Incorporation of medicines in the Unified Health System (SUS): comparison between oncology and the specialized component of pharmaceutical care. / Incorporação de medicamentos no SUS: comparação entre oncologia e componente especializado da assistência farmacêutica.

Compliance with legal deadlines for the assessment and incorporation of technologies in Brazil's Unified Health System (SUS) is essential to ensure public access to essential medicines. The scope of this paper was to analyze the compliance with legal deadlines for incorporation and availability of medicines in the SUS, comparing Oncology and the Specialized Component of Pharmaceutical Assistance (SCPA). A comparison was made of the drugs incorporated that were submitted to Conitec in the period from January 1, 2017, to April 30, 2020. A total of 85 drugs were recommended for incorporation by Conitec, of which 15 (17.64%) were for Oncology and 70 (82.36%) were for SCPA. The time between analysis and recommendation by Conitec until the publication of the decision by the Ministry of Health was, on average, 86 days longer for oncological drugs and the availability timeframe of technologies incorporated in the oncology area was, on average, 389 days longer than for SCPA. The major progress achieved with the creation of Conitec in Brazil is acknowledged, but the results of this study point to a pressing need to improve the process of making available technologies incorporated into the SUS, especially in oncology.

O cumprimento dos prazos legais para incorporação e disponibilização de tecnologias no Sistema Único de Saúde (SUS) é fundamental para o acesso da população aos medicamentos considerados essenciais. Objetivou-se analisar o cumprimento destes prazos comparando a Oncologia e o Componente Especializado de Assistência Farmacêutica (CEAF). Comparou-se os processos de incorporação de medicamentos no SUS da Oncologia e do CEAF que foram submetidos à Conitec no período de 01 de janeiro de 2017 a 30 de abril de 2020. No período, 83 processos de incorporação de medicamentos foram recomendados para incorporação pela Conitec, dos quais 13 (15,66%) eram da Oncologia e 70 (84,34%) eram do CEAF. Verifica-se que o tempo de análise e recomendação pela Conitec até a publicação da decisão pelo Ministério da Saúde foi, em média, 15 dias maior para processos que continham medicamentos oncológicos e o tempo para disponibilização das tecnologias incorporadas da área da oncologia foi, em média, 389 dias maior que do CEAF. Reconhece-se o importante avanço obtido com a criação da Conitec no Brasil, porém os resultados deste estudo apontam para a necessidade de aprimoramento do processo de disponibilização de tecnologias incorporadas no SUS, em especial da Oncologia.

Incorporação de medicamentos no SUS: comparação entre oncologia e componente especializado da assistência farmacêutica / Incorporation of medicines in the Unified Health System (SUS): comparison between oncology and the specialized component of pharmaceutical care

Resumo O cumprimento dos prazos legais para incorporação e disponibilização de tecnologias no Sistema Único de Saúde (SUS) é fundamental para o acesso da população aos medicamentos considerados essenciais. Objetivou-se analisar o cumprimento destes prazos comparando a Oncologia e o Componente Especializado de Assistência Farmacêutica (CEAF). Comparou-se os processos de incorporação de medicamentos no SUS da Oncologia e do CEAF que foram submetidos à Conitec no período de 01 de janeiro de 2017 a 30 de abril de 2020. No período, 83 processos de incorporação de medicamentos foram recomendados para incorporação pela Conitec, dos quais 13 (15,66%) eram da Oncologia e 70 (84,34%) eram do CEAF. Verifica-se que o tempo de análise e recomendação pela Conitec até a publicação da decisão pelo Ministério da Saúde foi, em média, 15 dias maior para processos que continham medicamentos oncológicos e o tempo para disponibilização das tecnologias incorporadas da área da oncologia foi, em média, 389 dias maior que do CEAF. Reconhece-se o importante avanço obtido com a criação da Conitec no Brasil, porém os resultados deste estudo apontam para a necessidade de aprimoramento do processo de disponibilização de tecnologias incorporadas no SUS, em especial da Oncologia.

