RESUMO
A recently developed process analytical technology (PAT) using artificial intelligence to form the framework of its model, combining frequency-domain acoustic emissions (AE) and elastic impact mechanics to accurately predict complex particle size distributions (PSD) in real-time. This model was modified in this study to give more accurate predictions for the more highly cohesive granules typical of pharmaceutical solid oral dosage formulations. AE spectra were collected from the granulated impacts of various formulations with ranging characteristics from largely elastic to highly inelastic collision responses. A viscoelastic (Hertzian spring-dashpot) and elastoplastic (Walton-Braun) contact force model were compared to understand how these different micro-mechanical approaches would affect the prediction accuracy of particle sizes relevant to granulation. Retraining the artificial intelligence model with the Walton-Braun transformation and a more comprehensive dataset of AE spectra spanning a broad range of granulated formulations showed the prediction error drop to as low as 2% compared to the original elastic version showing errors as large as 18.6% with representative formulations of the industry. The improved PAT shows good applicability to monitoring bimodal PSD that are typical of continuous twin-screw granulation.
Assuntos
Inteligência Artificial , Tecnologia Farmacêutica , Tamanho da Partícula , Composição de MedicamentosRESUMO
Two grades of commercial AFFINISOL™ HPMC HME were used as polymer binders to explore the influence of polymer viscosity and concentration on a novel heat assisted dry granulation process with a twin screw extruder. Contributions of other non-binder ingredients in the formulations were also studied for lactose, microcrystalline cellulose and an active pharmaceutical ingredient of caffeine. As sensitive indicators of processing conditions that expose the drug to high internally generated heat, dehydration of α-lactose monohydrate and polymorphic transformation of caffeine were monitored by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). Additionally, any decomposition of caffeine was determined by high-performance liquid chromatography (HPLC). Granular samples were characterized by particle size, circularity, fracture strength and their temperature on the exit of extruder. Higher screw speed and lower feed rate were found to help particles agglomerate by allowing feed particles a greater opportunity to increase in temperature. Lower binder molecular weight and higher binder concentration enable granules to build stronger strength and thereby lead to higher particle size. This new twin screw dry granulation was demonstrated as offering advantages over conventional hot melt granulation by minimizing thermal degradation of the tested ingredients.
Assuntos
Preparações Farmacêuticas/química , Polímeros/química , Parafusos Ósseos , Cafeína/química , Varredura Diferencial de Calorimetria/métodos , Celulose/química , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Temperatura Alta , Peso Molecular , Tamanho da Partícula , Pós/química , Difração de Raios X/métodosRESUMO
BACKGROUND: The aim of this study was to identify characteristics with independent predictive value for bowel cancer for use in the clinical assessment of patients attending colorectal outpatient clinics. METHODS: This was a 22-year (1986-2007) retrospective cohort analysis of data collected prospectively from patients who attended colorectal surgical outpatient clinics in Portsmouth. The data set was split randomly into two groups of patients to generate and validate a predictive model. Multivariable logistic regression was used to create and validate a system to predict outcome. Receiver operating characteristic (ROC) curves and Hosmer-Lemeshow test were used to evaluate the model's predictive capability. The likelihood of bowel cancer was expressed as the odds ratio (OR). RESULTS: Data from 29 005 patients were analysed. Discrimination of the model for bowel cancer was high in the development (C-statistic 0·87, 95 per cent c.i. 0·85 to 0·88) and validation (C-statistic 0·86, 0·84 to 0·87) groups. The most important co-variables in the final model were: age (OR 3·17-27·10), rectal (OR 31·48) or abdominal (OR 1·83-8·45) mass, iron deficiency anaemia (IDA) (OR 4·42-8·38), rectal bleeding and change in bowel habit in combination (OR 5·37), change in bowel habit without rectal bleeding, with or without abdominal pain (OR 2·12-2·52), and rectal bleeding with no perianal symptoms and without change in bowel habit (OR 2·91). Some 91·5 per cent of bowel cancers presented with these characteristics, 40·4 per cent with a mass and/or IDA. In patients with at least one of these characteristics the overall risk of having cancer was 10·0 (range 6·5-50·4) per cent, compared with 1·1 (0·3-2·3) per cent in patients without them. CONCLUSION: A clinical assessment that systematically identifies or excludes four symptom-age combinations, a mass and IDA (SAMI) stratifies patients as having a low and higher risk of having bowel cancer. This could improve patient selection for referral and investigation.
