Nurse-led renal cell carcinoma clinic: a single center review.

BACKGROUND: In 2015 our centre introduced a nurse-led renal cell cancer follow-up protocol and clinic for patients who have undergone partial or radical nephrectomy for organ-confined kidney tumours. The main aims of this clinic were to improve healthcare efficiency and standardize follow-up processes. OBJECTIVES: The primary objective was to assess the effectiveness of a nurse-led renal cell cancer follow up clinic in regard to surveillance protocol compliance and the timely identification and appropriate management of recurrences. A secondary objective was to evaluate this locally developed follow up protocol against the current European Association of Urology (EAU) guidelines surveillance protocol. PATIENT AND METHODS: All patients who underwent a partial or radical nephrectomy between 2015 and 2021 at a single Western Australia institution for a primary renal malignancy were included. Data was collected from local clinical information systems and protocol adherence, recurrence characteristics and management were assessed. The current EAU guidelines were applied to the cohort to assess differences in risk-stratification and theoretical outcomes between the protocols. RESULTS: After a mean follow up period of 31.2 months (range 0-77 months), 75.5% (185/245) of patients had all follow up imaging and reviews within 1 month of the timeframe scheduled on the protocol. 17.1% (42/245) had a delay in their follow up of more than a month at some stage, 5.7% (14/245) did not attend for follow up but had documented attempts to facilitate their compliance, and 0.4% (1/245) were lost to follow up with no evidence of attempted contact. 15.5% (38/245) of patients had recurrence of malignancy detected during follow up and these were all discussed in a multi-disciplinary team (MDT) meeting. The recurrence rate was 2.5% (3/119) for low risk, 17.7% (14/79) for intermediate risk, and 44.7% (21/47) for high risk patients when they were re-stratified according to EAU risk categories. No recurrences were detected through ultrasound (USS) or chest x-ray (CXR) in this cohort and our protocol tended to place patients in higher risk-stratification groups as compared to current EAU guidelines. CONCLUSION: Nurse-led renal cell cancer follow up is a safe, reliable and effective clinical framework that has significant benefits in regard to resource utilization. USS and CXR are ineffective in detecting recurrence and Computerized tomography (CT) should be considered the imaging modality of choice for this purpose. The EAU surveillance protocol appears superior to our protocol, and we have therefore transitioned to the EAU guideline protocol going forward.

Self-treatment for malaria: the evidence and methodological issues.

Malaria remains an important cause of death, especially in sub-Saharan Africa. Self-treatment with antimalarial drugs is a common practice that raises important issues for policy-makers. A number of important questions concerning factors related to self-treatment, adequacy of self-treatment and the role of self-treatment in malaria mortality remain unanswered. Although there are some common patterns, there is considerable diversity in treatment practices, even within a single country. Social science research on malaria treatment needs to move beyond description to evaluation of interventions. This will require a greater degree of methodological rigour and more attention to the generation of data that can be compared across time periods and studies. Definitions of malaria cases and the role of local disease categories in identifying cases need to be made more explicit. Illnesses should be classified by severity, using measures of perceived severity as well as biomedical signs of severity. Each treatment step should be considered in terms of four levels of analysis: who provided the treatment or advice, what the treatment was, where it was obtained and when it was taken in relationship to onset of illness.

SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo.

We describe here the identification and properties of SCH-C (SCH 351125), a small molecule inhibitor of HIV-1 entry via the CCR5 coreceptor. SCH-C, an oxime-piperidine compound, is a specific CCR5 antagonist as determined in multiple receptor binding and signal transduction assays. This compound specifically inhibits HIV-1 infection mediated by CCR5 in U-87 astroglioma cells but has no effect on infection of CXCR4-expressing cells. SCH-C has broad and potent antiviral activity in vitro against primary HIV-1 isolates that use CCR5 as their entry coreceptor, with mean 50% inhibitory concentrations ranging between 0.4 and 9 nM. Moreover, SCH-C strongly inhibits the replication of an R5-using HIV-1 isolate in SCID-hu Thy/Liv mice. SCH-C has a favorable pharmacokinetic profile in rodents and primates with an oral bioavailability of 50-60% and a serum half-life of 5-6 h. On the basis of its novel mechanism of action, potent antiviral activity, and in vivo pharmacokinetic profile, SCH-C is a promising new candidate for therapeutic intervention of HIV infection.

Piperazine-based CCR5 antagonists as HIV-1 inhibitors. II. Discovery of 1-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4- methyl-4-[3(S)-methyl-4-[1(S)-[4-(trifluoromethyl)phenyl]ethyl]-1-piperazinyl]- piperidine N1-oxide (Sch-350634), an orally bioavailable, potent CCR5 antagonist.

Truncation of the original piperidino-2(S)-methyl piperazine lead structure 2, from a family of muscarinic antagonists, gave compound 8 which has improved selectivity for the HIV-1 co-receptor CCR5 over muscarinic receptors. Further optimization for pharmacokinetic properties afforded Sch-350634 (1), a prototypical piperazine-based CCR5 antagonist, which is a potent inhibitor of HIV-1 entry and replication in PBMCs. The title compound (1) has excellent oral bioavailability in rat, dog, and monkey.