Abstract Compliance with legal deadlines for the assessment and incorporation of technologies in Brazil's Unified Health System (SUS) is essential to ensure public access to essential medicines. The scope of this paper was to analyze the compliance with legal deadlines for incorporation and availability of medicines in the SUS, comparing Oncology and the Specialized Component of Pharmaceutical Assistance (SCPA). A comparison was made of the drugs incorporated that were submitted to Conitec in the period from January 1, 2017, to April 30, 2020. A total of 85 drugs were recommended for incorporation by Conitec, of which 15 (17.64%) were for Oncology and 70 (82.36%) were for SCPA. The time between analysis and recommendation by Conitec until the publication of the decision by the Ministry of Health was, on average, 86 days longer for oncological drugs and the availability timeframe of technologies incorporated in the oncology area was, on average, 389 days longer than for SCPA. The major progress achieved with the creation of Conitec in Brazil is acknowledged, but the results of this study point to a pressing need to improve the process of making available technologies incorporated into the SUS, especially in oncology.

Thromboprophylaxis of Patients Submitted to Total Hip and Knee Arthroplasty: A Cost-Effectiveness Assessment From the Perspective of the Brazilian National Health System.

OBJECTIVES: Venous thromboembolism (VTE) is a serious national and international public health issue. Major orthopedic surgeries, such as a total hip (THA) and knee (TKA) arthroplasties, are associated with an increased risk of VTE, long-term complications, functional disability, and death resulting from hypercoagulability by surgical trauma. This pharmacoeconomic analysis aimed to identify the most cost-effective anticoagulant alternative in preventing VTE in patients undergoing THA and TKA. METHODS: A decision tree model was developed, comparing direct oral anticoagulants (rivaroxaban, apixaban, and dabigatran) with enoxaparin, with separate THA and TKA models a 3-month time horizon from the perspective of the Brazilian National Health System. The results were presented as incremental cost-effectiveness ratio (ICER), and the outcomes analyzed were avoided complications (ACs) after thromboprophylaxis. Comparative effectiveness was obtained from a published meta-analysis. A willingness to pay value of approximately R$ 15 000.00 was used per AC, and a probabilistic sensitivity analysis with the Monte Carlo simulation was conducted. RESULTS: Apixaban was the anticoagulant that presented the best ICER for patients undergoing THA (R$ 207.52/AC) and TKA (R$ 133.59/AC), followed by rivaroxaban (R$ 347.21/AC), dabigatran (R$ 372.56/AC), and enoxaparin (R$ 711.44/AC) for THA and by dabigatran (R$ 194.07/AC), rivaroxaban (R$ 221.12/AC), and enoxaparin (R$ 747.25/AC) for TKA. After ICER analysis, apixaban prevails over the other technologies analyzed for both surgical procedures, confirmed after sensitivity analysis. CONCLUSION: Our model suggests that, in the Brazilian National Health System, apixaban is the most cost-effective alternative in preventing VTE after THA and TKA.

Evidence for a contribution of the APOE (but not the ACE) gene to the sleep profile of non-demented elderly adults.

This study aims to investigate alleles of the human apolipoprotein E (APOE) and of the angiotensin-converting enzyme (ACE) genes as risk factors for poor quality of sleep in elderly individuals with no major cognitive decline. This cross-sectional, analytical study was conducted with 163 participants aged 75 years in average and 85% female. Sociodemographic, anthropometric and clinical data were gathered, and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth scale, with patient followed for years prior to these evaluations to rule out onset of major mental disorders. Genotyping of classic polymorphic sites for the ApoE (rs429358 and rs7412) and the ACE (rs4646994) genes used peripheral DNA. A total of 63% of the subjects reported poor quality of sleep assessed by the PSQI whereas 54 (33%) reported daytime sleepiness through the Epworth scale. A significant correlation was observed between APOE and PSQI, with a greater frequency of the poor nighttime sleep quality phenotype among ε2 carriers, whereas no correlation was found among any of the sleep scores and the ACE genotypes. Thus, we suggest a correlation between APOE alleles and scale-assessed sleep quality scores in older adults, with no implications for ACE alleles, in a context devoid of cognitive impairment.

Irreversible Renal Function Impairment Due to Silent Ureteral Stones.

