A comparison of HIV outpatient care in primary and secondary healthcare-level settings in Zimbabwe.

SETTING: Decentralisation of HIV care to nurse-led primary care services is being implemented across low- and middle-income countries in sub-Saharan Africa. OBJECTIVE: To compare services offered to clients attending for HIV care at a physician-led and a nurse-led service in Harare, Zimbabwe. DESIGN: A cross-sectional study was performed at Harare Central Hospital (HCH) and Budiriro Primary Care Clinic (PCC) from June to August 2018. An interviewer-administered questionnaire was used to collect sociodemographics, HIV treatment and clinical history from clients attending for routine HIV care. The Mann-Whitney U-test was used to evaluate for differences between groups for continuous variables. For categorical variables, the χ2 test was used. RESULTS: The median age of the 404 participants recruited was 38 years (IQR 28-47); 69% were female. Viral suppression was comparable between sites (HCH, 70% vs. PCC, 80%; P = 0.07); however, screening for comorbidities such as cervical cancer screening (HCH, 61% vs. PCC, 41%; P = 0.001) and provision of referral services (HCH, 23% vs. PCC, 13%; P = 0.01) differed between sites. CONCLUSION: Efforts to improve service provision in primary care settings are needed to ensure equity for users of health services.

[Technical aspects of protontherapy: Setup, equipment and radioprotection]. / Aspects techniques de la protonthérapie : installation, appareils, radioprotection.

The number of protontherapy facilities is still increasing rapidly with more than 30 ongoing projects and close to 60 currently under operation. Although the technology is now validated and robust, a proton facility cannot be considered as a standard radiation therapy equipment: its constraints in terms of building, services, project management are of paramount impact at the level of the hospital. Therefore, a protontherapy project must be carefully considered and prepared, which is mandatory for further fluid and efficient clinical operation.

An empirical model for calculation of the collimator contamination dose in therapeutic proton beams.

Collimators are used as lateral beam shaping devices in proton therapy with passive scattering beam lines. The dose contamination due to collimator scattering can be as high as 10% of the maximum dose and influences calculation of the output factor or monitor units (MU). To date, commercial treatment planning systems generally use a zero-thickness collimator approximation ignoring edge scattering in the aperture collimator and few analytical models have been proposed to take scattering effects into account, mainly limited to the inner collimator face component. The aim of this study was to characterize and model aperture contamination by means of a fast and accurate analytical model. The entrance face collimator scatter distribution was modeled as a 3D secondary dose source. Predicted dose contaminations were compared to measurements and Monte Carlo simulations. Measurements were performed on two different proton beam lines (a fixed horizontal beam line and a gantry beam line) with divergent apertures and for several field sizes and energies. Discrepancies between analytical algorithm dose prediction and measurements were decreased from 10% to 2% using the proposed model. Gamma-index (2%/1 mm) was respected for more than 90% of pixels. The proposed analytical algorithm increases the accuracy of analytical dose calculations with reasonable computation times.

TestMeEast: a campaign to increase HIV testing in hospitals and to reduce late diagnosis.

Late diagnosis occurs in almost half of those diagnosed in the UK (HIV Prevention England, 2013. Retrieved June 22, 2014, from HIV Prevention England: http://www.hivpreventionengland.org.uk/Campaigns-Current/National-HIV-Testing-Week ). Testing occurs mainly in sexual health and antenatal clinics despite recommendations to test more broadly [Ellis, S., & Curtis, H. (2012). HIV diagnoses and missed opportunities. Results of the British HIV association (BHIVA) National Audit 2010. Clinical Medicine, 12(5), 430-434]. We report the findings of an HIV-testing week campaign to offer testing to those who have blood tests as part of routine care within outpatient clinics and emergency departments of six London hospitals. The campaign target was to test 500 patients a day during the 2013 National HIV Testing Week (NHTW). Clinic staff and medical students were trained to offer routine HIV testing. Linkage to care was arranged for those who tested HIV-positive. During NHTW we tested 2402 of the planned 2500 test target. 2402/4317 (55.6% 95% CI 54.1-57.1%) of those who had routine blood tests were tested for HIV. There were eight HIV-positive tests; three were new diagnoses (all linked to care). The campaign hashtag #TestMeEast achieved a total Twitter "reach" of 238, 860 and the campaign had widespread news coverage. Our campaign showed that staff and students could be trained and mobilised to do thousands of routine HIV tests during a campaign.

[Current use and prospects for hadron therapy in 2015]. / Hadronthérapie : quelle place et quelles perspectives en 2015 ?