Assuntos
Neoplasias Colorretais/diagnóstico , Medição de Risco/métodos , Dor Abdominal/etiologia , Adulto , Fatores Etários , Anemia Ferropriva/etiologia , Defecação , Transtornos da Alimentação e da Ingestão de Alimentos/etiologia , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Reto , Estudos Retrospectivos , Fatores de Risco , Redução de PesoRESUMO
The influence of active pharmaceutical ingredient (API) hydrophobicity on continuous wet granulation was studied in twin screw granulation utilizing foamed binder delivery. The APIs examined were caffeine, acetaminophen, ibuprofen and griseofulvin and the drug load was maintained constant at 15 wt%. In order to understand the impact of these APIs on the granulation process, API and binder distribution, particle size, porosity, and fracture strength were analyzed on samples collected along the screw length. It was found that the API and binder distributions were uniform along the screws regardless of the hydrophobicity of the formulation, in contrast to literature results with liquid injection. The absence of de-mixing of the hydrophobic ingredient was hypothesized to be a result of the high spread-to-soak ratio of a foamed binder that 'cages' those particles within the mass of local hydrophilic solids.
Assuntos
Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Preparações Farmacêuticas/química , Tecnologia Farmacêutica/métodos , Composição de Medicamentos/instrumentação , Excipientes/química , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Preparações Farmacêuticas/administração & dosagem , PorosidadeRESUMO
Twin screw granulation (TSG) is a new process of interest to the pharmaceutical community that can continuously wet granulate powders, doing so at lower liquid concentrations and with better product consistency than found by a high shear batch mixer. A considerable body of research has evolved over the short time since this process was introduced but generally with little comparison of results. A certain degree of confidence has been developed through these studies related to how process variables and many attributes of machinery configuration will affect granulation but some major challenges still lay ahead related to scalability, variations in the processing regimes related to degree of channel fill and the impact of wetting and granulation of complex powder formulations. This review examines the current literature for wet granulation processes studied in twin screw extrusion machinery, summarizing the influences of operational and system parameters affecting granule properties as well as strives to provide some practical observations to newly interested users of the technique.
Assuntos
Química Farmacêutica/instrumentação , Química Farmacêutica/métodos , Desenho de Equipamento/instrumentação , Desenho de Equipamento/métodos , Excipientes/síntese química , Tamanho da Partícula , Pós/síntese química , MolhabilidadeRESUMO
The developed knowledge regarding use of twin screw granulators for continuous wet granulation has been primarily limited to immediate release formulations in the literature. The present study highlights an issue previously unreported for wet granulation with twin screw extruders when using formulations containing controlled-release (CR) excipients. Long (3-10 mm), twisted noodle-like granules can be produced in the presence of these excipients that are difficult to control and are anticipated to create complications in downstream unit operations to the granulator. Working with two different CR excipients, METHOCEL™ K4M and Kollidon® SR, each blended at different ratios with a mixture of 80% α-lactose monohydrate/20% microcrystalline cellulose, these unique particles were found to be produced in the conveying elements of the extruder, arising from a rolling action at the top of the screw flights. The CR excipients adhesively strengthen the wetted mass, forming this undesired granule shape such that they persisted to the exit of the machine; the shape appeared most strongly affected by screw speed, producing particles of higher aspect ratio as speed was increased. Adjusting the concentration of these CR excipients in the formulation, the flow rate or the type of compression element used in the screws proved ineffective in controlling the problem. Rather, a re-design of the extruder screws was required to prevent generation of these extended-form granules.