OBJECTIVE: To evaluate if renal function loss and hydronephrosis due to a silent ureteral stone might be reversed. MATERIALS AND METHODS: We prospectively selected patients with silent ureteral stones between January 2006 and January 2014. A silent case was considered if there were no specific or subjective symptoms related to the ureteral stone. Patient, stone, and kidney characteristics were evaluated preoperatively, 3 and 12 months postoperatively. Renal function was accessed in the same intervals with serum creatinine (SCr), glomerular filtration rate (GFR), and (99m)Tc-dimercaptosuccinic acid. Patients without complete pre- and postoperative evaluation were excluded. Primary end point was midterm progress of global and ipsilateral renal function. Secondary end points included the evaluation of renal and collecting system anatomy from diagnosis to 12 months after treatment. Analysis of variance with repeated measures and marginal homogeneity test were used to evaluate renal function and hydronephrosis progression. RESULTS: Twenty-six patients met our inclusion criteria. Mean preoperative SCr and GFR were 1.24 mg/dL and 72.5 mL/min, respectively. At initial scintigraphy, mean renal function was 33.4%. Laser ureterolithotripsy was performed in 84.6% of cases and all patients were rendered stone free. Two patients (8%) developed ureteral stenosis. There was no difference regarding SCr (P = .89), GFR (P = .48), and renal function at scintigraphy (P = .19) during follow-up. Hydronephrosis significantly improved from preoperatively to 3 months postoperatively (P < .0001), but not from 3 to 12 months (P = .065). CONCLUSION: Patients with silent ureteral stones present with significant impairment of ipsilateral renal function and hydronephrosis at diagnosis. On midterm follow-up evaluation, renal function of the affected unit remains stable whereas hydronephrosis improves after treatment.

Metabolic assessment of elderly men with urolithiasis.

OBJECTIVE: To assess the presence of metabolic disorders in elderly men with urolithiasis. METHODS: We performed a case-control study. The inclusion criteria were as follows: (1) men older than 60 years of age and either (2) antecedent renal colic or an incidental diagnosis of urinary lithiasis after age 60 (case arm) or (3) no antecedent renal colic or incidental diagnosis of urolithiasis (control arm). Each individual underwent an interview, and those who were selected underwent all clinical protocol examinations: serum levels of total and ionized calcium, uric acid, phosphorus, glucose, urea, creatinine and parathyroid hormone, urine culture, and analysis of 24-hour urine samples (levels of calcium, citrate, creatinine, uric acid and sodium, pH and urine volume). Each case arm patient underwent two complete metabolic urinary investigations, whereas each control arm individual underwent one examination. ClinicalTrials.gov: NCT01246531. RESULTS: A total of 51 subjects completed the clinical investigation: 25 in the case arm and 26 in the control arm. In total, 56% of the case arm patients had hypocitraturia (vs. 15.4% in the control arm; p = 0.002). Hypernatriuria was detected in 64% of the case arm patients and in 30.8% of the controls (p = 0.017). CONCLUSION: Hypocitraturia and hypernatriuria are the main metabolic disorders in elderly men with urolithiasis.

Percutaneous nephrolithotomy in obese patients: comparison between the prone and total supine position.

BACKGROUND: Percutaneous nephrolithotomy (PCNL) can be performed in the prone or in the supine position. Comparisons between the two techniques in obese patients are rare in the current literature. METHODS: The records of obese patients (body mass index >30) who underwent PCNL in the prone or complete supine positions were reviewed. All patients had a noncontrast CT before and after the procedure. Stones were graded according to the Guy stone score and complications according to the Clavien grading. The stone-free rates, operative time, surgical complications, and hospital stay were analyzed. RESULTS: A total of 56 PCNL were performed in 42 patients. Twenty-four PCNL were performed in the prone and 32 in the total supine position. Stone-free rate on the first postoperative day was 50% in the prone and 46.9% in the supine position (P=1.0). Final stone-free rates were 83.3% and 78.1%, respectively (P=0.74). Mean operative time was 164.6 minutes in the prone and 120.3 minutes in the supine position (P=0.0017), and hospital stay was 4.38 and 2.68 days (P=0.014), respectively. The transfusion rate was 20.8% in the prone and zero in the supine position patients (P=0.01). Excluding Guy IV stones, transfusion rate was 8.3% in the prone position (P=0.1). Significant surgical complications rate was 12.5% in the prone and 3.1% in the supine position (P=0.302). CONCLUSION: PCNL performed in the prone or in the complete supine position in obese patients presents similar outcomes. The supine decubitus position has the advantages of a significantly shorter operative time and hospital stay.