Hadron therapy (including protons and ions) is still expanding worldwide, although still limited by the cost and thus the number of available facilities. If the historical indications remain eye melanomas, skull base tumours and paediatric tumours for protontherapy; and salivary glands, paranasal sinus and nasal cavity tumours, and soft tissue sarcomas for carbon ions, no conclusion can be drawn about the role of these modalities for other tumours, such as prostate, lung cancers. Since 2013, more than 100 clinical trials are on-going, including comparisons between advanced photons modalities, protontherapy and carbon ions therapy. An important technological and scientific (physics, radiobiology) effort has been made in parallel in order to reduce the cost of the facilities and to fully take advantages of the beam properties: standardization of beam scanning, image guided treatment, robust and 4D planning. Furthermore, the increasing number of facilities, the development of hypofractionation and the selection of indications will contribute to find the true place of particle therapy, despite the "screening effect" of the cost. The long term effects assessment on large patient cohorts will allow or not to correlate adverse effects and dosimetric data, always evoked.

Use of gEUD for predicting ear and pituitary gland damage following proton and photon radiation therapy.

OBJECTIVE: To determine the relationship between the dose to the inner ear or pituitary gland and radiation-induced late effects of skull base radiation therapy. METHODS: 140 patients treated between 2000 and 2008 were considered for this study. Hearing loss and endocrine dysfunction were retrospectively reviewed on pre- and post-radiation therapy audiometry or endocrine assessments. Two normal tissue complication probability (NTCP) models were considered (Lyman-Kutcher-Burman and log-logistic) whose parameters were fitted to patient data using receiver operating characteristics and maximum likelihood analysis. The method provided an estimation of the parameters of a generalized equivalent uniform dose (gEUD)-based NTCP after conversion of dose-volume histograms to equivalent doses. RESULTS: All 140 patients had a minimum follow up of 26 months. 26% and 44% of patients experienced mild hearing loss and endocrine dysfunction, respectively. The fitted values for TD50 and γ50 ranged from 53.6 to 60.7 Gy and from 1.9 to 2.9 for the inner ear and were equal to 60.6 Gy and 4.9 for the pituitary gland, respectively. All models were ranked equal according to Akaike's information criterion. CONCLUSION: Mean dose and gEUD may be used as predictive factors for late ear and pituitary gland late complications after skull base proton and photon radiation therapy. ADVANCES IN KNOWLEDGE: In this study, we have reported mean dose effects and dose-response relationship of small organs at risk (partial volumes of the inner ear and pituitary gland), which could be useful to define optimal dose constraints resulting in an improved therapeutic ratio.

Calibration of CT Hounsfield units for proton therapy treatment planning: use of kilovoltage and megavoltage images and comparison of parameterized methods.

Proton beam range is of major concern, in particular, when images used for dose computations are artifacted (for example in patients with surgically treated bone tumors). We investigated several conditions and methods for determination of computed tomography Hounsfield unit (CT-HU) calibration curves, using two different conversion schemes. A stoichiometric methodology was used on either kilovoltage (kV) or megavoltage (MV) CT images and the accuracy of the calibration methods was evaluated. We then studied the effects of metal artifacts on proton dose distributions using metallic implants in rigid phantom mimicking clinical conditions. MV-CT images were used to evaluate relative proton stopping power in certain high density implants, and a methodology is proposed for accurate delineation and dose calculation, using a combined set of kV- and MV-CT images. Our results show good agreement between measurements and dose calculations or relative proton stopping power determination (<5%). The results also show that range uncertainty increases when only kV-CT images are used or when no correction is made on artifacted images. However, differences between treatment plans calculated on corrected kV-CT data and MV-CT data remained insignificant in the investigated patient case, even with streak artifacts and volume effects that reduce the accuracy of manual corrections.

Acquired epidermodysplasia verruciformis due to multiple and unusual HPV infection among vertically-infected, HIV-positive adolescents in Zimbabwe.

