Modular service provision for heterogeneous patient groups: a single case study in chronic Down syndrome care.

BACKGROUND: Service modularity could be promising for organizing healthcare delivery to heterogeneous patient groups because it enables cost reductions while also being responsive towards individual patients' needs. However, no research on the applicability of modularity in this context exists. To this end, we conducted a qualitative single-case study on chronic healthcare provision for Down syndrome patients, delivered by multidisciplinary pediatric Downteams in the Netherlands, from a modular perspective. METHODS: We conducted six semi-structured interviews with coordinators of multidisciplinary Downteams in six hospitals. In addition, we gathered data by means of observations and analysis of relevant documentation. We transcribed, coded, and analyzed the interviews utilizing the Miles and Huberman approach. The consolidated criteria for reporting qualitative research (COREQ) were applied in this study. RESULTS: In all six Downteams studied, the modular package for Down syndrome patients (i.e. the visit to the Downteams) could clearly be divided into modules (i.e. the separate consultations with the various professionals), and into different components (i.e. sub-elements of these consultations). These modules and components were linked by different types of customer-flow and information-flow interfaces. These interfaces allowed patients to flow smoothly through the system and allowed for information transfer, respectively. CONCLUSION: Our study shows a modular perspective is applicable to analyzing chronic healthcare for a heterogeneous patient group like children with Down syndrome. The decomposition of the various Downteams into modules and components led to mutual insight into each other's professional practices, both within and across the various Downteams studied. It could be used to increase transparency of delivered care for patients and family. Moreover, it could be used to customize care provision by mixing-and-matching components. More detailed research on chronic modular care provision for patients with DS is needed to explore this.

The long-term effects of early oral feeding following minimal invasive esophagectomy.

A nil-by-mouth regime with enteral nutrition via an artificial route is frequently applied following esophagectomy. However, early initiation of oral feeding could potentially improve recovery and has shown to be beneficial in many types of abdominal surgery. Although short-term nutritional safety of oral intake after an esophagectomy has been documented, long-term effects of this feeding regimen are unknown. In this cohort study, data from patients undergoing minimal invasive Ivor-Lewis esophagectomy between 04-2012 and 09-2015 in three centers in Netherlands were collected. Patients in the oral feeding group were retrieved from a previous prospective study and compared with a cohort of patients with early enteral jejunostomy feeding but delayed oral intake. Body mass index (BMI) measurements, complications, and nutritional re-interventions (re- or start of artificial feeding, start of total parenteral nutrition) were gathered over the course of one year after surgery. One year after surgery the median BMI was 22.8 kg/m2 and weight loss was 7.0 kg (9.5%) in 114 patients. Patients in the early oral feeding group lost more weight during the first postoperative month (P = 0.004). However, in the months thereafter this difference was not observed anymore. In the early oral feeding group, 28 patients (56%) required a nutritional re-intervention, compared to 46 patients (72%) in the delayed oral feeding group (P = 0.078). During admission, more re-interventions were performed in the delayed oral feeding group (17 vs. 46 patients P < 0.001). Esophagectomy reduces BMI in the first year after surgery regardless of the feeding regimen. Direct start of oral intake following esophagectomy has no impact on early nutritional re-interventions and long-term weight loss.

Atypical clinical presentation of internal herniation after laparoscopic Roux-en-Y gastric bypass.

A 60-years old women with history of Roux-en-Y gastric bypass presented with progressive abdominal pain, mainly at the left loin. Imaging was aspecific. Exploratory laparoscopy showed an internal herniation trough the Petersen space.

Mapping the lectin-like activity of tumor necrosis factor.

Tumor necrosis factor (TNF), but not lymphotoxin (LT), is directly trypanolytic for salivarian trypanosomes. This activity was not blocked by soluble 55-kilodalton and 75-kilodalton TNF receptors, but was potently inhibited by N,N'-diacetylchitobiose, an oligosaccharide that binds TNF. Comparative sequence analysis of TNF and LT localized the trypanocidal region, and synthetic peptides were trypanolytic. TNF molecules in which the trypanocidal region was mutated or deleted retained tumoricidal activity. Thus, trypanosome-TNF interactions occur via a TNF domain, probably with lectin-like affinity, which is functionally and spatially distinct from the mammalian TNF receptor binding sites.

Protein kinase activities in immune complexes of simian virus 40 large T-antigen and transformation-associated cellular p53 protein.