Assuntos
Química Farmacêutica/instrumentação , Preparações de Ação Retardada/síntese química , Excipientes/síntese química , Celulose/síntese química , Química Farmacêutica/métodos , Tamanho da PartículaRESUMO
The influence of filler selection in wet granulation was studied for the novel case where the binder is delivered as an unstable, semi-rigid aqueous foam to an extrusion process. The work primarily examined the impact of differing concentrations of microcrystalline cellulose (Avicel PH® 101) in a formulation with spray-dried α-lactose monohydrate (Flowlac® 100) in regards to wetting and granule nucleation for this relatively new technique known as continuous foam granulation. Foam stability was varied within the work to change its drainage and coarsening behavior atop these powder excipients, by use of different foamable binding agents (METHOCEL™ F4 PLV and METHOCEL™ Premium VLV) as well as by adjusting the foam quality. A static bed penetration test was first used to study the foam behavior in wetting these powders without the processing constraints of an extruder which limit possible liquid-to-solids ratios as well as introduce shear which may complicate interpretation of the mechanism. The test found that the penetration time to saturate these powders decreased as their water absorption capacity increased which in turn decreased the size of the formed nuclei. Differences in the stability of the foamed binder had minimal influence on these attributes of wetting despite its high spread-to-soak behavior. The size of granules produced by extrusion similarly demonstrated sensitivity to the increasing water absorption capacity of the filler and little dependency on foam properties. The different liquid-to-solids ratios required to granulate these different formulations inside the extruder highlighted an evolving concept of powder lubricity for continuous foam granulation.
Assuntos
Celulose/síntese química , Química Farmacêutica/métodos , Excipientes/síntese químicaRESUMO
This paper investigates foam granulation in a twin screw extruder as a new continuous wet granulation technique for pharmaceutical powder drug formulations. Foamed aqueous binder has a reportedly lower soak-to-spread ratio than drop or spray liquid addition in batch granulation. This work demonstrates a twin screw extruder configuration for foam granulation and subsequently compares the new approach against liquid injection in the granulation of α-lactose monohydrate with a methylcellulose binder. Trials were conducted at high powder output rates (20-40 kg/h) and high screw speeds (220-320 RPM) with two screw configurations. Process stability improved with the new technique allowing granulation with less binder. The extruded mass maintained a low exit temperature, being insensitive to operating conditions unlike the liquid injection approach, where temperatures rose significantly as flow rate increased. The particle size distribution by foam granulation reflected a more uniformly wetted mass with larger granule growth noted even for conditions where dry powder exited by liquid injection. Other factors were found similar between the two binder delivery methods such as consumed mechanical energy, as well as fracture strength and compressibility of produced granules.
Assuntos
Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Excipientes/química , Tecnologia Farmacêutica/métodos , Química Farmacêutica/instrumentação , Composição de Medicamentos/instrumentação , Lactose/química , Metilcelulose , Tamanho da Partícula , Pós/química , Tecnologia Farmacêutica/instrumentação , TemperaturaRESUMO
AIM: Preoperative short-course radiotherapy (SCRT) is increasingly recommended to reduce local recurrence after surgery for rectal cancer. Its avoidance may be beneficial, however, if the risk of local recurrence is low. We report a single centre experience which suggests that selective rather than uniform use of SCRT may be the best approach. METHOD: Analysis was carried out on a prospectively collected unselected series of 1606 patients with rectal cancer treated in one centre. Follow-up was 97% complete. SCRT was performed selectively and all patients had a mesorectal excision. RESULTS: Among 940 patients undergoing a potentially curative major resection the operative mortality was 4.6%, the permanent stoma rate 23% and the crude 5-year survival 61%. The local recurrence rate after curative anterior resection was 2.9% and 7.7% after abdominoperineal excision. The overall local recurrence rate after a potentially curative major resection was 4.0%. CONCLUSION: The routine use of preoperative radiotherapy for rectal cancer is probably not justified where local recurrence after curative rectal resection is uncommon.
