippocampal Sparing Versus Conventional Whole Brain Radiotherapy After Surgical Resection or Radiosurgery in Favourable Prognosis Patients With 1-10 Brain Metastases.

AIMS: To assess in patients with 1-10 brain metastases, each of which has been treated by neurosurgery or stereotactic radiosurgery, whether hippocampal sparing whole brain radiotherapy (HS-WBRT) better spares neurocognitive function (NCF) than standard WBRT. Further, to assess whether a phase III randomised trial of HS-WBRT would be feasible in the UK. MATERIALS AND METHODS: A multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT. The primary endpoint was decline in Total recall using Hopkins Verbal Learning Test Revised (HVLT-R) at 4 months post treatment. To assess this, we aimed to recruit 84 patients over 3 years. Secondary endpoints included further measures of NCF, quality of life, duration of functional independence, local control of treated metastases, development of new metastases, disease control within the hippocampal regions, overall survival, steroid and antiepileptic medication requirements, and toxicity. RESULTS: The trial closed prematurely due to slower than anticipated recruitment. From April 2016 to January 2018, 23 patients were randomised. Follow up was a median of 25 months. Fifteen patients (6 WBRT, 9 HS-WBRT) were assessed for the primary endpoint; of these, 1 in each arm experienced significant decline in the 4-month HVLT-R Total recall score (p = 0.8). Patients in the HS-WBRT arm experienced less insomnia (p < 0.01) and drowsiness (p < 0.01). There were no differences in other secondary endpoints. CONCLUSION: A phase III randomised trial of HS-WBRT was shown not to be feasible at this time in the UK. As most randomised trials of HS-WBRT reported to date share common endpoints, including NCF, an individual patient data meta-analysis should be undertaken.

Models of practice and training in psychotherapy: cross-national perspectives from Italy and Canada.

Internationally, there is ongoing concern about accessibility to mental health care and training. The goal of this study was to explore commonalities and differences within models of clinical psychology and psychotherapy in Ontario, Canada, and Lombardia, Italy, respectively, to inform improvements to the accessibility of mental health care and training. Using key informant sampling, we recruited ten students and professionals in Italy and Canada who study or work in psychology for semi-structured interviews. We analyzed the interview content using an inductive approach for thematic analysis within countries and meta-theme analysis across countries. The findings indicated three cross-national meta-themes: the need to integrate evidence with practice, the limited accessibility of training for students and treatment for patients, and the importance of the quality of training programs. Despite some differences regarding the amount of scientific training, personal therapy for trainees, and the prominence of cultural diversity training, Canadian and Italian psychology professionals and students shared experiences of psychotherapy practice and clinical psychology training. The three cross-national meta-themes indicate which issues in training and practice may be relevant worldwide and where to focus resources. The findings can inform international collaborations regarding training model structures that may increase access to psychology training and may increase consensus on professional recognition standards to improve mobility for professionals. These changes could reduce barriers to mental healthcare services for patients.

A treatment planning comparison of photon stereotactic ablative radiotherapy and proton beam therapy for the re-irradiation of pelvic cancer recurrence.

BACKGROUND: Patients who experience a pelvic cancer recurrence in or near a region that received initial radiotherapy, typically have few options for treatment. Organs at risk (OAR) have often reached their dose constraint limits leaving minimal dose remaining for standard re-irradiation (reRT). However, photon based stereotactic ablative radiotherapy (SABR) has been utilised for reRT with promising initial results although meeting OAR constraints can be challenging. Proton beam therapy (PBT) could offer an advantage. MATERIALS AND METHODS: SABR plans used for treatment for ten pelvic reRT patients were dosimetrically compared to PBT plans retrospectively planned using the same CT and contour data. PBT plans were created to match the CTV dose coverage of SABR treatment plans with V100% ≥95%. An 'as low as reasonably achievable' approach was taken to OAR tolerances with consideration of OAR dose from the initial radiation (using equivalent dose in 2 Gy fractions). RESULTS: Dosimetric comparison of relevant OAR statistics showed a decrease in OAR dose using PBT over SABR in all patients, with equivalent target coverage. The largest statistically significant reduction was seen for the colon D0.5 cm3 with a median reduction from 13.1 Gy to 5.9 Gy. There were statistically significant dose reductions in the median dose to small bowel, sacral plexus and cauda equina. CONCLUSION: PBT has the potential for significant dose reductions for OARs in the pelvic reRT setting compared to SABR. However, it remains unclear if the magnitude of these OAR dose reductions will translate into clinical benefit.