Laparoscopic ureteropyeloanastomosis in the treatment of duplex system.

PURPOSE: Duplex system is one of the most common anomalies of upper urinary tract. Anatomical and clinical presentation determine its treatment. Usually, the upper moiety has a poor function and requires resection, but when it is not significantly impaired, preservation is recommended. Laparoscopic reconstruction with upper pole preservation is presented as an alternative treatment. MATERIALS AND METHODS: Four female patients with duplex system, one presenting with recurrent urinary tract infection and the others with urinary incontinence associated to infrasphincteric ectopic ureter, were treated. Surgical procedure envolved a laparoscopic ureteropyeloanastomosis of the upper pole ureter to the pelvis of the lower moiety, with prior insertion of a double J stent. RESULTS: Surgical time varied from 120 to 150 minutes, with minimal blood loss in all cases. Follow-up varied from 15 to 30 months, with resolution of the clinical symptoms and preservation of the upper moiety function. CONCLUSION: Laparoscopic ureteropyeloanatomosis is a feasible and safe minimally invasive option in the treatment of duplex system.

Laparoscopic ureteropyeloanastomosis in the treatment of duplex system

PURPOSE: Duplex system is one of the most common anomalies of upper urinary tract. Anatomical and clinical presentation determine its treatment. Usually, the upper moiety has a poor function and requires resection, but when it is not significantly impaired, preservation is recommended. Laparoscopic reconstruction with upper pole preservation is presented as an alternative treatment. MATERIALS AND METHODS: Four female patients with duplex system, one presenting with recurrent urinary tract infection and the others with urinary incontinence associated to infrasphincteric ectopic ureter, were treated. Surgical procedure envolved a laparoscopic ureteropyeloanastomosis of the upper pole ureter to the pelvis of the lower moiety, with prior insertion of a double J stent. RESULTS: Surgical time varied from 120 to 150 minutes, with minimal blood loss in all cases. Follow-up varied from 15 to 30 months, with resolution of the clinical symptoms and preservation of the upper moiety function. CONCLUSION: Laparoscopic ureteropyeloanatomosis is a feasible and safe minimally invasive option in the treatment of duplex system.

Metabolic assessment of elderly men with urolithiasis

OBJECTIVE: To assess the presence of metabolic disorders in elderly men with urolithiasis. METHODS: We performed a case-control study. The inclusion criteria were as follows: (1) men older than 60 years of age and either (2) antecedent renal colic or an incidental diagnosis of urinary lithiasis after age 60 (case arm) or (3) no antecedent renal colic or incidental diagnosis of urolithiasis (control arm). Each individual underwent an interview, and those who were selected underwent all clinical protocol examinations: serum levels of total and ionized calcium, uric acid, phosphorus, glucose, urea, creatinine and parathyroid hormone, urine culture, and analysis of 24-hour urine samples (levels of calcium, citrate, creatinine, uric acid and sodium, pH and urine volume). Each case arm patient underwent two complete metabolic urinary investigations, whereas each control arm individual underwent one examination. ClinicalTrials.gov: NCT01246531. RESULTS: A total of 51 subjects completed the clinical investigation: 25 in the case arm and 26 in the control arm. In total, 56% of the case arm patients had hypocitraturia (vs. 15.4% in the control arm; p = 0.002). Hypernatriuria was detected in 64% of the case arm patients and in 30.8% of the controls (p = 0.017). CONCLUSION: Hypocitraturia and hypernatriuria are the main metabolic disorders in elderly men with urolithiasis.

