Good clinical practice guide for opioids in pain management: the three Ts - titration (trial), tweaking (tailoring), transition (tapering) / Orientação para boa prática clínica para opioides no tratamento da dor: os três "Ts" - titulação (teste), ajustes (individualização), transição (redução gradual)

ABSTRACT BACKGROUND AND OBJECTIVES: Achieving good clinical practice in the use of opioids as part of a comprehensive pain management regimen can face significant challenges. Despite guidelines from governmental and pain society/organization sources, there are still significant hurdles. A review of some basic tenets of opioid analgesia based on current published knowledge and experiences about this important healthcare imperative is warranted. CONTENT: Consistent with guidelines, the literature supports using the lowest total opioid dose that provides adequate pain control with the fewest adverse effects. Titration (or trial) during opioid initiation is a way of starting low and going slow (and assessing the appropriateness of a specific opioid and formulation). Recognizing that multiple factors contribute to an individual's personal experience of pain, the physical, psychological, social, cultural, spiritual, pharmacogenomic, and behavioral factors of the individual patient should be taken into account (tweaking, or tailoring). Finally, for those patients for whom transition (tapering) from opioid is desired, doing so too rapidly can have negative consequences and minimization of problems during this step can be achieved by proper tapering. CONCLUSION: We conclude that a simultaneously aggressive, yet conservative, approach is advocated in the literature in which opioid therapy is divided into three key steps (the 3 T's): titration (or trial), tweaking (or tailoring), and transition (or tapering). Establishment of the 3 T's along with the application of other appropriate good medical practice and clinical experience/judgment, including non-pharmacologic approaches, can assist healthcare providers in the effort to achieve optimal management of pain.

RESUMO JUSTIFICATIVA E OBJETIVOS: Uma boa prática clínica com o uso de opioides como parte de um regime abrangente de tratamento da dor pode enfrentar desafios significativos. Apesar das diretrizes provenientes de sociedades/organizações não governamentais para o manejo da dor, ainda existem obstáculos significativos. A revisão de alguns princípios básicos da analgesia com opioide com base na experiência e no conhecimento das publicações atuais sobre esse cuidado importante da saúde é justificável. CONTEÚDO: De acordo com as diretrizes, a literatura apoia o uso da dose total mais baixa de opioides que forneça o controle adequado da dor com menos efeitos adversos. A titulação (teste), ao iniciar a administração de um opioide, é uma maneira de começar com uma concentração baixa e ir devagar (avaliar a adequação da fórmula específica de um opioide). O ajuste (individualização) é reconhecer que vários fatores contribuem para a experiência pessoal da dor de um indivíduo, tais como fatores físicos, psicológicos, sociais, culturais, espirituais, farmacogenômicos e comportamentais. Finalmente, para aqueles pacientes nos quais a transição (redução gradual) do opioide é desejada, fazer essa transição muito rapidamente pode ter consequências negativas e é possível minimizar os problemas durante essa etapa por meio de uma redução gradual. CONCLUSÃO: Uma abordagem simultânea, agressiva, porém conservadora, é defendida na literatura em que a terapia com opioides é dividida em três etapas principais (os 3 Ts - em inglês: titration, tailoring, tapering): titulação (teste), ajuste (individualização) e transição (redução gradual). Estabelecer os três Ts, juntamente com a aplicação de outra boa prática médica e experiência/julgamento clínico, incluindo abordagens não farmacológicas, pode ajudar os profissionais de saúde no esforço para alcançar o tratamento ideal da dor.

The timing and sequence of emergence of permanent teeth in Malay schoolchildren in Kota Bharu, Malaysia

The purpose of this study was to determine the timing and sequence of emergence of the first 28 permanent teeth in a cross-section of Malay children in the district of Kota Bharu, in northeastern Peninsula Malaysia. The sample consists of 478 boys and 908 girls of Malay descent aged between 5-19 years. The criterion for tooth emergence was the appearance of the tooth through the gingivae. Descriptive statistics were calculated and probit regression analysis performed to determine the mean age of emergence of the permanent dentition. The mean age at emergence was found to conform to general trends, with emergence seen earlier in girls than in boys. Comparisons were made with the Chinese (Hong Kong) and the Punjabi (Chandigarh) profiles, which showed earlier emergence timings in those ethnic groups. The emergence timing in Malays, however, was earlier than in Thais (Central Thailand). The sequence of emergence was determined by referring to the mean age of tooth emergence of individual teeth and conforms to the general trend seen in other studies.