Immune complex kinase assays in the simian virus 40 system were performed by incubation of immunoprecipitates containing tumor antigens with [gamma-32P]ATP, followed by analysis of any phosphoacceptor proteins. These assays yielded mainly the viral large T-antigen and, in particular, the associated cellular p53 as endogenous substrates. The nature of these substrates was confirmed by proteolysis techniques. Under specific conditions, casein could be used as an exogenous substrate as well. The kinase reactions showed preference for ATP and MgCl2 instead of GTP or MnCl2. Both phosphoserine and phosphothreonine, but in no case phosphotyrosine, were detected after an immune complex kinase reaction. Apparently, several in vivo phosphorylation sites were recognized in vitro in both large T-antigen and p53, but the presence of some artifactual sites could not be completely excluded. Although contaminating kinases were detectable in the immune complexes, at least the p53 molecules were phosphorylated in vitro in a more specific way. This followed from several characteristics of the immune complex kinase reactions and especially from the strong inhibition of p53 phosphorylation by two anti-large-T monoclonal antibodies. It was shown that large T-antigen showed associated kinase activity, although none of our results could unambiguously demonstrate an intrinsic kinase activity of this protein. Finally, anti-p53 monoclonal antibodies only slightly affected in vitro phosphorylation reactions, whereas a p53 molecule from a simian virus 40-free, chemically transformed human cell line was not phosphorylated in vitro under any condition tested. Thus, it is highly unlikely that the p53 molecule per se carries intrinsic or even associated kinase activities.

Expression and processing of the activin-A/erythroid differentiation factor precursor: a member of the transforming growth factor-beta superfamily.

The biosynthesis and intracellular processing of the polypeptide precursor of the beta A-chain of the fertility hormone inhibin were assessed by infecting a wide spectrum of cell types with a recombinant vaccinia virus. Most cell lines, including follicular granulosa cells, secrete both prohormone and mature hormone as homodimers (activin) composed of disulfide-linked subunits of 54 kDa (proactivin-A) and 14 kDa (activin-A), respectively, and a small amount of prohormone-mature hormone heterodimers. Mature activin is secreted from mouse pituitary cells (AtT-20), while pig kidney cells [PK(15)] secrete mostly proactivin. More prohormone is secreted in the presence of NH4Cl, suggesting that prohormone processing is facilitated by low pH. Proactivin-A is not a ligand for the mannose-6-phosphate/insulin growth factor-II receptor. The recombinant activin stimulates FSH release from pituitary cells and differentiates erythroleukemia cell lines in vitro.

Model-based evaluation of single-round mass treatment of sexually transmitted diseases for HIV control in a rural African population.

OBJECTIVES: To compare the impact of single-round mass treatment of sexually transmitted diseases (STD), sustained syndromic treatment and their combination on the incidence of HIV in rural Africa. METHODS: We studied the effects of STD interventions by stochastic simulation using the model STDSIM. Parameters were fitted using data from a trial of improved STD treatment services in Mwanza, Tanzania. Effectiveness was assessed by comparing the prevalences of gonorrhoea, chlamydia, syphilis and chancroid, and the incidence of HIV, in the general adult population in simulations with and without intervention. RESULTS: Single-round mass treatment was projected to achieve an immediate, substantial reduction in STD prevalences, which would return to baseline levels over 5-10 years. The effect on syphilis was somewhat larger if participants cured of latent syphilis were not immediately susceptible to re-infection. At 80% coverage, the model projected a reduction in cumulative HIV incidence over 2 years of 36%. A similar impact was achieved if treatment of syphilis was excluded from the intervention or confined to those in the infectious stages. In comparison with sustained syndromic treatment, single-round mass treatment had a greater short-term impact on HIV (36 versus 30% over 2 years), but a smaller long-term impact (24 versus 62% over 10 years). Mass treatment combined with improved treatment services led to a rapid and sustained fall in HIV incidence (57% over 2 years; 70% over 10 years). CONCLUSIONS: In populations in which STD control can reduce HIV incidence, mass treatment may, in the short run, have an impact comparable to sustained syndromic treatment. Mass treatment combined with sustained syndromic treatment may be particularly effective.

Membrane interaction of TNF is not sufficient to trigger increase in membrane conductance in mammalian cells.