Co-ordinated changes in expression of cell adhesion molecules in prostate cancer.

The expressions of E-cadherin, the integrin subunits beta 1, beta 2, beta 3, CD44 and alpha-catenin were studied in parallel by immunohistochemistry in a series of 40 prostate biopsies comprising one normal, 11 benign prostatic hyperplasia (BPH), and 28 prostatic adenocarcinomas. As reported by others, there was a consistent loss of E-cadherin expression with increasing tumour grade and de-differentiation. However, a significant proportion of losses occurred at earlier grades than previously reported. The parallel nature of this study showed, for the first time in human prostate carcinoma, a reciprocal expression pattern of E-cadherin and beta 1 integrin in the higher grades of prostate cancer. A reciprocal expression pattern was also found for E-cadherin and CD44 between moderately and poorly differentiated tumours. alpha-Catenin expression was downregulated only in those cells which had previously lost E-cadherin expression, and beta 2 and beta 3 integrin were rarely expressed in prostate tumours. A loss of expression of the luminal epithelial specific keratins CK8 and CK18 was also observed in advanced stage, poorly differentiated carcinomas.

Rapid diagnosis of lung cancer from palpable metastases by needle thrust.

This study encourages the use of percutaneous FNB to diagnose and stage advanced lung cancer in patients with palpable metastases in supraclavicular lymph nodes or soft tissues. Percutaneous FNB of metastases is much easier to learn than transthoracic needle aspiration: the superficial target is anchored and sampled with multiple passes using a short needle grasped directly in the fingers. It is fast, accurate, economical and nearly free of risk and pain. The technique saves time and money because it is the only procedure needed by many patients with palpable disease in stage IIIB and IV. Bronchoscopy, transthoracic needle aspiration and open surgical biopsy thus can be avoided in most patients with palpable metastases. Prompt diagnosis by FNB of metastases speeds palliation for patients with urgent need. Tumor cell type from FNB correlated with cytologic findings from sputum samples, bronchoscopy specimens and autopsy results.

The relationship between rate of chest compression and compression:relaxation ratio.

One of the arguments put forward in support of a relatively fast rate of chest compression during CPR, is that it facilitates the achievement of a high compression:relaxation ratio. This has been shown to increase blood flow. In this study a group of volunteers carried out chest compression at the rate that each felt was correct and comfortable. There was no significant relationship between compression rate and compression:relaxation ratio. In a second study volunteers carried out chest compression on a manikin at rates of 40/min; 60/min; 80/min and 100/min. There was no significant rate related difference in the compression:relaxation ratios recorded. The ability to achieve a high compression duration is not related to compression rate, and should not be a consideration when guidelines on CPR are revised.

Four-step CPR--improving skill retention.

This study is an attempt to see if simplifying the teaching of basic life support leads to better skill acquisition and retention. Forty-eight lay volunteers received instruction in CPR; 24 were taught the standard 8-step sequence whereas 24 were taught a simplified 4-step sequence. Tests of performance were carried out on a manikin before and after training. Those in the 4-step group were significantly better than those in the 8-step group at remembering the sequence of skills immediately after training (P = 0.04), 1 week later (P < 0.001) and at 6 weeks (P < 0.001). Twenty-three out of the 24 volunteers in the 4-step group got the sequence completely correct each time they were tested, in contrast to only 2 out of the 24 in the 8-step group. There was no difference, however, in the quality of performance of the skills between the two groups. In addition, it was shown that use of the 4-step sequence should result in a useful reduction in the time taken before a rescuer calls for the emergency services and commences CPR. Whether such a radical change in teaching should be introduced is a matter for further discussion and research.

Wavelet compression in medical terahertz pulsed imaging.