Adjuvant tamsulosin or nifedipine after extracorporeal shock wave lithotripsy for renal stones: a double blind, randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the effects of the adjuvant use of tamsulosin or nifedipine after extracorporeal shock wave lithotripsy for nonlower pole kidney stones 5-20 mm in size. METHODS: We conducted a randomized double-blind trial involving 136 patients with radiopaque kidney stones. The patients received daily treatment with 0.4 mg tamsulosin, 20 mg nifedipine retard, or placebo for ≤30 days after 1 session of extracorporeal shock wave lithotripsy. Success was defined as plain film radiography showing the patient was completely stone free or with asymptomatic stone fragments ≤4 mm in size at any time during the weekly follow-up. RESULTS: The success rate was 60.5% (23 of 38) in the tamsulosin group, 48.6% (17 of 35) in the nifedipine group, and 36.8% (14 of 38) in the placebo group (P = .118). In the subgroup analysis, stones 10-20 mm had significantly greater success rates in the tamsulosin (13 of 21, 61.9%) and nifedipine (15 of 25, 60%) groups compared with the placebo group (6 of 23, 26.1%; P = .024), but not for stones 5-9 mm (P = .128). The number needed to treat was 2.9 for tamsulosin and 3 for nifedipine. Adverse events were more frequent in the nifedipine than in the placebo group (28.5% vs 2.6%, respectively, P = .009), but without a significant difference between the nifedipine and tamsulosin (28.5% vs 15.8%, P = .15) or the tamsulosin and placebo (P = .54) groups. No difference was found among the groups with regard to pain intensity, interval to clearance, or steinstrasse. CONCLUSION: The stone-free rates after extracorporeal shock wave lithotripsy with adjuvant tamsulosin or nifedipine were significantly increased only for nonlower pole renal stones 10-20 mm in size compared with placebo. Nifedipine was associated with more adverse effects than placebo.

Comparison between two shock wave regimens using frequencies of 60 and 90 impulses per minute for urinary stones.

PURPOSE: Two different regimens of SWL delivery for treating urinary stones were compared. METHODS: Patients with urinary stones were randomly divided into two groups, one of which received 3000 shocks at a rate of 60 impulses per minute and the other of which received 4000 shocks at 90 impulses per minute. Success was defined as stone-free status or the detection of residual fragments of less than or equal to 3 mm three months after treatment. Partial fragmentation was considered to have occurred if a significant reduction in the stone burden was observed but residual fragments of 3mm or greater remained. RESULTS: A total of 143 procedures were performed with 3000 impulses at a rate of 60 impulses per minute, and 156 procedures were performed with 4000 impulses at 90 impulses per minute. The stone-free rate was 53.1% for patients treated with the first regimen and 54.8% for those treated with the second one (p = 0.603). The stone-free rate for stones smaller than 10 mm was 60% for patients treated with 60 impulses per minute and 58.6% for those treated with 90 impulses per minute. For stones bigger than 10 mm, stone-free rates were 34.2% and 45.7%, respectively (p = 0.483). Complications occurred in 2.3% of patients treated with 60 impulses per minute and 3.3% of patients treated with 90 impulses per minute. CONCLUSION: No significant differences in the stone-free and complication rates were observed by reducing the total number of impulses from 4000 to 3000 and the frequency from 90 to 60 impulses per minute.

Comparison between two shock wave regimens using frequencies of 60 and 90 impulses per minute for urinary stones

PURPOSE: Two different regimens of SWL delivery for treating urinary stones were compared. METHODS: Patients with urinary stones were randomly divided into two groups, one of which received 3000 shocks at a rate of 60 impulses per minute and the other of which received 4000 shocks at 90 impulses per minute. Success was defined as stone-free status or the detection of residual fragments of less than or equal to 3 mm three months after treatment. Partial fragmentation was considered to have occurred if a significant reduction in the stone burden was observed but residual fragments of 3mm or greater remained. RESULTS: A total of 143 procedures were performed with 3000 impulses at a rate of 60 impulses per minute, and 156 procedures were performed with 4000 impulses at 90 impulses per minute. The stone-free rate was 53.1 percent for patients treated with the first regimen and 54.8 percent for those treated with the second one (p = 0.603). The stone-free rate for stones smaller than 10 mm was 60 percent for patients treated with 60 impulses per minute and 58.6 percent for those treated with 90 impulses per minute. For stones bigger than 10 mm, stone-free rates were 34.2 percent and 45.7 percent, respectively (p = 0.483). Complications occurred in 2.3 percent of patients treated with 60 impulses per minute and 3.3 percent of patients treated with 90 impulses per minute. CONCLUSION: No significant differences in the stone-free and complication rates were observed by reducing the total number of impulses from 4000 to 3000 and the frequency from 90 to 60 impulses per minute.

Management of chronic unilateral hematuria by ureterorenoscopy.