Tumor necrosis factor TNF can trigger increases in membrane conductance of mammalian cells in a receptor-independent manner via its lectin-like domain. A lectin-deficient TNF mutant, lacking this activity, was able to bind to artificial liposomes in a pH-dependent manner, but not to insert into the bilayer, just like wild type TNF. A peptide mimicking the lectin-like domain, which can still trigger increases in membrane currents in cells, failed to interact with liposomes. Thus, the capacity of TNF to trigger increases in membrane conductance in mammalian cells does not correlate with its ability to interact with membranes, suggesting that the cytokine does not form channels itself, but rather interacts with endogenous ion channels or with plasma membrane proteins that are coupled to ion channels.

An in vitro model for the study of microglia-induced neurodegeneration: involvement of nitric oxide and tumor necrosis factor-alpha.

The precise function of activated microglia and their secretory products remains controversial. In order to assess the role of microglial secretion products, we established an in vitro model of an inflammatory reaction in the brain by co-culturing microglial and neuronal cell lines. Upon stimulation with interferon-gamma and lipopolysaccharides, the microglial cells adopted an activated phenotype and secreted tumor necrosis factor-alpha (TNF-alpha), prostaglandin E(2) and nitric oxide (NO). Neuronal degeneration was quantified by measuring the concentrations of microtubule associated protein tau and neuron specific enolase, which are also used as diagnostic tool in Alzheimer's disease, in supernatants. In activated contact co-cultures, the levels of these neuronal markers were significantly raised compared to non-activated co-cultures. NO-synthase inhibitors significantly diminished the rise of tau in activated co-cultures, while indomethacin, superoxide dismutase, or a neutralizing TNF-alpha antibody did not. When a chemical NO-donor or TNF-alpha were added to pure neuronal cultures, cell viability was significantly reduced. TNF-alpha increased neuronal sensitivity towards NO. There were indications that a part of the cells died by apoptosis. This model demonstrates a neurotoxic role for NO in microglia-induced neurodegeneration and provides a valuable in vitro tool for the study of microglia-neuron interactions during inflammation in the brain.

Interleukin-2 induces tumor necrosis factor-alpha production by activated human T cells via a cyclosporin-sensitive pathway.

We examined requirements for TNF-alpha production by purified human blood T cells, completely depleted of monocyte-accessory cells, under different conditions of stimulation. Activation of T cells with immobilized anti-CD3 induced the appearance of mRNA for TNF-alpha and of functionally active TNF-alpha in the culture supernatant. Anti-CD3-induced TNF-alpha production could be inhibited by blocking the IL-2R with a combination of anti-Tac and Mik beta 1 (mAbs against the p55 and p75 chain of the IL-2R respectively) thus indicating an essential role of IL-2 in TNF-alpha induction. When purified T cells were activated with a combination of two anti-CD2 mAbs (9-1 and 9.6), additional signals (rIL-2 or rIL-1 beta or anti-CD28) were required for TNF-alpha mRNA production and protein secretion. rIL-1 beta supported anti-CD2-induced TNF-alpha production indirectly through an IL-2-dependent pathway. These same helper signals also enhanced TNF-alpha production by anti-CD3-stimulated T cells. IL-4, IL-6, GM-CSF and IFN-gamma had no effect on TNF-alpha production by T cells activated via either pathway. Addition of rIL-1 beta alone, rIL-2 alone or endotoxins to resting human T cells did not induce detectable amounts of TNF-alpha. Both helper/inducer CD4(+) and suppressor/cytotoxic CD8(+) subsets of T cells were shown to produce TNF-alpha upon stimulation. We conclude that CD3 or CD2 triggering are not sufficient for TNF-alpha production by T cells, but that the latter is dependent (apparently at the transcriptional level) on the interaction of IL-2 with its functionally active cell surface receptors. We could further demonstrate that TNF-alpha production was completely blocked by cyclosporin A. The inhibitory effect of this agent on TNF-alpha production was also observed in the presence of rIL-2, thus excluding an indirect effect through inhibition of IL-2 production.

STD/HIV prevention in Turkey: planning a sequence of interventions.

