[Digital therapeutics: Which barriers for market access?] / Les thérapies digitales : quels freins pour leur prise en charge ?

Integrated to the e-health field, digital therapeutics can be defined as "software, combined or not to a device, in the purpose of prevention, treatment or monitoring of a disease, participating actively in a mechanism of action and based on strong clinical evidence". The aim of this work was to assess the level of digital therapeutics clinical validation and to reflect on their business model. A qualitative study has been conducted and different health actors have been interviewed. The semi-guided interviews made have been analysed through a three-level coding. Twenty-two interviews have been analysed and six categories have been identified. The interlocutors highlighted the leading role of digital therapeutics in the follow-up and prevention, supporting the empowerment of patients. However, the absence of consensus in their definition has led to heterogeneity of definition and a difficulty to limit their scope. Furthermore, the conduct of clinical trials, not really suited for digital therapeutics, forced the editors/manufacturers to search for funding for which availability and continuity are uncertain. By raising the issue of clinical efficacy, demonstration of digital therapeutics, this study has led to new perspectives in assessment and business model. We could see in digital therapeutics a new nature of innovation associated with new organisations of our healthcare system and not necessarily by new therapeutics.

[Health technology assessment of innovative medical devices: Timing and decision at national and local level]. / Accès au marché des dispositifs médicaux innovants : articulation entre évaluations nationales et hospitalières.

INTRODUCTION: The Medical Device Committee (CODIMS) evaluates all innovative medical devices (MD) before their introduction in the hospitals of the Assistance publique-hôpitaux de Paris (AP-HP). At the national level, the Medical Device and Health Technology Evaluation Committee (CNEDiMTS) provides recommendation for MD with respects to reimbursement by the National Health Insurance Fund. The aim of this study is to compare the recommendations of both committees and to analyze their timing on a six-year period. MATERIAL AND METHOD: We selected all innovative MD assessed by the CODIMS between 2013 and 2018. We retrieved all the recommendations for these MD from the CNEDiMTS. We performed quantitative and qualitative analysis of data collected. RESULTS: On 30 innovative MD assessed by both the CODIMS and the CNEDiMTS, 11 (37%) evaluations were performed by the CODIMS before the CNEDiMTS evaluation. They occurred approximately a year before the CNEDiMTS recommendation (an average of 378 days). Among the 25 MD with a recommendation of both committees, the two opinions were consistent in 88 per cent of all cases. DISCUSSION/CONCLUSION: This study highlights that there is a good consistency between the recommendations of both committees. This suggests that the MD evaluations conducted at the hospital level are relevant and timely. Finally, a better coordination between the national and local levels should be promoted for the MD assessment.

[3D printed medical devices and anatomical models: What kind of distribution and which uses in French hospitals?] / Dispositifs médicaux et modèles anatomiques produits par impression 3D : quelle diffusion et quelles utilisations dans les établissements de santé français ?

3D printing plays an increasingly important role in the medical sector and particularly in surgery. Nowadays, numerous manufacturers benefit from this technology to produce their medical devices and some hospitals have also purchased 3D printers. In this context, the aim of the present study was to study the distribution and the use of 3D printing in French hospitals in order to its main features in surgery. By conducting a national survey, we targeted hospitals equipped with 3D printers and those using external providers to benefit from this technology. Forty-seven hospitals were identified as using 3D printing including eight equipped with in-house 3D printers. This work gives us a first picture of 3D printing for hospital use in France and it raises questions about hospital pharmacists' involvement in 3D printed medical device production.

[Introduction of Health technology assessment at hospital]. / Mise en place de l'évaluation des technologies de santé en milieu hospitalier.