The oral contraceptive pill effectively permits cycle batching for an intermittent in vitro fertilization programme in Trinidad and Tobago / Las Píldoras Anticonceptivas Orales Permiten la Agrupación Eficaz de los Ciclos para un Programa Intermitente de FIV en Trinidad y Tobago

Assisted reproductive technology (ART) in small island states like Trinidad and Tobago is usually provided in batches so as to minimize the cost of providing the service. As a result, patients 'cycles have to be synchronized in order to coincide with the arrival of a visiting embryologist. This is a retrospective study which evaluates the experience of pre-treatment with an oral contraceptive pill (OCP) as a means of batching cycles for an intermittent ART programme. Seventy-four in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles in which OCP usage was employed (Group A), were compared with 121 cycles which did not require pharmaceutical manipulation (Group B). In both groups more than 50 of women were older than 36-years. Two cycles were cancelled in Group A and seven in Group B, because of poor ovarian response. Although the pregnancy rate per treatment cycle was higher in Group A than in Group B (26.3 vs 17.3), this difference was not significant. More spontaneous miscarriages occurred in the non-OCP women and ovarian cyst formation was more common in these women. The authors experience indicates that the OCP is a simple, cheap and efficient means of batching patients for an intermittent ART programme and can be utilized in other small ART centres

La tecnología de reproducción asistida (TRA) en los pequeños estados insulares como Trinidad y Tobago, usualmente se ofrece por tandas a fin de minimizar los costos del servicio brindado. En consecuencia, los ciclos de las pacientes tienen que ser sincronizados de modo que coincidan con la visita del embriólogo. Éste es un estudio retrospectivo que evalúa la experiencia del pretratamiento con píldoras anticonceptivas orales (PAO) como medio de agrupar los ciclos con el propósito de organizar un programa intermitente de TRA. Setenta y cuatro ciclos de fertilización in vitro (FIV) e inyección intracitoplasmática de esperma (ICSI) en los que se recurrió al uso de PAO (Grupo A), fueron comparados con 121 ciclos que no requirieron manipulación farmacéutica (Grupo B). En ambos grupos, > 50% de las mujeres tenían más de 36 años de edad. Dos ciclos fueron cancelados en el grupo A y siete en el grupo B, debido a una respuesta ovárica pobre. Aunque la tasa de embarazo por ciclo de tratamiento fue más alta en el grupo A que en el grupo B (26.3% vs. 17.3%), esta diferencia no fue significativa. El número de abortos espontáneos fue mayor y la formación de quistes ováricos más común, en las mujeres que tomaron PAO. La experiencia de los autores indica que la PAO es un medio simple, económico y eficaz de agrupar a los pacientes en un programa intermitente de TRA, y puede utilizarse en otros centros pequeños de TRA.

A methodological approach for the construction of a radiation hybrid map of bovine chromosome 5

A bovine 5,000 rad WG-RH panel was used to construct an RH map of bovine chromosome 5 (BTA5). Twenty-one microsatellites and thirteen genes were scored in the panel using PAGE and radioactive labeling. Marker retention ranged from 8.9 percent-25.8 percent and averaged 17.8 percent. Pairwise locus analysis placed all markers in a single syntenic group with a LOD support of 4.0. At a LOD support of 8.0, a centromeric group of 23 syntenic markers was formed. Telomeric groups of 11 and 9 markers were assembled with a LOD support of 6.0 and 8.0, respectively. All markers were ordered by maximum likelihood methods using the program RHMAP. Only 13 markers were ordered with a LOD support of at least 3.0, while 25 and 29 markers were ordered with a support of at least 2.0 and 1.0, respectively. Total length of the comprehensive RH map was 435.9 cR5,000, with an average marker separation of 12.8 cR5,000. The largest gaps in the map were 55.0 and 30.4 cR5,000 in length. The locus orders of markers common to both the RH map and the USDA-MARC linkage map were identical. The relationship between the RH and linkage maps was calculated to be 3.74 cR5,000/cM.