BACKGROUND: We have previously described the presentation of epidermodysplasia verruciformis (EV)-like eruptions in almost a quarter of hospitalized adolescents with vertically-acquired human immunodeficiency virus (HIV) infection in Harare, Zimbabwe, a region with a high prevalence of HIV infection. METHODS: We performed a clinical case note review and skin biopsy from affected sites in 4 HIV-infected adolescents with EV-like lesions in Harare. Biopsies were processed for histology and for human papillomavirus (HPV) typing. RESULTS: All patients had long-standing skin lesions that pre-dated the diagnosis of HIV by several years. The histology of skin biopsies from all patients was consistent with EV. In each biopsy, EV-associated ß-HPV type 5 was identified (additionally, type 19 was found in 1 biopsy). Cutaneous wart-associated HPV types 1 and 2 were detected in all biopsies, together with genital lesion-associated HPV types 6, 16, and 52, (as well as ≥3 other genital lesion-associated HPV types). Despite immune reconstitution with combination antiretroviral therapy (cART), there was no improvement in EV-like lesions in any patient. CONCLUSIONS: EV is a disfiguring and potentially stigmatizing condition among this patient group and is difficult to treat; cART appears to have no impact on the progression of skin disease. Among adolescents with longstanding HIV-induced immunosuppression and with high levels of sun exposure, close dermatological surveillance for potential skin malignancy is required.

[Protontherapy: basis, indications and new technologies]. / La protonthérapie : bases, indications et nouvelles technologies.

With over 70,000 patients treated worldwide, protontherapy has an evolution on their clinical applications and technological developments. The ballistic advantage of the Bragg peak gives the possibility of getting a high conformation of the dose distribution to the target volume. Protontherapy has accumulated a considerable experience in the management of selected rare malignancies such as uveal melanomas and base of the skull chordomas and chondrosarcomas. The growing interest for exploring new and more common conditions, such as prostate, lung, liver, ENT, breast carcinomas, as well as the implementation of large pediatric programs advocated by many experts has been challenged up to now by the limited access to operational proton facilities, and by the relatively slow pace of technical developments in terms of ion production, beam shaping and modelling, on-line verification etc. One challenge today is to deliver dynamic techniques with intensity modulation in clinical facilities as a standard treatment. We concentrate in this paper on the evolution of clinical indications as well as the potentialities of new technological concepts on ion production, such as dielectric walls and laser-plasma interactions. While these concepts could sooner or later translate into prototypes of highly compact equipments that would make easier the implantation of cost-effective hospital-based facilities, the feasibility of their clinical use must still be proved.

Monte Carlo modelling of the treatment line of the Proton Therapy Center in Orsay.

This paper presents the main results of a Monte Carlo simulation describing the Orsay Proton Therapy Center (CPO) beam line. The project aimed to obtain a prediction of the dose distribution in a water phantom within 2% accuracy in the dose value and a 2 mm of range. The simulation tool used was MCNPX, version 2.5.0, and included all the elements of the CPO beam line. A new algorithm of multiple Coulomb scattering has been incorporated in MCNPX, resulting in a better prediction of the spatial dose distribution and absolute values of the deposited energy. The simulations of 3D dose profiles in water show a very good agreement with measured data to within 2%. We first performed a comparative analysis of the dosimetry in heterogeneous phantoms between the pencil beam algorithm and MCNPX. The simulations give a better agreement with experimental data compared to the pencil beam approach. In a second phase, we simulated the patient-dependent fields along with the spatial dose distributions in a water phantom. The simulated response of a Pixel chamber located 2 m upstream of the water phantom revealed a good agreement with the measured data to within 1%. The results presented herein support the applicability of Monte Carlo models for absolute dosimetry and for design purposes regarding existing and new beam lines at CPO. This work completes a series of publications reporting the progress in the development of a Monte Carlo simulation tool for the CPO beam line dedicated for the treatment of head and neck tumours.

Recurrence of cryptococcal meningitis in HIV-infected patients following immune reconstitution.

Two HIV-infected patients had recurrent cryptococcal meningitis (CM) despite treatment with fluconazole and immune reconstitution with combination antiretroviral therapy (CART). Following treatment of CM with fluconazole, lumbar puncture should be performed either after completion of induction treatment for CM or before starting CART, in order to confirm cerebrospinal fluid sterility.

[An original contention system for hadron therapy]. / Un système de contention original applicable à l'hadronthérapie.

In hadron therapy centers that have only fixed horizontal beams (i.e. most carbon ions centers and protons centers of first generation), the angulations of the beam remain technically limited, especially for the treatment of children under general anaesthesia with posterior-oblique (40 degrees or so) beams in supine position. We have been developing recently an original positioning system allowing for treatment with posterior-oblique beams, either from right or left directions, by keeping the child in the adequate position.

Cholangiocarcinoma presenting in an adolescent with vertically acquired HIV infection.

An adolescent with long-standing HIV infection who was severely immunosuppressed during HIV diagnosis developed cholangiocarcinoma 1.5 years after starting antiretroviral therapy.

