Arthritis Australia

By N. Armon. Northwestern College, Iowa. 2018.

Metformin induces reductions in plasma diovascular disease and hypoglycaemia in patients with type 2 diabetes: cobalamin and haptocorrin bound cobalamin levels in elderly diabetic patients flagyl 250 mg. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Clin Biochem 2010 order 200 mg flagyl with amex;43:75960. Obesity is associated with lower mor- ings of the rst international symposium on acarbose. Amsterdam: Excerpta tality risk in elderly diabetic subjects: The Casale Monferrato study. A double-blind cross-over comparison of an alpha-glucosidase and insulin sensitivity during a long-term (60 weeks) randomized study with inhibitor with metformin. A systematic review of the clinical effec- mentation does not augment muscle mass or affect glycemic control in elderly tiveness of pioglitazone in the treatment of type 2 diabetes mellitus. Rosiglitazone in the management of older patients with equately controlled type 2 diabetes mellitus. Treatment of elderly patients with type 2 diabetes mellitus: metformin, or glyburide monotherapy. A systematic review of the benets and risks of dipeptidyl peptidase-4 inhibi- 101. Rosiglitazone evaluated for cardio- elderly type 2 diabetes patients with inadequate glycemic control in taiwan. Long-term use of thiazolidinediones and frac- sitagliptin and sulfonylureas in elderly patients with type 2 diabetes melli- tures in type 2 diabetes: A meta-analysis. J Clin Endocrinol Metab weight change outcomes with alogliptin vs glipizide in older patients with type 2 2015;100:405966. Incidence and risk factors for and inadequate glycemic control: A randomized, double-blind, non-inferiority serious hypoglycemia in older persons using insulin or sulfonylureas. Risk and short-term prognosis of myo- elderly type 2 diabetes mellitus patients with mild hyperglycaemia: A pro- cardial infarction among users of antidiabetic drugs. Improved glucose control with reduced pital admission in type 2 diabetic patients aged 80 years or older. Exp Clin hypoglycaemic risk when linagliptin is added to basal insulin in elderly patients Endocrinol Diabetes 2010;118:21519. Alogliptin after acute coronary syn- in patients with type 2 diabetes treated with glimepiride versus glibenclamide. Can J Diabetes litus inadequately controlled with metformin: A 24-week, randomized, mul- 2015;39(Suppl. Ecacy and safety of lixisenatide in age with type 2 diabetes: Experience from nateglinide pooled database ret- elderly (65 years old) and very elderly (75 years old) patients with rospective analysis. Diabetes Care 2006;29:1918 once-weekly dulaglutide in patients with type 2 diabetes aged 65 and <65 20. Lixisenatide therapy in older patients tion with metformin, is effective and well tolerated in treatment-naive elderly with type 2 diabetes inadequately controlled on their current antidiabetic treat- patients with type 2 diabetes. Lixisenatide in patients with type 2 dia- and safety of sitagliptin in elderly patients with type 2 diabetes: Post hoc betes and acute coronary syndrome. Ecacy and safety of canagliozin com- treatments: A randomised, double-blind, placebo-controlled trial. Lancet pared with placebo in older patients with type 2 diabetes mellitus: A pooled 2013;382:141323. Ecacy and safety of canagliozin treat- 1, 2 and 3 studies: Glycaemic control and hypoglycaemia with new insulin ment in older subjects with type 2 diabetes mellitus: A randomized trial. Optimizing insulin absorption and insulin injection taneous insulin infusion and multiple daily injections of insulin on glucose vari- technique in older adults. A short easy test can detect ability neous insulin infusion in older patients with long-standing type 1 diabetes. Pre-lled insulin pen in newly insulin- and safe in elderly and young type 1 diabetes patients. Systolic Hypertension in the Elderly Program Coop- of biphasic insulin aspart in elderly type 2 diabetes patients. Systolic Hypertension in China (Syst-China) collabora- injections on blood glucose uctuations in the postprandial period in elderly tive group. Safety and effectiveness of biphasic insulin blockade in older patients with diabetes and systolic hypertension. Comparison of antihypertensive treat- patients with Type 2 diabetes: Ecacy and safety of lispro mix 25 vs. Diabet Med 2009;26:1147 from the Swedish Trial in Old Patients with Hypertension-2. Follow-up of renal function in treated repaglinide and insulin aspart 30 in treating aged type 2 diabetes mellitus.