Molecular cytogenetic assignment of genes to bovine chromosome 5

Seven genes were assigned by molecular cytogenetic methods to bovine chromosome 5. To accomplish this, specific primers were either publicly available or were designed from highly conserved regions of the publicly available mammalian gene sequences. The identity of the amplified segments was verified by sequencing and alignment with the published sequences. The optimized primers that amplified the desired bovine genes were used for screening a bovine bacterial artificial chromosome library. The positive clones were localized to a specific band of bovine chromosome 5 by fluorescence in situ hybridization. The genes HOXC4, SP1 and IGFBP6 were localized to band q21, COL2A1 was localized to bands q21-q23, IGF1 was localized to band q26, MB to band q31 and the gene CYP2D6 was localized to band q35. The cytogenetic assignment of SP1, IGFBP6, COL2A1, IGF1, MB and CYP2D6 is first reported here and the assignment of HOXC4 refines the previous assignment of this gene. The identification and localization of these genes further support the development of the human to bovine comparative map through characterizing the homologous segments conserved in the evolution of these species. This information will be useful for the future localization of genes that affect economically important traits in bovines

Brugia malayi in seven villages in South Kalimantan, Indonesia.

Seven villages in South Kalimantan were visited in 1971 and night peripheral blood smears from 2,764 people examined for microfilariae. Brugia malayi was found endemic in all villages with microfilarial rates of 12--46% (average 25%) and the median microfilarial density (MfD50) of 6 to 15 microfilariae per 20 microliter of blood. The microfilariae showed a typical subperiodic pattern. The disease was more common in males than females and the prevalence increased with age. Clinical manifestations of filariasis were found in 20% of 1,099 persons examined. Mansonia species are considered important vectors and cats important reservoir hosts. In addition to B. malayi, Dirofilaria repens and an unknown microfilaria were found in cats in the area and strains of the B. malayi and D. repens have been established in the laboratory.

Parasitology survey and seroepidemiology of amoebiasis in South Kalimantan (Borneo), Indonesia.

A parasitology surevy was conducted among inhabitants of 7 villages in 3 regencies in South Kalimantan Province, Indonesia. A total of 2,169 stool specimens, 2,756 blood smears and 1,027 serum specimens were obtained, representing samples from approximately 10%, 12% and 5% of the population, respectively. One to 8 different intestinal parasitic infections were detected in 97% of the people. Those parasites most frequently found were Trichuris trichiura (83%), Ascaris lumbricoides (79%), and hookworm (65%), followed by Entamoeba coli (37%), Endolimaxnana (12%), Entamoeba histolytica (12%), Iodamoeba bütschlii (11%), Giardia lamblia (5%), Entamoeba hartmanni (2%), Chilomastix mesnili (2%). Other parasites found were Enterobius vermicularis, Strongyloides stercoralis, Capillaria sp., Echinostoma sp., Hymenolepis diminuta, and Trichomonas hominis. Giardia lamblia was found more often in younger people and Entamoeba coli, Iodamoeba bütschlii and hookworm in the older age group. Ascaris lumbricoides occurred more frequently in females, and hookworm in males. Plasmodium vivax and Plasmodium falciparum were found in the blood smears of 4.4% of the people, mostly in the younger age groups. Seroepidemiological studies on amoebiasis were done by use of the indirect hemagglutination test with antigens prepared from the HK9 strain of Entamoeba histolytica maintained in axenic cultures. The frequency distribution of the reciprocal antibody titers showed a bimodal distribution with 34% of the population demonstrating positive reactions at titers of 1:128 or greater.