Piperazine-based CCR5 antagonists as HIV-1 inhibitors. I: 2(S)-methyl piperazine as a key pharmacophore element.

Optimization of the piperidino-piperazines 1 and 2 provided early leads 3 and 4, which showed good activity in the CCR5-RANTES binding assay and in antiviral assays. A systematic study around these structures showed that the 2(S)-methyl piperazine is essential for CCR5 affinity, which is further enhanced by forming the 2,6-dimethyl benzamide of the piperidine.

Metabolic stabilization of benzylidene ketal M(2) muscarinic receptor antagonists via halonaphthoic acid substitution.

The potential toxicological liabilities of the M(2) muscarinic antagonist 1 were addressed by replacing the methylenedioxyphenyl moiety with a p-methoxyphenyl group, resulting in M(2) selective compounds such as 3. Several halogenated naphthamide derivatives of 3 were studied in order to improve the pharmacokinetic profile via blockage of oxidative metabolism. Compound 4 demonstrated excellent M(2) affinity and selectivity, human microsomal stability, and oral bioavailability in rodents and primates.

Muscarinic agonists and antagonists in the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have been successfully treated with acetylcholinesterase inhibitors (tacrine, donepezil. rivastigmine, galanthamine), limited success has been achieved with direct M1 agonists, probably due to their lack of selectivity versus other muscarinic receptor subtypes. Muscarinic M2 antagonists have been reported to increase synaptic levels of acetylcholine after oral administration to rats (e.g. BIBN-99, SCH-57790), but their selectivity versus other muscarinic receptor subtypes is modest. Exploration of a series of piperidinylpiperidines has yielded the potent and selective M2 antagonist SCH-217443. This antagonist has excellent bioavailability in rats and dogs and shows activity in a rat model of cognition.

SCH 47112, a novel staurosporine derivative, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and epidermal hyperplasia in hairless mouse skin.

Protein kinase C (PKC) regulates keratinocyte growth and differentiation as well as inflammation in skin, processes which are abnormal in skin diseases such as psoriasis. 12-O-tetradecanoylphorbol-13-acetate (TPA) binds to and activates PKC. We investigated the effects of SCH 47112, a novel staurosporine derivative, which interacts with the catalytic domain of PKC, on TPA-induced inflammation and hyperplasia in hairless mouse skin and TPA-induced differentiation in cultured human keratinocytes. Dorsal mouse skin was treated with vehicle, TPA (2.0/ 2.5 nmol) or SCH 47112 followed by TPA. Epidermal thickness, and epidermal, upper dermal and deep dermal inflammation (assessed on an ordinal semiquantitative scale) were determined in biopsies taken 24 h and 48 h post-treatment. SCH 47112 (100 nmol) inhibited TPA-induced epidermal, upper dermal and deep dermal inflammation by 71%, 45% and 22%, respectively, at 24 h (n = 3, P < 0.05). TPA-induced epidermal hyperplasia was inhibited by SCH 47112 (400 nmol) by 38% at 48 h (n = 3, P < 0.05). In addition, in cultured human keratinocytes, SCH 47112 inhibited TPA induction of transglutaminase. I protein, which catalyzes the formation of crosslinked envelopes. These results indicate that SCH 47112 exhibits biological activity, inhibiting TPA-induced changes in hairless mouse skin in vivo and cultured human keratinocytes in vitro, and suggest that PKC inhibitors may have a therapeutic role in inflammatory skin diseases.

Treatment seeking for malaria: a review of recent research.

A review of literature on treatment seeking for malaria was undertaken to identify patterns of care seeking, and to assess what is known about the adequacy of the treatments used. There is considerable variation in treatment seeking patterns, with use of the official sector ranging from 10-99% and self-purchase of drugs ranging from 4-87%. The majority of malaria cases receive some type of treatment, and multiple treatments are common. The response to most episodes begins with self-treatment, and close to half of cases rely exclusively on self-treatment, usually with antimalarials. A little more than half use the official health sector or village health workers at some point, with delays averaging three or more days. Exclusive reliance on traditional methods is extremely rare, although traditional remedies are often combined with modern medicines. Although use of antimalarials is widespread, underdosing is extremely common. Further research is needed to answer the question of what proportion of true malaria cases get appropriate treatment with effective antimalarial drugs, and to identify the best strategies to improve the situation. Interventions for the private and public sector need to be developed and evaluated. More information is needed on the specific drugs used, considering resistance patterns in a particular area. In order to guide future policy development, future studies should define the nature of self-treatment, record multiple treatments and attempt to identify the proportions of all cases who begin treatment with antimalarials at standardized time intervals. Hypothetical questions were found to be of limited usefulness in estimating rates of actual treatments. Whenever possible, studies should focus on actual episodes of illness and consider supplementing retrospective surveys with prospective diary-type methods. In addition, it is important to determine the specificity of local illness terms in identifying true malaria cases and the extent to which local perceptions of severity are consistent with clinical criteria for severity and symptoms of complicated malaria.

