Prognosis in diabetic nephropathy.

OBJECTIVE--To assess the effect of long term antihypertensive treatment on prognosis in diabetic nephropathy. DESIGN--Prospective study of all insulin dependent diabetic patients aged under 50 with onset of diabetes before the age of 31 who developed diabetic nephropathy between 1974 and 1978 at Steno Memorial Hospital. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--Forty five patients (20 women) with a mean age of 30 (SD 7) years and a mean duration of diabetes of 18 (7) years at onset of persistent proteinuria were followed until death or for at least 10 years. INTERVENTIONS--Antihypertensive treatment was started a median of three (0-13) years after onset of nephropathy. Four patients (9%) received no treatment, and 9 (20%), 13 (29%), and 19 (42%) were treated with one, two, or three drugs, respectively. The median follow up was 12 (4-15) years. MAIN OUTCOME MEASURES--Arterial blood pressure and death. RESULTS--Mean blood pressure at start of antihypertensive treatment was 148/95 (15/50) mm Hg. Systolic blood pressure remained almost unchanged (slope -0.01 (95% confidence interval -0.39 to 0.37) mm Hg a year) while diastolic blood pressure decreased significantly (0.87 (0.65 to 1.10) mm Hg a year) during antihypertensive treatment. The cumulative death rate was 18% (8 to 32%) 10 years after onset of nephropathy, in contrast to previous reports of 50% to 77% 10 years after onset of nephropathy. As in previous studies, uraemia was the main cause of death (9 patients; 64%). CONCLUSIONS--The prognosis of diabetic nephropathy has improved during the past decade largely because of effective antihypertensive treatment.     

n of 1 trials comparing a non-steroidal anti-inflammatory drug with paracetamol in osteoarthritis.

OBJECTIVE--To evaluate the efficacy of paracetamol and a non-steroidal anti-inflammatory drug for symptom relief in osteoarthritis. DESIGN--Double blind, randomised, controlled trials in individual patients (n of 1 trials). Three treatment cycles with two weeks'' each of paracetamol (1 g twice daily) and diclofenac (50 mg twice daily) prepared in identical gelatin capsules. SETTING--General practices in metropolitan Sydney, Australia. SUBJECTS--25 patients (median age 64 years) with pain of osteoarthritis (median duration of disease eight years) considered by their general practitioners to require regular treatment. 20 were already taking non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES--Diary of pain and stiffness, function, and side effects. RESULTS--15 patients completed the study, five withdrew early but had made a therapeutic decision, and five dropped out very early. Results from 20 patients were analysed. Several patterns of response evolved. Eight of the 20 patients found no clear difference, symptoms being adequately controlled by paracetamol; five indicated a clear preference for the non-steroidal anti-inflammatory drug; two showed control of symptoms after their initial two weeks of the non-steroidal anti-inflammatory drug which continued throughout subsequent treatment changes; in five the non-steroidal anti-inflammatory drug may have been better but neither agent gave satisfactory control. After three months nine of the 20 patients had adequate symptom control with paracetamol alone. CONCLUSIONS--Of 1 studies--that is, randomised trials in individual patients--are clinically useful in deciding treatment in heterogeneous conditions which require long term symptomatic relief. In osteoarthritis many patients currently receiving or being considered for non-steroidal anti-inflammatory drugs may achieve adequate control with paracetamol.     

Development of long term use of psychotropic drugs by general practice patients

From 1984 to 1986 a prospective study was conducted of 104 general practice patients who started treatment with a benzodiazepine or an antidepressant drug. The duration of reported use of the drugs was two months for 45% of patients, four months for 17% of patients, and six months for 15%. Type of drug, age, and level of education were found to be predictive of continuing use.General practitioners have a significant effect on their patients'' use of drugs and, with careful selection and review when prescribing, may help to prevent dependence on psychotropic drugs.     

Long term antithyroid drug therapy for intractable cases of Graves' disease.