Difficult if anterior placenta or oligohydramnios Cordocentesis (Percutaneous umbilical blood sampling): from 18 weeks buy 400 mg flagyl overnight delivery. These people to be chosen by the Abortion supervisory committee generic flagyl 200mg with visa, with a view to expeditious access by any woman seeking an abortion. Supervisory committee also appoints/approves counselling services Ethics: Why is killing wrong: Violates the moral integrity of the entity killed It has negative consequences Evidences moral flaws in the killer Reasons for killing: to end suffering, to protect the innocent, lesser of two evils, to express societal condemnation Different views of the moral status of the fetus: Fetus has the same moral status: absence of a dividing line between a baby and a fetus does not show lack of difference Fetus has no moral status: Is seeking an abortion for trivial reasons wrong? Associated with preterm delivery Incomplete abortion: cervix is dilating, more pain, heavier bleeding. Usually active management to remove fetus Causes: None found most common Chromosomal abnormalities Hormonal imbalance: eg failure of corpus luteum to produce enough progesterone Maternal illness, abnormalities of the uterus (eg cervical incompetence), immunological factors Recurrent miscarriage = loss of 3 or more consecutive pregnancies, occurs in < 1% Ectopic pregnancy = Any implantation outside the uterine cavity. Atypical some initially have a fetus proliferation proliferating trophoblast Little invasive potential 10% invasive, Most have metastasised at Choriocarcinoma 5% diagnosis. Risk factors: Maternal age > 35 years Family history of diabetes Previous macrosomia, unexplained still birth Obesity Glycosuria on two or more separate occasions. Aiming for pretty tight control Insulin used if unable to control levels, or evidence of macrosomia. Even if tightly controlled, 4 5% risk of congenital abnormalities (2* general population). Aspirin (blocks thromboxane production preferentially make prostacyclin), antihypertensives, anticonvulsant prophylaxis (Magnesium sulphate). Have to stabilise before delivery Delivery is the only cure (although > half of fits occur post partum). Bleeding from an abnormal fetal vessel attached to the membranes over the internal os. Monitor retro-placental clot by serial ultrasound Rhesus haemolytic disease* Aetiology: if Rhesus ive mother is contaminated by blood from a Rhesus +ive baby anti-D IgG antibodies (isoimmunisation) Later in the pregnancy, or in a following pregnancy, IgG can cross the placenta causing Erythroblastosis Fetalis ( stiff oedematous lungs and hydrops widespread oedema) nd Test for anti-D antibodies in all Rhesus ive mothers at booking and in 2 trimester. Hard to diagnose regular uterine contractions are normal, cervical changes in labour can be subtle Braxton-Hicks contractions are usual from 30 weeks but are not painful History: Is it true labour: check nature of contractions, urinary frequency (? Can risk of infection Steroids: dexamethasone and betamethasone (crosses placenta, prednisone doesnt) - 2 shots 12 hours apart. Epidural analgesia preferable to narcotics ( respiratory depression) Reproductive and Obstetrics 367 Premature Rupture of Membranes* = Rupture of membranes before labour is established. Normally rupture of membranes follows establishment of labour Check: have they really ruptured? Continuous monitoring interventions) Intermittent auscultation every 15 30 minutes following a contraction. Only worry after 36 weeks it can turn fairly easily before then Transverse or oblique (1%) Fetal Attitude: posture of the fetus, eg extended neck Fetal Position: Relation of occiput (vertex) to the maternal pelvis. If engaged, you know the pelvic inlet is big enough Descent: Extension of fetal body. Usually descent through pelvis transverse, then need to rotate face downwards Extension: once head reaches vulva, occiput in direct contact with symphasis. Ritgen Manoeuvre upward pressure on chin through perineum from below, downward pressure on occiput (stop anterior tear) External Rotation/Restitution occiput goes back to original position (transverse) now realigned again with shoulder. Check for nuchal cord (around neck), clear nasopharynx Expulsion: anterior shoulder, followed by posterior shoulder. Gentle traction on chord with supra-pubic pressure (stops uterus coming down) or fundal massage and maternal bearing down without traction Can manually deliver (place hand into uterus and separate) if no haemorrhage then wait for anaesthesia Then inspection, repair, rectal exam Cord prolapse: Cord comes through cervix before head. During active stage, progress = either further dilation or further descent Can happen at any stage Causes of failure to progress: Prolonged latent phase Primary dysfunctional labour: never enters active phase. C-section if < 1000 gm (body comes through at 7 8 cm dilated and head gets