[Chordomas of the base of the skull and upper cervical spine. 100 patients irradiated by a 3D conformal technique combining photon and proton beams]. / Les chordomes de la base du crâne et du rachis cervical haut. A propos d'une série de 100 patients irradiés selon une technique conformationnelle 3D par une association de faisceaux de photons et de protons.

OBJECTIVE: To define prognostic factors for local control and survival in 100 consecutive patients treated by fractionated photon and proton radiation for chordoma of the skull base and upper cervical spine. PATIENTS AND METHODS: Between December 1995 and August 2002, 100 patients (median age: 53 years, range: 8-85, M/F sex-ratio: 3/2), were treated by a combination of high-energy photons and protons. The proton component was delivered by the 201 MeV proton beam of the Centre de Protonthérapie d'Orsay (CPO). The median total dose delivered to the gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (range: 60-71). A complete surgery, incomplete surgery or a biopsy was performed before the radiotherapy in 16, 75 and 9 cases, respectively. RESULTS: With a median follow-up of 31 months (range: 1-87), 25 tumours failed locally. The 2 and 4-year local control rates were 86.3% (+/-3.9%) and 53.8% (+/-7.5%), respectively. According to multivariate analysis, less than 95% of the tumour volume encompassed by the 95% isodose line (P=0.048; RR: 3.4 IC95% [1.01-11.8]) and a minimal dose less than 56 CGE (p=0.042; RR: 2.3 IC95% [1.03-5.2]) were independent prognostic factors of local control. Ten patients died. The 2 and 5-year overall survival rates were 94.3% (+/-2.5%) and 80.5% (+/-7.2%). According to multivariate analysis, a controlled tumour (P=0.005; RR: 21 IC95% [2.2-200]) was the lonely independent favourable prognostic factor for overall survival. CONCLUSION: In chordomas of the skull base and upper cervical spine treated by surgical resection followed by high-dose photon and proton irradiation, local control is mainly dependent on the quality of radiation, especially dose-uniformity within the gross tumour volume. Special attention must be paid to minimise underdosed areas due to the close proximity of critical structures and possibly escalate dose-constraints to tumour targets in future studies, in view of the low toxicity observed to date.

[Treatment with neutrons: hadrontherapy part II: physical basis and clinical experience]. / Le traitement par neutrons : hadronthérapie partie II : bases physiques et expérience clinique.

Neutrons have radiobiological characteristics, which differ from those of conventional radiotherapy beams (photons) and which offer a theoretical advantage over photons to fight radioresistance by the differential relative biological effect of them between normal and tumour tissues. Neutron therapy beneficed of great interest between 1975 and 1985. Many of phase III trials were conducted and indications have been definitively deducted of them. After briefly describing the properties of neutron beams, this review discusses the indication of neutron therapy on the basis of the clinical results. Salivary, prostate tumours and sarcomas are the main indications of neutron therapy. In concern to the prostate cancers, other alternative treatments reduce the neutron therapy field. For sarcomas, the lack of randomised trials limits the impact of the interest of neutrons. For other tumours, the ratio benefice/risk of neutron therapy is inferior to these obtained with photons and they could not be considered like classical indications.

[Treatment with charged particles beams: hadrontherapy part I: physical basis and clinical experience of treatment with protons]. / Le traitement par faisceaux de particules : hadronthérapie partie I : bases physiques et expérience clinique de la protonthérapie.

Protons have physical characteristics, which differ from those of photons used in conventional radiotherapy. Better shielding of critical organs is obtained by using their particular ballistic (Bragg peak and lateral narrow penumbra). Some indications as ocular melanoma, chordoma and chondrosarcoma of the base of skull are now strongly accepted by the radiation oncologist community. Others are still in evaluation: meningioma, locally advanced nasopharynx tumor and paediatric tumors. The aim of this review is to present the clinical results of a technic which seems "confidential" because of the rarety and the cost of equipments.

[Automatization and robotics of the set-up and treatment of patients irradiated for brain and base ot the skull tumors]. / Automatisation et robotisation du placement et de la mise en place des patients irradiés pour une tumeur de l'encéphale et de la base du crâne.

Progresses of the three-dimensional imageries and of the software of planning systems makes that the radiotherapy of the tumours of brain and the base of skull is increasingly precise. The set-up of the patients and the positioning of the beams are key acts whose realization can become extremely tiresome if the requirement of precision increases. This precision very often rests still on the visual comparison of digital images. In the near future, the development of the automated systems controlled by robots should allow a noticeable improvement of the precision, safety and speed of the patient set-up.

