PostExposure medicines(PEP) for HIV PEP =Post Exposure Prophylaxis for HIV typically consists of a 28-day regimen. Common regimens include:
Tenofovir disoproxil fumarate (TDF) 300 mg + Emtricitabine (FTC) 200 mg + Raltegravir 400 mg twice daily (preferred for most exposures). – Alternatively, TDF 300 mg + FTC 200 mg + Dolutegravir 50 mg once daily (if raltegravir is unavailable or contraindicated). – For higher-risk exposures, boosted protease inhibitors (e.g., darunavir/cobicistat) may be added. – Rationale: Guidelines (e.g., CDC, WHO) recommend these regimens due to high efficacy and tolerability. – Effectiveness: If initiated within 72 hours of exposure, PEP reduces HIV transmission risk by ~80%. – Adherence to the full 28-day course is critical for effectiveness. – Rationale: Early initiation and adherence prevent viral replication and integration. – Side Effects: Common: Nausea, fatigue, headache, diarrhea (usually mild and transient). – Less common: Elevated liver enzymes, renal impairment (with TDF), or rash (with integrase inhibitors). – Severe: Rare, but monitor for hypersensitivity reactions or lactic acidosis (with older NRTIs). – Rationale: Side effects are generally manageable; dose adjustments or regimen switches may be needed.
Definition: Traveler’s diarrhea (TD) is defined as the passage of ≥3 unformed stools in 24 hours, often accompanied by abdominal cramps, nausea, vomiting, or fever, typically occurring within the first 2 weeks of travel to endemic areas. –
Risk Factors: Destination (high-risk: Latin America, Africa, South Asia). – Season (warmer months). – Dietary habits (street food, raw produce, contaminated water). –
Prevention: Vaccination: No widely available vaccine; consider Dukoral (cholera vaccine) for high-risk travelers. – Chemoprophylaxis: Not routinely recommended; consider for high-risk groups (e.g., immunocompromised, inflammatory bowel disease). –
Rationale: Risk of resistance and side effects outweigh benefits for most travelers. – Behavioral: Food/water precautions (avoid ice, uncooked foods, unpeeled fruits; drink bottled/boiled water). –
Diagnosis: Clinical: Based on symptoms; stool culture not routinely needed unless severe (bloody diarrhea, fever, systemic symptoms). –
Laboratory: Stool culture, PCR, or microscopy if symptoms persist >72 hours or severe. Traveler’s diarrhea (TD) is defined as ≥3 unformed stools in 24 hours with at least one symptom (abdominal pain, cramps, fever, nausea, vomiting). –
Severity classification: Mild: <4 stools/day, no fever, no blood. – Moderate: 4–5 stools/day, mild fever, no blood. – Severe: ≥6 stools/day, fever ≥38°C, blood, or severe dehydration. –
Management : Oral Rehydration and Salt Intake Essential for all cases; use oral rehydration solutions (ORS) or salty broths. –
Treatment Options Mild cases: Symptomatic management (loperamide, bismuth subsalicylate). – Loperamide (4 mg initial, then 2 mg after each loose stool, max 16 mg/day). – Bismuth subsalicylate (2 tablets 4x/day). –
Moderate/severe cases: Antibiotics (azithromycin 500 mg single dose, or ciprofloxacin 500 mg single dose). –
Rationale: Reduces duration and severity; azithromycin preferred due to fluoroquinolone resistance in some regions. –
Antibiotic Prophylaxis: Not routinely recommended; reserved for high-risk travelers (e.g., immunocompromised, inflammatory bowel disease). –
Options: Rifaximin 200 mg/day or azithromycin 500 mg/week. – Special Considerations Children: Same as adults but adjust doses (e.g., azithromycin 10 mg/kg single dose). –
Pregnancy: Avoid fluoroquinolones; use azithromycin or loperamide. –
Norovirus summary from Mikai Leading cause of outbreaks of gastroenteritis worldwide (~50% of reported outbreaks in the U.S.). –
Predominantly transmitted via fecal-oral route; also present in vomitus. –
Spread by asymptomatically infected individuals and symptomatic persons before symptom onset and for weeks post-recovery. –
Prolonged viral shedding in immunocompromised individuals. –
Pathogenesis: Exact cellular receptors and attachment sites under investigation. – Infects mature enterocytes in the small intestine, leading to villous atrophy and malabsorption. – Incubation period: 12–48 hours. –
Clinical Features: Acute onset of nausea, vomiting, diarrhea (non-bloody), abdominal cramps, and low-grade fever. – Symptoms typically resolve within 2–3 days; dehydration is the main concern. –
Diagnosis: Primarily clinical; stool PCR for confirmation in outbreaks. – Rapid antigen tests available but less sensitive than PCR. –
Treatment: Supportive care (oral rehydration, IV fluids if severe dehydration). – No specific antiviral therapy; vaccination not yet available. –
Prevention: Hand hygiene, proper food handling, and disinfection with bleach (1:10 dilution) due to virus stability. – No post-exposure prophylaxis. Rationale: Norovirus is a significant global health concern due to its high infectivity, rapid spread, and lack of specific treatments. Supportive care remains the mainstay of management.