Molecular epidemiology of Shigella sonnei in Pima County, Arizona: evidence for a Mexico-related plasmid.

In 1984, the incidence of shigellosis was 32.4 per 100,000 population in Pima County, Arizona. To investigate sources, Shigella isolates and epidemiologic data were collected for 79 cases of infection with Shigella sonnei, the most common species. Since S. sonnei has a single serotype, plasmid isolation was attempted to refine the epidemiologic analysis. There were seven plasmid patterns containing 17, 13, 4, 22, 9, 2, and 3 isolates. Twelve of 17 isolates associated with recent travel to Mexico were in a group distinguished by a 5.1-kilobase (kb) plasmid. This plasmid was used to probe Southern blots of plasmids from strains of all groups. The Mexico-related plasmid probe hybridized to all the 5.1-kb plasmids and to 5.5- and 7.4-kb plasmids from three other groups. Of the 79 isolates, 50 contained plasmids homologous to the Mexico-related plasmid probe, suggesting association with travel to Mexico.

The politics of immunization in public health.

The role of socio-political and psychological factors in the decision to immunize is explored using data collected in a county health department in the United States. Decisions regarding the administration of post-exposure immunizations for hepatitis A and rabies are described, and a tendency toward unnecessary use noted. At times these interventions function more to reduce the anxiety of a patient or clinician than they do to prevent an infection. These findings may have implications for analyses of clinical decision making that involve other types of interventions.

The epidemiology of S. sonnei and S. flexneri in Pima County, Arizona: an exploratory study.

Investigation of 189 cases of shigellosis reported to the Pima County, Arizona Health Department in 1986 revealed that 23 per cent of cases could be attributed to travel to Mexico, and 10 per cent to day care attendees and their household contacts. No source of infection or high-risk activity could be demonstrated for 43 per cent of the cases. Households in which S. flexneri occurred were more likely to be characterized by crowded living situations and to have no known source of infection.

Risk for measles related to immunization status in two Tucson high schools.

An outbreak of measles occurred in Tucson, AZ, in 1985; 112 of the 225 cases were among students at two large high schools. A review of the immunization records of all students at both schools was undertaken in order to assess the risk of a person contracting measles in relation to that person's immunization status. Two factors, the lack of an immunization record and immunization prior to 12 months of age, showed a positive association with contracting measles. The association was statistically significant at one high school but not the other. At the first high school, students who were immunized at 12 to 14 months of age had a greater risk of infection than those immunized at 15 months or older. However, age at immunization of 12 to 14 months was not associated with a significantly higher risk when persons with multiple doses of vaccine were excluded from the analysis. Students of both schools showed a lower attack rate for those who had received multiple doses of vaccine, but the difference was not statistically significant.

Folk flu and viral syndrome: an epidemiological perspective.

Public health officials and medical social scientists both recognize the importance of the relationship between culture and infectious disease. However, the divergence that exists between the medical model and the epidemiological model has not been well studied. During the course of enteric disease surveillance in the southwest United States, the categories 'flu' and 'viral syndrome' were identified. The relationship between 'flu', a popular illness category, and 'viral syndrome', part of the medical model, is discussed. From the standpoint of an epidemiologist, both of these concepts act as obstacles to disease investigation and control.

Tonsillectomy as a co-factor in the development of AIDS.

Hypotheses regarding the factors that predispose individuals to developing AIDS after exposure to HTLV-III/LAV are beginning to emerge. It is suggested here that surgical removal of tonsils in childhood may increase the risk of developing opportunistic infections after infection with this newly discovered retrovirus.

The cultural impact of the 'AIDS' test: the American experience.

In March 1985 an ELISA test for serum antibodies to human T-cell leukemia/lymphotropic virus type III (HTLV-III) was licensed for use in screening commercial blood products. Controversy over the appropriate use and interpretation of this test continues, and some public health officials in the United States have advocated different counselling strategies for high and low risk individuals with the same test results. The response to AIDS illustrates that contagion has a social definition, even in the context of Western scientific medicine.

KIE: The ELISA (enzyme-linked immunosorbent assay) test for serum antibodies to human T-cell leukemia/lymphotropic virus type III (HTLV-III) was licensed for use in screening commercial blood products in March 1985 as a means of controlling the spread of acquired immunodeficiency syndrome (AIDS) through blood transfusions. The test has also been implemented in a variety of other medical and nonmedical settings, where its use is often highly controversial and based on very loose social or epidemiological criteria. In addition, opposing strategies have been advocated for counseling high and low risk individuals with the same test results. McCombie discusses how the rapid diffusion of HTLV-III testing programs, despite questions about their appropriateness, illustrates the extent to which cultural beliefs and attitudes affect public health and medical practice.