INTRODUCTION: The Medical Devices Committee (CODIMS) of the Assistance publique-Hôpitaux de Paris (AP-HP) is responsible for deciding whether innovative and costly sterile medical devices (SMD) should be adopted for the AP-HP network and for issuing recommendations on their proper use. The aim of this study was to qualify retrospectively the level of evidence of clinical studies used for the device evaluations by the CODIMS in 2012 and 2013 and to analyze the relationship between levels of evidence and decisions. MATERIAL AND METHOD: Executive summaries written in 2012 and 2013 about studied SMD was analyzed and the level of evidence of clinical studies used was qualified in high/low levels of evidence according to the scale of Sackett et al. Then, levels of evidence were correlated to decisions published by the CODIMS. RESULTS: Sixty-one files of SMD (72.1% of implantable MD) have been evaluated (225 clinical studies). Among them, only 28% of clinical studies had a high level of evidence (and 28.6% of MD at-risk) and 18% did not have any clinical studies. The CODIMS delivered an unfavourable opinion for 16 SMD: only 28 clinicals studies were available for evaluation. Among these, only 6 studies had a high level of evidence. DISCUSSION ET CONCLUSION: The amount and level of evidence of clinical studies is naturally correlated to admittance of SMD. These findings suggest that the clinical evidence used to demonstrate safety and efficacy for high-risk medical devices is based on clinical studies with poor quality data, making more difficult the evaluation of SMD in hospital. The development of a multi-criteria tool to help decision-making would improve the process of SMD evaluation by the CODIMS.

[Hospital-based health technology assessment in France: how to proceed to evaluate innovative medical devices?]. / Évaluation des technologies de santé en milieu hospitalier : quelle organisation pour évaluer et acquérir des dispositifs médicaux innovants ?

Innovative medical devices offer solutions to medical problems and greatly improve patients' outcomes. Like National Health Technology Assessment (HTA) agencies, hospitals face numerous requests for innovative and costly medical devices. To help local decision-makers, different approaches of hospital-based HTA (HB-HTA) have been adopted worldwide. The objective of the present paper is to explore HB-HTA models for adopting innovative medical devices in France and elsewhere. Four different models have been conceptualized: "ambassador" model, "mini-HTA" model, "HTA unit" model and "internal committee". Apparently, "HTA unit" and "internal committee" (or a mixture of both models) are the prevailing HB-HTA models in France. Nevertheless, some weaknesses of these models have been pointed out in previous works. Only few examples involving hospital pharmacists have been found abroad, except in France and in Italy. Finally, the harmonization of the assessment of innovative medical devices in France needs a better understanding of HB-HTA practices.

Costs analysis of cochlear implantation in children.

OBJECTIVES: The study assessed the direct medical costs of the cochlear implantation pathway from the healthcare payer's perspective, in children with bilateral severe to profound hearing loss, from diagnosis to 3 years' follow-up after first implantation. We also compared costs between two populations: congenital and progressive deafness. MATERIAL AND METHODS: A retrospective costs analysis was performed for 56 children who received a cochlear implant in one French pediatric ENT center. The children had severe to profound hearing loss, and were implanted before the age of 10 years. We calculated direct medical costs in 3 phases: diagnosis to pre-implantation assessment, surgical and hospital management of implantation, and 3 years' follow-up. RESULTS: Mean costs were €64,675 (range, €38,709-113,954) per child from diagnosis to 3 years after first implantation. Mean costs in congenital deafness detected on neonatal screening and on progressive deafness were respectively €65,420 and €63,930 (P=0.7). CONCLUSION: The global cost was €64,675 per child from diagnosis to 3 years after first implantation. There was no difference in cost according to congenital versus progressive hearing loss.

Organizational and budget impact model (OBIM) of same™ a new autotransfusion medical device.