Assuntos
Carcinoma/radioterapia , Carcinoma/cirurgia , Recidiva Local de Neoplasia/etiologia , Radioterapia Adjuvante , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/etiologia , Carcinoma/patologia , Colostomia/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Humanos , Ileostomia/estatística & dados numéricos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/prevenção & controle , Seleção de Pacientes , Neoplasias Retais/patologia , Taxa de SobrevidaRESUMO
This study investigated the effectiveness of cellulose nanocrystals derived from potato peel waste as a reinforcement and vapor barrier additive. The nanocrystals were derived from cellulosic material in the potato peel by alkali treatment and subsequently acid hydrolysis. TEM images revealed the average fiber length of the nanocrystals was 410 nm with an aspect ratio of 41; its aspect ratio being considerably larger than cotton-derived nanocrystals prepared using similar reaction conditions. Cellulose nanocrystals (CNC)-filled polyvinyl alcohol (PVA) and thermoplastic starch (TPS) films were prepared by solution casting method to maintain uniform dispersion of the 1-2% (w/w) filler content. An increase of 19% and 33% (starch composite) and 38% and 49% (PVA composite) in tensile modulus was observed for the 1% and 2% CNC-reinforced composites, respectively. Water vapor transmission measurements showed a marginal reduction of water permeability for the PVA composite, whereas no effect was observed for the thermoplastic starch composite.
Assuntos
Celulose/química , Nanocompostos/química , Nanopartículas/química , Solanum tuberosum/química , Amido/química , Difração de Raios X/métodosRESUMO
PURPOSE: The National Bowel Cancer Audit Project (NBOCAP) collects data from hospitals in the UK and aims to improve surgical outcomes and quality of care for patients. The aims of this study were to understand why trusts were/were not participating in the NBOCAP and how to improve the quality of data collected and feedback. METHODS: This was a prospective e-survey on colorectal surgeons' attitudes towards and opinions of the NBOCAP, within trusts in the UK. A questionnaire was emailed to members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI). RESULTS: Of the 171 trusts contacted by email, 66% of trusts (n = 117) had at least 1 consultant respond. Of the 117 trusts that responded, 60 (51.2%) had submitted data to the NBOCAP. A total of 549 consultants received the questionnaire, and 159 (29.0%) consultants responded. Fifty-one per cent (n = 60) of the trusts had submitted data to the NBOCAP. Reasons for data submission included the following: comparison of a units' data with national data (56.8%), a national audit improves outcomes (45.9%) and generation of information for use at a local level (42.6%). The main reasons for non-submission were as follows: lack of technical support (23.6%), lack of funding (19.6%) and lack of dedicated audit time (18.9%). Ninety-six (60.4%) consultants felt that the audit report should identify individual trust results. Fifty-three per cent of consultants (n = 87) rated their trusts' resources for audit as being very poor or poor. CONCLUSION: Consultant members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) within hospital trusts in the UK feel participation in the National Bowel Cancer Audit improves patients' quality of care and surgical outcomes. Increased awareness of the benefits of the NBOCAP and improved allocation of resources from hospital trusts could improve participation.
Assuntos
Atitude do Pessoal de Saúde , Neoplasias Colorretais/cirurgia , Auditoria Médica , Melhoria de Qualidade , Humanos , Irlanda , Médicos , Estudos Prospectivos , Inquéritos e Questionários , Reino UnidoRESUMO
BACKGROUND: Socioeconomic inequalities in cancer survival are well documented but they vary for different cancers and over time. Reasons for these differences are poorly understood. PATIENTS AND METHODS: For England and Wales, we examined trends in socioeconomic survival inequalities for breast cancer in women and rectal cancer in men during the 32-year period 1973-2004. We used a theoretical framework based on Victora's 'inverse equity' law, under which survival inequalities could change with the advent of successive new treatments, of varying effectiveness, which are disseminated with different speed among patients of different socioeconomic groups. We estimated 5-year relative survival for patients of different deprivation quintiles and examined trends in survival inequalities in light of major treatment innovations. RESULTS: Inequalities in breast cancer survival (921,611 cases) narrowed steadily during the study (from -10% to -6%). In contrast, inequalities in rectal cancer survival (187,104 cases) widened overall (form -5% to -11%) with fluctuating periods of narrowing inequality. CONCLUSIONS: Trends in socioeconomic differences in tumour or patient factors are unlikely explanations of observed changes over time in survival inequalities. The sequential introduction into clinical practice of new treatments of progressively smaller incremental benefit may partly explain the reduction in inequality in breast cancer survival.