Mechanism: Inhibits ATP citrate lyase, reducing cholesterol synthesis. – Dose: 180 mg once daily. – Use: Heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) with statin intolerance. – Side effects: Hyperuricemia, gout, elevated liver enzymes.
What it is: An oral medication that is part of the class of drugs called ACLY inhibitors. How it works: Inhibits the ACLY enzyme in the liver, which reduces the production of cholesterol. It also has other metabolic and anti-inflammatory effects. Primary use: To lower LDL cholesterol in adults with heterozygous familial hypercholesterolemia, or other high-risk patients who require additional LDL reduction. Administration: Oral tablet. Key considerations: Can increase uric acid levels, potentially leading to gout. It also increases the blood concentration of some statins, so caution and dose adjustments are needed when co-administered with certain statins.
Inclisiran (Leqvio) Mechanism: Small interfering RNA (siRNA) that reduces PCSK9 production, increasing LDL receptor activity. – Dose: 300 mg subcutaneously every 6 months. – Use: HeFH or ASCVD with elevated LDL-C despite maximally tolerated statin therapy. – Side effects: Injection-site reactions, flu-like symptoms.
Evolocumab (Repatha) Mechanism: Monoclonal antibody that inhibits PCSK9, increasing LDL receptor activity. – Dose: 140 mg every 2 weeks or 420 mg monthly. – Use: HeFH or ASCVD with elevated LDL-C despite statin therapy. – Side effects: Injection-site reactions, flu-like symptoms, diabetes.
Alirocumab (Praluent) Mechanism: Monoclonal antibody that inhibits PCSK9, increasing LDL receptor activity. – Dose: 75–300 mg every 2 weeks. – Side effects: Injection-site reactions, flu-like symptoms, myalgia.
Ezetimibe (Zetia) Mechanism: Inhibits cholesterol absorption in the small intestine. – Dose: 10 mg once daily. – Use: Primary hyperlipidemia, HeFH, or ASCVD with elevated LDL-C. – Side effects: Diarrhea, abdominal pain, headache. –
Bococizumab
Bococizumab is a monoclonal antibody (mAb) that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein involved in low-density lipoprotein (LDL) receptor degradation. – Mechanism: Binds to PCSK9, preventing it from binding to LDL receptors, thereby increasing LDL receptor availability on the liver surface and enhancing LDL clearance from the bloodstream. – Indication: Used for the treatment of heterozygous familial hypercholesterolemia (HeFH) and clinical atherosclerotic cardiovascular disease (ASCVD) to reduce LDL cholesterol (LDL-C) levels. – Administration: Subcutaneous injection, typically administered every 2 weeks or monthly, depending on the dosing regimen. – Efficacy: Demonstrated significant reductions in LDL-C levels (up to 50–70% from baseline) in clinical trials, but its use has been limited due to concerns about immunogenicity and injection-site reactions. – Rationale: PCSK9 inhibitors like bococizumab are crucial for managing patients with refractory hypercholesterolemia or high ASCVD risk who do not achieve adequate LDL-C reduction with statins and ezetimibe. What it is: A humanized monoclonal antibody that targets the PCSK9 protein. How it works: By binding to and inhibiting PCSK9, it prevents the degradation of LDL receptors on liver cells, leading to more LDL being cleared from the blood. Primary use: In clinical trials to lower LDL cholesterol and reduce the risk of major cardiovascular events in high-risk patients. Administration: Subcutaneous injection, typically every two to four weeks. Key considerations: Although it has shown efficacy, long-term responsiveness may be affected by the development of anti-drug antibodies
Basilar Migraine (BM): Definition: A rare subtype of migraine with aura, characterized by symptoms originating from the brainstem and/or both hemispheres of the brain.