Among the 504 patients with Graves' disease in whom the author initiated antithyroid drug therapy between 1956 and 1968 are 14 to whom the administration of antithyroid drug has been continued for 8 to 21 years because of recurrence shortly after the discontinuation of drugs. During these periods, no side effects were observed and three patients went into complete remission after 8, 9 and 20 years of antithyroid drug administration, respectively. It is suggested therefore that the long term administration of antithryoid drugs can be a useful treatment for intractable cases.     

非药物干预治疗物质使用障碍

物质使用障碍（substance use disorder,SUD）是一个全球性的卫生和社会问题。针对大多数成瘾性物质，目前还没有有效的治疗药物，普遍还是采用心理治疗和行为矫治。近年来，针刺、深部脑刺激（DBS）、重复经颅磁刺激（rTMS）、经颅直流电刺激（tDCS）和运动等非药物干预手段在治疗神经系统疾病的有效性逐渐得到重视。越来越多的研究也开始关注非药物干预手段在治疗SUD中的应用。本综述在文献检索（如PubMed、Google Scholar等）的基础上总结了针刺、DBS、rTMS、tDCS和运动等非药物干预手段对阿片类药物、精神活性物质、尼古丁、酒精等不同成瘾性物质的心理渴求、戒断时间、使用剂量和成瘾伴随的情绪、认知功能障碍等的影响。研究表明，针刺、DBS、rTMS、tDCS和运动等非药物干预手段可以有效降低成瘾性物质引起的心理渴求、降低物质摄入量、增加戒断时间，同时改善长期使用成瘾性物质引起的认知障碍、焦虑和抑郁样行为等。如果非药物干预手段结合药物、心理等治疗方式，效果更佳。尽管非药物干预方法在现阶段主要作为辅助性治疗手段，未来的研究应注重明确非药物干预手段的神经生物学机制，...     

Nosocomial Candidemia; Risk Factors and Prognosis Revisited; 11 Years Experience from a Norwegian Secondary Hospital

The aim of the study was to review the epidemiology and prognosis of candidemia in a secondary hospital, and to examine the intra-hospital distribution of candidemia patients. Study design is a retrospective cohort study. Trough 2002–2012, 110 cases of candidemia were diagnosed, giving an incidence of 2, 6/100000 citizens/year. Overall prognosis of candidemia was dismal, with a 30 days case fatality rate of 49% and one year case fatality rate of 64%. Candidemia was a terminal event in 55% of 30 days non-survivors, defined as Candida blood cultures reported positive on the day of death or thereafter (39%), or treatment refrained due to hopeless short-term prognosis (16%). In terminal event candidemias, advanced or incurable cancer was present in 29%. Non-survivors at 30 days were 9 years (median) older than survivors. In 30 days survivors, candidemia was not recognised before discharge in 13% of cases. No treatment were given and no deaths or complications were observed in this group. Candidemia patients were grouped into 8 patient categories: Abdominal surgery (35%), urology (13%), other surgery (11%), pneumonia (13%), haematological malignancy (7%), intravenous drug abuse (4%), other medical (15%), and new-borns (3%). Candidemia was diagnosed while admitted in the ICU in 46% of patients. Urology related cases were all diagnosed in the general ward. Multiple surgical procedures were done in 60% of abdominal surgery patients. Antibiotics were administered prior to candidemia in 87% of patients, with median duration 17 (1–108) days. Neutropenia was less common than expected in patients with candidemia (8/105) and closely associated to haematological malignancy (6/8). Compared with previous national figures the epidemiology of invasive candidiasis seems not to have changed over the last decade.     