Objectives: This study aimed to assess the budget and organizational impact of progressively replacing the intraoperative cell salvage centrifugation-based systems currently installed in French hospitals with the same™ system, a new autotransfusion medical device.Methods: An Organizational and Budget Impact Model (OBIM) was developed based on two methodological guidelines issued by the French Health Authority (Haute Autorité de Santé, HAS). The OBIM was also developed based on a pragmatic literature review, hospital data and hospital pharmacists' expertise.Results: Considering an average hospital cohort of 600 cardio-thoracic surgery patients, with 57% experiencing mild hemorrhages, 23% moderate hemorrhages, and 20% massive hemorrhages, and a same™ market share of 33% in Year 1, the implementation of same™ resulted in significant savings. With an average allogeneic transfusion of 4.19 packed red blood cells (RBC) and 0.62 platelet concentrate per patient based on National Hemovigilance Report of the ANSM (French National Agency for the Safety of Medicines and Health Products) and when using same™ system a reduction of 45% of RBC transfusion associated with a reduction of 60% and 90% of platelet use for moderate and massive hemorrhages respectively, the first year annual saving amounted to €44,601 and the cumulated saving over 5 years to €535,206.Discussion: This model structure was developed based on overall hospitals' needs and acknowledged guidelines, with inputs based on French literatures and hospital data, so findings were specifics to a context. Among the inputs, the number of annual same™ procedure is not based on device capability but rather on hospital capability with the number of operating rooms used for cardio-thoracic surgery equipped with the device.Conclusions: The results of this OBIM demonstrated the economic and organizational benefits of same™ for hospitals. This benefit results mainly of a reduction in the use of allogeneic blood products (RBCs, platelets).

[Computerized prescription for medical devices: examples, interest and limits]. / Vers la prescription informatisée des dispositifs médicaux : exemples d'application, intérêts et limites.

INTRODUCTION: Related to the good practice contract implemented in hospitals, the prescription dedicated to medical devices, such as pharmaceuticals, could promote safety and good practice. MATERIAL AND METHOD: We attempted to implement a computerized prescription for medical devices. In order to illustrate the method, two examples were selected: the Negative Pressure Wound Therapy (NPWT) and the Drug Eluting Stents (DES). RESULTS: In partnership with the medical teams was elaborated a computerized protocol which included all the needed items for the good use of NPWT. For DES, a pre-existing questionnaire was used. We updated it in order to integrate new items such as the prescriber's name, the patient's name, the characteristics of the wound, the DES references and the indications. DISCUSSION AND CONCLUSION: Computerized prescriptions for high-risk and expensive medical devices seem to be an interesting approach to guarantee the patient care safety and to reduce the budget impacts. In order to monitor the indications funded as fee-for-service medical devices, a prescription will emerge as a gold standard in the future in France. Eventually, this study highlights a new activity of clinical pharmacy for hospital pharmacists dealing with medical devices.

Methotrexate pharmacokinetics in childhood acute lymphoblastic leukaemia: a prognostic value?

WHAT IS KNOWN AND OBJECTIVE: In industrialized countries, acute lymphoblastic leukaemia (ALL) is the most frequent cancer in children aged less than 15 years. High-dose methotrexate is a common component of many chemotherapeutic protocols for childhood with ALL. Our objective was to retrospectively evaluate the pharmacokinetics and plasma levels of high-dose methotrexate as it relates to event-free survival (EFS) in children with ALL. METHODS: Relapsed patients and subjects in EFS were compared for MTX serum concentrations 24, 36, 48 and 72 h after the start of 24 h infusion. Clearance (Cl), area under the curve (AUC) and volume of distribution (V(d) ) of the drug were estimated by the NONMEM computer program and also compared between both groups. RESULTS AND DISCUSSION: Among 69 children included, 54 (78·3%) were still in EFS, whereas 15 (21·7%) relapsed. The difference between relapsed and EFS patients for the pharmacokinetic parameters studied was not significant. On the contrary, the cohort studied was representative and known prognostic factors for relapse in ALL were significantly associated with relapse. WHAT IS NEW AND CONCLUSION: Serum concentrations and pharmacokinetic parameters of MTX are not associated with outcome in ALL. Prognoses based on single-drug pharmacokinetic estimates within a complex multiple-agent protocol appear to be unreliable. However, therapeutic drug monitoring of high-dose methotrexate remains a useful tool for early detection of impaired elimination and for avoiding systemic toxicity.