– Diagnosis: Criteria (IHS): At least two attacks with fully reversible symptoms (e.g., dysarthria, vertigo, tinnitus, diplopia, ataxia, decreased level of consciousness) lasting 5–60 minutes, followed by headache. –
Exclusion: Other causes (e.g., stroke, epilepsy) must be ruled out via imaging (MRI, MRA) and EEG. – Prevalence: Estimated at 1–2% of migraine patients, more common in adolescents and young adults. –
Onset: ระยะเวลาเริ่มเกิดโรค มักเป็นในเด็กหรือวัยรุ่น แต่อาจเกิดในผู้ใหญ่ได้ ที่เรียกว่า(Latent Autoimmune Diabetes in Adults, LADA).
Subtype:
เบาหวานแบบขาดอินสุลินแต่ไม่พบแอนติบอดี้ เจอในเอเชีย แอฟริกา Idiopathic Type 1 Diabetes: No autoimmunity, more common in Asian and African populations.
1.2 โรคเบาหวานแบบไม่ขาดอินสุลิน Non Insulin dependent diabetes (T2DM)
Cause:สาเหตุ เกิดจากการดื้อต่อการออกฤทธิ์ของอินสุลินในอวัยวะต่างๆ โดยที่ระดับอินสุลินไม่ได้ขาด Insulin resistance with relative insulin deficiency.
Pathophysiology: กลไกการเกิด มักสัมพันธ์กับบกรรมพันธ์ ที่มีบิดามารดาเป็น ส่วนใหญ่จะสัมพันธ์กับภาวะความอ้วนลงพุง และ เมตาบอลิกซินโดรม Strong genetic predisposition, associated with obesity, metabolic syndrome, and β-cell dysfunction.
Onset: ระยะเวลาที่เริ่มเป็น จะเป็นในอายุ มากกว่า ชนิด 1 เป็นในผู้ใหญ่ แต่ก็อาจเจอในคนอายุน้อยที่อ้วนได้ More common in adults but increasing in younger populations due to obesity.
Long-term exposure to PM2.5 contributed to 4.14 million deaths globally in 2019, accounting for 62% of all air pollution-related deaths. This represents a 23% increase over the past decade(2).
In China, PM2.5 exposure in 2019 was linked to 21,113 all-cause deaths, with significant declines in cardiovascular and respiratory deaths compared to 2015 due to improved air quality measures(9).
Cardiovascular and Respiratory Diseases:
PM2.5 is associated with premature death in individuals with heart or lung disease, nonfatal heart attacks, irregular heartbeat, and aggravated asthma(3).
It can penetrate deep into the lungs and bloodstream, causing inflammation, oxidative stress, and genotoxicity, which contribute to cardiovascular and respiratory disorders(10)(12).
Systemic Effects:
Beyond the lungs and heart, PM2.5 exposure affects the renal, neurological, gastrointestinal, and reproductive systems. It has been linked to chronic kidney disease, neurodegenerative disorders like Alzheimer’s, and adverse birth outcomes(10)(12).
Vulnerable Populations:
Children, older adults, and individuals with preexisting conditions are more susceptible to PM2.5-related health issues. Low socioeconomic status and minority populations often face higher exposure levels(3).
Mechanisms of PM2.5-Induced Health Damage Oxidative Stress and Inflammation:
PM2.5 triggers the production of reactive oxygen species (ROS), leading to cellular damage and inflammation. This process is a key mechanism behind its toxic effects(10)(12).
Immune System Activation:
Exposure to PM2.5 activates immune responses, including the release of pro-inflammatory cytokines like IL-6 and TNF-α, which exacerbate tissue damage(10).
Genotoxicity:
PM2.5 can cause DNA damage, increasing the risk of cancer and other chronic diseases(12).
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reference
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An update on adverse health effects from exposure to PM2.5
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Health and Environmental Effects of Particulate Matter (PM)
Particles less than 10 micrometers in diameter pose the greatest problems, because they can get deep into your lungs, and some may even get into your bloodstream. Fine particles (PM2.5) are the main cause of reduced visibility (haze).
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