This paper concerns the robustness of discrete wavelet transform (DWT) compression in terahertz pulsed imaging (TPI). TPI datasets consist of terahertz time-domain series which are sampled at each 'pixel' of the image, leading to file sizes which are typically of the order of several megabytes (MB) per image. This makes efficient compression highly desirable for both transmission and storage. However, since the data may be required for diagnostic purposes it is essential that no relevant information is lost or artefacts introduced. We show that for a nylon step wedge the estimates of refractive index and absorption coefficients are not significantly altered when the terahertz data are reconstructed from only 20% of DWT coefficients.

Identification of a region of the alcelaphine herpesvirus-1 genome associated with virulence for rabbits.

The gammaherpesvirus Alcelaphine Herpesvirus 1 (AHV-1) causes the fatal lymphoproliferative disease known as malignant catarrhal fever (MCF), in susceptible hosts. The virulent C500 isolate of AHV-1 became attenuated for the laboratory model, the rabbit, as a result of serial passage in cells of bovine origin. This work describes the identification of a region of the central unique sequence of the C500 genome, located close to the terminal repeat units of the molecule, which is altered on attenuation. The virulent C500 genome contains two copies of a sequence of approximately 2 kbp, contained within a 7 kbp region of the unique DNA located adjacent to the terminal repeats at the left end of the molecule. In the genome of the attenuated virus, there are also two copies of the 2 kbp sequence but they are located at the ends of the attenuated genome unique region, adjacent to the terminally repeated sequences. One open reading frame (ORF), designated putative polypeptide 5, was altered on attenuation such that the 3' sequence was lost. The location of this ORF, coupled with the loss of its 3' sequence, suggests that this ORF may encode a gene involved in the virulent mechanisms of this virus, in a manner similar to that of the transforming proteins of Herpesvirus saimiri (HSV).

Critical appraisal and further development of the methodology for open circuit calorimetry in neonates.

A non-invasive technique for open circuit calorimetry based on a Vickers 79 incubator as the gas collection chamber was developed and evaluated. The technique, which involved drawing air from the incubator hood at 11 1/min for gas analysis, did not have a significant cooling effect on the infant and the noise levels within the incubator did not exceed current safety standards. A new technique for checking the calibration of the whole system was developed as the traditional alcohol burn method proved unsatisfactory. Either pure oxygen or carbon dioxide were fed into the incubator hood at controlled physiological rates using a calibrated throttling valve. Over a number of calibration checks the mean error of the system proved to be +/- 4.3% for oxygen and +/- 4.45% for carbon dioxide. Less than a fifth of this error was attributable to the pump and flow meter. When oxygen is introduced to the system at a constant physiological rate it takes 30 min for a plateau to be reached. Therefore it is recommended that this system is used when readings are to be taken in a steady state situation or data is to be cumulated over a long period of time such as in an energy balance study. A run in period of 30 min before collecting data is essential. It is recommended that a calibration check is performed before each study.

Anogenital warts in prepubertal children: pathogenesis, HPV typing and management.

The incidence of anogenital warts in prepubertal children is increasing. Modes of transmission of human papillomavirus to the anogenital area include perinatal, autoinoculation and heteroinoculation, sexual abuse and possibly indirect transmission via fomites. It was previously thought that childhood sexual abuse was the most common mode of transmission and human papillomavirus types 6 and 11 were most often detected. More recent studies, however, would suggest that perinatal infection and autoinoculation or heteroinoculation may be much more prevalent than originally thought. It has been increasingly reported that human papillomavirus type 2 is present in a significant proportion of cases. Assessment of children should be multidisciplinary and sexual abuse should be considered in every case. Treatment modalities, although similar to adult disease, are particularly dependent on individual factors. In view of the as yet unknown risk of subsequent anogenital neoplasia it is recommended that individuals should have regular follow-up on a long-term basis.

Ten year follow-up study of women presenting to a genitourinary medicine clinic with anogenital warts.