Roflumilast inhibits leukocyte-platelet interactions and prevents the prothrombotic functions of polymorphonuclear leukocytes and monocytes.

UNLABELLED: ESSENTIALS: Thrombosis is a major comorbidity in patients with chronic obstructive pulmonary disease (COPD). Roflumilast is a selective phosphodiesterase type-4 (PDE4) inhibitor approved for treatment of severe COPD. PDE4 blockade by roflumilast inhibits prothrombotic functions of neutrophils and monocytes. PDE4 inhibitors may reduce thrombotic risk in COPD as well as in other vascular diseases. BACKGROUND: Roflumilast, an oral selective phosphodiesterase type 4 inhibitor, is approved for the treatment of severe chronic obstructive pulmonary disease (COPD). A recent meta-analysis of trials on COPD revealed that treatment with roflumilast was associated with a significant reduction in the rate of major cardiovascular events. The mechanisms of this effect remain unknown. OBJECTIVES: We tested the hypothesis that roflumilast N-oxide (RNO), the active metabolite of roflumilast, curbs the molecular mechanisms required for leukocyte-platelet (PLT) interactions and prevents the prothrombotic functions of polymorphonuclear leukocytes (PMNs) and monocytes (MNs). METHODS: Using well-characterized in vitro models, we analysed the effects of RNO on: (i) PMN adhesiveness; (ii) the release of neutrophil extracellular traps (NETs); and (iii) tissue factor expression in MNs. Key biochemical events underlying the inhibitory effects of RNO were defined. RESULTS AND CONCLUSIONS: In PMNs, RNO prevented phosphoinositide 3-kinase (PI3K)-dependent phosphorylation of Akt on Ser473, and Src family kinase (SFK)-mediated Pyk2 phosphorylation on Tyr579-580, while inducing protein kinase A-mediated phosphorylation of C-terminal Src kinase, the major negative regulator of SFKs. Modulation of these signaling pathways by RNO resulted in a significant impairment of PMN adhesion to activated PLTs or human umbilical vein endothelial cells, mainly mediated by inhibition of the adhesive function of Mac-1. Moreover RNO curbed SFK/PI3K-mediated NET release by PMNs adherent on fibrinogen-coated surfaces. In MNs interacting with activated PLTs, RNO curbed PI3K-mediated expression of tissue factor. The efficacy of RNO was significantly potentiated by formoterol, a long acting ß-adrenergic receptor agonist. This study reveals novel antithrombotic activities by which roflumilast may exert protective effects against cardiovascular comorbodities in COPD.

Differences in the glutathione system of cultured aortic smooth muscle cells from young and aged rats.

We studied the relation between the glutathione (GSH) system and cell proliferation in a model of smooth muscle cells (SMC) derived from the thoracic aorta of 4-6-week-old (young) and 15-month-old (aged) rats. SMC from aged rats showed greater levels of total non-protein thiol compounds (T-SH), increased glutathione transferase (GST) and increased glutathione reductase (GSSG-Red) activities compared with cells from young rats. These changes were associated with an increased proliferation rate of SMC from aged rats. To evaluate the role of GSH on cell proliferation better, a specific inhibitor of gamma-glutamyl-cystein synthetase, DL-buthionine-SR-sulphoximine (BSO) was used. BSO showed a dose-dependent inhibition of cell growth, with an IC50 of 10(-4) M, after 48-72 h of incubation. Removal of BSO restored cell growth, further suggesting a link between GSH levels and vascular cell proliferation. The inhibitory effect of BSO was about two times greater on SMC from young than on SMC from aged rats. BSO showed 56% inhibition on the proliferation of SMC from young rats and 32% inhibition on SMC from aged rats (10(-4) M, 72 h of incubation). A parallel reduction of GSH levels of 38% and 19% for SMC from young and aged rats, respectively, was observed, suggesting that age-related factors may influence the involvement of GSH system in cell proliferation.