stuck = entrapment of after-coming head) or > 3600 or 4000 gm. C-section becoming more routine for any breech Face (rather than occiput first). Converts to either face or occiput cant deliver as brow Occiput transverse: Head cant flex and rotate from transverse to occiput anterior. Cant be induced if previous Caesar strong contractions against a closed cervix risk of rupture Risk of placenta growing in the scar next time. Only approx 1% of babies infected but approx 50% mortality if infected Perinatal Asphyxia Asphyxia: cessation of gas exchange hypoxia and hypercarbia. Varies from region to region th th 372 4 and 5 Year Notes Reasons for perinatal death: Hypoxia (eg placenta separated, maternal hypertension) Prematurity Congenital abnormality (eg heart defect, spina bifida) Trauma (eg difficult birth) Maternal Death: Death associated with pregnancy or trophoblastic disease up to 3 months after the event (required to be reported to Medical Officer of Health) Causes: Obstetric causes 70%. Eg in anything that causes large uterus twins, polyhydramnios, etc Genital tract trauma during delivery (7%) Coagulation defect Management: Resuscitate mother. Pelvic organ by ~10 days Lochia: red for day 1 3, yellow next 10 days, white until 6 weeks Reproductive and Obstetrics 373 Puerperal Pyrexia = temperature of at least 38 C on any 2 of the first 14 days after abortion or delivery, exclusive of the first 24 hours Incidence: After vaginal delivery: 1 3 % After Caesarean: ~10% Pathogenesis: assume infection until proven otherwise. Can deteriorate quickly need rapid assessment Sources: Clots, retained placenta, etc can facilitate growth Generally an ascending infection Lower genital tract (eg anaerobes). Treat with Pavlik harness Genitals: Check boys for undescended testes (cryptorchidism) 2%, especially if premature, spontaneous descent unlikely beyond 3 months, surgery at 9 12 months.

In this section we discuss three distinctive characteristics and sources of value provided by antibiotics: enabling 500mg flagyl visa, option/insurance and diversity value purchase 250 mg flagyl with visa. Antibiotics have become necessary in modern medicine to enable invasive surgical or immunosuppressive medical procedures that depend on preventing infection in the patient. Procedures such as organ transplantation, cancer chemotherapy, hip or knee replacement surgery, transrectal biopsy or appendectomy require the routine use of prophylactic antibiotics that are effective. By keeping a stock of unused antibiotics that are not affected by resistance, lives could potentially be saved. All of these elements have to be established before the fire (infection), since buildings burn (and patients die) far more quickly than infrastructure can be built. The introduction of antimicrobials with diverse and novel mechanisms of action can help existing and future antibiotics to remain effective by reducing selection pressure. It depends on the number of existing therapeutic options and the extent to which these can be displaced by a new antibiotic. This includes performing a sensistivity analysis at the population level of the impact of resistance to the new antibiotic, both initially and over time. The direct costs and benefits associated with treating one patient with an antibiotic, where relevant, should also take account of the indirect benefits from avoided onward transmission, and diversity benefits from the protective effects on existing antibiotics currently in use. A literature review was undertaken to identify both published and grey literature containing theoretical or existing economic incentives for stimulating any type of biopharmaceutical innovation (see Appendix B). Focus groups and a further literature review gathered potential incentives from other industries such as defence. Feedback from stakeholders was then integrated into the design of the models prior to further internal review and model refinement. There is no one size fits all solution to incentivizing antibiotic innovation in a global market with a variety of unmet needs, healthcare systems and access requirements. A menu of incentives is required that can be adapted to the local context, and yet still achieve the same goal of stimulating antibiotic innovation. We reviewed 35 incentives designed to stimulate greater innovation within pharmaceutical R&D as well as incentives from other industries. For an incentive to be considered promising, it had to be rated as effective by all three groups of voting members (academic, industry and policy) for stimulating innovation, and able to build in equitable availability and sustainable use mechanisms. On the basis of this review, we found four incentives best suited to fill the antibiotic pipeline and ensure that critical antibiotics continue to be accessible: Grants: non-repayable funds to academic institutions, companies and others, paying for R&D. Pull incentives