This study was initiated to assess which mix of early STD/HIV prevention interventions would potentially be effective, cost-effective and sustainable in Turkey; and to program an intervention sequence to maximize synergy among the interventions. During rapid assessment we: 1) reviewed past issues of 3 leading newspapers; 2) collected information on TV coverage; 3) interviewed key informants including taxicab drivers, hotel employees, grocery store owners, academicians in public health and law, investigators of STD/HIV and reproductive tract infections, and officials in the ministry of health; 4) reviewed available evidence on STD/HIV morbidity, sexual behavior patterns, migration patterns and same/opposite gender sex trade. We found: 1) discrepancies between decision makers' perceptions and social realities with respect to the epidemiology of sexual behavior and STDs, and the state of public health programs; 2) discrepancies between sexual practices and public expression regarding sexual practices; 3) economic, demographic, and political pressures in Turkey and in surrounding countries for the expansion of prostitution; 4) a sexual double standard and gender specific migration patterns which sustain a high demand for commercial sex; 5) patterns of health care seeking behaviors and provision of STD clinical services which indicate other STDs may play a very important role in spread of HIV infection; 6) an important mass media role in opinion formation; 7) consensual denial of risk for the majority based on beliefs embedded in machismo, nationalism and religion, and a resulting marginalization and externalization of STD/HIV risk; 8) high prevalence of syphilis among both Turkish and immigrant female prostitutes in Istanbul (early latent 8 and 13%; late latent 0 and 4%; previous history 9 and 22%) 9) and high rates of syphilis among male prostitutes (early latent 11%, late latent 21% and previous history 58%). We concluded that interventions should initially include, in the following order; 1) awareness raising for decision makers and opinion leaders including members of parliament and mass media; 2) awareness raising for members of the general population; 3) needs assessment and intervention development for sex workers; 4) training in HIV and other STDs for medical personnel; and 5) quality assurance and control for laboratory procedures for STDs/HIV.

Impact of counselling on safer sex and STD occurrence among STD patients in Malawi.

In developing countries where professional manpower and basic supplies are lacking for STD control, low-cost prevention strategies must be explored. This study assesses the impact of counselling on STD treatment and prevention in Malawi. Increases in safer sex practices are used as indicators of prevention behaviour. A pre-test post-test control group design over a 4-month interval was conducted in 1991 in 2 comparable hospitals approximately 100 km apart. STD was diagnosed symptomatically and Knowledge Attitude Practice and Behaviour (KAPB) data collected using a structured questionnaire. In one group, trained counsellors discussed modes of transmission and prevention of STD/AIDS including a condom demonstration; symptoms and treatment of STDs; partner notification; risk taking and reasons for doing so; and motivations for behaviour change. The results show that counselling reduces the occurrence of STDs; increases concern for sexual partners; increases knowledge about and use of condoms; reduces mean number of partners; and reduces health costs due to fewer hospital visits. Although the observed behaviour change was short term, these outcomes argue in favour of counselling as a low-cost effective strategy for STD control.

Management of STDs and cost of treatment in primary health care centres in Pikine, Senegal.

We studied the current management of STD-related syndromes by urban health facilities in Pikine (Senegal) in 252 consecutive patients presenting with STD-related complaints, to assess the cost and effectiveness of services and to estimate the potential benefit by introducing management protocols. Most common presenting complaints for women were vaginal discharge and low abdominal pain, reported for 122 (82.9%) and 22 (15.0%) of 147 female patients. Urethral discharge and genital ulceration were reported for 80 (76.2%) and for 17 (16.2%) of 105 male patients. The average cost was 4.01 ECU (1 European Currency Unit = 1.2 US$ = 334 Franc CFA) for male patients (ranging from 0.57 to 25.70 ECU) and 12.75 ECU for female patients (ranging from 0.57 to 37.60 ECU). Only 20 of 80 patients with urethral discharge (25%) received effective treatment. Effectiveness was not related to cost of therapy or qualification of staff. Utilization of management protocols improves the quality and accessibility of care for STD, by potentially doubling effectiveness and reducing the costs for patients to 12% of the current level.

Declining syphilis prevalence in pregnant women in Nairobi since 1995: another success story in the STD field?

Untreated maternal syphilis during pregnancy will cause adverse pregnancy outcomes in more than 60% of the infected women. In Nairobi, Kenya, the prevalence of syphilis in pregnant women of 2.9% in 1989, showed a rise to 6.5% in 1993, parallel to an increase of HIV-1 prevalence rates. Since the early 1990s, decentralized STD/HIV prevention and control programmes, including a specific syphilis control programme, were developed in the public health facilities of Nairobi. Since 1992 the prevalence of syphilis in pregnant women has been monitored. This paper reports the findings of 81,311 pregnant women between 1994 and 1997. A total of 4244 women (5.3%) tested positive with prevalence rates of 7.2% (95% CI: 6.7-7.7) in 1994, 7.3% (95% CI: 6.9-7.7) in 1995, 4.5% (95% CI: 4.3-4.8) in 1996 and 3.8% (95% CI: 3.6-4.0) in 1997. In conclusion, a marked decline in syphilis seroprevalence in pregnant women in Nairobi was observed since 1995-96 (P<0.0001, Chi-square test for trend) in contrast to upward trends reported between 1990 and 1994-95 in the same population.