Polymorphonuclear leukocyte-platelet interaction: role of P-selectin in thromboxane B2 and leukotriene C4 cooperative synthesis.

In PMN/platelet suspensions stimulated by fMLP giant mixed aggregates are formed and TxB2 and LTC4 are synthesized as the result of the cooperation in the arachidonic acid (AA) metabolism during cell/cell contact. PMN-derived cathepsin G induced the expression of P-selectin on platelet surface. GE12, an antibody against P-selectin, significantly reduced mixed cell aggregates. GE12 did not affect platelet aggregation induced by PMN-derived supernatants, indicating that the inhibitory effect of GE12 on mixed cell aggregation depends on inhibition of PMN/platelet adhesion. GE12 significantly reduced TxB2 and LTC4 production in PMN/platelet mixed cell suspensions stimulated by fMLP. As previously reported, synthesis of 3H-TxB2 in 3H-AA-labeled PMN/unlabeled platelets indicates that platelets utilize 3H-AA from PMN. 3H-LTC4 production in unlabeled PMN/3H-AA-labeled platelets indicates that bidirectional routes are utilized in this system for LTC4 synthesis. GE12 significantly reduced 3H-TxB2 and 3H-LTC4 synthesis. These results show that cathepsin G released by activated PMN induces the expression of P-selectin on platelet membrane: this adhesive glycoprotein modulates cell-cell contact and transcellular metabolism of AA.

Polymorphonuclear leukocyte apoptosis is inhibited by platelet-released mediators, role of TGFbeta-1.

Platelets regulate several polymorphonuclear leukocyte (PMN) functions. We have found that thrombin-stimulated platelets potently inhibited PMN apoptosis. Cell-free supernatant from increasing concentrations of stimulated platelets inhibited PMN apoptosis in a dose-dependent manner, with an effect similar to that of corresponding concentrations of platelets. At the plateau, platelet supernatant inhibited PMN apoptosis by 54.6 +/- 6.8%, the anti-apoptotic activity being higher than that of GM-CSF and comparable to that of LPS. Neither IL-1ra nor a combination of anti-IL1alpha + betamAb affected the activity of platelet supernatant. In contrast a mAb recognizing the active form of TGF-beta1 significantly decreased this activity. Moreover, exogenous TGF-beta1 inhibited PMN apoptosis in a dose-dependent manner. The active form of this cytokine was indeed present in the supernatant of stimulated platelets at a concentration able to elicit an anti-apoptotic effect. The p38 MAPK inhibitor SB203580 prevented the anti-apoptotic effect of TGF-beta1 in a dose-dependent manner. Interestingly, it also prevented the anti-apoptotic effect of IL-1alpha, but not that of GM-CSF, LPS and dexamethasone. In conclusion, we report for the first time that PMN apoptosis is potently inhibited by platelet-released mediators, that TGF-beta1 mediates an important part of this effect, and that p38 MAPK is involved in the TGF-beta1 signaling leading to its anti-apoptotic effect. These results provide novel evidence to support the central role of platelets in inflammation.

Asthma, cardiac arrhythmias, and albuterol aerosol.

Twenty asthmatic patients clinically free of heart disease were studied for the possible arrhythmogenic action of albuterol (salbutamol). Two puffs of either albuterol or placebo were inhaled four times per day on two consecutive days and continuous ECG recordings obtained during each 24-hour period. Sixteen patients had atrial extrasystoles, four with albuterol, one with placebo, and 11 with both drugs. The extrasystoles/hour were 6.55 (23.75 SD) with albuterol and 8.37 (33.82) with placebo, a nonsignificant difference. Ventricular extrasystoles were shown in 11 patients, two with albuterol, two with placebo, and seven during both treatments. The extrasystoles/hour were 2.57 (6.36) and 3.10 (7.61) with albuterol and placebo, respectively. This difference was not significant. These findings suggest that therapeutic doses of albuterol aerosol in asthmatic patients without evidence of heart disease and severe hypoxemia should not be considered a cause of cardiac arrhythmias.