Predictors of Post-operative Mycetoma Recurrence Using Machine-Learning Algorithms: The Mycetoma Research Center Experience

Post-operative recurrence in mycetoma after adequate medical and surgical treatment is common and a serious problem. It has health, socio-economic and psychological detrimental effects on patients and families. It is with this in mind, we set out to determine the predictors of post-operative recurrence in mycetoma. The study included 1013 patients with Madurella mycetomatis causing eumycetoma who underwent surgical excision at the Mycetoma Research Centre, Khartoum, Sudan in the period 1991–2015. The clinical records of these patients were reviewed and relevant information was collected using a pre-designed data collection sheet. The study showed, 276 patients (27.2%) of the studied population developed post-operative recurrence, 217 were males (78.6%) and 59 were females (21.4%). Their age ranged between 5 to 70 years with a mean of 32 years. The disease duration at presentation ranged between 2 months and 17 years. The majority of the patients 118 (42.8%) had mycetoma of 1 year duration. In this study, students were the most affected; 105 (38%) followed by workers 70 (25.4%), then farmers 48(17.3%). The majority of the patients were from the Central Sudan 207 (75%), Western Sudan 53 (19.2%) while 11 patients (4%) were from the Northern part. Past history of surgical intervention performed elsewhere was reported in 196 patients (71.1%). Family history of mycetoma was reported in 50 patients (18.1%). The foot was the most affected site, 245 (88.7%), followed by the hand seen in 19 (6.8%) patients and 44 (4.5%) had different sites involvement. Most of the patients 258 (93.5%) had wide local surgical excisions while 18 had major amputation. The model predicted that the certain groups have a high risk of recurrence, and these include patients with disease duration greater than 10 years and extra-pedal mycetoma. Patients with disease duration between [5–10] years, with pedal mycetoma, who had previous surgery, with positive family history and underwent wide local surgical excision. Patients with disease duration [5–10] years, with pedal mycetoma, had previous surgery, with no family history but presented with a disease size (> 10 cm), were non- farmers and underwent wide local surgical excision. Other groups are patients with disease duration (≤5 years), with pedal mycetoma, age <59 years, living in the Western /Eastern / Southern regions of the Sudan and with positive family history and had wide local surgical excision. Also included patients with disease duration (≤5 years), with pedal mycetoma, aged <59 years, living in the northern or central region, with no family history but presented with a disease size >10 cm, working as farmers or students and underwent wide local surgical excision. In conclusion, these groups of patients need special care to reduce the incidence of post-operative recurrence with its morbidity and detrimental consequences. In depth studies for the other predisposing factors for post-operative recurrence such as genetic, immunological and environmental factors are needed.     

Treatment in England of Canadian Patients Addicted to Narcotic Drugs

The method of treatment and the results obtained from the treatment of 50 Canadian patients addicted to narcotic drugs who went to England are recorded. These patients were first stabilized on the minimal dose of narcotic drug which permitted them to work, and to acquire security and self-respect. Then, after psychiatric treatment dealing with the basic problem of their personality disorder, complete withdrawal treatment of the narcotic drug was undertaken.Nine of 10 patients aged between 20 and 30, of good social and cultural background, have been relieved of dependence on drugs for over two years.The other 40 patients came from a different background. Nearly all had been imprisoned for drug offences and they had come to England to obtain treatment and to avoid further prison sentences in Canada.The 31 patients whose prison sentences had been directly connected with drug offences are working steadily and leading an apparently normal life.The remaining nine patients had been convicted of criminal acts before becoming addicted to narcotic drugs and, with two exceptions, the results of their treatment compare unfavourably with the other patients, seven having been convicted and imprisoned in London.     

Plastic surgery and psychotherapy in the treatment of 100 psychologically disturbed patients

This paper reviews the senior author's long-term experience with the surgical-psychiatric treatment of 100 aesthetic surgery patients with significant psychological disturbances. Patients with psychological disturbances of a magnitude generally considered an "absolute contraindication" for surgery were operated on and later assessed to determine the psychological impact of surgery. Patient follow-up averaged 6.2 years (maximum follow-up 25.7 years). Of the 87 patients who underwent operation (7 patients were refused surgery and 6 voluntarily deferred surgery), 82.8 percent had a positive psychological outcome, 13.8 percent experienced "minimal" improvement from surgery, and 3.4 percent were negatively affected by surgery. There were no lawsuits, suicides, or psychotic decompensations. Patients with severe psychological disturbances frequently benefited from combined surgical-psychiatric treatment designed to address the patient's profound sense of deformity. This study suggests that plastic surgeons are "passing up" a significant number of patients who may be helped by combined surgical-psychological intervention.     