Assuntos
Neoplasias da Mama/economia , Neoplasias da Mama/mortalidade , Atenção à Saúde , Neoplasias Retais/economia , Neoplasias Retais/mortalidade , Inglaterra , Feminino , Humanos , Masculino , Classe Social , Fatores Socioeconômicos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , País de GalesRESUMO
AIM: Treatments for pilonidal sinus disease are numerous and prone to failure. In complex disease, the morbidity is high. In contrast with complex operations, the cleft closure procedure can be done simply and successfully with better cosmetic results. We present the results of a single-centre experience of this procedure. METHOD: One hundred and fifty patients had the operation; most were treated as a day case and many were operated under local anaesthetic. RESULTS: Primary healing occurred in 83 (60%) of 139 patients. Recurrences requiring surgery have been seen in 5.3%. The long-term cosmetic appearance has been noted to approach normality. CONCLUSION: Cleft closure is a simple and highly effective operation to treat recurrent or extensive pilonidal sinus disease.
Assuntos
Procedimentos Cirúrgicos Ambulatórios/métodos , Seio Pilonidal/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Estudos Prospectivos , Recidiva , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To determine current delays in diagnosis and treatment of bowel cancer, when and why they occur, and what effect they have on survival. METHOD: A detailed review of the literature based on the development of the GP referral guidelines in 2000. RESULTS: There is no evidence of a reduction in the delay to diagnosis and treatment of bowel cancer over the last 60 years. There is no strong theoretical basis for a benefit from earlier diagnosis of symptomatic bowel cancer and this is consistent with observational studies. CONCLUSION: Campaigns to earlier diagnose bowel cancer will not be successful unless new strategies are developed. There is substantial evidence that earlier diagnosis of symptomatic bowel cancer will not improve survival in the majority of patients. However as excessive delays still occur in some patients it is reasonable to continue to aim to diagnose and treat all bowel cancer within 6 months of the onset of symptoms with an overall median of 3-4 months.
Assuntos
Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/cirurgia , Diagnóstico Precoce , Humanos , Qualidade da Assistência à Saúde , Encaminhamento e Consulta , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Reino Unido , Listas de EsperaRESUMO
AIM: This study was carried out to determine whether rectal bleeding is related to stage of bowel cancer and whether earlier diagnosis and treatment are associated with improved survival. METHOD: Eight hundred and forty-five patients were identified in the Wessex Bowel Cancer Audit (1991-1994). Presenting symptoms were identified from case notes. Outcome measures included 5-year survival, Dukes' stage, metastatic disease at surgery and time from onset of symptoms to treatment, in patients presenting with rectal bleeding or other symptoms and signs. RESULTS: Six hundred and seventy-six (80%) of 845 patient case notes were reviewed. Of these, 408 (60.4%) patients had rectal or sigmoid cancer, and 255 (62.5%) of these 408 patients, who presented with rectal bleeding, had significantly earlier stage disease than those with a change in bowel habit and/or abdominal pain (Dukes' stage A: 23.1%vs 3.6%; Dukes' stage D: 14.5%vs 23.4%; P < 0.001), fewer metastases visible at surgery (14.9%vs 22.6%; P < 0.001) and significantly better 5-year survival (54.8%vs 40.9%; P < 0.001). There was no further significant improvement in 5-year survival in patients treated within 6 months of the onset of symptoms (55.1%vs 53.5%). Hazard ratios showed that 5-year survival was independently associated with age, Dukes' stage and emergency treatment, but not with rectal bleeding, change in bowel habit, abdominal pain or delay in treatment. CONCLUSION: Bowel cancer patients presenting with rectal bleeding had earlier stage disease and significantly better survival than patients presenting with a change in bowel habit or abdominal pain. There was no reduction in 5-year survival in those patients who had a delay in treatment for > 6 months from the onset of symptoms.