One hundred heterosexual women presenting at our clinic in 1979 with anogenital warts, were reviewed 10 years later. Median duration of warts following initial clinic attendance was 2 months (range 0-120 months). In 1979 cervical PAP smear results were available for 76 patients; cervical intraepithelial neoplasia (CIN) was seen in 15/76 (19.7%) women; 3 (4%) women had low grade CIN, 12 (15.7%) women had high grade CIN. Nineteen women had had treatment for CIN between 1979 and 1989, 7 laser ablation, 9 cone biopsy, 2 laser ablation and cone biopsy, and one woman laser ablation, cauterization and cone biopsy. At 10-year follow-up in 1989 4/100 women had anogenital warts, 12/100 women had cytological evidence of CIN (7 low grade, 5 high grade), and 37/100 women had CIN detected on colposcopic biopsy (31 low grade, 6 high grade). No women developed invasive cervical carcinoma during the study period. CIN lesions, detected in 1979, regressed without any treatment in 2 women. Colposcopic biopsy was 3.1 times more sensitive than single cervical PAP smear at detecting CIN (4.4 times as sensitive in detecting low grade CIN; 1.2 times as sensitive in detecting high grade CIN). In 1989 CIN was detected in 7/19 (36.8%) of women who had undergone cervical treatment between 1979 and 1989, and in 35/81 (43.2%) of women having no cervical treatment within this period (chi squared P greater than 0.5). These findings suggest that cervical laser ablative therapy and cone biopsy do not in the long term influence the natural history of cervical human papilloma virus-associated disease (CIN) in women with anogenital warts.(ABSTRACT TRUNCATED AT 250 WORDS)

Anogenital warts in prepubertal children; sexual abuse or not?

Forty-two prepubertal children presenting with anogenital (AG) warts (15 boys and 27 girls) were prospectively followed up (mean 15.9 months, SD 12.24). Most (73.8%) of these children had perianal condylomatous-type warts and 11 (26.2%) had concurrent non-genital (NG) warts. None had any other AG infections or sexually transmitted disease (STD). Twelve (28.6%) children acquired their AG warts by vertical transmission from an infected maternal birth canal, 3 (7.1%) by autoinoculation from common hand warts and 2 children (4.8%) through sexual abuse. In the remaining 25 children (59.5%) mode of acquisition of AG warts was uncertain but not thought to be sexual. Human papilloma virus (HPV) DNA (types 6/11, 16/18 or 31,33,35-31+) was detected in 10/32 (31.3%) of AG warts biopsied from these children, types 6/11 in the majority of positive biopsies (9/10). Detection of HPV DNA (types 6/11, 16/18 or 31+) in a child's AG warts was significantly associated with either vertical or sexual transmission (P < 0.02). Thirty-one children had their warts treated with a combination of scissor excision and electrocautery under general anaesthesia. Warts recurred in 10 (31.4%) of these children all within 4 months following treatment. Spontaneous resolution of AG warts was seen in 9 (21.4%) children. Of 42 children with AG warts 10 (23.8%) had at least one adult family member with AG warts, 13 (36.9%) on adult family member with another AG infection or STD, and 23 (62.2%) had a mother with cervical intraepithelial neoplasia (CIN). Twenty (47.6%) of these children had a family member with NG warts.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of inert carriers in regulatory biodegradation tests of low density poorly water-soluble substances.

Many poorly water-soluble compounds fail regulatory ready biodegradation tests as the method of test material preparation limits the bioavailability of the chemical. The recognised method for delivery of poorly soluble materials into biodegradability tests consists of coating test material inside the test vessel or onto inert substrates (i.e., glass cover slide, boiling beads, filter paper, or Teflon stir bar) that are placed inside the vessels. Volatile solvents are often used to augment this process. Although these substrates work fairly well for delivering many poorly soluble materials into biodegradability tests, they have not been effective in keeping low density, poorly water-soluble substances in the test medium. Soon after medium is added to the test vessels, these chemicals break loose from the substrates and float on the surface where they have limited contact with micro-organisms in the test medium. Hence, there is a reduced potential for measuring substantial biodegradability in the test. This paper describes the work undertaken to establish a standard method of adding low density, poorly water-soluble substances into test vessels of biodegradability studies to ensure these materials remain in contact with micro-organisms in the test medium. The substances are prepared for testing by adsorption onto silica gel followed by dispersion into the culture medium. This method of delivery may provide greater intra- and inter-laboratory consistency in biodegradability test results for low density, poorly water-soluble substances and it may more closely mimic the probable transport and fate of these substances in the environment.