provide rewards to developers for delivering products with characteristics specified by the funder. Each can be implemented in customized ways depending on the health need to be addressed. These models do not operate in isolation and are designed to be complementary to maximize the impact on the antibiotic pipeline. If, as a result of the availability of diagnostic results after the initiation of therapy, the decision is made to de-escalate the novel therapy, the price for the first few days use would be set to a lower price comparable to the de- escalated therapy. This model reduces financial concerns related to the use of newer antibiotics to address multi-drug- resistant infections when the patients diagnosis is still uncertain but with risk factors that warrant appropriate empiric coverage that is not achieved with alternative antibiotics. Relatedly, some members were concerned that the full duration price might need to be high in order to achieve an attractive return on investment, and that this might inhibit access. With appropriate care, the model could be tested in well-developed health systems that are able to provide access to diagnostics and that have stewardship systems in place to support appropriate use and de-escalation. Conversely, the model is not feasible in markets with limited healthcare infrastructure. Push incentives seek to overcome two major R&D bottlenecks: scientific challenges and clinical development costs. It was created to encourage public-private partnerships and technology transfer from academic research to industry, and to support R&D of technologies, including biotechnology, with national defence and public health potential. The advantages of grant funding reside in the opportunity for targeted approaches to R&D, where the objectives of the research programme can be tailored to tackle public health needs, and to focus research on areas that create major scientific and technological bottlenecks. But this has not yet resulted in coordination, where funders target common goals and work together to identify R&D gaps. The first group has broad research objectives, mainly focused on basic and early, applied scientific research. Through this funding mechanism, research would be targeted towards public health needs (e. The main recipients of these grants would be academic research groups and research institutes. Mid-stage grants are designed to help project advancement from the preclinical stage, toxicology and manufacturing to the end of phase I clinical trials. Developers should not have to collaborate and should be allowed access to needed funding on their own account. These grants aim to progress antibiotics towards clinical development by offsetting the opportunity costs that arise when a developer has competing projects in its portfolio and/or limited financial resources. In addition, this incentive should help developers attract investors by reducing the financial risk of clinical trials. The developer could apply for this financing mechanism directly, and be subject to peer review, or could proceed from previous mid-stage grant funding conditional on successfully accomplishing a phase I and review process.

Supervisory committee also appoints/approves counselling services Ethics: Why is killing wrong: Violates the moral integrity of the entity killed It has negative consequences Evidences moral flaws in the killer Reasons for killing: to end suffering discount 200 mg flagyl free shipping, to protect the innocent buy flagyl 200mg without prescription, lesser of two evils, to express societal condemnation Different views of the moral status of the fetus: Fetus has the same moral status: absence of a dividing line between a baby and a fetus does not show lack of difference Fetus has no moral status: Is seeking an abortion for trivial reasons wrong? Associated with preterm delivery Incomplete abortion: cervix is dilating, more pain, heavier bleeding. Usually active management to remove fetus Causes: None found most common Chromosomal abnormalities Hormonal imbalance: eg failure of corpus luteum to produce enough progesterone Maternal illness, abnormalities of the uterus (eg cervical incompetence), immunological factors Recurrent miscarriage = loss of 3 or more consecutive pregnancies, occurs in < 1% Ectopic pregnancy = Any implantation outside the uterine cavity. Atypical some initially have a fetus proliferation proliferating trophoblast Little invasive potential 10% invasive, Most have metastasised at Choriocarcinoma 5% diagnosis. Risk factors: Maternal age > 35 years Family history of diabetes Previous macrosomia, unexplained still birth Obesity Glycosuria on two or more separate occasions. Aiming for pretty tight control Insulin used if unable to control levels, or evidence of macrosomia. Even if tightly controlled, 4 5% risk of congenital abnormalities (2* general population). Aspirin (blocks thromboxane production