Assuntos
Diagnóstico Tardio , Hemorragia Gastrointestinal/etiologia , Neoplasias Retais/patologia , Neoplasias do Colo Sigmoide/patologia , Dor Abdominal/etiologia , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/etiologia , Defecação/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Retais/complicações , Neoplasias Retais/diagnóstico , Reto , Estudos Retrospectivos , Neoplasias do Colo Sigmoide/complicações , Neoplasias do Colo Sigmoide/diagnóstico , Análise de Sobrevida , Fatores de TempoRESUMO
OBJECTIVES: To investigate the relationship between organisational structure, process and surgical outcomes for bowel cancer surgery. METHODS: An e-survey was sent to the members of the Association of Coloproctology of Great Britain and Ireland to determine the organisational structure of their Trusts. Responses were combined with the National Bowel Cancer Audit (NBOCAP) data. Items investigated included; number of consultants, nurse specialists, volume of cases and intensive care facilities. Main outcome measures included: 30-day risk-adjusted mortality, length of stay (LOS), lymph node yield and circumferential margin involvement (CRM). RESULTS: One hundred and seventeen Trusts responded (65.8%), matched to 7666 patient episodes (NBOCAP data) from 54 (62.8%)Trusts who submitted data to the audit. Trusts treating <190 cases/annum (p > 0.001), <4 colorectal consultants (p > 0.001), <4 HDU beds (p > 0001) and <8 ITU beds (p > 0001) were more likely to have a 30-day-risk-adjusted mortality twice that of the national mean. Sixty five percent (n = 1603) of Trusts treating ≥ 190 cases/annum harvested ≥ 12 lymph nodes vs. 58.3% (n = 1435) in Trusts <190 cases/annum (p < 0.001). Trusts with ≥ 2 pathologists with an interest in bowel cancer harvested ≥ 12 lymph nodes more frequently (p=<0.001) and were more likely to identify extramural vascular invasion in the specimen (p = 0.015). Negative CRM was achieved in 81.4% (n = 81.4) of patients in Trusts treating ≥ 190 cases vs. 66.5% (n = 569) in Trusts<190 cases/annum (p < 0.001). Trusts offering fast track discharge were more likely to have a LOS < 15 days (p = 0.006). Surgeons treating ≤ 35 cases/annum had increased major post-operative complications (<35 cases = 70.2% vs. ≥ 35 cases = 21.9%; p < 0.001), however 30 day risk adjusted mortality was not increased in surgeons treating <35 cases/annum. CONCLUSIONS: This study shows that the organisational infrastructure of hospitals appears to have as great an impact on patient outcomes as the volume of cases performed by hospital Trusts.
Assuntos
Atenção à Saúde/organização & administração , Neoplasias Intestinais/cirurgia , Política Organizacional , Avaliação de Resultados em Cuidados de Saúde , Humanos , Auditoria Médica , Reino UnidoRESUMO
BACKGROUND: Pilonidal disease is a common and usually minor disease. Although wide excisional surgery has been common practice, there are more simple alternatives. This review focused on the aetiology and management of pilonidal disease. METHODS: A comprehensive review of the literature on pilonidal disease was undertaken. MEDLINE searches for all articles listing pilonidal disease (1980-2010) were performed to determine the aetiology and results of surgical and non-surgical treatments. Single papers describing new techniques or minor modifications of established techniques were excluded. Further articles were traced through reference lists. RESULTS: Patients with minimal symptoms and those having drainage of a single acute abscess can be treated expectantly. Non-surgical treatments may be of value but their long-term results are unknown. There is no rational basis or need for wide excision of the abscess and sinus. Simple removal of midline skin pits, the primary cause of pilonidal disease, with lateral drainage of the abscess and sinus is effective in most instances. Hirsute patients with extensive primary disease and deep natal clefts, or with recurrent disease and unhealed midline wounds, may also require flattening of the natal cleft with off-midline skin closure. These more conservative procedures are usually done as a day case, require minimal care in the community and are associated with a rapid return to work. They also avoid the occasional debilitating complications of surgical treatment. CONCLUSION: Simple day-case surgery to eradicate midline skin pits without wide excision of the abscesses and sinus is rational, safe and effective for patients with pilonidal sinus disease.