Epidemiología de la acromegalia en España

Epidemiology of acromegaly in Spain does not differ from that reported in other published series. Prevalence rate is approximately 60 cases per million, peak incidence occurs in middle age, more women are affected (61%), and there is a substantial delay between occurrence of the first symptoms and diagnosis. Studies REA (Spanish Acromegaly Registry) and OASIS analyzed the epidemiology, clinical characteristics, and management of the disease in Spain. Surgery, performed in more than 80% of patients, has been (and continues to be) the main treatment for the past four decades. In the past decade, however, more patients have received somatostatin analogs (SSAs) as first-line treatment. Use of radiation therapy has significantly decreased in recent decades. Somatostatin analogs (SSAs) are the most commonly used drugs, administered to 85% of patients; however, only 12%-15% continue on drug treatment alone. The surgical remission rate was 38.4% in the last decade, with a significant improvement over decades. Preoperative treatment with SSAs has no influence on surgical cure rates. Second-line therapies used after surgical failure in the past decade included SSAs in 49% of patients, repeat surgery in 27%, radiotherapy in 11%, pegvisomant in 15%, and dopamine agonists in 5%. Mean cost of acromegaly treatment was 9.668€ (data estimated in 2009 and adjusted in 2010), of which 71% was due to the cost of SSAs. Patients treated with pegvisomant have a more aggressive form of the disease and higher comorbidity rates.     

后路脊柱术后切口感染病原菌特征及不同治疗方案的疗效观察

目的:探讨后路脊柱术后切口感染病原菌分布特征及不同治疗方案的治疗效果,为临床治疗提供参考。方法:选择32例2015年8月-2019年12月于我院进行后路脊柱术治疗且术后切口出现感染的患者,对其标本进行细菌分离培养鉴定,分析病原菌分布情况并测定细菌药敏性。对浅层切口感染患者采用常规换药治疗,而深部感染者在早期进行扩创冲洗引流,并根据药敏结果选用抗生素治疗,观察不同治疗方案的治疗效果。结果:32例术后切口感染患者中,共检出36株病原菌,革兰阴性菌17株,占47.22%,革兰阳性菌19株,占52.78%。前四位病原菌分别为金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌、溶血葡萄球菌。大肠埃希菌及铜绿假单胞菌对亚胺培南全部敏感,耐药率为0.00%;黄色葡萄球菌及溶血葡萄球菌对万古霉素、替考拉宁全部敏感,耐药率均为0.00%。浅层切口感染及深部切口感染患者全部治愈,所有患者愈后均随访3个月,未见复发感染病例。结论:后路脊柱术后切口感染以金黄色葡萄球菌为主,临床应对深部切口感染患者行早期行扩创冲洗引流,并根据耐药性结果合理选用抗生素。     

Occurrence and clinical course of drug-induced agranulocytosis

A report of 27 drug induced agranulocytosis is presented in a period of 13 years. The rate of the disease was 0.12% of the total number of patients. Cases due to cytostatical and radiation treatment were not included. According to bone-marrow cellularity patients were divided into hypo- and hyper-cellular groups. The clinical findings were similar in both groups and the majority of patients recovered. Two patients died, both in the hypocellular group: the first due to mycotic pulmonary infection, the other after massive pulmonary embolism but after complete haematological recovery. Bone-marrow plasmocytosis was slightly expressed in the hypocellular group. The normal leukocyte number appeared after treatment within 3-25 days. Recurrent agranulocytosis was observed in four patients and permanent leukopenia developed in five. The leukocyte-agglutination test was positive in 10 cases only, but the leukocyte migration test was positive in all investigated cases except two. Five patients had a previous history with idiosyncrasy. Treatment was started with antibiotics, corticosteroids and with antimycotic drugs. Sterile island and granulocyte-transfusion was applied in seriously ill patients with septicemic complications only.     