Nutritional antioxidants as antidegenerative agents.

In this study, primary cultures of cerebellar granule neurons were prepared from eight-day-old Wistar rats, and maintained in an appropriate medium containing a high (25 mM) concentration of KCl. All experiments were performed with fully differentiated neurons (eight days). To induce apoptosis, culture medium was replaced with a serum-free medium (containing 5 mM KCl) eight days after plating. In another series of experiments, apoptosis was induced by application of glutamate (50 microM) to the cell cultures. Apoptosis was measured by flow cytometry, the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick end-labeling) method, and by the classical method of DNA fragmentation. Since there is evidence that an increased formation of reactive oxygen species (ROS) is involved in the apoptosis induced by both low K(+) concentrations and glutamate, a series of natural antioxidants and a red wine lyophilized extract (which is rich in antioxidant compounds) were tested in our experimental model. It was found that ascorbic acid (30 microM) and a red wine lyophilized extract (5 microgram/ml) were capable of blocking the apoptotic process. Addition of the following natural antioxidants did not have any protective effect on apoptosis induced by low K(+) concentrations: trans- and cis-resveratrol (5-200 microM), alpha-tocopherol (100-200 microM), reduced glutathione (100-400 microM), 3-hydroxytirosol (25-100 microM), epicatechin (25-100 microM), or quercetin (25-50 miroM). It is concluded that only a limited number of natural antioxidants are provided with antiapoptotic activity in cultured cerebellar granule neurons. This effect is probably exerted by reducing ROS formation, and by blocking caspase-3 activity.

Results of surgical treatment of neurocysticercosis in 69 cases.

The clinical course of 69 patients with neurocysticercosis who underwent surgery to control increased intracranial pressure (ICP) or cyst removal is analyzed. Increased ICP was caused by hydrocephalus in 63 patients, by cerebral edema in four, and by giant cysts in two. Skull x-ray films showed calcifications in 14% and signs of elevated ICP in 46%. Examination of cerebrospinal fluid (CSF) revealed pleocytosis with eosinophils in 52% of cases and a positive complement fixation test for cysticercosis in 66%. Ventriculography allowed localization of the CSF obstruction and ventricular cysts, and generally differentiated between an obstruction due to cysts and an inflammatory process. Computerized tomography showed cysts in the cerebral parenchyma and ventricular dilatation. Ventricular cysts were best seen when intraventricular metrizamide was used. Intracranial shunting and posterior fossa exploration were less effective in the treatment of hydrocephalus than was ventriculoatrial (VA) or ventriculoperitoneal (VP) shunting, although VA or VP shunting was associated with a high percentage of complications. Quality of survival was good in 87% of the cases in the first 3 postoperative months and in 93% of patients who survived 2 years after surgery. Forty-seven patients (68%) were readmitted one or more times for CSF shunt revision; 14 of them for shunt infection (meningitis). The early operative mortality rate was 1.8% for patients with VA or VP shunt placement and 5.3% for those with posterior fossa exploration. The authors conclude that placement of CSF shunts is indicated in the treatment of hydrocephalus, and cyst removal is indicated only when the cyst exhibits tumor-like behavior. Surgical exploration is also indicated when the diagnosis is uncertain.

Once-daily budesonide/formoterol in a single inhaler in adults with moderate persistent asthma.