PIP: This study presents the trend in syphilis prevalence among 81,311 pregnant women in Nairobi, Kenya, from 1994 to 1997. Clinic nurses performed syphilis serology using a rapid plasma reagin (RPR) card test in 10 NCC clinics and Chi square; these were used to study trends over time. Results showed that a total of 4244 women (5.3%) tested positive with prevalence rates of 7.2% (95% CI: 6.7-7.7) in 1994, 7.3% (95% CI: 6.9-7.7) in 1995, 4.5% (95% CI: 4.3-4.8) in 1996, and 3.8% (95% CI: 3.6-4.0) in 1997. Thus, a significant decrease in syphilis seroprevalence among pregnant women in Nairobi was observed since 1995-96, by contrast with the rising trend in syphilis prevalence reported in 1990 and 1994-95 in the same population. This decline was attributable in large part to the syphilis control program initiated in Nairobi in June 1992, which focused on sexual behavior modifications, changes in health care seeking behavior and improved health care services.

Syphilis control in pregnancy: decentralization of screening facilities to primary care level, a demonstration project in Nairobi, Kenya.

A decentralized syphilis control program in pregnant women was implemented in nine Nairobi City Council antenatal clinics between July 1992 and August 1993, whereby pregnant women were screened for syphilis, treated before leaving the clinic if RPR seroreactive, and counselled on the importance of partner treatment and sexual abstinence during treatment in order to protect their unborn babies from getting congenital syphilis. A total of 13,131 pregnant women were screened for syphilis (RPR test), 87.3% of seroreactive women were treated on site and 50% of partners returned to the clinic and were treated. The prevalence of RPR reactivity was 6.5%. Based on other data the program could theoretically have prevented 413 cases of congenital syphilis at a cost of approximately 50 USD per prevented case. This demonstration project shows that decentralized prevention of congenital syphilis in antenatal clinics by nurses is feasible and inexpensive and should receive priority in resource allocation in reproductive health and child survival programs.

The provision of safe blood--policy issues in the prevention of human immunodeficiency virus transmission.

The AIDS epidemic has focused attention on the constraints and deficiencies present in many blood transfusion services in the developing world. We discuss a variety of options for reducing transfusion-related HIV transmission, and suggest how new transfusion strategies may be implemented. We show that a transfusion service cannot rely solely on the screening of donor blood for anti-HIV antibodies and that a more comprehensive approach is needed. Important components of this approach include donor selection and improved clinical practice, in which blood and blood products are prescribed only when really necessary.

[Development and evaluation of screening algorithms for sexually transmitted diseases in pregnant women at Libreville, Gabon]. / Elaboration et évaluation d'algorithmes de dépistage des MST chez la femme enceinte à Libreville, Gabon.

The struggle against sexually transmitted diseases (STD) constitutes a priority of public health in developing countries: STD cause complications, particularly in pregnant women, and facilitate the transmission of HIV. One of the strategies in the struggle against STD is the diagnosis and the early treatment of these infections. The STD, and in particular infections of Neisseria gonorrhea and Chlamydia trachomatis, are difficult to diagnose in women without complementary analyses, which primary health care may not be able to supply. Health care provided to patients could be standardized and improved by considering the signs and symptoms. We studied the prevalence and risk factors of STD among 192 pregnant women consulting the health clinic in Libreville, Gabon, in September 1993. The prevalence of STD was high (13.5% rate of cervical infection with gonorrhea or Chlamydia trachomatis). We then evaluated the different diagnostic strategies or algorithms. Regardless of the type of examination (medical interview, simple clinical examination or examination with a speculum), the use of scores integrating risk factors, the clinical signs and symptoms outperformed hierarchical algorithms. This approach was more sensitive and specific and easy to perform. Use of this method may enable more effective screening of STD and also avoid most maternal and perinatal complications.