[Comparison with dose-volume histograms of two conformal irradiation techniques used for the treatment of T2N0M0 nasopharyngeal cancer, one with association of photons and protons and another with photons alone]. / Comparaison par les histogrammes dose-volume de deux techniques d'irradiation conformationnelle des cancers du nasopharynx classés T4N0M0, l'une par photons et protons et l'autre par photons seuls.

Purpose- There is a relationship between the local control rate of the nasopharyngeal cancer and the total dose delivered within the tumoral volume. In contrast, the relation between the dose and the irradiated volume and the risk of complication is not clearly defined. That is why, in patients presenting with a locally advanced nasopharyngeal cancer, we compared the dose-volume distribution of irradiated tissues, obtained from two 3D conformal irradiation techniques. Patients and methods- Between January 2000 and June 2001, 5 patients, 3 males and 2 females, with a median age of 32 years and presenting with a T4N0M0 nasopharyngeal cancer received a chemoradiotherapy. Radiotherapy combined photons and protons beams and the platin-based chemotherapy was delivered in three intravenous injections at d1, 22, 43 of the irradiation. To calculate the dosimetry, a CT scan and a MRI were performed in all the patients. The gross tumor volume (GTV) was delineated from the imagery, three clinical tumor volumes were defined, the CTV1 was the GTV and the whole nasopharynx, the CTV2 was the CTV plus a 10 mm-margin and the CTV3 was the CTV2 and the nodes areas (cervical and subclavicular). Prophylactic dose within node areas was 44 Gy. Prescribed doses within CTV2 and GTV or CTV1 were 54 Gy/CGE (Cobalt Gy Equivalent, for an EBR = 1,1) and 70 Gy/CGE, respectively. Irradiation was delivered with fractions of 1.8 or 2.0 Gy/CGE, with 44 Gy or 54 Gy by photons and with 16 or 26 CGE by protons. According to dose-volume histograms obtained from the dosimetry planning by protons and photons and from the theoretical dosimetry by photons lonely, for the different volumes of interest, GTV, CTV2, and organs at risk (optic nerves, chiasm, internal ears, brainstem, temporal lobes), we compared the averages of the maximum, minimum and mean doses and the averages of the volumes of organs of interest encompassed by different isodoses.Results- Calculated averages of minimum, maximum and mean doses delivered within GTV were superior for the treatment with combined photons and protons than with photons alone. The average GTV encompassed by the 70 Gy/CGE isodose was larger by 65% with the association compared to photons alone. The conformation ratio (tissue volume encompassed by the 95% isodose/GTV encompassed by the 95% isodose) was 3.1 with the association compared to 5.7 with photons alone. For the CTV2, there were no differences in different criteria according to the both irradiation techniques. For the critical, radiosensitive organs, the comparison of the majority of the criteria was in favour of the association of protons and photons. Overall, 78% of the criteria were in favour of the association.Conclusion- For locally advanced nasopharyngeal cancer without clinical adenopathy, irradiation by photons and protons increases the tumor volume irradiated at the prescribed dose and decreases the volume or critical organs irradiated and the total dose delivered within them.

[Results of proton beam irradiation for treatment of choroidal melanoma]. / Résultats du traitement du mélanome de la choroïde par faisceau de protons.

PURPOSE: To evaluate the results of proton beam irradiation of choroidal melanomas on a large series of patients. PATIENTS AND METHODS: Retrospective analysis of a series of patients treated with proton beam irradiation between 1991 and December 1998. The data were analyzed to evaluate the local tumor control as well as the general progression and metastatic rate of the patients. Statistical analysis served to isolate risk factors for relapse or metastasis. RESULTS: We treated 1062 patients during the study period, with a median follow-up of 38 months. Local control was obtained for 97.1% of the patients. Tumors anterior to the equator were at risk for relapse. The survival rate was 92% at 2 years and 78% at 5 years. 73.1% of the 1062 patients died from metastasis, 6.1% of living patients presented with metastatic disease. The risk factors for death were the initial diameter, the age of the patient, and large tumor volume at diagnosis. Metastasis were essentially hepatic (94.6%). Risk factors for metastasis were: a large tumor volume, a lesion anterior or straddling the equator and the age of the patient. Ocular complications may induce a visual loss of 0.1 and less in 47% of the patients, due to optic nerve head and macular ischemia. 6% of the patients required secondary enucleation due to local complications (neovascular glaucoma). CONCLUSION: Proton beam irradiation of choroidal melanoma allows good tumor control and eye retention. The survival prognosis is associated with the initial volume of the tumor. The functional results may be improved and new therapeutics are needed to treat metastatic disease.