preferentially make prostacyclin), antihypertensives, anticonvulsant prophylaxis (Magnesium sulphate). Have to stabilise before delivery Delivery is the only cure (although > half of fits occur post partum). Bleeding from an abnormal fetal vessel attached to the membranes over the internal os. Monitor retro-placental clot by serial ultrasound Rhesus haemolytic disease* Aetiology: if Rhesus ive mother is contaminated by blood from a Rhesus +ive baby anti-D IgG antibodies (isoimmunisation) Later in the pregnancy, or in a following pregnancy, IgG can cross the placenta causing Erythroblastosis Fetalis ( stiff oedematous lungs and hydrops widespread oedema) nd Test for anti-D antibodies in all Rhesus ive mothers at booking and in 2 trimester. Hard to diagnose regular uterine contractions are normal, cervical changes in labour can be subtle Braxton-Hicks contractions are usual from 30 weeks but are not painful History: Is it true labour: check nature of contractions, urinary frequency (? Can risk of infection Steroids: dexamethasone and betamethasone (crosses placenta, prednisone doesnt) - 2 shots 12 hours apart. Epidural analgesia preferable to narcotics ( respiratory depression) Reproductive and Obstetrics 367 Premature Rupture of Membranes* = Rupture of membranes before labour is established. Normally rupture of membranes follows establishment of labour Check: have they really ruptured? Continuous monitoring interventions) Intermittent auscultation every 15 30 minutes following a contraction. Only worry after 36 weeks it can turn fairly easily before then Transverse or oblique (1%) Fetal Attitude: posture of the fetus, eg extended neck Fetal Position: Relation of occiput (vertex) to the maternal pelvis. If engaged, you know the pelvic inlet is big enough Descent: Extension of fetal body. Usually descent through pelvis transverse, then need to rotate face downwards Extension: once head reaches vulva, occiput in direct contact with symphasis. Ritgen Manoeuvre upward pressure on chin through perineum from below, downward pressure on occiput (stop anterior tear) External Rotation/Restitution occiput goes back to original position (transverse) now realigned again with shoulder. Check for nuchal cord (around neck), clear nasopharynx Expulsion: anterior shoulder, followed by posterior shoulder. Gentle traction on chord with supra-pubic pressure (stops uterus coming down) or fundal massage and maternal bearing down without traction Can manually deliver (place hand into uterus and separate) if no haemorrhage then wait for anaesthesia Then inspection, repair, rectal exam Cord prolapse: Cord comes through cervix before head. During active stage, progress = either further dilation or further descent Can happen at any stage Causes of failure to progress: Prolonged latent phase Primary dysfunctional labour: never enters active phase. C-section if < 1000 gm (body comes through at 7 8 cm dilated and head gets stuck = entrapment of after-coming head) or > 3600 or 4000 gm. C-section becoming more routine for any breech Face (rather than occiput first). Converts to either face or occiput cant deliver as brow Occiput transverse: Head cant flex and rotate from transverse to occiput anterior. Cant be induced if previous Caesar strong contractions against a closed cervix risk of rupture Risk of placenta growing in the scar next time. Only approx 1% of babies infected but approx 50% mortality if infected Perinatal Asphyxia Asphyxia: cessation of gas exchange hypoxia and hypercarbia. Varies from region to region th th 372 4 and 5 Year Notes Reasons for perinatal death: Hypoxia (eg placenta separated, maternal hypertension) Prematurity Congenital abnormality (eg heart defect, spina bifida) Trauma (eg difficult birth) Maternal Death: Death associated with pregnancy or trophoblastic disease up to 3 months after the event (required to be reported to Medical Officer of Health) Causes: Obstetric causes 70%. Eg in anything that causes large uterus twins, polyhydramnios, etc Genital tract trauma during delivery (7%) Coagulation defect Management: Resuscitate mother. Pelvic organ by ~10 days Lochia: red for day 1 3, yellow next 10 days, white until 6 weeks Reproductive and Obstetrics 373 Puerperal Pyrexia = temperature of at least 38 C on any 2 of the first 14 days after abortion or delivery, exclusive of the first 24 hours Incidence: After vaginal delivery: 1 3 % After Caesarean: ~10% Pathogenesis: assume infection until proven otherwise. Can deteriorate quickly need rapid assessment Sources: Clots, retained placenta, etc can facilitate growth Generally an ascending infection Lower genital tract (eg anaerobes). Treat with Pavlik harness Genitals: Check boys for undescended testes (cryptorchidism) 2%, especially if premature, spontaneous descent unlikely beyond 3 months, surgery at 9 12 months. Complete a screening survey such as the Edinburgh Postnatal Depression Questionnaire.