BACKGROUND AND PURPOSE: Chronic unilateral hematuria is characterized by intermittent or continuous gross hematuria that cannot be diagnosed using standard radiology and hematology methods. In the past, it was managed with partial or total nephrectomy. In the age of minimally invasive procedures, however, endoscopy has enabled more accurate diagnosis and management. We analyzed our experience with transurethral ureterorenoscopy using a flexible ureteroscope to determine the feasibility and success of endoscopic management of renal hematuria. PATIENTS AND METHODS: We reviewed the records of 13 patients who presented with chronic unilateral hematuria, in whom radiologic and laboratory tests failed to reveal the source of bleeding. In the cases in which the lesion was identified, after complete inspection of the collecting systems, the bleeding site was treated ureteroscopically with a holmium: yttrium-aluminum-garnet (YAG) laser. RESULTS: Follow-up ranged from 4 to 60 months (mean 26 mos). During the follow-up of the 13 patients, 11 remained symptom-free, with only one session of flexible ureterorenoscopy necessary. Relapse occurred in two patients after 4 months and 6 months, respectively; during a second session of flexible ureteroscopy, the bleeding site was successfully identified and cauterized with a holmium:YAG laser. No surgical complications occurred. CONCLUSIONS: Conservative treatment of patients with chronic unilateral hematuria should always be considered. Laser ureteroscopic treatment is an excellent method and should be considered as the first option for the management of chronic unilateral hematuria.

Doença de Castleman / Castleman's disease

A Doença de Castleman (DC) é rara, sendo também conhecidacomo hiperplasia linfonodal gigante. É mais comumenteencontrada em adultos jovens, com predileção pelo mediastino,embora possa ocorrer em qualquer local do sistema linfático. DC édividida em dois subtipos clínicos, unicêntrico e multicêntrico e doistipos histológicos, hialino-vascular e plasmocítico. Relata-se ocaso de paciente de 19 anos, com uma história clínica de massacervical há sete anos. O diagnóstico definitivo foi feito após aressecção e exame histopatológico, que mostrou lesão tipo hialinovascular.Não houve sinais de recidiva após um ano deseguimento.

Castleman's disease (CD) is a rare disorder, also known as giantlymph node hyperplasia. It's more commonly found in young adults,with predilection to mediastinum, although it may occur in any partof the lymphatic chain. CD is divided into two clinical subtypes,unicentric and multicentric, and two histological types, hyalinevascular and plasma cell. A case of a 19-year-old woman, with ahistory of a cervical mass for 7 years is reported. The definitivediagnosis was made after resection and histopathologicalexamination, which showed hyaline vascular type. There was nosign of recurrence after 1 year.

Laparoscopic dismembered pyeloplasty in 47 cases.

PURPOSE: To evaluate the results of a sequence of 47 laparoscopic Anderson-Hynes pyeloplasties for the treatment of patients with ureteropelvic junction obstruction, independently of the etiology. MATERIALS AND METHODS: Twenty male and 27 female patients diagnosed with ureteropelvic junction obstruction were treated by Anderson-Hynes transperitoneal laparoscopic dismembered pyeloplasty from April 2002 to January 2006. The age of the patients ranged from four to 75 years, with a mean age of 32.3 years. The follow-up ranged between six and 30 months, with a mean follow-up time of 24 months. The outcomes were evaluated through the assessment of symptoms and imaging studies. RESULTS: In 44 (93.6%) of the 47 patients, resolution of the pain and a reduction in ureteropelvic dilation were observed. The mean operative time was 157 minutes (ranging from 90 to 270 minutes). Neither blood transfusion nor conversion to open surgery was required. The mean hospital stay was 2.2 days. The presence of crossing vessels over the ureteropelvic junction was verified in 26 patients (55%), and vessel transposition in relation to the urinary tract was performed in 25 of these cases. In one patient, the crossing vessel was mobilized out of the ureteropelvic junction with a perivascular suture to the renal capsule associated with the pyeloplasty. CONCLUSIONS: The outcome of transperitoneal Anderson-Hynes laparoscopic pyeloplasty used for different causes of pyeloureteral obstruction presented a success rate similar to a previously-published open procedure, with the advantage of being less invasive. This procedure may be considered the first option for the treatment of ureteropelvic junction obstruction.