Assuntos
Procedimentos Cirúrgicos Ambulatórios/métodos , Seio Pilonidal/cirurgia , Drenagem/métodos , Humanos , Seio Pilonidal/etiologia , Retalhos Cirúrgicos , CicatrizaçãoRESUMO
A series of studies have shown that the heavy burdens of diarrheal diseases in the first 2 formative years of life in children living in urban shanty towns have negative effects on physical and cognitive development lasting into later childhood. We have shown that APOE4 is relatively common in shanty town children living in Brazil (13.4%) and suggest that APOE4 has a protective role in cognitive development as well as weight-for-height in children with heavy burdens of diarrhea in early childhood (64/123; 52%), despite being a marker for cognitive decline with Alzheimer's and cardiovascular diseases later in life. APOE2 frequency was higher among children with heaviest diarrhea burdens during the first 2 years of life, as detected by PCR using the restriction fragment length polymorphism method, raising the possibility that ApoE-cholesterol balance might be critical for growth and cognitive development under the stress of heavy diarrhea burdens and when an enriched fat diet is insufficient. These findings provide a potential explanation for the survival advantage in evolution of genes, which might raise cholesterol levels during heavy stress of diarrhea burdens and malnutrition early in life.
Assuntos
Apolipoproteínas E/genética , Diarreia Infantil/genética , Polimorfismo Genético/genética , Apolipoproteínas E/metabolismo , Brasil , Desenvolvimento Infantil , Pré-Escolar , Cognição , Estudos de Coortes , Diarreia Infantil/complicações , Diarreia Infantil/metabolismo , Feminino , Frequência do Gene , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Mucosa Bucal/citologia , Reação em Cadeia da Polimerase , Fatores SocioeconômicosRESUMO
A series of studies have shown that the heavy burdens of diarrheal diseases in the first 2 formative years of life in children living in urban shanty towns have negative effects on physical and cognitive development lasting into later childhood. We have shown that APOE4 is relatively common in shanty town children living in Brazil (13.4 percent) and suggest that APOE4 has a protective role in cognitive development as well as weight-for-height in children with heavy burdens of diarrhea in early childhood (64/123; 52 percent), despite being a marker for cognitive decline with Alzheimers and cardiovascular diseases later in life. APOE2 frequency was higher among children with heaviest diarrhea burdens during the first 2 years of life, as detected by PCR using the restriction fragment length polymorphism method, raising the possibility that ApoE-cholesterol balance might be critical for growth and cognitive development under the stress of heavy diarrhea burdens and when an enriched fat diet is insufficient. These findings provide a potential explanation for the survival advantage in evolution of genes, which might raise cholesterol levels during heavy stress of diarrhea burdens and malnutrition early in life.
Assuntos
Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Apolipoproteínas E/genética , Diarreia Infantil/genética , Polimorfismo Genético/genética , Apolipoproteínas E/metabolismo , Brasil , Desenvolvimento Infantil , Cognição , Estudos de Coortes , Diarreia Infantil/complicações , Diarreia Infantil/metabolismo , Frequência do Gene , Genótipo , Mucosa Bucal/citologia , Reação em Cadeia da Polimerase , Fatores SocioeconômicosRESUMO
BACKGROUND: The government's proposals to openly report clinical outcomes poses challenges to the National Bowel Cancer Audit now funded by the UK department of health. AIM: To identify the benefits and risks of open reporting and to propose ways the risks might be minimized. METHODS: A review of the literature on clinical audit and the consequences of open reporting. RESULTS: There are significant potential benefits of a national audit of bowel cancer including protecting patients from sub-standard care, providing clinicians with externally validated evidence of their performance, outcome data for clinical governance and evidence that increases in government expenditure are achieving improvements in survival from bowel cancer. These benefits will only be achieved if the audit captures most of the cases of bowel cancer in the UK, the data collected is complete and accurate, the results are risk adjusted and these are presented to the public in a way that is fair, clear and understandable. Involvement of clinicians who have confidence in the results of the audit and who actively compare their own results against a national standard is essential. It is suggested that a staged move to open reporting should minimise the risk of falsely identifying an outlying unit. CONCLUSION: The fundamental aim of the National Bowel Cancer Audit is the pursuit of excellence by identification and adoption of best practice. This could achieve a continuous improvement in the care of all patients with bowel cancer in the UK. The ACPGBI suggests a safer way of transition to open reporting to avoid at least some of its pitfalls.