Patients with moderate persistent asthma (n = 523; mean FEV1 77.4%) not fully controlled with inhaled corticosteroids (ICS; 400-1000 microg/day) were randomized to receive either once-daily budesonide/formoterol (160/4.5 microg, two inhalations); or twice-daily budesonide/formoterol (160/4.5 microg, one inhalation); or budesonide (400 microg) once-daily for 12 weeks. Once-daily dosing was administered in the evening and twice-daily dosing was administered in the morning and evening. All patients received twice-daily budesonide (200 microg) during a 2-week run-in. Compared with budesonide alone, change in mean morning and evening peak expiratory flow was greater in the once-daily budesonide/formoterol group (27 and 171 min(-1), respectively; P < 0.001) and twice-daily budesonide/formoterol group (23 and 24 l min(-1), respectively; P < 0.001). Night awakenings, symptom-free days, reliever-use-free days and asthma-control days were all improved during once-daily budesonide/formoterol therapy vs. budesonide (P < or = 0.05). Similar improvements were also seen with twice-daily budesonide/formoterol (P < or = 0.05). The risk of a mild exacerbation was reduced after once- and twice-daily budesonide/formoterol vs. budesonide (38% and 35%, respectively; P < 0.002). All treatments were well tolerated. Budesonide/formoterol, once- or twice-daily, in a single inhaler improved asthma symptoms and exacerbations compared with budesonide. In the majority of patients with moderate persistent asthma requiring ICS and long-acting beta-agonists, once-daily formoterol/budesonide provided sustained efficacy over 24 h, similar to twice-daily dosing.

[Surgical treatment of hydrocephalus in children. I. Clinical development and mortality]. / Tratamento cirúrgico do hidrocéfalo em crianças. I - Evolução clínica e mortalidade.

The authors analized the clinical evolution and the mortality of fifty seven children with hydrocephalus due to congenital malformation (41.1%), meningitis (36.8%) and tumors (21.1%), that were submitted to surgical treatment for hydrocephalus, from 1970 to 1980. Insertions of ventriculostomy reservoir and of external ventricular drainage were satisfactory used to control the expanding hydrocephalus in children with meningitis, that wait insertion of the valve. The use of hypothalamic ventriculostomy with catheter has showed satisfactory results in the treatment of children with hydrocephalus due to non inflammatory origin. Ventriculoatrial shunts were utilized in few cases but were useful in the treatment of hydrocephalus in children. The operative mortality rate was 25.7%. Ventriculoperitoneal shunts showed good results in the treatment of hydrocephalus in 89.4% of the cases in the immediate post-operative time and this number drop to 88.2% at the eighteen post-operative month. The overall mortality rate was 34%. At the end of the third post-operative month 27.3% of the survivors of the children with hydrocephalus due to congenital malformation and meningitis submitted to ventriculoperitoneal shunts showed normal neuromotor development and at the end of the second post-operative year this number increased to 50%. The operative mortality rate in this group was 25% and the majority of death occurred due to meningitis.

[Surgical treatment of hydrocephalus in children. II. Complications]. / Tratamento cirúrgico do hidrocefalo em crianças. II - Complicações.

The authors analized the complications of fifty seven children with hydrocephalus due to congenital malformation (42.1%), meningitis (36.8%) and tumor (21.1%), that were submitted to surgical treatment for hydrocephalus, from 1970 to 1980. External ventricular drainage and insertion of ventriculostomy reservoir were used to control the expanding hydrocephalus in children with meningitis. Complications weren't observed in the first procedure. Cutaneous abscess, brain abscess, cerebrospinal fluid leakage, wound dehiscence, malposition of the reservoir and local tumor were observed in the use of the ventriculostomy reservoir and these complications caused a revision rate of 0.47 revisions per patient. Hypothalamic ventriculostomy with catheter showed complications (catheter obstruction and meningitis) that caused a revision rate of 0.57 revisions per patient. Ventriculoatrial shunting procedure showed several complications (malposition of the distal catheter, malfunction of the valvular system without obstruction and infection and thrombosis of the superior vena cava), that caused a revision rate of 0.57 revisions per patient. Ventriculo-peritoneal shunting procedure showed infections in 30.8%, malfunction of the valvular system in 32.2% cerebrospinal fluid leakage in 17.3%, malposition of catheter in 13.5%, catheter disconnection in 9.6%, transient abdominal distension in two cases and overdrainage phenomena, ascites and abdominal pseudocyst in one case.