The incidence of Legionella pneumophila as the cause of acute ambulatory lower respiratory tract infection.

Seventy-nine ambulatory patients with acute lower respiratory tract infection were evaluated for Legionella pneumophila by acute and convalescent antibody titers. None of the patients met the traditional criteria for the diagnosis of acute infection caused by Legionella pneumophila. Currently accepted criteria for diagnosing legionellosis by serologic means may or may not be applicable to mild respiratory tract infections.

The cost effectiveness of early management of acute appendicitis underlies the importance of curative surgical services to a primary healthcare programme.

INTRODUCTION: Appendicitis in the developing world is a cause of significant preventable morbidity. This prospective study from a regional hospital in South Africa constructs a robust cost model that demonstrates the cost effectiveness of an efficient curative surgical service in a primary healthcare-orientated system. METHODS: A prospective audit of all patients with acute appendicitis admitted to Edendale Hospital was undertaken from September 2010 to September 2011. A microcosting approach was used to construct a cost model based on the estimated cost of operative and perioperative interventions together with the associated hospital stay. For cost analysis, patients were divided into the following cohorts: uncomplicated appendicitis, complicated appendicitis with localised intra-abdominal sepsis, complicated appendicitis with generalised intra-abdominal sepsis, with and without intensive care unit admission. RESULTS: Two hundred patients were operated on for acute appendicitis. Of these, 36% (71/200) had uncomplicated appendicitis and 57% (114/200) had perforation. Pathologies other than appendicitis were present in 8% (15/200) and these patients were excluded. Of the perforated appendices, 45% (51/114) had intra-abdominal contamination that was localised while 55% (63/114) generalised sepsis. The mean cost for each patient was: 6,578 ZAR (£566) for uncomplicated appendicitis; 14,791 ZAR (£1,272) for perforation with localised intra-abdominal sepsis and 34,773 ZAR (£2,990) for perforation with generalised intra-abdominal sepsis without intensive care admission. With intensive care admission it was 77,816 ZAR (£6,692). The total cost of managing acute appendicitis was 4,272,871 ZAR (£367,467). Almost 90% of this total cost was owing to advanced disease with abdominal sepsis and therefore potentially preventable. CONCLUSIONS: Early uncomplicated appendicitis treated appropriately carries little morbidity and is relatively inexpensive to treat. As the pathology progresses, the cost rises exponentially. An efficient curative surgical service must be regarded as a cost effective component of a primary healthcare orientated system.

Quantifying the disparity in outcome between urban and rural patients with acute appendicitis in South Africa.

BACKGROUND: Acute appendicitis in South Africa is associated with higher morbidity than in the developed world. Objective. To compare outcomes of urban and rural patients in KwaZulu-Natal and to determine whether there are disparities in outcome. METHODS: We conducted a prospective study from September 2010 to September 2012 at Edendale Hospital in Pietermaritzburg, South Africa. All patients who presented with acute appendicitis were included. The operative and clinical course of urban and rural patients was compared. Results. A total of 500 patients were included, with 200 patients in the rural group and 300 in the urban group. Those from the rural group had a significantly longer duration of symptoms prior to presentation. All septic parameters were significantly worse in the rural group. Significantly more patients from the rural group required a laparotomy (77% v. 51% urban; p<0.001). Inflamed, non-perforated appendicitis was more commonly seen in the urban group (52.3% v. 21% rural; p<0.001), while perforated appendicitis was much more common in the rural group (79% v. 47.7% urban; p<0.001). Perforation associated with generalised, four-quadrant intra-abdominal contamination was significantly higher in the rural group than the urban group (60.5% v. 21%, respectively; p<0.05). Significantly more patients from the rural group required an open abdomen (46% v. 12% urban; p<0.001) and ≥1 re-laparotomies to control severe intra-abdominal sepsis (60.5% v. 23.3% urban; p<0.001). CONCLUSION: We have identified rural origin as an independent indicator of poor outcome. Possible reasons may include difficulty in accessing the health system or delay in transfer to a regional hospital. These need to be investigated further.