多模式术后镇痛在腹腔镜结肠手术中的应用

目的:理论上联合使用不同机制镇痛药较镇痛药单独使用镇痛效果更完善,在妇科、骨科等手术中已有结论;笔者观察比较腹腔镜结肠手术术使用单一止痛药及联合使用不同机制镇痛药在术后镇痛的效果以及各自不良反应的发生率。方法:择期腹腔镜结肠手术患者90例,随机分为3组,每组30例。A组使用地佐辛+氟比洛酚酯行术后镇痛为多模式镇痛组;B组使用地佐辛行术后镇痛;C组使用氟比洛酚酯行术后镇痛。记录每组术后4、8、12、24 h视觉模糊评分(VAS)及术后不良反应包括嗜睡、躁动、恶心呕吐的发生率。结果:A组术后4 h、8 h的VAS评分低于B、C两组,差异有显著性,A组无嗜睡及躁动发生,发生呕吐1例,不良反应发生率A组低于B、C两组,差异有显著性。结论:地佐辛+氟比洛酚酯联合用药可安全有效应用于腹腔镜结肠手术术后镇痛,是一种有效的多模式术后镇痛方式,在减弱疼痛的放大效应及对中枢神经的作用两方面起效,因而较单独使用地佐辛及氟比洛酚酯有更好的镇痛效果,且不良反应低于单独使用地佐辛及氟比洛酚酯。     

MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party.

The main aim of the trial was to determine whether drug treatment of mild hypertension (phase V diastolic pressure 90-109 mm Hg) reduced the rates of stroke, of death due to hypertension, and of coronary events in men and women aged 35-64 years. Subsidiary aims were: to compare the course of blood pressure in two groups, one taking bendrofluazide and one taking propranolol, and to compare the incidence of suspected adverse reactions to these two drugs. The study was single blind and based almost entirely in general practices; 17 354 patients were recruited, and 85 572 patient years of observation have accrued. Patients were randomly allocated at entry to take bendrofluazide or propranolol or placebo tablets. The primary results were as follows. The stroke rate was reduced on active treatment: 60 strokes occurred in the treated group and 109 in the placebo group, giving rates of 1.4 and 2.6 per 1000 patient years of observation respectively (p less than 0.01 on sequential analysis). Treatment made no difference, however, to the overall rates of coronary events: 222 events occurred on active treatment and 234 in the placebo group (5.2 and 5.5 per 1000 patient years respectively). The incidence of all cardiovascular events was reduced on active treatment: 286 events occurred in the treated group and 352 in the placebo group, giving rates of 6.7 and 8.2 per 1000 patient years respectively (p less than 0.05 on sequential analysis). For mortality from all causes treatment made no difference to the rates. There were 248 deaths in the treated group and 253 in the placebo group (rates 5.8 and 5.9 per 1000 patient years respectively). Several post hoc analyses of subgroup results were also performed but they require very cautious interpretation. The all cause mortality was reduced in men on active treatment (157 deaths versus 181 in the placebo group; 7.1 and 8.2 per 1000 patient years respectively) but increased in women on active treatment (91 deaths versus 72; 4.4 and 3.5 per 1000 patient years respectively). The difference between the sexes in their response to treatment was significant (p = 0.05). Comparison of the two active drugs showed that the reduction in stroke rate on bendrofluazide was greater than that on propranolol (p = 0.002). The stroke rate was reduced in both smokers and non-smokers taking bendrofluazide but only in non-smokers taking propranolol. This difference between the responses to the two drugs was significant (p = 0.03).(ABSTRACT TRUNCATED AT 400 WORDS)     

基于铁死亡的抗结直肠癌药物的应用

结直肠癌（colorectal cancer，CRC）是癌症相关死亡的第二大主要原因，且患者趋于年轻化，化疗、免疫治疗及靶向治疗等药物治疗虽然取得进展，但因药物的毒性、耐药及价格昂贵严重影响CRC的综合治疗效果，因此寻求新的、更敏感有效的药物和药物靶点是目前研究的热点。铁死亡作为一种近期发现的细胞死亡调节方式，它与癌症药物耐药性、敏感性密切相关，激活铁死亡成为克服传统癌症治疗耐药机制的潜在策略，诱导铁死亡的药物研发应用有望成为治疗CRC的有效手段。本文综述在CRC中铁死亡相关代谢途径药物研究的最新进展，以便整体认识基于铁死亡的药物在CRC中作用的具体机制，充分发掘其治疗潜力，为CRC的诊疗和耐药性的解决提供新的思路。     

细胞凋亡抑制蛋白cIAP 与卵巢癌耐药性的研究进展

卵巢恶性肿瘤是女性生殖系统三大恶性肿瘤之一,其发病率在女性生殖系统肿瘤中占第三位,而死亡率却高居首位。目前对于晚期卵巢癌(Ⅲ或Ⅳ期)多倾向于用新辅助化疗+肿瘤细胞减灭术+术后周期性化疗的治疗方法。但是,尽管多数患者在最初对化疗药物较敏感,但仍有60%~80%最终死于卵巢癌,这些患者大部分都对化疗药物产生了耐药性,在更换新的化疗方案初期是有效的,但最终仍会耐药。近年来,有关细胞凋亡抑制蛋白(cIAP,cellular inhibitors of apoptosis proteins)在卵巢癌复发耐药中的作用机制的研究越来越受到重视。研究证实,cIAP在耐药肿瘤细胞中呈高表达,并与多种因子共同参与形成了上皮性卵巢癌的耐药机制,抑制了化疗药物引起的肿瘤细胞的凋亡。这些发现为攻克卵巢癌的耐药机制提供了重要线索,也为卵巢癌化疗药物的应用指出了新的方向。     

Discovery and development of SQ109: a new antitubercular drug with a novel mechanism of action

Existing drugs have limited efficacy against the rising threat of drug-resistant TB, have significant side effects, and must be given in combinations of four to six drugs for at least 6 months for drug-sensitive TB and up to 24 months for drug-resistant TB. The long treatment duration has led to increased patient noncompliance with therapy. This, in turn, drives the development of additional drug resistance in a spiral that has resulted in some forms of TB being currently untreatable by existing drugs. New antitubercular drugs in development, particularly those with mechanisms of action that are different from existing first- and second-line TB drugs, are anticipated to be effective against both drug-sensitive and drug-resistant TB. SQ109 is a new TB drug candidate with a novel mechanism of action that was safe and well tolerated in Phase I and early Phase II clinical trials. We describe herein the identification, development and characterization of SQ109 as a promising new antitubercular drug.     

New drugs for the treatment of human African trypanosomiasis: research and development

Chemotherapy of human African trypanosomiasis is problematic because of the high frequency of severe adverse events, the long duration and high cost of treatment, and an increasing number of treatment-refractory cases. New cost-efficient, easy-to-use drugs are urgently needed. Whereas basic research on potential drug targets is anchored in academia, the complex, highly regulated and very expensive process of preclinical and clinical drug development is almost exclusively in the hands of pharmaceutical companies. Jennifer Keiser, August Stich and Christian Burri here review, from the angle of industrial drug research and development, the past ten years of research activities at different stages of the development of trypanocidal drugs, and assess future prospects. The absence of compounds in clinical development Phases I-III indicates no new drugs will become available in the next few years.